Science and National Security in the Post-9 11 Environment Issue briefs and links to useful resources on key issues related to the topic of balancing national security and scientific openness. AAAS - Science and National Security Log In | Join | Search | Site Map | Contact Home About AAAS Programs Membership Publications News Career Support Advanced search AAAS Events Links Events AAAS Board AAAS Council AAAS Elections AAAS Statements AAAS Store Annual Meeting Archives Awards Development Education Employment Experts Governance International Make a Gift Media Relations Membership Organization Press Releases Science Science Books Film Science Policy Science and Security in the Post-9 11 Environment Since 9 11, the challenge of finding the right balance between serving our national security and maintaining the openness required for the advancement of science has become more vexing than ever. By providing issue briefs and links to useful resources on key issues related to this topic, this website aims to aid scientists, policy makers, and the general public as they struggle to meet this challenge. Has your research or that of your colleagues been affected by post-9 11 security policies? Click here to participate in this AAAS study. Issues in Focus Foreign Students and Scholars Because of concerns about terrorism, it is becoming increasingly difficult for students and scholars in science and technology fields to obtain visas, a situation that could have serious consequences for scientific progress. More... Select Agent Rules The federal government has implemented a new regulatory program to monitor and oversee the use of biological agents considered to pose a threat to public health and safety. While aimed at decreasing the threat of bioterrorism, these new rules may make it more difficult to conduct legitimate scientific research. More... Federal Grants and Contracts Universities have recently encountered several attempts by federal agencies to impose restrictions on research grants or contracts that impinge on academic freedom. More... Scientific Publication Policies The scientific community, which thrives on free and open communication of information, must decide whether and to what extent restriction of the publication of certain studies is necessary to protect national security. More... "Sensitive But Unclassified" Information Increasingly, the U.S. government has sought to restrict access to information deemed "sensitive but unclassified," a designation that has caused serious concern in the scientific community. More... Other AAAS Resources Scientist on Trial This free blog kept by news reporters for Science chronicles the trial of Thomas Butler, a researcher at Texas Tech University accused of breaking laws on the handling of biological agents. More... Fear of "Foreigners" May Slow Scientific Progress International students play an important role on U.S. campuses, but since a shaken U.S. government tightened visa rules in the wake of terrorist attacks, the backlog of visa applications from young scholars has grown. More... Science Technology in a Vulnerable World In the wake of 9 11, the ST community must consider carefully the contributions that it can make to combating terrorism and at the same time consider the impacts that security measures will have on the nations research and education institutions. This volume reproduces six talks on these issues presented at the 2002 AAAS Colloquium ST Policy. More... Click here for more resources from AAAS on science and national security. Related Projects at Other Organizations Several other organizations are also studying aspects of these issues. For example, policies affecting foreign students and scholars have attracted interest from The National Academies, NAFSA, AAU, and NASULGC, among others. More... Copyright 2005. American Association for the Advancement of Science. All rights reserved. Read our privacy policy . Contact info. Mission | History | Organization | Fellows | Annual Meeting | Affiliates | Awards | Giving Education | Science Policy | International Initiatives | Centers Join | Renew | Benefits | Member Sections | Membership Categories | Log in Science Online | Books Reports | Newsletters | SBF | Annual Report | Store Press Room | Events | Media Contacts | News Archives Science Careers | Next Wave | Fellowships | Internships | Employment at AAAS Post-9 11 Home About Us Contact Us Center for Science, Policy, and Outcomes A non-profit think tank that works with the U.S. Congress on issues involving science policies and their effects on society. Includes issues papers and analyses on current topics. CSPO - Consortium For Science, Policy Outcomes - About Us Glowing Meat Alarms Australians: Australians have been told there is no need to panic after a recent "glow-in-the-dark pork chop" scare. November 16, 2005 Wildfires decimating saguaros: After decades of survival, the giant saguaro is under a withering assault by wildfires, an enemy now more insidious than all others combined . November 13, 2005 A desert without saguaros: It could happen, researchers say: Saguaros could disappear because of the fragmenting of their habitat through development and wildfire. November 13, 2005 A More Social Science: An interview with Dan Sarewitz about the Center for Nanotechnology in Society's approach to socially responsible scientific research. CSPO is co-sponsoring the First World Forum on Science and Civilization in March 2006: Tomorrow's People: The Challenges of Technologies for Life Extension and Enhancement CSPO and the Center for Nanotechnology in Society have employment opportunities at undergraduate, graduate, and post-doctoral levels: Find out more Building Amish Community with Technology: Regulating Machines and Techniques to Forward Social Goals: An article by Jameson Wetmore submitted to IEEE Technology Society Magazine Managing the Next Disaster: An opinion piece by Daniel Sarewitz and Roger Pielke in the September 23rd edition of the LA Times. Scientists' Participation in University Research Centers: What are the Gender Differences? An article by Elizabeth Corley and Monica Gaughan in the Journal of Technology Transfer. High Technology Military Dominance: The Opiate of Modern Empire: To those who lack experience with the limits of military power, military prowess, embodied in incredible potent technological capabilities, acts like a drug, leading to dysfunctionally oversimplistic policy choices. Just as countries rich in oil or other resources tend to squander their opportunities, especially in the absence of strong governance, countries rich in military-technological power may be seduced by it into misperceiving their true sources of power. By Brad Allenby Courses Email Subscription Events Positions Journals Governance Globalizing Society Social Change Environment Human Health Privacy Policy . Copyright 2004 . Arizona State University Consortium for Science, Policy Outcomes College of Liberal Arts and Sciences PO Box 874401, Tempe AZ 85287-4401, Phone: 480-727-8787, Fax: 480-727-8791 cspo@asu.edu Association for Politics and the Life Sciences Interdisciplinary association concerned with problems or issues that involve politics or public policy and one or more of the life sciences. Journal and newsletter, online membership form, reading lists on various topics, and other information. Association for Politics and the Life Sciences The Association for Politicsand the Life Sciences (APLS) is an international and interdisciplinaryassociation of scholars, scientists, and policymakers concerned with problemsor issues that involve politics or public policy and one or more ofthe life sciences. The association, founded in 1980, publishes a journal,Politics and the Life Sciences; a newsletter, APLS News;and a membership directory, The APLS Directory. The association'sannual conference is held in late August or early September, concurrentlywithbut independently ofthe annual meeting of the American Political Science Association. Center for Advanced Studies in Science and Technology Policy The Center for Advanced Studies in Science and Technology Policy is a private, non-partisan research and advisory organization focused on information, technology, and national security policy and related issues. The Center for Advanced Studies in Science and Technology Policy Overview Executive Director Project Partners Download about.pdf Featured Articles Forthcoming Publications Working Papers Recent Presentations Information Policy Enabling Technologies Security Applications Research Projects Policy Advisory Security Advisory Corporate Advisory Related Research Projects Catherine Yang, " The State of Surveillance ," BusinessWeek Cover Story (August 8, 2005). BusinessWeek Online, " Surveillance Society: The Experts Speak " (August 8, 2005). Justin Rood, "All-Star Privacy Panel Assembled by LexisNexis," Congressionl Quarterly, Homeland Security - Technology (March 30, 2005). [ related ] ACM TechNews, " Center for Advanced Studies Releases Policy Appliance Reference Model, " Volume 7, Issue 748 (Jan. 31, 2005). Markle Weekly Digest, New Reports and Papers2, Policy Appliance Reference Model: An Overview , Vol. 4 No. 5 (Jan. 28, 2005). See also U. S. Newswire (Jan. 27, 2005). Bruce Schneier, "Good analysis [by the Center for Advanced Studies] of the security implications of not giving illegal aliens drivers licenses," CRYPTO-GRAM (Jan. 15, 2005). Joe Feuerherd, "Republicans line up on both sides of illegal immigrant drivers debate," NCReporter (Jan. 14, 2005). Kim Zetter, " Brave New Era for Privacy Fight ," Wired News (Jan. 13, 2005). News Story, "Not Issuing Drivers' Licenses to Illegal Aliens May Be Bad for National Security," Government Technology (Dec. 21, 2004). Sarah Lai Stirland, " Panel Raises Questions About Government Information Sharing ," GovExec.com National Journal's Technology Daily (Nov. 9, 2004). KDnuggets News 04:21 (Nov. 09, 2004). "Government Should Not Rush to Massive ID Surveillance System," PLENSIA (Oct. 29, 2004) [ more ] Justin Rood, "Experts Disagree on Balance Between Intelligence, Privacy Protections," Congressional Quarterly, Homeland Security - Intelligence (Oct. 15, 2004). E-Brief, "Civil Liberties," National Journal's Technology Daily (Oct. 15, 2004). A Panel of National Policy Experts Debated the Security and Privacy Impacts of New Information Technologies in the War On Terror, PLENSIA (Oct. 14, 2004) [ more ] More news ... CAS Executive Director Kim Taipale spoke at The Heritage Foundation roundtable "Science and Technology: Identity Theft" in Washington, DC, Nov. 2, 2005. [ related ] CAS Executive Director spoke on "Technical and Policy Challenges: Implications for Evolving Business Models" at the 16th Annual Economic Crimes Institute Conference in Tysons Corner, VA, Oct. 24, 2005. [ related ] CAS Executive Director presented "The Future of the Nation State: Confronting Hostile Adaptive Networks," GISP, New York, NY, Sept. 28, 2005. CAS Executive Director presented "Data Mining and Counterterrorism: Methodology and Policy," at "Advancing Analytic Techniques in Counterterrorism Analysis," in Arlington, VA, August 19, 2005. CAS Executive Director participated in National Science Foundation workshop on "Emerging Technologies in Security Evaluations," Arlington, VA, July 13-14, 2005. CAS Executive Director spoke on "Information Policy and the Intelligence Enterprise," McLean, VA, Apr. 12, 2005. CAS Executive Director presented " Information as Warfare: Disrupting Terrorist Networks " at the "Global Flow of Information " Conference, Yale Law School, New Haven (Apr. 1-3, 2005). CAS Director spoke at the Computer Science and Telecommunications Board workshop on Biometrics , The National Academies, Washington, DC, Mar. 15-16, 2005. [ more ] The Center announced the release of its Policy Appliance Reference Model as part of the Global Information Society Project at the World Policy Institute (Jan. 27, 2005). [ more ] "Not Issuing Driver's Licenses to Illegal Aliens is Bad for National Security," said CAS Executive Director regarding the Real ID Act in a statement released at a PLENSIA forum in New York, Dec. 17, 2004. [ more ] CAS Executive Director spoke on "Public Safety vs. Personal Privacy: The Case For and Against Secure Flight" at the InfoSecurity 2004 conference in New York on Dec. 8, 2004. [ more ] CAS Executive Director spoke on "Counterterrorism Technology and Privacy" at the ABA Standing Committee on Law and National Security conference on "National Security Law in a Changed World: The 14th Annual Review of the Field," in Arlington, VA on Nov. 18-19, 2004. [ more ] CAS Execuitve Director participated in The Potomac Institute for Policy Studies program, "How Should the US Implement Information Sharing? A Discussion of the Executive Order Strengthening the Sharing of Terrorism Information to Protect Americans" in Arlington, VA, Nov. 9, 2004. [ more ] CAS Executive Director spoke on "Technology for Security and Safety: Industry's Role," at a conference hosted by the International Chamber of Commerce on Oct. 25, 2004 in Paris, France. CAS Executive Director moderated "Law Enforcement and National Security in the Information Age: Technology, Security, and Privacy in the War on Terror," a panel discussion hosted by the Center for Advanced Studies and the World Policy Institute, Oct. 14, 2004, in New York. [ more ] More events ... CAS Executive Director Kim Taipale to present "Destabilizing Hostile Networks: Information Operations in the War on Terrorism," GISP, New York, NY, December 14, 2005. Center for Advanced Studies to release "ID-me: Using Identity Registrars to Eliminate Identity Theft and Protect Privacy," Preliminary Proposal (Jan. 2006). [ related ] View recent events. Global Information Society Project Program on Law Enforcement and National Security in the Information Age Program on Telecommunications and Cybersecurity Policy Program on Information Warfare World Policy Institute Home| About | Research | Services | Publications | News | Contact | Privacy Copyright Office of Science Technology Reports focus on research and development policy changes and trends in Europe and the U.S. Office of Science Technology About OST Programs Projects Publications Research Tools Contact Us Search Network of Researchers | Policy Consulting | Cooperation | Site Map Building bridges of knowledge and expertise between Austria and North America is the motto of the Office of Science Technology at the Embassy of Austria in Washington, DC. As a strategic crossroads for Austria and North America in the sciences, research, and research policy, the OST's main focus is in the following areas: The establishment and maintenance of a network of Austrian scientists and scholars in North America Policy consulting in the sciences, research and technology Consulting and support in initiation of new RD cooperation ***Austrians Coming To The US Now Require a US Visa*** The US Department of Homeland Security has issued a letter stating that certain Austrian passport holders are temporarily ineligible to enter the US under the Visa Waiver Program. Click here to see if you are affected by this new regulation. bridges Volume 7 - now on-line! Click here to see our newest edition. EURYI Awards - 3rd Call for Proposals The European Young Investigator Awards have been created to enable outstanding young researchers from all over the world to come and work for the benfit of European Science while gaining excellent experiences. The application deadline is November 30, 2005. Click here for more information. Help Develop the European Institute of Technology (EIT) The European Commission would like your input on developing the European Institute of Technology. To find out how you can share your thoughts and suggestions, visit here ! Faculty Positions Available At the IMP Vienna Applications for Group Leader and Staff Scientists openings at the Research Institute of Molecular Pathology in Vienna must be submitted by November 30, 2005. Click here for more information. Prof. Rudolf Taschner, Austrian Scientist of the Year, to present "The Magic of Mathematics" at Austrian Embassy The OST is pleased to announce another lecture in its Austrian Science Series. The lecture by Prof. Taschner will be held on November 7th at the Austrian Embassy. RSVP is required. For more information please visit here . AustroMars Project Needs Crew Members The Austrian Space Forum (WF) will conduct a Mars landing simulation. The event will take place in April 2006 in Utah, USA. To read about the project, please visit here . 10th Annual Conference of the BioFeedback Foundation of Europe to be held in Vienna The BioFeedback Foundation is holding its 10th Anniversary meeting in Vienna. The event is being held in conjunction with the Austrian Society for Biofeedback and Psychophysiology (BfP). Click here for more information. Copyright 2005 OST - All Rights Reserved About OST | Programs Projects | Publications | Research Tools | Contact Us | Network of Researchers | Policy Consulting | Cooperation | Site Map Conseil de la science et de la technologie Science, technology and innovation policy. Many publications available online. Advisory agency to the Qubec government. Conseil de la science et de la technologie du Qubec - English Latest News from the Conseil Communiqu La culture scientifique et technique : une responsabilit collective Rapport de conjoncture 2004 du Conseil de la science et de la technologie Tlchargez ce communiqu (pdf format, 322k) Communiqu Sainte-Foy, July 2000. The Conseil des ministres, at its June 1 session, made the following nomination. Madame Hlne P. Tremblay has been appointed member and President of the Conseil de la science et de la technologie as of 21 August 2000. Communiqu The Conseil de la science et de la technologie recommends that Qubec benefit fully from research in social sciences and the humanities, an essential contibution to innovation Sainte-Foy, 22 February 2000. The Interim President of the Conseil de la science et de la technologie, Mr Camil Guy, announced today the publication of an Advisory Report concerning measures to be taken to best benefit from research in social sciences and the humanities. Entitled Social innovation and technological innovation: The contribution of research in the social sciences and the humanities, this Advisory Report has been transmitted to Mr Jean Rochon, Minister of Research, Science and Technology. The complete document is available in pdf format on the publications page of the Conseil. The Summary of the Advisory Report is available for consultation in English. Communiqu Sainte-Foy, 11 February 2000. Mr. Camil Guy, Secretary General of the Conseil de la science et de la technologie, has been named Member and Interim President of the Conseil. Communiqu Sainte-Foy, 7 February 2000. Mr. Camille Limoges leaves the presidency of the Conseil de la science et de la technologie. Mr. Limoges has been named, as of 7 February, Deputy Minister of the Ministre de la Recherche, de la Science et de la Technologie. Montral, 3 February 2000. The Montral office of the Conseil de la science et de la technologie has moved. Our new location is 2021, avenue Union, 9th floor, Suite 9.35, Montral (Qubec) H3A S29. Telephone and fax numbers remain unchanged. Full information is available on the appropriate page on our site. Communiqu. The Conseil de la science et de la technologie recommends increased funding and a networking approach to support technology transfer centers Sainte-Foy, 26 January 2000. The President of the Conseil de la science et de la technologie, Mr Camille Limoges, announced today the publication of an Advisory Report concerning the set of technology transfer centers which receive ongoing funding from the Qubec government. Entitled Catalyzing Innovation. Transfer Centers and Their Funding, this Advisory Report has been transmitted to Mr Jean Rochon, Minister of Research, Science and Technology. The complete document is available in pdf format on the publications page of the Conseil. The Summary of the Advisory Report is available for consultation in English. Communiqu. The Conseil de la science et de la technologie recommends increased funding to assure competitive support for university research Sainte-Foy, 16 November 1999. The President of the Conseil de la science et de la technologie, Mr Camille Limoges, announced today the publication of an Advisory Report concerning the state of university research in Qubec. Entitled To Understand and To Innovate. Assuring Competitive Means for University Research, this Advisory Report has been transmitted to Mr Jean Rochon, Minister of Research, Science and Technology. The complete document is available in pdf format on the publications page of the Conseil. The Summary of the Advisory Report is available for consultation in English. 23 August 1999. At its meeting of 18 August 1999, the Conseil des ministres proceeded with nominations of the members of the Conseil de la science et de la technologie. The renewed membership of the Conseil may be consulted on the page Mandat et membres . July 1999. Se puede leer, en espaol, una descripcin de las actividades del Consejo de la ciencia y de la tecnologa , una lista de sus miembros y de sus mas recientes publicaciones. Se puede tambien consultar el resumen del mas reciente aviso del Consejo, intitulado El Estado, agente de la innovacin. The Summary of Conseil publications is henceforth available in Spanish. Communiqu The Conseil de la science et de la technologie recommends the strengthening of scientific and technical activities necessary for government to play its role as an actor in innovation. Sainte-Foy, 5 July 1999. The President of the Conseil de la science et de la technologie, Mr. Camille Limoges, made public today an Advisory Report entitled L'tat acteur de l'innovation. La science et la technologie dans l'administration gouvernementale. This report was delivered to Mr. Jean Rochon, minister responsible for Research, Science and Technology. Mr. Limoges said that governments play a number of important roles in the innovation system, as recent reports of the Conseil have shown. This report looks at one of the less well-known aspects: the role of government in pursuing research and other scientific and technical activities, either to support innovation or, more generally, to assist the state in exercising its responsibilities. The Advisory Report is available on the web site of the Conseil, as is an English-language Summary . Communiqu The Conseil de la science et de la technologie recommends the implementation of an innovation policy guided by three broad priorities Sainte-Foy, 24 February 1999. The President of the Conseil de la science et de la technologie, Mr. Camille Limoges, made public today an Advisory Report in which the Conseil reiterates the urgency for Qubec to adopt a policy on innovation. The current state of the innovation system in Qubec as portrayed in the Conseil's various reports demands that the implementation of a Qubec innovation policy be guided by three broad priorities. The report, Strengthening Innovation: the Priorities was delivered to Mr. Jean Rochon, minister responsible for Research, Science and Technology. The Advisory Report is available on the web site of the Conseil, as is an English-language Summary . Communiqu The Conseil de la science et de la technologie recommends governmental action adapted to the sectoral realities of innovation Sainte-Foy, 3 February 1999. The President of the Conseil de la science et de la technologie, Mr. Camille Limoges, made public today an Advisory Report devoted to a study of the factors and efforts of innovation in three industrial sectors: aerospace, pharmaceuticals and forest products. The report, Innovation: A Sectoral Outlook (Aerospace, Pharmaceuticals, Forest Products) was delivered to Mr. Jean Rochon, minister responsible for Research, Science and Technology. The Advisory Report is available on the web site of the Conseil, as is an English-language Summary . Publications of the Conseil are available to the public online. These publications usually appear in French. The Conseil has the mandate to advise the Minister responsible for Research, Science and Technology on issues related to science and technological development in Qubec. Tax holiday for foreign researchers. The law creating the Ministre de la Recherche, de la Science et de la Technologie was sanctioned on 8 June 1999. The Ministry assumes henceforth the responsibility for issuing the qualification certificates required for the tax holiday for foreign researchers. Please communicate with Mr. Nghip L Hng of the Direction du soutien l'innovation technologique of the Ministre de la Recherche de la Science et de la Technologie at (514) 982-3001, for information concerning this programme. The Conseil maintains and develops a web page concerning the principal actors in science, technological development and innovation in Qubec. See the Rseau science-technologie Qubec . Address, phone, fax, and e-mail information is available. Return to top of the page Accueil Courrier Plan du site Nouveau Mandat et membres Publications Rseau science-technologie Section Perspectives STS Site CEST Dernire mise jour : le 27 octobre 2004. Science-Metrix - Measurement and evaluation of science and technology Evaluation and measurement of science, technology and innovation (STI). Mainly downloadable reports on STI policy and strategy. Science-Metrix - Science and Technology Evaluation and Measurement Society and Science - The British Council Description of the British Council's policy in science, engineering and environment. Society and Science - British Council - Science Text only Print | E-mail this page | Add to favourites | Suggest similar pages Society science Science matters to every single on of us. It affects our everyday lives in thousands of different ways, and the scientific advances of today will shape how our lives change in the future. People around the world are interested in creating wealth, using and adapting technologies for their own needs, having a say in democratic processes, using new media and engaging with popular arts, literature and culture. Particularly for the young, science and modernity are inseparable, and technology is culture. Images of a modern UK are unthinkable without science, engineering and technology. Culture Lab UK Want to know more about the latest innovations from the UK? Why not visit our online magazine, updated every month with articles on design, digital technology, fashion, life, film, and music. Find out more Caf Scientifique Caf Scientifique engages a wider audience with science and the impact it has on society through informal debate on topical issues. Find out how you can get involved. Women in science Read our special feature on women in science , engineering and technology (SET) for information on the policies, initiatives and actions in the UK that open the doors of SET to women. Sci-art In the field of public engagement, many scientists seek to communicate their ideas through a crucial partner, the artist. Read more about how art and science work together as mutual sources of inspiration. Science literature The UK is home to some of the best writing about science, not just explanatory texts, but fiction and poetry inspired by science as well. Read more about the diversity of science literature in the UK. Science Discovery Science centres and museums can play a major role in engaging the public in a genuine dialogue about science and the issues that it raises for society. Visit the following websites for examples of interactive visitor experiences: Magna Science Adventure Centre, Rotherham, UK (pictured above) Dynamic Earth, Edinburgh British Interactive Group Resources Art and Science: a new partnership The purpose of this briefing sheet is to give some sense of the range and the purpose of current sci-art activities in the UK. If you are new to the field, find out how you can get involved. Public understanding of science This briefing sheet provides details of the UK's policy and response to the task of increasing public awareness of science. Read about how the UK tackles this issue. Women in SET: the UK experience This briefing sheet shows how the role of women in science and engineering can be promoted effectively at different levels, from international networks and overarching government policies to local courses. We are registered in England as a charity. Our privacy and copyright statements. Our Freedom of Information Publications Scheme . Double-click for pop-up dictionary . Geology Public Policy Join the GPP List Serve or Geology in Government Mentor Program. Be a Congressional Science Fellow. Read congressional and federal actions which affect the geoscience community. Geological Society of America - Policy Government Affairs Position Statements GPP List Serve Monthly Review (AGI) Geology Public Policy Committee Critical Issues Congressional Science Fellowship Institute for Earth Science and The Environment Geology Public Policy Kansas Denied Use of National Science Education Standards The National Academy of Sciences and the National Science Teachers Association have refused to grant copyright permission to the Kansas State Board of Education to make use of publications by the two organizations in the state's science education standards. According to a statement from the two groups, the new Kansas standards are improved, but as currently written, they overemphasize controversy in the theory of evolution and distort the definition of science. (10 28) [ read statement ] What Can Be Learned from Hurricanes Katrina and Rita? GSA is a sponsor of a congressional briefing hosted by the U.S. Geological Survey (USGS) on 28October 2005. The focus is how science can help reduce Americas risk from hurricanes and their aftermath. (10 28) [ read more ] HOW DO I GET INVOLVED? GSA expresses concern about the House Committee on Energy and Commerce's request sent to three scientists on climatechange. [ read letter ] Communicate! You can contact your member of Congress about earth science and environmental issues of concern. Visit your representative at the district office or in Washington. It is an excellent opportunity to impress your scientific expertise upon him or her. Ensure that the geoscience community is being represented on the Hill! Supporting information and materials can be found on these Web sites. American Association for the Advancement of Science (AAAS) RD Congressional Visits Day Council of Scientific Society Presidents (CSSP) Coalition for National Science Funding Stay informed by joining GSA's Geology Public Policy ListServe . Explore current issues marrying science, government and policy. Check out the congressional and federal actions which affect the geoscience community. Get involved and communicate with your senators and representatives. Work on CapitolHill Check out our Congressional Science Fellowship program. Your work as a geoscientist greatly impacts society and Earth. Why not make an impact on our government as well? We are currently seeking candidates for 2006-2007 (deadline: 1Feb. 2006). Become a mentor! Join our Geology in Government MentorProgram . Official GSA Position Statements Geoscience DataPreservation Adopted in October 2005 Geoscience and Natural Hazards Policy Adopted in October 2005 Visas for Foreign Scientists and Students Adopted in May 2005 Open Access to Data Adopted in May 2005 The Importance of Teaching Earth Science in the PublicSchools Adopted in April 2004 The Value of Geologic Mapping Adopted in November 2003 Scholarship and Professional Activity in Geoscience Public Policy and GeoscienceEducation Adopted in May 2001 Evolution Adopted in May 2001 You can use the above statements when you work with local citizens or contact your member of Congress about earth science and environmental issues ofconcern. Proposed Position Statements The Evaluation of Scientific Information Co-chairs: George Fisher and Mark Peters "Never doubt that a small group of thoughtful, committed citizens can change the world. Indeed, it's the only thing that everhas." MargaretMead top Bookstore | Online Journals | Publications Services | Meetings Excursions | Membership | About GSA Employment | GeoMart | Grants, Awards Recognition | Education | Interns Mentors | Students Sections | Divisions | Public Policy | GSA Foundation | Geoscience Links | Newsroom GSA Home | Contact Us | FAQs | Site Search | Site Map | Privacy Policy 2005 The Geological Society of America Last Revised on 14 November, 2005 AAAS Science and Technology Policy Fellowships Provide opportunities for accomplished postdoctoral to mid-career scientists and engineers to contribute to the public policymaking process. AAAS - The World's Largest General Scientific Society Log In | Join | Search | Site Map | Contact Home About AAAS Programs Membership Publications News Career Support Education | Science Policy | International Activities Advanced search AAAS Events Links Events AAAS Board AAAS Council AAAS Elections AAAS Statements AAAS Store Annual Meeting Archives Awards Development Education Employment Experts Governance International Make a Gift Media Relations Membership Organization Press Releases Science Science Books Film Science Policy WHAT'S NEW? Online application system now open Register start your application today! HEADLINES October 2005 Christophe McCray, 2005-06 Defense Policy Fellow, focuses on battlefield forensics research in the Office of Naval Research at the Department of Defense. More Headline News AAAS Science Technology Policy Fellowships The fellowships help to establish and nurture critical links between federal decision-makers and scientific professionals to support public policy that benefits the wellbeing of the nation and the planet. The Fellowships are designed to: educate scientists and engineers on the intricacies of federal policymaking; provide scientific expertise and analysis to support decision-makers confronting increasingly complex scientific and technical issues; foster positive exchange between scientists and policymakers; empower scientists and engineers to conduct policy-relevant research that addresses challenges facing society; and increase the involvement and visibility of scientists and engineers in the public policy realm. The Fellowship support the AAAS objectives to improve public policymaking through the infusion of science, and to increase public understanding of science and technology and are part of AAAS Science Policy Programs . For more information about particular fellowship opportunities, please click the links under the Fellowship Programs menu option on the left. Copyright 2004. American Association for the Advancement of Science. All rights reserved. Read our privacy policy . Contact info. 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Marian Koshland Science Museum of the National Academy of Sciences Plan Your Visit: Hours, admissions, directions and information for group visits. Follow the clues to solve the forensic mystery during a two part event on November 17th and 19th. Bringing science back to life thoughts on goal-oriented science funding. Bringing science back to life Notify Blogger about objectionable content. What does this mean? BlogThis! Random thoughts about this scientist's life and work and about drug discovery and the pharmaceutical industry Archives 01 01 2004 - 01 31 2004 02 01 2004 - 02 29 2004 03 01 2004 - 03 31 2004 04 01 2004 - 04 30 2004 05 01 2004 - 05 31 2004 06 01 2004 - 06 30 2004 07 01 2004 - 07 31 2004 09 01 2004 - 09 30 2004 10 01 2004 - 10 31 2004 11 01 2004 - 11 30 2004 01 01 2005 - 01 31 2005 02 01 2005 - 02 28 2005 03 01 2005 - 03 31 2005 11 01 2005 - 11 30 2005 Recent posts Greenhouse gases vs traffic victims Meeting of minds Stem cells and cancer Of directories and websearches Meeting and networking Time for change New Year resolutions Stem cells don't exist The wonders of modern science Global warming versus world AIDS Bringing science back to life Mail comments to Nick Henriquez Google search Interesting med-science METABRE breast-cancer research project website Interesting Pharma-Blog Site Feed Friday, November 04, 2005 Greenhouse gases vs traffic victims Gee has it really been that long? Must be all those sleepless nights that made me think it was only "yesterday" I last posted. Anyway, a majority of dutch elected representatives have decided that it would be an excellent idea to start making laws that oblige people to always drive with their lights on. Apparently this would save up to 45 lives per year. I would love to see how they calculate such a thing, I bet I would have one or two comments to make regarding facts, statistics and wild guesses. What has been calculated though is that cars use up to several percentage points more fuel when their lights are on. Now I am not advocating for one second that people should always leave their lights off to save our planet. However I would like to see those number crunchers include the adverse effects of increased fumes and greenhouse gases on deaths to determine whether the net effects of having lights on at all times are positive. I doubt this will be the case in my country once environmental effects are factored in. The equation is likely to be different in various countries and situations but to decide such a thing based on a guesstimate regarding traffic victims... Well, not in my name! Needless to say I have written to several of our so-called representatives, let's see if they are a smart as their suits.... - posted by Nick @ 19:50 | Saturday, March 26, 2005 Meeting of minds I'm almost off to Keystone where many of the best will come to tell us about the role of the protein TGFb in disease. And to ski of course.... Just before I go I wanted to give a brief update on the cancer stem-cell issue. In many cancers people have indeed shown that a subpopulation of the cells has a relatively large potential to cause new cancers. Removal of that same subpopulation reduces or removes the ability of the rest of the cancer to cause new cancers. This has led to the conclusion that there are "cancer stem cells" against which I have no argument at all; it was clear from the onset that the only cell-type which can originate cancer is going to be stem-cell-like in many respects. The proof in my view still hasn't been found for most cancers and we can always argue about "proof" in science but apart from neurons the only cell type known to have sufficient longevity to collect many cancer-inducing "hits" is at least stem cell-like. The problem is CAN WE TREAT THEM? Of course it will be possible to target stem-cells in certain ways, and in experimental settings this may have beneficial effects. In fact the papers are out there to show that indeed this does have beneficial effects.. However, from bitter experience we should by now know that every time we "specifically target" a cell-type in real life also other cell types are affected. We also know that the treatments we now give to people deplete their stem-cells already and cause "early ageing syndrome" as well as new kinds of diseases including secondary cancers. Curing cancer is no picknick, especially not for the cancer survivor. My prediction remains that cancer stem-cells will be sufficiently like other stem-cells in that we will affect the normal stem-cell population. This will have even more detrimental effects to long-term health as it depletes precisely that population which has allowed people to recover from anticancer treatments up to now. Targeting stem cells is about as good an idea as removing an organ from the body. It may cure the cancer but it won'thelp the patient (much). To all of those out there who say "well he she would die if we don't intervene" I say True, but we all die sometime. The most important thing is how we live not how long. Stem-cell targeted therapy should be used only with the utmost care and NEVER in someone young. - posted by Nick @ 08:28 | Tuesday, February 15, 2005 Stem cells and cancer Like so many senior post-docs my boss came back from an interesting meeting chock-full of new ideas. The latest "fashion" in cancer biology is the resurgence of the stem-cell concept and he had been convinced that we should be studying this in more detail. In this concept the reason cancer recurs is that we have been targeting the wrong (sub)population of cells, the proliferating compartment, whereas the pool of "cancer-stem-cells" is left relatively unaffected. What worried me was that, like so many scientists these days, he had been convinced that cancer-stem-cell ablating therapy is the way forwards. I completely disagree with that point of view. The short version of my reasons is that like all cancer therapy anti-cancer-stem-cell therapy will negatively affect normal cell populations in the body of patients. Unlike the proliferative populations we kill off with current therapies stem-cells likely to be killed off then cannot easily be regenerated by the human body, if at all. The problem here is that we would not even be able to properly measure how we are affecting the normal stem-cell population as we in large part don't yet know what they look like nor where they are. Therapy targeting the stem-cell compartment of tumours would thus in my opinion likely be even more deadly than the cancer itself. What is my solution? Well, like the native americans we shouldn't object to a few well-behaved settlers. To stick with this analogy we should only interfere when those (cancer-stem-cell) settlers start to obstruct normal access to resources, i.e. by preventing normal stem-cells from accessing their proper niche, or when they start to "build cities". It is not the settlers but their behaviour that needs to be controlled. In the next few days-weeks I will explain and elaborate some more on this in a more scientific manner. - posted by Nick @ 06:55 | Saturday, February 12, 2005 Of directories and websearches Time for another blog. This one a random rant about web directories and the increasing difficulty to obtain relevant hits from a search. The rant is frequently intiated when I try to do a broad search for lets say a new cancer medicine to see if there have been lay publications or to see what the trade-name is for what I know as drug XYZ123 in the lab. No sooner have you entered the search in Google (or any other search engine you choose) and your screen is filled with paid-for links to on-line drugs which have absolutely nothing to do with your search apart from the fact that drugs are sold there. With a bit of luck you will get to page three of links having skipped through several links selling viagra, a few porn-touting sites and finally find one or two about what you were actually looking for. A sideways related phenomenon to this is that as a blogger and "owner" of my own domain I apparently rate as someone to trade links with. Just today I had (yet another) offer from someone who was "willing to upgrade my link in web-directory X, thus increasing my traffic" if I would put a link to his site on my site. Of course I was listed in completely the wrong part of the directory. Some web-directories have put me under various technologypolicy-related headings because at one point (long-long-ago) I blogged a few times about the difference in funding mechanisms between academia and companies and the influence thereof on science. Obviously few if any actually bother to visit to find that I am non-commercial and completely uninterested in high traffic . It is directories like these that "upgrade links" and copy inaccurate files from eachother that are in large part to blame for Googles decreasing efectiveness in determining actually interesting pages. They found a way to abuse what was originally a great idea to separate corn from chaff. I guess what I really want is for the moneygrubbers to keep their spam-links off the internet. Unfortunately some people manage to make money out of spam and like those pushing drugs and committing violent crime, as long as there's a buck to be made someone will do it. Just a shame that this is (mostly) legal...... - posted by Nick @ 21:38 | Saturday, January 15, 2005 Meeting and networking One of the many "perks" of being a scientist is that you get to travel a lot to meetings where you can discuss your (and their) work with peers from other countries. Of course someone (in fact many ones) have to organise these meetings. The large ones tend to be organised by professionals with limited oversight and input from the participants but smaller ones are still organised by anyone from small groups like ours to the administrators of large institutes depending on size and complexity. This week it was our turn to organise a meeting between our various collaborators within our MetaBre consortium. People from Italy to Poland to the UK would descend upon the city of Leiden. Granted, there were only about thirty of us but it was the first time that I have had to be at the forefront of organising anything like this. As a consequence some things went very well but others didn't which makes it difficult for me to accept the compliments heaped upon me and my boss for organising "a perfect meeting". One embarrasing problem I encountered was that a restaurant where I had taken a few of us who had arrived the evening before the start did not take credit cards. A common thing in my country where pretty much everyone has pin-cards which don't cost the proprietors as much in fees and surcharges levied by credit card companies. Next time I'll know better.... Also I had expected only a couple of the juniors to come out as it was in honour of someones birthday but suddenly we were "saddled" with a bevy of proffessors and discussing science rather than getting to know eachother. Not a problem, only the venue was not where I would normally take senior people. It was a cosy but not very sophisticated cafe with as main drawing points being near to the hotel and serving good (but very simple) food for a low price. Oh well, another one for the continuous education files I guess. Remains to say that otherwise people did enjoy both fruitful discussion as well as the surroundings of our small but very beautiful Leiden. I guess that the praise means that at least some people didn't mind the glitches of the first night. One thing though; I'll never again snap at a harassed organiser who hasn't got my file at hand. I have become rather awestruck by the amount of detail that one needs to take care of. Apart from multi-year projects such as the Cassini Huygens or e.g. buidling the next particle accellerator I don't know of any scientific endeavour requiring quite that amount of forethought and planning. My hat of to all those secretaries and volunteers who really make these meetings work! - posted by Nick @ 14:48 | Sunday, January 09, 2005 Time for change Time for another blog. Once again not about science but about the shocking frivolity of the rich West in the face of suffering. With the scenes of the tsunami still seared into me I was relieved to find that the US government had, after considerable "encouragement", decided to increase it's pledge for help from an embarrassing $ 35 million to $ 350 million. As the dutch and UK citizenry combined had already given more than that this still wasn't earth shattering but in the league of nations the US no longer comes bottom. My relief was to be very brief however, as I almost immediately found that the president's inaugural event is going to cost an estimated $ 50 million. And people wonder why the US is not very popular.... Spend less on parties and give more to the needy. I find it completely obscene when not just abroad but even within the richest nation on earth people lack for food and can't pay for education or medical insurance that people would even consider spending so much on something so useless...... - posted by Nick @ 17:51 | Saturday, January 01, 2005 New Year resolutions Like many people I have made some New Year resolutions. Not because the 1st of the new year is so significant but because the past holiday period has given me sufficient time to think about things I would like to see changed and what I can cannot do about that. Of course the devastation of countries around the Indian Ocean by the tsunami has affected me. Although I was lucky enough not to lose anyone in that disaster myself, the dead-toll and perhaps more worryingly the number of people without homes livelyhoods still increases by the hour. Instead of buying fireworks which we traditionally fire off in this country at midnight on the 31st I donated (more) money to the relief operation. I sincerely hope that we can help the people out there to rebuild quickly and prevent future recurrence of this type as much as possible. My condolences go out to all who have lost (one of) their loved ones. Although I think it is understandable that the world is gripped by this most recent natural disaster there are still many man-made ones unsolved. I hope the world will not forget for instance the ongoing genocide in Darfur or the continuing conflict between Israel and the still not quite nation Palestine.Solving those problems is of course beyond my control. Cancer seems a "luxury problem" when seen in this light but this is something where I can actually make a difference (beyond sending a comparably paltry sum of money). So I have resolved to work better harder. Another place where I can make a difference is to my family and friends, perhaps I can also contribute meaningfully to some charity operating locally. The main message is that those of us who are doing well should try harder to help others. A message present in all faiths I know even a little bit about so not necessarily a Christian thought. Maybe we should all pay more attention to those parts of our various faiths that bind us rather than those that set us apart. Hopefully in the new year working together to solve the dreadful hurts in Asia will help to move a divided world closer together again. - posted by Nick @ 13:20 | Joint Global Change Research Institute | University of Maryland Publications and information from a joint Pacific Northwest Lab University of Maryland institute dedicated to examining the problems associated with global climate change. The Joint Global Change Research Institute | University of Maryland www.globalchange.umd.edu About Groups Publications Staff Links Models Seminars Contact Us Home Featured Research Assessing Vulnerability in India and Indian States Click for Details New: International Trends in Energy Research Development The Joint Global Change Research Institute houses an interdisciplinary team dedicated to understanding the problems of global climate change and their potential solutions. Joint Institute staff bring decades of experience and expertise to bear in science, technology, economics, and policy. 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( more ) Policy Resources USACM News Activities Newsletter: Washington Update Tech Policy Weblog Issue Areas Copyright IP -DMCA -DRM -P2P E-voting and Standards Internet Governance Privacy -Encryption -National ID Systems -Spam UCE Research and Development -Access to Scientific Information -Database Protection -Reverse Engineering -UCITA Security About About USACM -USACM Members -Policy Office FAQ -Policy Office Staff About ACM -ACM Press Room -Join ACM Contact Us ACM Public Policy Office 1100 17th Street, NW Suite 507 Washington, DC 20036-4632 Tel: 202.659.9711 Fax: 202.667.1066 usacm_dc [AT] acm.org Search USACM Policy Resources ACM Portal Weblog Content RSS RSS Link USACM News Activities ( more ) November 1, 2005 ACM Washington Update, Vol. 9.10 (October 31, 2005) CONTENTS [1] Newsletter Highlights [2] USACM Chair Warns Against Underfunding Cybersecurity Research [3] USACM and Others Criticize DoD Export Proposal [4] Data Security Legislation Moving Forward in Congress [5] U.S. Passports to Get RFID Chips [6] U.S. Resisting U.N. Pressure on Internet Governance [7] Events in November [8] About USACM [An archive of all previous editions of Washington Update is available here .] (more) Link | 6:22 am ET October 27, 2005 USACM Chair cautions against underfunding cybersecurity research USACM Chair Gene Spafford testified today at a House Armed Services Committee hearing as part of a cybersecurity panel on Asymmetric and Unconventional Threats. He was joined on the panel by David Grawrock (Intel) and Paul Kurtz (Cyber Security Industry Alliance). Spaffords written testimony can be found here . In his oral comments, Spafford stressed several points: The interconnectedness of systems today, meaning that a vulnerability or attack in one system can lead to problems for other systems; The fuzzy line now between civilian and military infrastructure (e.g., many military bases rely on civilian power grids, civilian networks, etc.) The danger in underfunding and shortening the horizon for cybersecurity research; and The need for more well-trained cybersecurity professionals. Well have more on this hearing in our forthcoming October newsletter . Meanwhile, Peter Harsha (CRA) has an excellent post about the hearing and some of the background. Link | 2:15 pm ET October 13, 2005 USACM and others criticize DOD export proposal USACM and more than 100 other respondents recently filed comments with the Department of Defense criticizing its proposed changes to the Defense Federal Acquisition Regulation Supplement (DFARS). Among other things, the proposal mandates that all DOD contracts include a clause requiring contractors to Create and maintain unique badges for foreign nationals and foreign persons employed by the entity; Build segregated work areas for these persons; and, Prevent these individuals from gaining any access to export-controlled technology without first obtaining a specific license, authorization or exemption, even if these individuals may be working under the longstanding fundamental research exemption. USACMs comments express its concern that the proposal, among other things, would place a costly new burden on research, discriminate against foreign researchers, and jeopardize the fundamental research exemption that has long promoted an open and fertile research environment. USACM is also worried that DOD, in issuing this proposal, has not given enough consideration to a similar advanced notice of proposed rulemaking issued recently by the Department of Commerces Bureau of Industry and Security. USACM and others were critical of this proposal, as well. USACMs full statement on the DOD proposal is available here . (more) Link | 10:15 am ET Tech Policy Weblog ( more ) November 16, 2005 Tech Issues Flood The Hill This Week Its November and Congress is supposed to be long gone, but finalizing this years budget remains a key sticking point . While trying to strike a deal, they are looking into a host of other things. There is a bit too much going on for us to analyze right now, so we thought we would post highlights of some of this weeks developments: (more) Link | 10:21 pm ET November 14, 2005 IT heavyweight joins push for preemptive federal privacy legislation Recently, Microsoft added its voice to those calling for uniform federal privacy legislation that preempts individual state laws. Brad Smith, a senior VP and general counsel for the company, made the announcement at a recent Congressional Internet Caucus gathering : Over the past few years several factors have altered the privacy landscape in such a way and to such a degree that we now believe the time has come to support national privacy legislation as a component of a multifaceted approach to privacy protection. As a strong supporter of free-market solutions, Microsoft did not come to this decision without careful consideration. But it is one we now believe is the right course in order to provide meaningful protections for individuals, while avoiding unnecessary obstacles to legitimate business activities. As we see it, the goal of federal privacy legislation should be twofold: to establish baseline privacy protections for consumers, and to provide organizations with a uniform standard on which they can build effective privacy policies and compliance efforts [] Smith goes on to suggest a framework for federal privacy legislation that includes (more) Link | 2:58 pm ET November 4, 2005 Turing Award Winners Honored Again, Win Nations Highest Civilian Award Update 11 9 05: The White House announced that it will host an online chat with Cerf and Kahn today at 4:00 EST. If you follow the link you can submit questions right now! Yesterday the White House announced that Bob Kahn and Vinton Cerf are being awarded the Presidential Medal of Freedom for their pioneering work on Internet protocols. The White House notes that they have been at the forefront of a digital revolution that has transformed global commerce, communication, and entertainment. This award caps a big year for the research team. As we reported earlier, they won ACMs Turing Award, which is considered the Noble Prize for computing. Kahn and Cerf will receive the award along with a 12 other winners at a White House ceremony next week. The winners are quite a diverse selection. Among the winners are Muhammad Ali, Alan Greenspan, General Richard B. Myers, Jack Nicklaus, and Frank Robinson. About the Presidential Medal of Freedom: Established by Executive Order 11085 in 1963, the Medal may be awarded by the President to any person who has made an especially meritorious contribution to (1) the security or national interests of the United States, or (2) world peace, or (3) cultural or other significant public or private endeavors. Link | 4:29 pm ET ACM Privacy Policy | Code of Ethics Questions? Comments? Email us Civil Society and the EU Masters degree thesis suggests increased participation in research policy by groups not representing business or science. Civil Society and the Eu: the Case of Research Policy Civil Society and the EU. The Case of Research Policy Thesis Supporting material Personal Thesis Abstract Download About Euromasters *** Latest developments Online Documents Links *** About me Contact N.B . Italic links lead to a new page M.A. Thesis Mag. Daniel Spichtinger (Euromasters, University of Bath, 2002 ) Civil Society and the EU. An Analysis Focusing on the Interactions between the Commission and Civil Society Organisations, with Particular Emphasis on Research Policy. Abstract T his thesis takes a multidisciplinary look at the concept of civil society and its application at the EU level, focusing in particular on the interactions between civil society organisations and the Commission. In the first chapter it will be analysed how various schools of thought conceptualise the relationship between civil society, the state and the economic sector. In this regard I will distinguish between broad and inclusive and narrow and exclusive theories of civil society. Secondly, it will be established that a broad conception of civil society is used at the EU level. We will then look at how civil society interacts with the Commission, what the dangers of civil society involvement are and whether economic actors can be said to be dominant. Another issue will be whether a truly European civil society exists. After some intermediary conclusions I will single out research policy as a case study of civil society involvement. Using both secondary sources and empirical means I will arrive at the conclusion that business and science actors still dominate networks in RD policy. While the participation of civil society is presently rather limited, the Commission has started several initiatives to support the inclusion of civil society organisations in research policy. Finally, we will arrive at some policy recommendations derived from both the general analysis and the case study. Download Download the study here (online version, pdf, 978KB) Download my article Civil Society Interaction with the Commission in EU Research Policy (2003) , an update and a summary of my research. click on the blue text above to load the pdf file in your browser. Right click and choose save (target) as to save on your harddisk . About Euromasters Euromasters (MA in Contemporary European Studies) is a postgraduate programme offered jointly by serveral universities across Europe and the US (coordinated by the university of Bath). It offers a broad comparative understanding of European or EU-US politics, policy and social evolution as well as specialist knowledge of key issues in the Euro-Atlantic area. Altough the University of Bath is comparatively young it is already ranked among the top five British universites by the London Times. In a recent external subject review of politics and economics the departement recieved the highest possible score (24 out of 24). The two markers agreed on A- as the mark for my M.A. thesis. For further information see the Euromasters Webpage Supporting Material Latest Developments 10 08 2003 Article Civil Society Interaction with the Commission in EU Research Policy available under "download" 12 06-13 06 2003 Conference Governance of the European Research Area: The Role of Civil Society (Brussels) Click here for more information. 06 06 2003 review and update of website Online Documents Links Personal About me Contact: Daniel Spichtinger Schlsselgasse 3 12 A-1080 Vienna, Austria phone: 0043 676 924 7111 e-mail: dspichtinger@yahoo.de web: www.geocities.com d_spichtinger Disclaimer: Pictures taken from www.europa.eu.int and www.cordis.lu for academic purposes. No copyright infringement intended! The owner of this website is not in any way responsible for the content of external links 2002-2003 geovisit(); Nanodot News and Discussion of Coming Technologies: Weblog devoted to nanotechnology-related news stories, with attached discussion forum. (based on Slashdot software) Nanodot: Nanotechnology News and Discussion Information Technologies and Social Development UNRISD project exploring how new information and communications technologies can be used in developing countries. Events, publications, unpublished papers, and researcher profiles. Some content in French. UNRISD: Research | Technology, Business and Society | Information Technologies and Social Development English Franais Espaol Information Technologies and Social Development Project from: 2000 to: 2005 Programme Area: Technology, Business and Society This project is designed to explore the institutional and policy environment affecting the likelihood that new information and communications technologies can be used to improve the lives of large numbers of people in developing countries. Thematic studies on prominent global trends including patterns of concentration within the global IT industry and the changing nature of international regulatory policy in this field constitute one area of work within the project. At the same time, UNRISD is sponsoring new research by Third World scholars, businessmen and activists on the specific uses of information technologies in developing countries today. The first of these country studies has been carried out in Senegal, co-ordinated by Momar-Coumba Diop, which will be a prototype for future studies. Readers interested in global trends should find the papers by Manuel Castells, Cees Hamelink, Robert Mc Chesney and Dan Schiller particularly interesting. They might also consult the UNRISD co-publication by Sen OSiochr and Bruce Girard, with Amy Mahan, titled Global Media Governance: A Beginners Guide (Boulder: Rowman and Littlefield UNRISD, 2002). And they can watch for further information on a series of Briefing Papers for the World Summit on the Information Society, to be prepared within the UNRISD InfoTech network. More on this Project About the Project This Project's... The need to strengthen civil society has become a truism within the development debatesomething that can be stated without further analysis or discussion. But civil society is a complex of different forms of organization, developing within specific contexts. The global debate on democratization and human rights can be sharpened by paying greater attention to specific problems of political and institutional reform at the local, national and international levels. This programme provides an opportunity to learn from recent experiences in countries, beset by economic crisis, where efforts are being made to create an enabling environment for democratic governance. Identities give structure and meaning to life. They provide a basis both for conflict and for cohesion, anddespite attempts to paint them as eternalthey are constantly undergoing adaptation. This programme asks how an emphasis on certain identities affects patterns of exclusion and solidarity in a globalizing world. Social Policy and Development is one of the main research areas at the Institute. UNRISD defines social policy as public policies and institutions that aim to protect citizens from social contingencies and poverty, and ultimately to enable them to strive for their own life goals. The world is caught up in a rapidly accelerating process of scientific and technological change that can benefit the majority of humankind or, on the contrary, only benefit the few. This programme examines the politics and economics of efforts to ensure that new technologies are used in socially responsible ways. UNRISD supplements the work carried out in the five Programme Areas with a number of activities that allow the Institute to respond to special requests for collaboration, or to take up new challenges to contribute to the development debate. The European Commission, Official Documents Contains official documents of the European Commission, including documents on their science and technology policy. 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National Science Board The National Science Board is the US science policy advisor to the President and the Congress. Their homepage contains many documents on the US science and technology policy. NSF: National Science Board Last Updated: 11 07 2005 The National Science Board is an independent policy body established by Congress in 1950 with dual responsibilities to: Oversee and guide the activities of, and establish policies for, the National Science Foundation; and Serve as an independent national science policy body that provides advice to the President and the Congress on policy issues related to science and engineering that have been identified by the President, Congress or the Board itself. The Board has 24 members appointed by the President and confirmed by the Senate, plus the NSF Director as an ex officio member. More Click on member's face to be directed to biographical sketch. 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Publication Search RAND Science Technology Science and Technology Policy Institute Archive Site archives as of December 1, 2003 (amended 7 21 04) The Science and Technology Policy Institute at the RAND Corporation Historical Overview, 1992 to 2003 Our History and Work More about the Institute A Report to the President: Analytic Perspectives on the Science and Technology Issues Facing the Nation National Science Foundation Authorization Act of 1998 Research Areas Research History 1992 - 2003 The U.S. RD Portfolio and International Science and Technology Health and the Environment Space and Transportation Public Safety, Security, Critical Infrastructure Protection Education and Training Special Projects and Events Bioterrorism Beyond: A Framework for a National Information Technology Infrastructure Partnerships: Building a New Foundation for Innovation E-Vision 2000: Key Issues That Will Shape Our Energy Future Achievement for All Complex Systems and Policy Analysis: New Tools for a New Millennium Technet Think Tank on Identifying Critical Technologies Technet Archives Seminar Series Archives Area Home Pages International Science and Technology Environment Education and Training Publications 1992 - 2004 (amended 3 14 04) U.S. RD Portfolio and International Science and Technology Health and the Environment Space and Transportation Public Safety, Security, and Critical Infrastructure Protection Education and Training Non-RAND Publications with ST PI Input Directors and Associates 1992 - 2003 Search Search the entire ST Policy Institute site. RAND Science and Technology | RAND Corporation Home RAND operated the STPI from 1992 - 2003 and maintains this Web site only as an archive of the work that was done during that time. If you have any questions about the work referenced on this Web site, please contact us via email . Back to Top RAND Home | About RAND | Privacy Policy | Research Areas | Books Publications | Opportunities | Search RAND is a registered trademark. Copyright 1994-2005 RAND Corporation. Last modified: July 21, 2004 Foresight: Making the future work for you The UK Foresight programme is managed by the Office of Science and Technology and brings together key people, knowledge and ideas to look beyond normal commercial time horizons to identify potential opportunities from new science and technologies and actions to help realise those opportunities. Foresight Home | A-Z | Whats New | Search | Help | Contact Us Projects: Obesity Intelligent Infrastructure Systems Detection and Identification of Infectious Diseases Brain Science, Addiction and Drugs Previous Projects HORIZON SCANNING CENTRE Foresight: About Foresight Previous Rounds Publications e-sight Newsletter Website Info Related Websites Register Your Interest Welcome to Foresight The current projects are: Brain Science, Addiction and Drugs ; Detection and Identification of Infectious Diseases , Intelligent Infrastructure Systems and Obesity What is Foresight? NEW:Two more Foresight projects that launched their findings last year have been reviewed. Flood and Coastal Defence , Cyber Trust and Crime Prevention . Foresight, and its associated horizon scanning centre aims to provide challenging visions of the future, to ensure effective strategies now. It does this by providing a core of skills in science-based futures projects and unequalled access to leaders in government, business and science. The current round of Foresight - launched in April 2002 - operates through a fluid, rolling programme that looks at 3 or 4 areas at any one time. The starting point for a project area is either: a key issue where science holds the promise of solutions; or, an area of cutting edge science where the potential applications and technologies have yet to be considered and articulated. For more about the projects, please click on the appropriate button on the left panel. For more background information on the UK Foresight Programme click here . DIID image copyright and courtesy of London School of Hygiene and Tropical Medicine. Please take the time to read this Disclaimer, Rights and Data Protection notice before providing feedback on the site. The Science Foresight Project The first completely Internet-based international science foresight activity. The goal was to identify emerging research developments in the physical and engineering sciences using experts selected by purely objective methods. Science Foresight Project Contact Sylvan Katz Managers: SPRU - Sylvan Katz, Dstl - Sally Stewart Advisors: SPRU - Professor Ben Martin, Dstl - Dr. Theresa Gow Assistants: SPRU - Alexandre Caldas Home News Table of Contents Science Foresight Project Collaborators SPRU Dstl Definitions General Specific Final Report Complete Report Selected Sections Abstract Executive Summary Observations and Recommendations Presentation Databases Description Highly co-cited papers Predictions Short term Long term Foresight Resources UK Foresight programme Cordis RTD 2002 Japan Foresight Institute Dynamic Foresight Project Review The Science Foresight Project The final report for the Science Foresight Project is now available in pdf format to download or view on-line (see the Final Report section in menu on the left). Also, the Abstract, the Executive Summary and the Observations and Recommendations chapters can be viewed in html format. In addition, the 481 highly co-cited papers used as the source of experts for this project and the short and long term predictions about emerging research developments are available as searchable databases. Project Objective The objective of the Science Foresight Project was to identify emerging and potentially important research areas primarily in the physical and engineering sciences using internationally recognized experts selected by co-citation analysis . The Collaborators The Science Foresight Project is a collaborative project between SPRU , the Science and Technology Policy Research institute located on the University of Sussex campus and Dstl , the UK Defence Science and Technology Laboratory part of the UK Ministry of Defence. Selecting The Experts The Science Foresight Project used co-citation patterns to scientific and technical publications indexed in the Institute for Scientific Information's (ISI) 1999 Research Fronts database to identify approximately 500 highly co-cited research papers in a variety of physical science and engineering fields . This database contains bibliographic and citation information on 20,000 clusters of related research papers. These clusters of papers, which ISI calls research fronts, were identified using co-citation analysis to establish subject similarity among documents by finding pairs of papers, cited above a minimum threshold (6 times) that were often cited together by other research papers published in 1999. Co-citation analysis is more immune to the effects of self-citing than conventional citation techniques. The authors of the selected papers were invited to identify short and long term emerging and potentially important research areas. The Challenge One of the main challenges in the Science Foresight Project was to establish a robust and repeatable way to identify highly co-cited papers for use in the study. The details of the technique are given in the methodology section of the final report. The authors of highly co-cited papers were considered to be experts in their fields and they were invited to participate in the study. They were asked to identify interesting and exciting emerging short and long term opportunities in their areas of research. This peer-review recognition based technique for selecting experts is a significant departure from traditional foresight activities. Traditional methods usually use social and political networks as a source of experts. It is hoped that this novel selection technique produced a collection of experts who have been internationally recognised by their peers as making a high impact research contribution in their fields and that these experts have in turn identifed some emerging research frontiers. In other words, these authors were asked to act as spokes people for others in their research communities. An author was chosen because his her name appeared on a highly cited and co-cited paper that occurred in a cluster of a large number of papers on a similar research topic. Authors were not chosen because their papers necessarily contained research findings that were in emerging research frontiers but rather because their research findings may be used in emerging research frontiers. However, since their work has had a significant impact on their communities it is likely they may be aware of significant research progress in their fields and have a sense of emerging developments in the short to long term. Last updated: October 8, 2004 contact webmaster Dr. J. Sylvan Katz Technology Policy Assessment Center This Georgia Institute of Technology Center engages in interdisciplinary research and analysis of technology-intensive issues occurring at the interface of engineering, management and technology policy. TPAC - Technology Policy and Assessment Center at the Georgia Institute of Technology CAMPUS MAP DIRECTORIES SITE MAP SEARCH: Mission Hottech Georgia Tech School of Public Policy Contact Us Home Major Areas High Tech Indicators Technology Opportunities Analysis Industrial Modernization Research Evaluation Research Value Mapping More HotTech Information Security Intelligent Agents Training Education Analysis of Emerging Technologies (password required) Executive Education Papers Projects Key Center Associates Protected Papers Links Partner Organizations What's New The School of Public Policy (Phil, Barry, Susan) is a part of the National Science Foundation award for a new Center for Nanotechnology and Society (CNS-ASU), headquartered at Arizona State University and involving the University of Wisconsin-Madison, the Georgia Institute of Technology, North Carolina State University, Rutgers University, the University of Colorado-Boulder, and other universities, individuals, and groups in the academic and private sector CNS-ASU will implement a program of research and engagement called "real -time technology assessment" (RTTA), which consists of four methods of inquiry: mapping research dynamics of the NSE enterprise and its anticipated societal outcomes; monitoring the changing values of the public and of researchers regarding NSE; engaging researchers and various publics in deliberative and participatory forums; and reflexively assessing the impact of the information and experiences generated by its activities on the values held and choices made by the NSE researchers in its network. Through RTTA, CNS-ASU will probe the hypothesis that trajectories of NSE innovation can be steered toward socially desirable goals, and away from undesirable ones, by introducing a greater capacity for reflexiveness - that is, social learning that can expand the range of conscious choice - into knowledge-producing institutions. It organizes the research around two broad NSE-in-society themes - freedom, privacy, and security; and human identity, enhancement and biology - which also provide topic areas for study in RTTA activities such as research program assessment and scenario development. See http: www.cspo.org projects nanotechnology At Georgia Tech, a group of faculty associated with the Georgia Tech School of Public Policy (SPP) and other units will be part of CNS-ASU. The Georgia Tech team includes: Research and Innovation Systems Assessment - research to characterize the technical scope and dynamics of the NSE enterprise. Key faculty: Philip Shapira (SPP and Georgia Tech Project Director), Alan Porter (SPP ISYE). Associated faculty: Jan Youtie (EDTV), Mario Iacopetta (Economics). Public Value Mapping - research to assess the societal outcomes or public value of NSE research activities. Key faculty: Barry Bozeman (SPP). Deliberation and Participation - research to develop visions of NSE-enabled futures and to elucidate public preferences. Key faculty: Susan Cozzens (SPP). Other Georgia Tech faculty in the nanosciences are also associated as technical advisors. CNS-ASU is sponsored for a five year term, beginning October 2005 (with NSF funding at approx $6.2 million). Georgia Tech team is scheduled to receive CNS funding via NSF of just over $698,000. CNS-ASU is the largest in a network of newly funded NSF activities on nanotechnology and society, including a second center at University of California-Santa Barbara and additional projects at Harvard University and the University of South Carolina. This national network will support research and education on nanotechnology and social change, as well as provide educational and public outreach activities and international collaborations. Malaysian Knowledge Economy Study Released A team from the Georgia Tech Technology Policy and Assessment Center (in the School of Public Policy) and Intelligent Information Services Corporation (IISC), Atlanta, began work in 2002 on a national study of knowledge content in the Malaysian economy (MyKe) sponsored by the Malaysian Economic Planning Unit, Malaysian Prime Ministers' Office, and the United Nations Development Programme (UNDP). The official study was released a few days ago in Kuala Lampur, Malaysia, by the Economic Planning Unit (EPU) of the Malaysian Prime Minister's Office. The full official report documents are available at http: www.epu.jpm.my New%20Folder MyKe%202004.htm . This is the EPU report (for which they are fully responsible), but it draws extensively on the methodology and analysis that TPAC pioneered in Malaysia and that TPAC has documented elsewhere. The foreword to the first issue of International Journal of Foresight and Innovation Policy (IJFIP) Other News TPAC located in Ivan Allen College of the Georgia Institute of Technology of Atlanta, Georgia. Copyright All rights reserved. Reproduction of this publication in any form without prior written permission is forbidden. The Decline of Unfettered Research Essay explaining the reasons for the decline of "unfettered" or "curiosity-driven" research. The Decline of Unfettered Research The Decline of Unfettered Research Andrew Odlyzko ATT Bell Laboratories amo@research.att.com Revised Version October 4, 1995 1. Introduction We are going through a period of technological change that is unprecedented in extent and speed. The success of corporations and even nations depends more than ever on rapid adoption of new technologies and operating methods. It is widely acknowledged that science made this transformation possible. At the same time, scientific research is under stress, with pressures to change, to turn away from investigation of fundamental scientific problems, and to focus on short-term projects. The aim of this essay is to discuss the reasons for this paradox, and especially for the decline of unfettered research. What do I mean by unfettered research? In the discussions of federal science policy it has also occasionally been called "curiosity-driven." It is exemplified by the following reminiscences of Henry Ehrenreich [Ehr]. When I arrived at the General Electric Research Laboratory at the beginning of 1956, fresh from a PhD at Cornell, I was greeted by my supervisor, Leroy Apker, who looked after the semiconductor section of the general physics department. I asked him to suggest some research topics that might be germane to the interests of the section. He said that what I did was entirely up to me. After recovering from my surprise, I asked, "Well, how are you going to judge my performance at the end of the year?" He replied, "Oh, I'll just call up the people at Bell and ask them how they think you are doing." In this style of work, the researcher is allowed, and even required, to select problems for investigation, without having to justify their relevance for the institution, and without negotiating a set of objectives with management. The value of the research is determined by other scientists, again without looking for its immediate effect on the bottom line of the employer. The assumption that justifies such a policy is that "scientific progress on a broad front results from the free play of free intellects, working on subjects of their own choice, in the manner dictated by their curiosity." (This quote is from the famous report of Vannevar Bush [Bush] that formed the cornerstone of U.S. federal funding for research after World War II.) Unfettered research is not a boondoggle, simply indulging scientists' curiosity. There were good historical reasons for Vannevar Bush to advocate it. Many of the stunning scientific and technological advances that have shaped our world have come from unfettered research. A good recent example is the invention of public key cryptography by Diffie, Hellman, and Merkle in the 1970s. Their work was funded by Hellman's NSF grant in information theory. Since the grant terms were flexible, without negotiated work plans or deliverables, they were free to work on an audacious idea that was not mentioned in the grant proposal, and that formed a foundation stone for the information society. The unfettered research that Ehrenreich encountered at GE in 1956 is almost universally taught at universities as the only real research. However, this type of research is now almost totally gone from industrial and government laboratories, and is under pressure even in academia. Industrial leaders stress the need to "focus on customers' needs." The pressure is to do work with quick payback, and to justify everything that is undertaken on the basis of its relevance to the corporation [Coy]. The trend is not confined to the U.S. For example, the Canadian Finance Minister introduced a proposed new budget with the stipulation that "[i]n the future, [Canadian] science and technology efforts will be concentrated more strategically on activities that foster innovation, rapid commercialization and value-added production ... to stretch government's science dollars further and more effectively." Today researchers, even when they are not working on well defined projects, are increasingly required to submit plans for their research, and to explain not just how their work might help their employer, but what steps they are taking to ensure their results are utilized to the fullest. Scientists are in effect asked to become engineers, where the term engineer is not used in a derogatory sense, but, in the words of Vannevar Bush (as quoted in [Zachary]), describes a person who is "not primarily a physicist, or a business man, or an inventor, but [someone] who would acquire some of the skills and knowledge of each of these and be capable of successfully developing and applying new devices on the grand scale." Much of the distress experienced by scientists is caused by this pressure to understand and justify how their work fits into a much larger setting. At a time when growth in knowledge requires more training and much greater specialization, they are being asked to become generalists, and to deemphasize leading-edge work in their fields. Many of the popular explanations for the decline in unfettered research are unsatisfactory. Short-sighted management is often blamed. However, the decline has been going on for a long time, and different companies have followed varying policies, so that if traditional unfettered research were the best method for a corporation, its superiority should have become evident by now. That has not happened, and most of the rapidly expanding high-tech companies appear to do little long-term research, unfettered or not. Another explanation that is often proffered is that the end of the Cold War has cut back funding for RD in general. Again, though, one might expect that reductions in military-related RD would have led to lower demand for scientists and engineers in general, and therefore to lower salaries, which would have made civilian RD cheaper and thus more attractive. Thus this explanation also seems to be inadequate. (In addition, this explanation leaves open the question why the Cold War should have spurred unfettered research in the first place. Why weren't all available resources put into building more tanks and submarines?) Novel management theories (cf. [RSE]) are often blamed by themselves, but as is true of most management theories, they tend to be derived from observations of what companies perceived to be successful are doing, and only systematize and justify such procedures. Competition and pressure for quick financial payoffs are often cited as causes of the decline in unfettered research in industry. However, Wall Street can be remarkably sensitive to technological advances and extremely patient in waiting for profits. This is demonstrated by the recent initial public offering of Netscape Communications, Inc. A company that had been in existence for less than two years, had racked up total sales of less than $20 million, and had only losses and no profits, was suddenly judged to be worth $2 billion. The reason was that the Netscape Navigator browser that Andreessen, Bina, and their colleagues built won the popularity contest among Internet users. Several companies were pursuing the same strategy as Netscape, of giving out their browsers for free. It was Netscape's technical superiority that won the contest (even though this superiority was slight, and much of the programming was of poor quality, as was shown by the security flaws that were discovered in the Netscape program). It will be a long time (if it ever happens) before Netscape earns enough profit to justify its initial stock market valuation. However, the prospects of leveraging control of the most popular World Wide Web browser into control of Internet software were sufficiently enticing for Wall Street that it was willing to assign an outlandish value to this company. Thus in cases where there is a clear connection between technical excellence and market applications, financiers can temper their demand for profits. Hence financial pressure alone does not explain the cutbacks in unfettered research. This note proposes a somewhat different explanation for the decline of unfettered research. I feel that it was caused primarily by internal developments in the world of science and technology, not by arbitrary outside decisions. There seem to be three main (and closely interrelated) themes that help explain the turn towards short term, directed research: (a) dramatic increase in volume of research, (b) steady and rapid progress in all areas of technology, (c) unprecedented opportunities in applying existing knowledge. These themes arose from the success and growth in research. I am not implying that research is finished as an important activity. I do not share the opinion of a former head of the U.S. Patent Office, who resigned a century ago and recommended that his position be abolished, since "everything that can be invented has been invented." Nature has a limitless supply of secrets to be explored and exploited. I am convinced that research is important to society's economic welfare, will continue to advance human knowledge, and can be an intellectually rewarding career. This note is not even intended as an attack on unfettered research. My intention is to explain why this type of research is on the decline, and so I concentrate on the negative side. I am not attempting a balanced treatment of the role of RD and the optimal level or form of support for research. Most of this note is descriptive, not prescriptive. It is necessary to emphasize that RD spending as a whole, and even research by itself, have generally been going up at a steady pace. There is a sense that cutbacks might come, and that the relationship of science to society might have to be reexamined (cf. [ByerlyP]), but no substantial cuts in overall RD budgets have materialized so far. Even within U.S. industry, there has been growth [Coy], with cutbacks at some corporations more than balanced by growth in others. Worldwide, even unfettered research is probably increasing, with universities in the rapidly industrializing countries expanding their faculties. The only area where there is a clear decrease is in unfettered research in industry. This type of research has never been a large part of the total RD budget. However, it has been the most visible type of research, in that it tended to garner public attention and Nobel prizes. That is one reason for discussing its decline. Another is that the decrease in unfettered research is symptomatic of a general shift in RD towards much more directed and shorter-term type of work. Not all directed investigations are short-term (the invention of the transistor is a good example of successful long-term directed research), and the correlation between unfettered research and long-term one is not perfect, but there is a correlation, so that the decline in unfettered work serves as a measure of the how far into the future one looks. The turn towards short-term work is a phenomenon that has occurred at most industrial laboratories, even those that had never engaged in unfettered research [Coy]. Is this a trend that will continue much further? Will it spread to research at universities? An examination of the reasons for the decline in industrial unfettered research suggests that the answer to both questions is yes. 2. Research as a commodity The basic reason the role, style, and image of research are changing is that there is much more research than a few decades ago. There used to be much less competition, and the intervals between invention and marketing of a product were long. As an example, xerography was invented by Carlson in 1937, but it was only commercialized by Xerox in 1950. Furthermore, there was so little interest in this technology that during the few years surrounding commercialization, Xerox was able to invent and patent a whole range of related techniques, while there was hardly any activity by other institutions. This enabled Xerox to monopolize the benefits of the new technology for over two decades. Xerography was not an isolated case. When the transistor was invented by Bardeen, Brattain, and Shockley at Bell Labs in 1948, several years elapsed before other laboratories acquired enough expertise in the semiconductor area to make significant contribution. Had ATT not been prevented both by its culture and by regulation from exploiting this dramatic discovery, it could have erected a patent barrier around its discovery that would have allowed it to keep most of the profits from commercial developments. Today such opportunities are extremely rare. For example, when Bednorz and Mueller announced their discovery of high-temperature superconductivity at the IBM Zurich lab in 1987, it took only a few weeks for groups at University of Houston, University of Alabama, Bell Labs, and other places to make important further discoveries. Thus even if high-temperature superconductivity had developed into a commercially significant field, IBM would have had to share the financial benefits with others who held patents that would have been crucial to developments of products. The era of extensive unfettered research started only after World War II. Until then, "curiosity-driven" research was practiced at universities and a few academies and research laboratories, but it was done on a small scale. During the last century universities developed the view that research is one of their main missions, along with teaching. However, their resources, while adequate for small scale and low-overhead work in theoretical areas, could not cope with the increasing number of researchers and their ever more costly equipment in experimental areas. (Recall the years that Einstein spent working in the Swiss patent office, before he could obtain a university position.) During the period between the two world wars, scientists and engineers were devoting an inordinate effort to chasing after the few funding sources that were available [Burke]. After World War II, support for research expanded tremendously, first in the United States, and then, as their economies recovered or developed, in other countries. Science and technology had played a vital role in the war. The Bomb was the most famous development of that period, but there were many others, such as radar, plastics, and jet engines. There were also striking advances in non-military areas, such as the almost total (for a time, at least) conquest of infectious bacterial diseases by penicillin and other antibiotics. The technologies and products that captivated the public's attention were the results of concentrated development efforts. (The Manhattan Project was more of an engineering than a scientific enterprise, although many of the best physicists, chemists, and mathematicians spent their full war-time careers in it.) However, they were correctly perceived to be the culminations of the unfettered research carried out in the preceding decades. The nuclear era, for example, is often traced back to the serendipitous discovery of radioactivity by Becquerel at the end of the 19-th century. The policy makers and the general public responded with an unprecedented increase in support for scientific and engineering research. Governments proceeded to fund extensive research and development in all areas, not only in universities, but also at their own laboratories and through industry. Universities vastly expanded their own commitment to research, decreasing teaching loads, and placing more emphasis on scholarly achievement than on teaching. Industry also proceeded to build up RD staffs. Under the leadership of people like Vannevar Bush [Burke], who had bitter memories of the lean years between the wars, policy makers allocated substantial fractions of available funding to unfettered research, in the belief that scientists would themselves be best able to select the most promising direction for their work. To get a graphic appreciation for the growth in the research establishment, it is instructive to look at pictures of participants at any of the Solvay congresses held between the world wars. There are only a few dozen people in any one of these pictures, but they usually contain most of the creators of modern physics, scientists like Bohr, Einstein, and Heisenberg. Today, a typical physics conference has hundreds or thousands participants, and there are many more conferences than before. When we talk of the decline in unfettered research, we should remember that there would be no difficulty in providing an unfettered research environment for Einstein today, were he still alive. The difficulty is that there are now thousands of theoretical physicists who would like to be treated like Einstein. The growth of the research establishment is not a new trend, but it accelerated after World War II. The number of scientists has been increasing at an exponential (in the strict mathematical sense of the word) rate for centuries. The number of scientific papers published annually has been doubling every 10-15 years for the last two centuries [Price]. With the spurt in funding after World War II, the rate of increase rose. For example, the number of abstracts in Chemical Abstracts just about doubled every decade from 1945 to 1985, when it reached about half a million per year (and has increased at a lower rate since then). The volume of technical publications today is more than 10 times what it was at the end of World War II. Although there have been frequent complaints about the inadequate level of federal government support for science, the U.S. National Science Foundation has doubled the number of researchers it supports in the last 20 years. It was always clear that this rate of increase could not be sustained indefinitely, but it continued for a long time. Now, however, there are clear signs of a leveling off, at least in the developed countries. The end of the era of exponential growth appears to have arrived, and this all by itself may be responsible for many of the complaints about poor job prospects and low morale. While exponential growth had to stop at some point, why did it have to happen now, and not after another doubling in the population of scientists and engineers, say? There does not seem to be any persuasive answer. Nobody even has a good theory of what the optimal rate of investment in RD should be. As an empirical matter, no advanced industrial country invests more than 3% of its GNP in RD. The prospects of going above that figure seem dim. Cutbacks in RD spending are talked about more frequently than boosts. To maintain some balance, we should mention that the traditional image of unfettered research is not completely accurate. Research has seldom been totally unfettered. Ehrenreich's experience at GE, cited in the Introduction, can be ascribed to GE's interest in the then brand new field in semiconductors, where almost any research was likely to be of commercial value. Had Ehrenreich suddenly decided to switch to genetics, he would surely have found his freedom much more limited than it seemed. Even university researchers are much more fettered than is popularly imagined. Except for tenured professors in theoretical areas, almost all researchers depend on grants or contracts in their work, and to get them, they have to survive peer review scrutiny that sharply limits what they can do. Cocke's invention of RISC (reduced instruction set computers) is an example of unfettered research, in that IBM allowed him to work on whatever he chose. However, Cocke had already made valuable contributions to the design of IBM mainframes, and was working on computer architectures, which were of obvious relevance to IBM. Thus it was not surprising that he was given the freedom to pursue "the free play of free intellect." Industrial research laboratories have been giving such freedom to a few select individuals for a long time (Steinmetz at GE over a century ago may have been one of the earliest ones) and surely will continue to do so in the future. What is remarkable about the era of unfettered research that is ending now is that even brand new Ph.D.s were being offered such freedom in large numbers. The purpose of this essay is to explain why less freedom is being offered today. The general decrease in support for RD and for unfettered research in particular are surely strongly connected to the rapid growth in research. Whatever the optimal level of RD spending is, even if it is twice the present level, we are surely much closer to it now than we were three or four decades ago. With the large current community of scientists and engineers, the public and the decision makers are no longer dealing with a few souls laboring in obscurity in their ivory towers, but with a large community that can easily be seen as just another "special interest group" looking for its "entitlements." The growth and increasing competitiveness of any field can easily affect the public perception of that field. In sports, for example, it is common for commentators to talk of how some famous figure of old, such as Babe Ruth, was the greatest player of all time. Such assertions are made only about sports such as baseball or boxing, where teams or individuals compete against each other, and there is no objective measurement that can be used to compare performance over time. In sports such as swimming or running, where the clock determines the winner, such assertions are never made, since the evidence there is clear, that the performance of the top athletes has been steadily improving. The explanation for this phenomenon is that the performance of the best athletes has been improving in all fields, and the reason Babe Ruth stood out so much among his contemporaries is that he was the best from a smaller, less selective, and less well trained crowd. Today, the variation in performance among the leaders tends to be much smaller. Similar phenomena appear to operate in other fields. In science, Einstein attained a degree of public reverence that has not been accorded to any other researcher. However, if we could resurrect Einstein and clone 100 copies of him, the public would not treat each of these individuals with the same respect they accorded the original. It is not only the public perception of research that has changed. The very nature of research has changed. A few decades ago, independent individual investigators or at most small labs were the norm. Today we are dealing with elementary particle accelerators that cost billions of dollars, and require teams of hundreds of scientists to operate. Even in mathematics, there is much more collaborative work, with the extreme example being the classification of finite simple groups, a great achievement of modern algebra that required dozens of researchers to work for several decades, and took 15,000 journal pages to document. Large research projects are hard to fit into the traditional model of unfettered research. Just how much freedom to pursue "the free play of free intellect" (in the word of Vannevar Bush [Bush]) does a scientist working on dampening vibrations for the $300 million laser interferometry gravitational observatory have? The entire project may be aimed at unlocking Nature's deepest secrets, and may be without any foreseeable practical application, but isn't she just as fettered as an engineer developing a new air bag? The gap between leading researchers and the general public has widened in most areas, with scientists pursuing topics that are increasingly esoteric. On the other hand, the gap between what researchers can do and what is available to the public in areas that the public sees first hand has narrowed considerably. As recently as 20 years ago, the best computational device that was widely available was a non-programmable pocket calculator, whereas researchers at leading institutions had access to supercomputers. This was a gap in computational capability of 8 to 10 orders of magnitude. Today, the Pentium processor in a home PC is not all that much less powerful than the fastest computers available at supercomputing sites, with the gap only two or three orders of magnitude. The Pentium PC is often more powerful than the workstation that a typical engineer or scientist uses. Similarly, in speech or optical character recognition, all that existed 20 years ago were research systems, available only in a few labs. Today, in contrast, one can buy much more capable "shrink-wrap" software for a PC. What is most remarkable, though, is that this software does not differ all that much in performance from the most advanced research systems. The time between invention and a commercial product has shrunk dramatically in many areas, so that research is not far ahead of the rest of the world, and therefore has fewer advanced toys to impress the public with. The main justification for unfettered research was that scientific discoveries could not be predicted, and that allowing researchers to follow their intuition in selecting problems to work on was the best policy, one that would result in enough significant new results that some of them would pay off handsomely for the sponsoring organization. Roentgen's discovery of X-rays and Fleming's of penicillin are two examples of such unpredictable discoveries that both had great impact. For that argument to be valid, though, many significant scientific advances have to occur, a large fraction have to be of interest to the sponsor, and there have to be opportunities to exploit them. These assumptions are no longer believed by industrial RD managers, and are being questioned by national policy makers. The change in the role of research can be summarized in several interrelated points. a. There are few big "hits" Neither unfettered research nor any other kind has been producing the kinds of striking results that truly impress the public. Jonas Salk's recent death led to recollections of the dramatic impact his vaccine had in defeating polio 40 years ago. Today, in spite of tens of billions of dollars spent on the "War on Cancer" over the last two decades, we have yet to see any treatment for cancer that can compare in its definitiveness to that of the Salk vaccine. Our knowledge of cancer has advanced tremendously, and current techniques are far more sophisticated than anything that Salk had at his disposal, but no "Magic Bullet" has been produced. The nice easy solutions have largely been found already. The problems we are facing are much harder. Therefore the payoff from investment in research is lower. There are great successes across the whole spectrum of scientific knowledge, from Wiles' proof of Fermat's Last Theorem to the elucidation of the functioning of aspirin. However, they are hard to explain to the public. b. Better technology does not always win The world does not always beat a path to the door of the inventor of the better mouse trap, as Dvorak and other inventors of keyboards more efficient than the traditional QWERTY one have found out. In video recorders, VHS beat the Beta format in spite of Beta's technical superiority. Nobody seriously claims that the Intel x86 chip architecture was superior to that of RISC microprocessors, which typically had twice the performance with much smaller development efforts than Intel processors of the same period. Similarly, Microsoft Windows (3.1, 95, etc.) operating systems are only now beginning to catch up to where the Macintosh systems were several years ago. However, Intel has the lion's share of the world microprocessor market, and Microsoft of the operating system market. One way to interpret this observation is to say that the basic technology is not the crucial issue, and that interoperability and related problems are. What that means, though, is that even a brilliant invention in chip design or operating systems is unlikely to make a big impact unless it is incorporated into either the Intel or the Microsoft products. Even in the scientific and technical marketplace, tools require polished interfaces, so that it is often said that a tool for professionals will sell if it has a nice GUI, no matter what the basic technology is at the back end, whereas a wonderful new invention that requires the user to work at mastering it will be neglected. This again shows the decreasing importance of basic technology, a result of the greater competition in research that leads to competing products being close to each other. In contrast, there were few people who opted to consult witch doctors in preference to taking the Salk vaccine. c. There are many ways to skin a cat With the huge growth in research, there are many competing technologies that can be used for solving most problems. A decade ago, Narendra Karmarkar invented interior point methods for solving linear programming problems. This was a great advance, since it made many more resource allocation problems accessible. However, his discovery spurred researchers working on the traditional simplex methods to improve them so that today they are competitive with the interior point methods on most commonly encountered problems. Twenty years ago, the most common modems were 300 bps ones, with acoustic couplers. Ten years ago, 9.6 kbps modems showed up. Now, as a result of improvements in microelectronics and in mathematical coding algorithms, 28.8 kbps modems are common, and 33.6 kbps ones are beginning to show up. There is work on modems that might get even closer to the absolute limit of 64 kbps that is imposed by central office equipment. If the 64 kbps limitation were truly absolute, each advance would be hailed as fantastic progress. However, for the customer, each advance has to be judged in light of other possibilities, and there are alternates to the use of modems. ISDN already offers 128 kbs, coax from cable TV companies promises several megabits per second, and optical fiber will eventually provide several hundred megabits per second. Thus advances in modems are valuable, but cannot be judged alone, and have to be compared to what other technologies offer. d. It's a complicated world In most situations, a new product or service has to interoperate with others. This severely limits what can be done, and in particular limits potential profits for the inventor. A new coding scheme that leads to higher speed modems has to be accepted as an industry standard before consumers will buy it. Similarly, most control schemes for ATM networks have to be adopted by the whole industry before they can be used. Therefore the company that comes up with even a great invention can usually only obtain profits from licensing the patents and from a slight lead in marketing a new product. e. Incrementalism wins Incremental improvements have been much more important than striking new inventions. For example, commodity microprocessors have killed (at least for a while) the high performance computers based on exotic parallel architectures. Also, over the last two decades, there has been a series of predictions that progress in silicon integrated circuits was about to stop, and that new materials and devices had to be developed. Yet silicon still reigns supreme, while work on challengers, such as Josephson junctions or gallium arsenide (of which it has been said that "Gallium arsenide is the material of the future, and always will be") is languishing. Formidable technical obstacles had to be overcome in silicon technologies to bring them to the present state, but at least to the public, this work appears incremental. Incremental improvements have probably always been more important than new inventions in economic growth. Watt's contribution to steam engine development is famous, but it was dwarfed in effectiveness by the cumulative impact of many other inventions in that area. This is a common phenomenon. To quote from p. 199 of [Schmookler], a careful study of this subject, [d]espite the popularity of the idea that scientific discoveries and major inventions typically provide the stimulus for inventions, the historical record of important inventions in petroleum refining, paper making, railroading, and farming revealed not a single, unambiguous instance in which either discoveries or inventions played the role hypothesized. Instead, in hundreds of cases the stimulus was the recognition of a costly problem to be solved or a potentially profitable opportunity to be seized; in short, a technical problem or opportunity evaluated in economic terms. In a few cases, sheer accident was credited. However, at least until recently, this was not understood properly. Great credit was given to the perceived breakthroughs. Today, though, there is much more evidence on the subject, and much more stress is placed on incremental work [Gomory, FloridaK]. f. "Moore's Law" and the predictability of science One form of "Moore's Law" says that microprocessors double in computing power every 18 months. This "law" has been followed closely over the last 20 years, and experts assure us that it will hold for at least another 10 before we encounter any serious barriers to further improvements in processors. (The main barriers seem to be more economic than technological, with the costs of fabrication facilities increasing rapidly.) Tremendous progress has to be made on a range of technologies, not only in devices but also in circuit designs, architectures, and software to continue this rate of advance. However, what we should note is that all large companies have been able to keep up with the progress predicted by Moore's Law. TI has done it, Motorola has done it, and so have Intel, IBM, Toshiba, and others. Further, not a single one of these companies has been able to get far ahead of others for an extended period. In addition, it is understood what resources are needed to keep up this rate of advance. As long as no big mistakes are made, anybody with enough money can hire enough knowledgeable scientists and engineers to produce state of the art microprocessors. This goes against the popular image (that fits in with the justification for unfettered research) of a lone inventor having that one critical insight that changes a whole area. Management is not telling a researcher, "You are the best we could find, here are the tools, please go off and find something that will let us leapfrog the competition." Instead, the attitude is "Either you and your 999 colleagues double the performance of our microprocessors in the next 18 months, to keep up with the competition, or you are fired." An extreme example of the view of what research has evolved into was expressed by a distinguished researcher, Jay Forrester [TR]: "... science and technology is now a production line. If you want a new idea, you hire some people, give them a budget, and have fairly good odds of getting what you asked for. It's like building refrigerators." 3. Racing against a moving escalator The idea of technological progress is only a few centuries old. Before then, all the way through the Renaissance and even a century or two after, there was an astonishing respect and nostalgia for the ancients. In the end, it seems that it was only the Industrial Revolution that led to a transformation in the mindset of most people, so that steady improvements in technology are now expected. However, until recently, such improvements were perceived as discrete steps, such as the invention of the Hall process for extracting aluminum or the discovery of penicillin. Today, in contrast, we are living in a world of constant, rapid, and to some extent predictable progress. Microprocessors double in power just about every 18 months, in accordance with "Moore's Law." This helps explain phenomena such as the continued dominance of the Intel x86 architecture. In a more stable world, with only occasional discrete steps forward, RISC chips, which used to have double the performance of Intel x86 CISC ones for a comparable price, would have displaced the latter ones, just as jet planes displaced propeller-driven ones. However, in an environment that is governed by "Moore's Law," Intel chips, just like RISC ones, doubled in performance every 18 months, so that by sticking with the Intel architecture, a customer only gave up 18 months, less than the life cycle of computer equipment. (The distinction between x86 CISC chips and RISC ones is narrowing today, but there used to be a sharp distinction.) This allows other factors, such as compatibility, to play the dominant role in determining what products to use. The IBM acquisition of Lotus can be understood only in this light. IBM paid $3.5B for Lotus Notes. Now Notes is an innovative and important product, and no competitor has yet been able to produce a package with all the features of Notes. In a more stable world, though, it would not take long to develop a competitive product, which would limit the profit potential of Notes. What IBM has bought for $3.5B is a place a bit ahead of everybody else on the moving escalator, in the hopes that this will enable it to dominate an area that will likely be a crucial one for the information society we are developing. The idea of constant change and having to keep up with the competition helps explain why there are so many bugs in commercially successful software products. The speed of delivery of new features is more important than quality. (Cf. [StalkH].) The idea of rapid technological progress is deeply embedded in the minds of managers in high-tech areas. Several leaders of advanced development projects have told me, when asked what the main technical barriers were in their projects, that they did not see any. Those views were not entirely true, in that those managers could not go to market with the technology that was available then. However, they were taking for granted that microprocessors would get faster, and various other advances would be made. It's just that they were so sure these improvements would be available, they did not have to concern themselves with them. What this means for a researcher is that much more effort is required to have an impact. A 25% improvement in some process is always valuable. In a static world, it might be a breakthrough that could lead to great payoff. However, in a world governed by "Moore's Law," a 25% improvement is just 6 months along the technology curve. Hence the researcher who has an innovative way to save 25% or speed something up by 25% has to find a way to incorporate this improvement into all the other systems that are involved without delaying the project by more than 6 months. In effect, radically new ideas have to compete against the relentless progress of other technologies. 4. The digital revolution The final theme that appears to play a major role in the decline in support for unfettered research is that of the information revolution. (Just as the previous theme, it is reminiscent of points made by Alvin Toffler in his books [Toffler1, Toffler2, Toffler3].) The examples of technological developments that have been cited so far, as well as phenomena such as "Moore's Law," are drawn largely from the computing and communications areas. This reflects to some extent my own background, but I believe it also reflects the reality that those areas are the ones that drive technological, economic, and social change today. The 21-st century may well be dominated by biology, but today it is computing and communications that appear to be most important, especially since they pervade all other areas. (Interestingly enough, while most technological forecasts have been incorrect, primarily because of overoptimism, the one area where these forecasts have consistently been too conservative has been in computing [Schnaars].) The developments in communication and computing are leading to a fundamental transformation of human life. The technological developments that make this transformation possible, the fruits of extensive research, have been going on at a steady pace for a couple of decades. However, they have now reached a critical point where they are having a revolutionary impact. For example, the Internet has been growing at a steady pace for the last 25 years. It has caught public attention only recently because it became large enough to be noticeable and because its usefulness increased dramatically as more people got involved. Similar threshold effects operate in other areas. Information storage, retrieval, and processing are now rapidly passing performance levels that make more and more tasks doable in new ways. Automatic teller machines eliminated many bank clerk positions a decade ago, relatively primitive word-spotting voice recognition eliminated most telephone operator jobs a few years ago, and middle-management jobs are increasingly being squeezed out through new information systems. This Schumpeterian "creative destruction" is bound to continue for a long time. Technology takes a while to diffuse through society. It took several decades before the introduction of electric power to factories led to big productivity improvements, since entire manufacturing processes had to be reengineered. Change is faster today, but it still takes time to develop the organizational framework that takes full advantage of the best information technologies. Even if all progress in integrated circuit technologies stopped, we would still experience rapid and fundamental change in our lives. However, progress in all the crucial technologies has been steady, and is widely expected to continue for at least another decade. Thus we are bound to experience at least two decades of turmoil, as new technologies are absorbed by society. Neither new fundamental physical phenomena nor dramatically new mathematical or software tools are needed to make this possible. Rapid advances in science and engineering mean there is a high return on investment in new technology. (This does not have to mean a sustained increase in profitability of corporations, even though Wall Street seems to think it does. Earlier eras of large investments in new opportunities opened up by novel technologies, such as those of the canals, then the railroads, then cars, did not lead permanent increases in profits. Competition saw to that. However, the penalty for failure to adopt new technologies has been, and continues to be, severe, as companies such as Wang Labs or Smith-Corona have demonstrated recently. In that sense there is a high return on new investment, as it provides a chance for an organization to survive.) This would seem to argue for greater investment in long term research. Paradoxically, though, it seems to have just the opposite effect. Research is an investment in the future. It therefore requires belief that there will be a future. A farmer will not engage in crop rotation and other soil conservation measures if there is a high expectation that a flood will carry all the topsoil away next year. However, that farmer will also not invest in improving the land (or even in cultivating it at all) if a risk-free bank deposit will earn a guaranteed 50% return per year. High current returns mean that future payoffs have to be discounted at high rates to get their present values, and therefore even ventures that are expected to be very profitable won't be attractive if their returns are far off in the future. The high returns that are obtainable from building products and services based on present knowledge lead decision makers to deemphasize research on basic knowledge, and to ask the RD community to "just do it." This phenomenon also seems to explain the paradox that while it was clearly primarily the work in the physical sciences that gave us the computing and communication capabilities that are creating the digital revolution, research in those sciences is deemphasized. Even Intel, the prototypical hardware company, is increasing its efforts in systems and software, since it sees the main barriers in those areas. Although the gap from basic insight to a marketable product is short in some areas, in others, especially where an entire new infrastructure is required, it is often still 15-30 years. Optical amplifiers took around 20 years from concept to deployment. Combinatorial chemistry, which only now appears to be coming into widespread use, is about three decades old. In fields where such delays are common, it is hard for managers to justify basic research. 5. Future prospects The factors listed in the preceding sections have led to a shift towards short term, directed research in industry. These factors are all operating, and seem likely to continue to be in force for several more decades. They are also affecting research in universities and government laboratories. The question is whether this is good or bad, and what should be done about it. The decreasing number of "big hits" is not necessarily a good argument for cutting back on research. The story is told that somebody once asked Einstein, "Professor Einstein, where do you get all your wonderful ideas?" That sage replied, "I don't really know, I have only had two or three in my life." There simply aren't that many brilliant new insights to be had, and the easy ones have probably already been found. Much greater effort may be an unavoidable price to pay for technological progress. Some of the negative arguments about research can be interpreted as arguing for greater support of relatively unfettered investigations. For example, Section 2 discussed the evidence that in many of the areas of greatest interest to society, research is not far ahead of the marketplace. Does this not argue, though, that in those areas much more research is needed? Also, Section 2 argued that research results often are difficult to implement because of the need for industry standards, interoperability with other systems, and related concerns. However, since this is so, and because technology choices have such a huge impact on society, and once made, continue to have an influence for extended periods, it is important to do as much as possible to ensure good selections. Industry estimates [Stewart] are that running a PC with the MS-DOS or Windows 3.1 operating system in a business environment for 5 years costs at least $5,000 more than a Macintosh one, which results in unnecessary total costs in the tens of billions of dollars per year. Does this not argue for much more research to enable better choices? RD spending as a whole has been increasing, and even spending on research itself has been increasing. Even when some companies or countries cut back, others more than pick up the slack. There seems to be little danger of a wholesale retreat from technology any time soon. It is true that China in ancient times repeatedly turned away from promising technological and economic developments. However, during those periods China was run by a centralized government that could exert tight control over society. Today's world is broken up into many nation states that compete economically, a situation reminiscent of Europe during the formative stages of the current technologically oriented Western civilization. The success of governments is measured by the rate of growth of their economies. Further, economies of scale require participation in the world market. Therefore even though the changes that technology is bringing are socially disruptive, they are tolerated, as the primary goal is to maintain or increase international economic competitiveness. Since RD is crucial for success in this environment, it is unlikely to decrease. However, the subject of this essay is the form of RD that is undertaken, and especially how much of it will be D and how much R, and what form of R is to be favored. To what extent is today's decline in unfettered research a passing fad? Trendy policies do change, and forecasts are often wrong. As was mentioned in the Introduction, a century ago the U.S. patent commissioner thought that no significant discoveries remained to be made. Around 1940, it was widely thought that the nature of research had changed. A U.S. government report (quoted on p. 17 of [FloridaK]) stated that in "large industrial laboratories ... research has itself become a mass-production industry." (Compare this to the Forrester 1995 quote from [TR] at the end of Section 2.) Even such perceptive observers of the economic scene as Joseph Schumpeter shared this view. Yet the following few decades saw the greatest flowering ever of industrial as well as university unfettered research. Are we likely to experience something similar in the future? The current trend towards directed, short-term research can be thought of as a triumph of the Japanese style of RD management. It was Japan that perfected the incremental improvement approach to technology. By adopting the quality improvement approach pioneered by Shewhart at Bell Labs, and extended by Deming and Juran, the Japanese blurred the lines between RD and production, with even assembly line workers contributing to quality and efficiency gains. Their research was extremely goal-oriented, and usually would have been called advanced development in the U.S. There were close ties between RD personnel and production and marketing groups. This approach triumphed in the marketplace, and gave Japan a lead in producing high-technology hardware, a lead that is still growing, as is shown by trade figures (provided those are adjusted for Japanese exports of production tools and sophisticated components to other Asian countries). (For more evidence of this lead, see [Hamilton], which shows that most of the potential bottlenecks in the manufacture of PCs are in Japan.) This approach is also what was adopted by the rapidly industrializing countries, and is what American and European firms seem to be striving for. However, the Japanese were cognizant of their borrowing of basic science from the West, and during the 1980s were making plans for increasing their investment in research, including the unfettered type. These plans seems to have been shelved during the 1990s, and the question is whether this was a result of a reassessment of their needs, or of the recession and deflation of the Japanese financial bubble. Even though their profits have plummeted, Japanese companies have not decreased their RD efforts (which already account for a larger fraction of GNP than in any other country), and the Japanese government is increasing its commitment to unfettered research [Normile]. The question is what will happen when the Japanese economy recovers. Japanese companies might be more inclined than Western ones to invest in long-term research. They tend to concentrate on the production of goods (where the lead times between initial ideas and marketplace applications appear to be longer than in systems and services). Also, their keiretsu structure makes its easier to justify long-term work, since the probability that some company in a grouping will be able to benefit from some unforeseen technological development is much easier than if just one narrowly focused company were involved. However, so far what little information there is seems to point towards greater focus on short-term work even in Japan. In American and European industry, the prospects for a return to unfettered research in the near future are slim. The trend is towards concentration on narrow market segments. Two decades ago, the hard disk market was dominated by vertically integrated manufacturers such as IBM and CDC. Today, leading firms, such as Seagate, basically do only system design, assembly, and marketing of their disks. They buy their disk controllers, motors, and other components from outside suppliers. The reason they can do this is that technology is widely available, and any basic research results are likely to be incorporated by the suppliers into their products and be available for anyone to buy. Ford's River Rouge plant was the embodiment of vertical integration, with "iron ore and coal coming in at one end, and Model Ts rolling out the other." There was justification for this integration, since outside suppliers could not be relied on to provide the necessary quality and consistency of supply. Today the atmosphere is entirely different. The head of a business unit of a large corporation, whose division competes in a market where at least temporarily everyone appears to be losing money, mentioned publicly his efforts to persuade the other business unit heads to subsidize his division, to have assurance of supplies in the future. They were not interested, and even told him that they felt if his division went out of business, the other competitors would become stronger, and would therefore be able, through economies of scale, to lower their prices. This attitude is extreme, but apparently not uncommon. At this point it is worth stating again that this essay is not meant to be a balanced account of research policies. It is intended to explain the reasons for the decline in unfettered research, and the turn towards more directed work. Therefore it emphasizes the negatives. There are valid arguments to be made for unfettered research, even in industry. I will not devote much space to explaining them, but they do include public relations, maintenance of ties with university researchers, and recruiting. Probably the most important reason is the need to have a window on future technological developments, to anticipate new threats and promising new directions for a company to pursue. All these reasons will presumably preserve some unfettered research in industry. However, these reasons have always been valid, and therefore in view of the negative developments listed in previous sections, they are not likely to lead to a reversal of current policies. The arguments for taxpayer support of unfettered research are easier to make, since the benefits of wide-ranging undirected inquiry are more likely to be exploited someplace in a large economy than in a single corporation. However, even there the issue of "free-loaders" or "the tragedy of the commons" arises, since basic scientific advances diffuse rapidly around the world, and the taxpayers in the country funding a long-term project in basic research may not benefit much from it. Questions are also being raised about the rationale for government support of all basic research. I will not deal with all the issues that arise in this context (see [Armstrong, ByerlyP, NAS1], for example), but will assume that government funding will be provided, and will concentrate on the issue of what type of research should be supported. Universities are still a stronghold of unfettered research. However, they are also facing increasing pressure to change. Most of the factors discussed in earlier sections apply to university research as well, and there are additional special ones that apply in academia. The increasing size and specialization of the research enterprise, even in academic settings, means that what professors do is getting further removed from what they teach. This raises into question the justification of research as a crucial qualification for a teacher. Universities are also still set up for continuing exponential growth, and there are few of the negative feedback loops in operation that would stop the overproduction of Ph.D.s (cf. [Goodstein]). Further, the Ph.D.s that are produced are trained primarily for unfettered research. That preparation is inadequate for the non-academic jobs that more and more of them are taking. Hence there is increasing recognition that graduate education will need to be rethought and reformed [NAS2]. The general growth of scientific knowledge means that interdisciplinary research offers increasingly attractive opportunities. However, universities, with their rigid division into departments, are poorly positioned to take advantage of this. (One can go even further, and say that the fierce competition for tenure and grants is forcing faculty into extremely narrow and esoteric areas of research, which undermines the rationale for unfettered research. For a discussion of the deficiencies of the present peer review system, see [Lederberg].) Further, the same factors that operate in industry (the high payoff from short-term work, the relative lack of dramatic new innovations, the increasing scale of research projects, etc.) also influence the decisions makers who fund university research. There are frequent calls for publicly funded work to be more relevant. With increasing reliance on industrial funding or collaboration, there will be additional pressure on academic researchers to prove that what they do is of value to society. Even military-funded research was often relatively unfettered compared to what is often required in work with industry [Ghoshroy]. The need for large scale efforts in some areas of research, and the commingling of potentially profit-making work with pure research, will continue to put strains on academic institutions. On the positive side, two factors (in addition to the inertia of the byzantine academic system) will serve to preserve at least some traditional unfettered research at universities. One is that the best way to prepare students for careers in science and technology in a world that is changing rapidly is not to train them in the narrow skills that happen to be in hottest demand at the current moment, since those are likely to be obsolete in a few years. It is better to train them in more general skills, and in particular to concentrate on fundamental phenomena. That is also the way to attract the ablest students to science and technology, since they usually want to feel they are doing something basic that advances human knowledge, and not just tweak some process to increase profits. Another factor that is likely to preserve a large fraction of the unfettered research being performed at universities, and perhaps even a small fraction of what used to be done in industry, is general unease with the trend towards short term research. Even industrial leaders who demand immediate payback from research in their companies recognize the value of fundamental research as a public good, and speak up in favor of government funding [Coy, NAM, PT]. The idea that we can proceed without looking far forward, dealing with technical problems only as they come up, seems implausible. While we can certainly do that for a while, living off the advances made in the past, such a strategy is unlikely to be successful for long. Even if it were possible to dispense with long range research, it would not be advisable. As a simple example, the discovery of public key cryptography, mentioned in the Introduction, could be called premature, in that it is only now, almost 20 years after the basic invention, that public key cryptosystems are coming into widespread use. (Computers and communication networks had to become widespread for the need for public key systems to become acute.) However, the knowledge that this technology existed was of tremendous value, as it showed that electronic commerce and related goals could be achieved at low cost. This, in turn, facilitated planning for the information age, and forestalled unnecessary research for alternatives. While one can justify some support for unfettered research, the case is not easy. Further, there seems to be no way to get back to the days in which individual researchers had to make hardly any justification for their projects, and areas grew with the stimulation of bountiful funding for all. Choices will need to be made, especially choices between fields. Scientists can show that they have been making good choices, given all the uncertainties involved, in deciding on directions within subjects. (Even there, though, there have been many mistakes, such as a famous university eliminating matrix theory from the requirements for an undergraduate degree in physics in the early 1920s, just a few years before the invention of quantum mechanics.) However, scientists have been notoriously bad in deciding on priorities between subjects. Unfortunately, such choices seem inescapable. While scientists usually feel that knowledge is good by itself, the public is unlikely to support the large scale research enterprise we have without utilitarian justification. Claiming that the superconducting supercollider would have absorbed a smaller fraction of the US federal budget than Tycho Brahe's Uraniborg observatory did of King Frederick II's revenue did not persuade many people to vote for the $15B project. The lack of measurable payoff for the economy from the last 50 years of experimental high energy physics (combined with the lack of pork barrel appeal) seemed to play a bigger role. We do not have a convincing way to justify any particular split between unfettered versus directed research. We do not even know what the optimal level of total RD effort is. Many scientists and mathematicians feel that their personal projects are crucial for the development of human knowledge. However, while one can perhaps make a similar case in art (if Verdi had been diverted from music towards a more mundane occupation, such as banking, would anyone else have composed the Manzoni Requiem, for example?), it is hard to argue this in science or mathematics. Most researchers are Platonists, and believe that they discover more than invent. It is impossible to dismiss out of hand the argument that long-range unfocused research should be abandoned or at least sizably decreased in favor of shorter-term projects with greater payoff. Fundamental discoveries that are not made soon as a result of such a downsizing would simply be made later. One can even argue that in the long run, human knowledge might benefit from such redirection, since the improved technology developed during the next decade or two of the digital revolution, as well as the higher standard of living and better education that result from it, will enable much faster progress on a broader front in the future. There are numerous examples of ambitious projects, such as machine language translation in the 1960s or Ted Nelson's hypertext Xanadu project in the 1970s and 1980s, that were attempted too early, before the tools (hardware, software, and basic knowledge) to carry them out were available. It is even dangerous to argue that in some fields we are relying on discoveries of unfettered research made a century ago. That argument can quickly be turned around, to say that if we haven't yet fully exploited the last century's work in those fields, why should be go much further in them now? A much more persuasive case for research, including relatively unfettered one, can be made by citing extended research programs that have only recently started to have an impact in the marketplace, but are crucial today. The Computing Research Association has compiled an excellent report on just such developments [CRA]. It shows how a decades-long collaboration of universities, government, and private industry has provided the basic tools for the information society. Broad programs, directed at areas that appear to be especially promising or important, but ones that leave substantial freedom for individual investigators, may be the most promising approach. This may not be exactly "the free play of free intellect" advocated by Vannevar Bush, but it should be easier to justify to the public, promote technological change, and advance human knowledge. As Langmuir is supposed to have said, "You can't predict what you will find, but you can make sensible bets on where to look." Acknowledgements: I thank John Armstrong, Sam Bleecker, Greg Blonder, Joe Buhler, Rob Calderbank, Elise Cawley, David Cohen, Mel Cohen, Bill Coughran, Peter Denning, Henry Ehrenreich, Stephen Elliott, Alan English, Joan Feigenbaum, Paul Ginsparg, Stevan Harnad, Albert Henderson, Joe Kilian, Kathy Krisch, Bob Kurshan, Susan Landau, Lou Lanzerotti, Jeff Lagarias, Leslie Lamport, Ed Lazowska, Joshua Lederberg, Mike Lesk, Peter Littlewood, Ron Loui, David Maher, Gary McDonald, Jim Mazo, Charles Molnar, Larry O'Gorman, Arno Penzias, John Poate, Raghu Raghavan, Peter Renz, Bruce Reznick, Bruce Richmond, Avi Silberschatz, Larry Shepp, Neil Sloane, Warren Smith, Harold Stone, Al Thaler, Chris Van Wyk, Hal Varian, and Stephen Wolfram for their comments on an earlier version of this article. References: [Armstrong] J. A. Armstrong, Is basic research a luxury our society can no longer afford?, The Bridge (quarterly published by Nat. Acad. Eng.), vol. 24, no. 2, 1994. [Burke] Colin Burke, "Information and Secrecy: Vannevar Bush, Ultra, and the Other Memex," The Scarecrow Press, 1994. [Bush] V. Bush, "Science: The Endless Frontier," Government Printing Office, Washington, D.C., 1945. [ByerlyP] R. Byerly Jr. and R. A. Pielke Jr., The changing ecology of United States science, Science 269, Sept. 15, 1995, pp. 1531-2. [CRA] Computing research: driving information technology and the information industry forward, report prepared by the Computing Research Association, available online at URL http: www.cs.washington.edu homes lazowska cra [Coy] P. Coy, Blue-sky research comes down to Earth, Business Week, July 3, 1995, pp. 78-80. [Ehr] H. Ehrenreich, Strategic curiosity: Semiconductor physics in the 1950s, Physics Today, Jan. 1995, pp. 28-34. [FloridaK] R. Florida and M. Kenney, "The Breakthrough Illusion: Corporate America's Failure to Move from Innovation to Mass Production," Basic Books, 1990. [FL] H. I. Fusfeld and R. N. Langlois, eds., "Understanding RD Productivity," Pergamon Press, 1982. [Ghoshroy] S. Ghoshroy, Universities face RD cuts as defense budgets decline, in The Institute (IEEE member newsletter), vol. 19, no. 6, June 1995. [Gomory] R. Gomory, Of ladders, cycles, and economic growth, Sci. Am., June 1990, p. 140. [Goodstein] D. Goodstein, The big crunch, available on line at URL http: www.caltech.edu ~goodstein crunch.html. (Previous versions published in several journals, including American Scholar, vol. 62, no. 2, spring 1993.) [Hamilton] D. P. Hamilton, Computer makers face hidden vulnerability: supplier concentration, Wall Street Journal (Eastern ed.), Aug. 27, 1993, p. A1. [Lederberg] J. Lederberg, Research and the culture of instrumentalism, in issue 1.1, spring 1995, Columbia - 21st Century. [NAS1] Science, technology, and the federal government: National goals for a new era, National Academy Press, 1993. [NAS2] Reshaping the graduate education of scientists and engineers, National Academy Press, 1995. Summary available online at URL http: www.nas.edu nap online grad summary.html [NAM] National Association of Manufacturers, press release, July 1995. [Normile] D. Normile, Japan expands graduate postdoc slots, Science 269, Sept. 8, 1995, pp. 1335-6. [PT] Letter to Senator Dole, dated March 13, 1995, from 15 industrial leaders, reprinted in Physics Today, May 1995, p. 54. [Price] D. J. Price, The exponential curve of science, Discovery 17 (1956), pp. 240-243. [RSE] P. A. Roussel, K. N. Saad, and T. J. Erickson, "Third Generation RD: Managing the Link to Corporate Strategy," Harvard Business School Press, 1991. [Schmookler] J. Schmookler, "Invention and Economic Growth," Harvard Univ. Press, 1966. [Schnaars] S. P. Schnaars, "Megamistakes," The Free Press, 1989. [StalkH] G. Stalk, Jr., and T. M. Hout, "Competing Against Time: How Time-based Competition is Reshaping Global Markets," Free Press, 1990. [Stewart] T. A. Stewart, What information costs, Fortune, July 10, 1995, pp. 119-121. [TR] The legacies of World War II, (a roundtable discussion with H. Brooks, J. W. Forrester, P. Morrison, A. Roland, S. van Evera, E. C. Weaver, H. Woolf), Technology Review, May June 1995, pp. 50-59. [Toffler1] A. Toffler, "Future Shock," Random House, 1970. [Toffler2] A. Toffler, "The Third Wave," Morrow, 1980. [Toffler3] A. Toffler, "Powershift," Bantam, 1990. [Zachary] G. Pascal Zachary, Vannevar Bush on the engineer's role, IEEE Spectrum 32, no. 7, July 1995, 65-69. US President's Council of Advisors on Science and Technology (PCAST) PCAST consists of 18 members from the private sector plus the Assistant to the President for Science and Technology who serves as the Committee's Co-Chair. PCAST HOME PAGE Co-Chairs John H. Marburger III, Ph.D. , Director, Office of Science and Technology Policy, Co-Chair, PCAST Floyd Kvamme, Co-Chair, PCAST Membership List President's Council of Advisors on Science and Technology (PCAST) On September 30, 2001, President Bush signed Executive Order 13226 to form the Presidents Council of Advisors on Science and Technology (PCAST). On March 28, 2001, President Bush named Floyd Kvamme PCAST's Co-Chair. PCAST was originally established by President George Bush in 1990 to enable the President to receive advice from the private sector and academic community on technology, scientific research priorities, and math and science education. The organization follows a tradition of Presidential advisory panels on science and technology dating back to Presidents Eisenhower and Truman. Since its creation PCAST has been expanded and currently consists of 23 members plus the Director of the Office of Science and Technology Policy who serves as the Council's Co-Chair. 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NATIONAL ACADEMY OF SCIENCES NATIONAL ACADEMY OF ENGINEERING INSTITUTE OF MEDICINE NATIONAL RESEARCH COUNCIL Current Operating Status STEP HOME ABOUT STEP MEMBERS AND STAFF PUBLICATIONS PROJECTS NEWSLETTER RELATED LINKS STEP FEEDBACK LOCAL SEARCH What's New at STEP Innovation Policies for the 21st Century The National Academies Board on Science, Technology, and Economic Policy is convening a high-level conference on "Innovation Policies for the 21st Century." The objective of the conference is to provide an overview of major technology partnership programs, identifying their goals, structure, funding levels, mechanisms, and impact while providing a basis for assessing best practice. This is an unprecedented event which will involve high-level participation from several European, Asian, and U.S. programs. The agenda lays out more clearly the diversity of programs, nations, and regions that will be included in the discussions which, along with registration information, can be obtained by contacting McAlister Clabaugh . Symposium on Patent System Reform STEP joined with the American Intellectual Property Law Association and the Federal Trade Commission in a series of regional meetings on US patent reform in late winter and spring 2005. The purpose of these meetings was both educational and to discuss differences of detail in the largely consistent recommendations of the three organizations in anticipation of congressional hearings. A summary symposium is currently planned for Washington, DC - June 9, 2005. The agenda is available. There is no cost for registration Contact Craig Schultz . PDF summaries of the STEP report, A Patent System for the 21st Century geared for the academic community and the legal corporate community can be found at the preceding links. Intellectual Property Rights in Genomic and Protein-Related Inventions In a joint project with the Science, Technology, and Law Program, this committee reviewed the patenting and licensing of human genetic material and proteins, which represents an extension of intellectual property rights to naturally occurring biological material and scientific information, much of it well upstream of drugs and other disease therapies. The study will document the types of patents that have been issued and to whom (or applied for and by whom), differences in the criteria being applied by the U.S. and other major patent offices to the examination of such applications, and, to the extent, possible, the licensing arrangements for different types of patented materials. In view of the substantial evidence that patents play an important role in certain kinds of biomedical innovations, especially the development of therapeutic drugs, the committee will carefully consider the impact of its recommendations on investments in RD and the commercialization of their results. Transcripts and presentations for the first three workshops are available from the link below. A final report of the committee is forthcoming. [FIND OUT MORE] October 2005 39th Meeting of the STEP Board Washington, DC October 13-14 November 2005 November 17, 2005 IP Genomics and Proteomics Public Briefing Washington, DC A Patent System for the 21st Century From issues raised in a February 2000 conference, Intellectual Property Rights: How Far Should They Be Extended?, the STEP Board commissioned empirical research in areas ranging from patent examiner productivity and quality to licensing in pharmaceuticals and biotechnology. The papers have been published under the title Patents in the Knowledge-Based Economy . Yale University President Richard Levin and retired Xerox Senior Vice President Mark Myers co-chaired a committee which considered the impact of IPR policies on performance and communication of academic research, mobility of highly trained personnel, initial and subsequent innovation, and competition and industry structure. The final report of the committee, A Patent System for the 21st Century , is available at the National Academies press and can be downloaded as a free PDF . Last month the American Intellectual Property Law Association issued a response to the report, largely agreeing with the committees findings and recommendations. The report was also cited in the statement introducing H.R. 5299, a bill sponsored by Howard Berman (D-CA) to create a post-grant opposition procedure. [FIND OUT MORE] Measuring and Sustaining the New Economy This study will examine how best to measure the economic impact of new technologies and how to sustain their contribution to non-inflationary growth and high employment. The initial focus will be on the information technology-producing sector -- semiconductors, computers, software, and communications equipment -- with particular attention to measurement of prices and quality and monitoring of investment and technological trends. The project will also consider the application of information technologies across other sectors of the economy including financial and communications services. The Board will identify the main features of the public policy framework best suited to advancing these technologies and their applications. [FIND OUT MORE ] Innovation Models for Aerospace Technologies The Board on Science, Technology and Economic Policy has convened an ad hoc panel, chaired by Dr. Alan Schriesheim, Director Emeritus, Argonne National Laboratory, which organized a workshop to present examples of successful innovation models used by industries, universities, and the government for the development of pioneering tools, processes and technologies. The project committee will issue a report identifying how and when to incorporate best practices from industrial research activities that are appropriate to different mission needs, technology requirements, industrial sectors, and the stage of technology development and for attracting private sector parties to use those instruments. Full panel roster can be viewed here and the agenda for the June 28, 2004 meeting can be viewed here . Presentations and speaker biographies are available at the link below. [FIND OUT MORE] Research and Development Data Needs: Proceedings of a Workshop A Patent System for the 21st Century Patents in the Knowledge-Based Economy Government-Industry Partnerships for the Development of New Technologies: Summary Report Productivity and Cyclicality in Semiconductors: Trends, Implications, Questions Summer Deconstructing the Computer Software, Growth, and the Future of the U.S. Economy Innovation Models for Aerospace Technologies Intellectual Property in Genomic and Protein-Related Research and Innovation Research and Development Data Needs In cooperation with the Committee on National Statistics Panel on RD Statistics at the National Science Foundation , t he STEP Board held a workshop on April 7, 2003 to consider how to adapt the National Science Foundation's surveys of federal and industrial RD to changes in the organization, composition, and time horizons of RD performance and innovation. A workshop report, due later this year, will inform the deliberations of the CNSTAT committee. [Meeting Materials and Verbatim Transcript] [Information on the CNSTAT Panel] Government-Industry Partnerships Under the direction of Gordon Moore, Chairman Emeritus of Intel, the STEP Board has conducted a broad-based study designed to identify and address the policy issues associated with public-private collaboration in the development of enabling technologies. The project is to address current trends in leading U.S. industries such as semiconductors, a major enabling technology; information technologies such as computers, communications, and software; and expanding biomedical industries based on advances in genomic research. The study established a record of program-based research in close interaction with policymakers - no comparable study has been undertaken in the United States. By reviewing the drivers of industry-university-government cooperation necessary to develop new technologies, it has directed substantial attention to the role and contribution current "generic" U.S. partnerships, e.g., the Advanced Technology Program and the Small Business Innovation Research program as well as sector specific initiatives, e.g., bioinformatics. The study committee has placed major emphasis on sectoral differences, the necessity and means of evaluation, the experience of foreign-based partnerships, and current trends in U.S. RD allocations. [FIND OUT MORE] For a list of current publications from STEP, as well as links to online versions of conference publications , please visit our publications page. Mailing Address: STEP Board 500 Fifth Street NW Washington, DC 20001 202-334-2200 (phone) 202-334-1505 (fax) To Sign-up for STEP's monthly newsletter, email step@nas.edu | Subscribe to e-newsletters | Feedback | Back to Top Copyright 2005. National Academy of Sciences. 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John Marburger Director, Office of Science and Technology Policy 7-27 Statement by Richard Russell before the House Subcommittee on Energy and Resources, Committee on Government Reform, United States House of Representatives 7-08 FY 2007 Administration Research and Development Budget Priorities Release 6-20 PITAC RELEASES NEW REPORT - COMPUTATIONAL SCIENCE: ENSURING AMERICA S COMPETITIVENESS 5-26 OSTP Announces New Director of National Information Technology RD Coordination Office 5-24 PRESIDENT TO NOMINATE OSTP OFFICIALS TO NEW POSTS 5-18 PCAST RELEASES FIRST REPORT ON NANOTECHNOLOGY RD 11-15 Science, Math, and Engineering Mentors Receive Presidential Honors 6-13 White House Announces 2004 Awards for Early Career Scientists and Engineers. 5-16 White House Honors Science, Math and Engineering Mentors 4-12 President Honors Nation's Leading Elementary School Math and Science Teachers 1-14 U.S. Announces Plan for an Improved Tsunami Detection and Warning System 1-14 FACT SHEET: U.S. Plan for Improved TSUNAMI Detection 1-6 Fact Sheet on U.S. Space Transportation Policy 12-15 Fact Sheet on U.S. Space-based Positioning, Navigation, and Timing Policy - UPDATED - 10-5-2005 Information for Researchers and Institutions Affected by Hurricanes Katrina or Rita (CLICK IMAGE TO VIEW PLAN) "Science and technology have never been more essential to the defense of the nation and the health of our economy" President George W. 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Final report from the workshop, " Support of Graduate Students and Postdoctoral Researchers in the Sciences and Engineering: Impact of Related Policies Practices ," held at AAAS June 17 18, 2004 and co-sponsored by the National Science Foundation, the National Institutes of Health and the Council of Graduate Schools. Note: Link is to the report as a pdf file. The AAAS Research Competitiveness Program (RCP) draws upon the resources of the American science and engineering community to assist universities, government agencies, research consortia, and other institutions in planning, reviewing or evaluating programs and initiatives in research, development, and innovation. In 1993, with support from the National Science Foundation Experimental Program to Stimulate Competitive Research (EPSCoR), AAAS began to examine the concept of "competitiveness" as it relates to research institutions. Building on these efforts, AAAS initiated the Research Competitiveness Program under a 1996 NSF grant to provide services to institutions in those states which participate in the NSF EPSCoR Program. Since 1999, the RCP has worked to assist researchers, universities, research institutions and state government agencies that support RD to improve their research competitiveness. The links in the navigation bar on the left lead to detailed information regarding the programs within the RCP. Return to the top . Copyright 2005. American Association for the Advancement of Science. All rights reserved. Read our privacy policy . Contact info. 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Information About S Search: Lycos Tripod Planet Share This Page Report Abuse Edit your Site Browse Sites Previous | Top 100 | Next Information About ST Policy Developments in India This site aims to provide a forum for interaction on matters of ST Policy developments in India. The author of this site is pursuing research in the field of ST policy and management. He has wide experience of working in the field of ST policy and management at different levels in the national RD system. The main areas of interest are transfer of technology, commercialisation of RD, Consultancy development, University - industry linkages, international cooperation in science and technology, RD management, Science indicators and intellectual property rights. Please contact for any relevant information in this regard ST Policy Reforms Intellectual Property Rights Reforms S T Policy Documents Contact Next Page The site was last updated on 7th July,2001. The site has had this number of vists Discussion Board... to let our visitors publically discuss topics of interest FastCounter by LinkExchange Technopolis An innovation policy consultancy, which specialises in the evaluation, comparative analysis and implementation of government science and technology policy and SME support programmes. Technopolis Home Welcome to the Technopolis web site Technopolis provides high quality, practical, knowledge-based research, advice and management support services to policy makers and those responsible for putting policy into practice. We focus on science, technology and innovation and policies for economic and social development. We support the entire policy development and implementation cycle from concepts through policy development and programme design, management and evaluation. The common thread in our activities is that we work with the creation of knowledge and its practical application in society. The Technopolis group is a European organisation with a staff of over 40, based in Amsterdam, Brighton, Brussels, Paris, Stockholm and Vienna. We have working experience of over 25 additional countries; as a result we bring an international perspective to our projects at the regional, national and international level. This web site provides information about the Technopolis group and examples of what we do. Some of our reports and articles may be obtained from the 'Downloads' section. If you have any comments, suggestions or requests, please contact us at info@technopolis-group.com Technopolis 2004 Technopolis drafts background papers and final declaration and report for EU Ministerial Conference on the knowledge economy with a view to preparing for the 2007-13 Structural Fund programming period It Takes More than a Bridge to Make a Region - The resund Contracts as Instruments for Cross-Border RD Cooperation ( Presentation , AEA Toronto, October 2005) Meta-Evaluation of the EU Framework Programmes - Report (PDF) The synthesis report of the comparative study Non-Nuclear Energy Research in Europe, written by Technopolis and published by the European Commission, is now available to download . 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TESTA A ROUND TABLE ON SCIENCE , LETTER AND ART NIC'S CORNER FROM THE STARS TO THE MIND Molecular Diseases MOLECULAR AND MICROBIAL DISEASES PIGMENTS AGEING, AGGRESSIVITY AND CHEMICAL BRAIN PATHOLOGY ASTROCHEMISTRY AND SCIENCE HISTORY LETTERS AND FINE ARTS SUSTAINABLE DEVELOPMENT PARKINSON, HUNTINGTON, ALZHEIMER AND NEUROMELANIN Patricia : Paracas Alpenforum Aggressivity, a new theory History of Science Astrochemistry A Hidden Treasure Art and Magics Chemical Pathology and Suicide Droga e Violenza Drugs and Violence info@brunonic.org Visitor Counter : Revised : November. 2005 ZENSCI - Making sense of science Participatory site (blog with comments etc.) on science and society issues. zenSCI | Our Measure is REALITY zenSCI Our Measure is REALITY All groups... | Artificial Intelligence | Biomimetics | Energy | Fertility | SymBioSE About | Blogs | Events | Feedback | Forum | Home | RSS | SiteMap Welcome to zenSCI! Hello visitor. We wish to be a medium of good science journalism by building a community that brings together journalists and scientists. Have a look around, or, better yet, become a registered user. Membership is free! As a registered user you can: *create content for zenSCI *write your own personal blog *create a userprofile *see other profiles *contact other members *create groups *subscribe to relevant groups Read more here New groups Artificial Intelligence Energy Fertility Biomimetics SymBioSE Science News Rich nations' greenhouse gas emissions may rise-UN Parliament backs new EU law on toxic chemicals Euro-MPs back chemicals law DaimlerChrysler vows to push biofuel technology Parliament backs new EU law on toxic chemicals Ariane rocket launch breaks payload record UR r@ is in the trap The food you eat may change your genes for life Aids may help spread of bird flu Rich nations' greenhouse gas emissions may rise: UN Indonesia activates tsunami early warning buoys UN debut for $100 laptop for poor India unlikely to agree to Kyoto caps SARS survivor tells of pandemic fears NASA wants private sector help for space Statins may delay effects of Alzheimer's -study Heavy-lift Ariane-5 rocket launches two satellites Heavy-lift Ariane-5 rocket orbits two satellites Satellite gap may jeopardize US weather predicting Heavy-lift Ariane flies skyward more Technology News Tunisia slated over net controls Strong performances boost Vivendi Five readies for satellite launch More pain for Sony over CD code Cost of making games set to soar UN predicts 'internet of things' Literary classics become txt msgs UN debut for $100 laptop for poor Mobile industry tests the wi-fi airwaves Mobile industry tests the wi-fi airwaves Mobile industry tests the wi-fi airwaves 'Lost' deal hatched for mobile UK 'most wanted' site launched Sony, NEC to form optical drive pact Blu-ray, HP at odds over high-def DVD launch plan Microsoft tests next Office Microsoft tests next Office TV networks say digital recorders raise viewership TV networks say digital recorders raise viewership Motorola sees launching new Rokrs in 2006 more Active forum topics Book: Freakonomics, A Rogue Economist Explores the Hidden Side of Everything Anybody interested in doing some live blogging from this years SymBioSE? Groups The Symbionts database more New forum topics Book: Freakonomics, A Rogue Economist Explores the Hidden Side of Everything Groups The Symbionts database Anybody interested in doing some live blogging from this years SymBioSE? more Looking through the profiles - so many interesting stories! Submitted by Lennart on Thu, 11 08 2005 - 20:23. Editorial | Sci. communication Hi all users and guests of zenSCI, Lately I have not had much time to write things here at zenSCI. I know, of course, that the rest of you people are probably as busy as me - so I understand perfectly why none of you are writing anything here. But then again, as I looked through all the new profiles that had been made since my last visit here - I thought: So much knowledge, so many interesting subjects. In the profiles of course what you get is a keyword, which only sufices to trigger your appetite for more. I am sure many guests and users here at zenSCI would love to know more about what lies behind subjects such as 'fire ecology' and 'space robotics'! I for one sure would. So do not be shy, write a blog, an article or whatever about your subject and your relation to it, put it into societal perspective if you want. Tell us about it :-) add new comment | read more Commercial biomimetics meeting Bath Biomimetics Start: 23 09 2005 - 09:00 End: 23 09 2005 - 16:00 Timezone: Etc GMT Hi On Friday the 23rd of September the Centre for Biomimetics and Natural Technologies at the University of Bath, UK will host a one day meeting on the commercial aspects of biomimetics. If interested please find more details in the attached pdf file. Best wishes, Thomas add new comment | calendar | 1 attachment Science and Politics - the case of Genetics Fertility Start: 15 09 2005 - 09:00 End: 16 09 2005 - 16:00 Timezone: Etc GMT-2 Symbiont Jens kne has asked me to announce the following event which will take place in Oslo, Norway. Genetics has been involved in a series of political controversies through the 20th century. It thus provides an appropriate case for investigating the interactions of science and politics. The workshop will focus on two periods with particularly lively debates. During the middle decades, from the 1930s to the 1950s, eugenics and race were major political issues. Toward the end of the 20th century and into the 21st the political controversies around the development and use of genetic knowledge and technology in human reproduction has again become central issues of general politics. add new comment | calendar | read more Promising developments in solar energy by Ris Submitted by Mikkel on Sat, 30 07 2005 - 16:03. News Energy Ris National Laboratory is developing a new type of solar panels which holds much promise for the future of exploiting solar power. Ris have been working on cells made of plastic, instead of the normal silicium based cells. Using plastic instead of silicium will reduced the cost of a solar panel drastically. Today one square meter of silicium based solar panel cost roughly 800 USD, whereas made in plastic it will cost less than 15 USD. So far the problem with plastic panels have been their durability. Panels made of silicium last 25 years, but until now plastic ones have not lasted much more than two weeks. However, Ris have been working on the durability aspect, and have developed cells that will last two and a half year years. 1 comment | read more Book: Freakonomics, A Rogue Economist Explores the Hidden Side of Everything Submitted by Mikkel on Sat, 30 07 2005 - 14:07. Controversial Science Anyone read this book? It sounds quite interesting, and perhaps a bit controversial ;-) Excerpt from homepage : "Freakonomics establishes this unconventional premise: if morality represents how we would like the world to work, then economics represents how it actually does work. It is true that readers of this book will be armed with enough riddles and stories to last a thousand cocktail parties. But Freakonomics can provide more than that. It will literally redefine the way we view the modern world." 3 comments | read more 1 2 next page last page User login Username: Password: Create new account Request new password Navigation create content feedback recent posts groups categories news aggregator syndication By type - Analysis - Article - Editorial (1) - News (4) - Press Release By topic - Ethics - Higher Education - Sci. communication (1) Who's new flaviu_tomescu RuiRodrigues marjan Rubella sasa Who's online There are currently 0 users and 3 guests online. Recent comments Interesting 2 weeks 4 days ago After 2 weeks 5 days ago Password 3 weeks 1 day ago Hi everybody, after long 12 weeks 6 days ago Podcasting and Password 13 weeks 6 days ago Movie password protected 13 weeks 6 days ago Hi Lennart,you definetly 13 weeks 6 days ago Hi Sebastian,Thanks for the 13 weeks 6 days ago podcasting 14 weeks 3 hours ago New solar cell technology 15 weeks 2 days ago All content at this site 2005 by respective authors, all rights reserved. Powered by Drupal GWC Instruments Produces instruments which use Surface Plasmon Resonance (SPR) to measure absorption of thin films on gold surfaces. This technique is used to study interactions between proteins, DNA, and RNA. Includes a list of products. GWC Technologies GWC Technologies info@gwctechnologies.com 608.441.2720 505 S. Rosa Road Madison, WI 53719, USA Label-Free Detection For Life Science and Materials Science GWC Technologies offers detection systems and sensor chips to meet a broad range of research needs. Whether your interests are in Protein Interaction Analysis, Antibody Characterization, Nucleic Acid Detection or Surface Analysis, GWC has affordable products that can help your research. Label-free detection in an array format Lets you analyze interactions involving proteins, peptides, nucleic acids and carbohydrates. The array format facilitates robust experimental controls. Advanced wavelength-scanning SPR The ultimate in Surface Plasmon Resonance analysis of surfaces and biomolecular interactions. Integrated with Thermos FT-IR spectrometers . SpotReady chips provide an easy route to manual fabrication of arrays. SPRchip substrates provide the greatest flexibility for fabricating probe arrays. SSD 74 SSD 100 - Demodulators for PM-IRRAS measurements. Home | Label-Free Arrays | Advanced Spectroscopy Technology Applications | Contact | About GWC Join our Mailing List | Careers at GWC Copyright GWC Technologies, 2004. All right are reserved. Privacy Policy Bioslide Technologies Specializing in the production of Super Clean Slides and microarray slides, hand-screened and quality tested for immobilization and hybridization with oligonucleotides at Walnut, California. BIOSLIDE TECHNOLOGIES INC. Account Login Account Info Register Shopping Cart Order Tracking Contact Us HOME PAGE Bioslide HELP DESK 1-909-444-0888 COVER GLASS GLASS LABWARE MICROARRAY SLIDES MICROSCOPE SLIDES GUEST 0 $0.00 Providing the Tools Scientists Need Welcome to Bioslide! Bioslide provides high quality microarray products, laboratory glassware and equipment with cutting-edge technologies for life science laboratory professionals worldwide. 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Mail Us at : sales@bioslide.com Eiber-Lab Laboratory Equipment German exporter of Laboratory equipment and medical instruments Medical and laboratory equipment Die Eiber International GmbH gehrt zu den fhrenden exportierenden Hndlern fr deutsche und Europische Laborprodukte. Wir liefern vornehmlich komplette "Laborsets" d.h. komplett ausgestattete Laboratorien oder Segmente and Universitten, Krankenhuser und Foschungsinstitute im asiatischen Bereich. Eiber International GmbH is one of the leading German exporters of laboratory equipment and medical instruments, made in Europe and made in Germany. Our main Export area is the Asian continent where we ship parts or complete labs. Eiber-Lab We furnish your Laboratory ! 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Wildlife Materials International, Inc. 1202 Walnut Street Murphysboro, Illinois 62966 USA FAX -- 618-687-3539 PHONE -- 618-687-3505 U.S.A. -- 1-800-842-4537 CANADA -- 1-800-626-2704 EMAIL -- sales@wildlifematerials.com Copyright 2005, Wildlife Materials International, Inc., Warranty Information Chiral Purification Services Products include chiral chromatography and pure enantiomers. Offers custom purification services and chromatographic supports. Based in France. Chirosep - Products Services Our URL has changed to http: www.tradewithfrance.org icatalog chirosep-services.html Loading page, please be patient... Solutions for Bioresearch Products and services for molecular biological research and diagnostics, such as DNA sequencing, laboratory automation, kits and reagents. Explains products and output capabilities. Includes photos. Westburg - Solutions for bioresearch Scie Plas Limited Provides electrophoresis and radiation protection products, along with the associated peripherals. Lists products and distributors. Scie-Plas Ltd in Southam Warwickshire England Company Profile Scientific Products Customised Plastic Products Scientific Catalogue Instruction manuals Distributors News Contact Us Welcome to the Scie-Plas website. Scie-Plas is one of the world's leading manufacturers of high quality Gel Electrophoresis Equipment and Radiation Protection Products. Click here to go to the scientific site Scie-Plas is one of the UK's leading manufacturers of P.O.S. units and general fabricated products Click here to enter the fabrication site Scie-Plas is a member of the Biochrom Group of Companies ResGen Inc. Products for genomic research including microarrays, tissue arrays, clones, libraries, peptides, antibodies, peptides, RNA, cDNA, reagents, primers, markers and probes. Includes description of products and an online catalogue. Invitrogen MapPairs Online Catalog | Investors | Careers Invitrogen Clones Main MapPairs - MapPair Info - MapPair Viewer BAC PAC Yeast Clones - Yeast Info - BAC PAC Info - Order FTP Resources home products services mappairs and bac, pac, yeast clones Welcome! We have recently incorporated all ResGen products into our Invitrogen product families and online ordering systems. Please choose from the list below to obtain specific product information and to order any of the following items: MapPairs Microsatellite Markers BAC PAC Clones Yeast Deletion Clones Custom Antibodies Custom Peptides Clones Custom Services Tissue Arrays FTP Resources Home | Contact Us | Feedback Copyright 2004 Invitrogen Corporation. All rights reserved. Please read our Privacy Policy . High Speed Air Thermocyclers Features articles explaining the different thermal cycler products, for genetic identification, that this company has to offer. Idaho Technology Inc. - Thermocyclers, Detection, High Res. Melters, Reagents, Probes and Primers All Idaho Technology Products R.A.P.I.D. System RAZOR System RapidCycler 2 Instrument LightScanner Instrument HR-1 Instrument LCGreen Melting Dye Freeze-Dried Reagents Wet Reagents Buffer IT BioChem Contact Us | About Us | Work With Us December 10 - 14 American Public Health Association Annual Meeting - APHA Philadelphia, PA, USA View Recent News and Events Legal Notices Privacy Policy Contact Webmaster 2001-2005Idaho Technology Inc. All Rights Reserved Idaho Technology Inc. Home Pelletlab Our specialty is a fast-growing and popular science project, the study of Barn Owl pellets. Mountain Home Biological - 800 958 9629 - www.pelletlab.com OWL PELLETS Astronomy Books Videos CD Roms Chemicals Dissection Guides Kits Mats Electricity Geology Lab Supplies Filtering Glassware Incubators Magnetism Magnifiers Measurement Pipettes Plastic Labware Porcelain Ware Safety Equipment Stands Supports Test Tubes Thermometers Tools Supplies Vacuum Pumps Life Science Kits FOSS STC Life Science Videos Living Materials Algae Cultures Aquarium Supplies Bacteria Bulk Material Butterflies Culture Media Fungi Invertebrate Life Science Videos Plants Protozoan Cultures Microscopes Accessories LW Scientific Shinco 30X Swift Models Charts Charts Models Plastic Embedments Riker Mounts Physics Electricity Gases Heat Light Optics Magnetism Miscellaneous Pulleys Sound Wave Physiology Scales Weights Slides Individual Slides Slide Sets Specimens Dissection Guides Dissection Mats Plastic Embedments Preserved Material *KIDS* ~ How to Order Shipping Chart About Us Contact Us Links Welcome 1-800-958-9629 Greetings from Mountain Home Biological. We are a family-owned business in Washington State, and are proud to provide quality laboratory and school science products, and a real voice at the end of your telephone line! Buy on the Web * 24 7 WORLDWIDE * It's Easy Safe Paypal, Check, Money Order, Credit Card by Phone Owl Pellets Our specialty is a fast-growing and popular science project, the study of Barn Owl pellets. In addition, we offer a large selection of resources for virtually any type of biology project. What are barn owl pellets? The Barn Owl swallows prey whole, and dissolves it in a fore stomach. What is not digested, the bones, hair or feathers, is regurgitated. These bones remain intact, and are identifiable using bone sorting charts or posters. New! Bird Pellets Occasionally barn owls will consume other birds. The resulting pellet provides a unique opportunity to explore the skeletal anatomy of a bird! The following are answers to some common questions that we receive: How much do Barn Owl pellets cost? 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Echelon Biosciences Inc. - Technology Development for Accelerated Drug Discovery SEARCH Home About Echelon Contact Us My Account View Cart Logon ASSAYS AND REAGENTS FOR DRUG DISCOVERY IN LIPID SIGNALING PATHWAYS PRODUCT CATEGORIES Antibodies and Lipid Recognition Proteins Assays Enzymes Inhibitors Intracellular Lipid Delivery Systems Isoprenoids Lipid-Protein Interaction Tools Lysophospolipid Products MEP Pathway intermediates Phosphionositides and derivatives Phospholipase Substrates Sphingolipid Products PATH WAY DISTRIBUTORS TECHNICAL SUPPORT FAQ NEWS TECHNICAL DATA SHEETS PROTOCOLS PUBLICATIONS BROWSE BY PATHWAY FEEDBACK SUBMIT PRODUCT IDEAS Direct:801-588-0455 Fax:801-588-0497 PI(3,4,5)P3 Synthetic PI(3,4,5)P3 reagents available in diC8, diC16, More... PtdIns(3,4,5)P3 diC16, D-myo-Phosphatidylinositol 3,4,5-trisphosphate PtdIns(3,4,5)P3 diC8, D-myo-Phosphatidylinositol 3,4,5-trisphosphate New Assays This Month Your best source for assays for all your research use. PTEN ELISA 96 well ELISA kit measures PTEN activity, Echelon exclusive PTEN ELISA FS-3 - New Fluorogenic lysoPLD Substrate Lysophospholipase D (LysoPLD), also known as Autotaxin (ATX), a potent mitogen that as been implicated in the pathophysiology of ovarian cancer... FS-3 (lysoPLD Autotaxin substrate) Methylerythritol Phosphate (MEP) publications - Check out Echelons publication abstract about the exciting possibilities of the MEP pathway! MORE... New Phospholipid review article from Glenn D. Prestwich, "Visualization and perturbation of phosphoinositide and phospholipid signaling" What do you think of Echelon's newsletter? Click here to submit feedback Download Echelon's Newletter; The Echelon Review Visit our booth at ASCB , Dec 10-14 in San Francisco, CA 2005 Echelon All Rights Reserved | powered by corezon Biotech Holdings Bioanalytical laboratories specialized in customized gels and reagents for electrophoresis and related services, latex protein testing, fine cosmetics, collagen type II, and kits for educational market. Biotech Holdings - Gelux, Inc. Home Page GELUX GELUX II Prolatex Collanet Iso Electric Focusing Industry Related Links American Chemical Society The Electrophoresis Society Society for Biomaterials BioSupplyNet SciQuest Edison BioTechnology Center Biotech Holdings BHI was established in 1990 to offer only the highest quality customized products and services for research laboratories. Now Operating with Four Divisions GELUX : Customized bioanalytical laboratory services and consulting. The leading industry resource for high-end electrophoresis products offering the broadest range of precast custom electrophoresis gels available on the market. Welcome to our web site. It represents our commitment to progress. Please click on the left side to visit our departments. GELUX II : Manufacturing custom precast gels for electrophoresis in the research and educational markets: 1-D, 2-D, IEF, Sequencing. Replacements for: Zaxis, Owl, Stratagen (CastAway), Hoeffer - Dalt II Highly professional, not mass merchandise, only fresh! ONLY GLASS CASSETTES, ANY SIZE! Prolatex Labs : Standard testing for analysis of proteins in natural latex and related products Collanet Lab : Extracellular matrix preparations, with special emphasis on Collagen Type II (chicken sternae). Electrophoresis for collagen samples. Determination of Hyaluronic Acid and GAGs. Company Profile Mission: To offer only customized products and services for research laboratories, industry, and educational markets. Our commitment to excellence is: "TOTAL CUSTOMER SATISFACTION" History: BHI was formed in January of 1990 as a state-of-the-art bio-analytical and manufacturing laboratory for pre-cast gels, collagens and kits. In June of 1996 the new Biotech Holdings Gelux, Inc. group was founded to reflect the GELUX patent and new ownership that brings new capabilities with bioanalytical testing, consulting and precast gel manufacturing. Statistics: Established: 1990 Employees: Ohio: 6 International: 10 Business Activities: Manufacturing, RD, Distribution, Importing Exporting, Contract Manufacturing, Contract RD, Contract Distribution, Contract Importing Exporting, Consulting, and more. Markets: Research Laboratories at hospitals, universities, and biotech companies, biological laboratories in schools, quality controls which require protein testing, enzyme activity testing, and analytical and preparative electrophoresis. Research Expertise: Electrophoresis-related technologies, Collagen Type II preparations, bioanalytical testing of proteins and enzymes. New capabilities include preparative electrophoresis and enzyme kinetics. Biotech Holdings Gelux Bucharest - ROMANIA (European Branch) ANNOUNCEMENT: Due to the high demand from our Clients from USA, we will reopen the main offices in Akron, OH in October E-mail: gelux@operamail.com geluxusa@netscape.net gelux@msn.com Peter Lugojan, Ph.D. Chairman CEO Res. Dir. Michelle Lugojan President Copyright 1998 Biotech Holdings, Inc. Updated Sept. 5, 2005 Thank you for visiting. If we can be of service, please give us an e-mail. Elisa Test Kits Manufactures enzyme immunoassays for the detection of residues in food and feed, as well as human infectious diseases. Welcome to R-Biopharm AG homepage Again R-Biopharm belongs to Germanys Technology Fast 50 in 2005 R-Biopharm ranks amongst the 50 fastest-growing companies in Germany in the year 2004 and was in the position to repeat this success in the year 2005. NEW at R-Biopharm: RIDASCREEN Enro Cipro a competetive ELISA for quantitative analysis of Enrofloxacin and Ciprofloxacin in milk, meat, fish and shrimp. RIDASCREENFAST Hazelnut (R6802) R-Biopharm AG successfully took part in the inter-laboratory study "Detection of hazelnut residue in dark chocolate" conducted by the German Consumer Safety and Food Safety Office. Rida Soft Win Rida Soft Win version 1.44 is available. NEW at R-Biopharm: RIDASCREEN Haptoglobin The health status of farm animals can be easily monitored with the acute phase protein Haptoglobin. High level of Haptoglobin indicate infections, inflammations or neoplasia. NEW at R-Biopharm: RIDASCREEN Campylobacter ELISA for the direct and highly specific antigen detection of C. jejuni and C. coli in stool samples. R-Biopharm Food and Feed Analysis New Distribution Network in Eastern Europe and Austria Effective 1st of July 2004 we reconstructed our distribution in Eastern Europe and Austria. R-Biopharm Food and Feed Analysis New Distribution in Canada Effective 1st of July 2004 we changed distribution in Canada. RIDASCREEN Chloramphenicol with our new lot no.: 04134 expiry february 2005 we changed the product leaflet regarding the sample preparations. NEW PRODUCT: RIDACOUNT - the test sheet that counts for you To meet the increasing demands in routine microbiological analysis, R-Biopharm offers an interesting new answer. RIDA Quick Cryptosporidium RIDA Quick Cryptosporidium Giardia Combi R-Biopharm has completed its panel of one step immunochromatographic rapid test. Both parameters are offered along with Giardia, Rotavirus and Rotavirus Adenovirus Combi in different formats, as cassettes and dipsticks. New Product: RIDAQUICK DON R-Biopharm is launching a quick immunochromatographic test Reliable Almond Detection in Food The new RIDASCREENFAST Mandel Almond (R6901) is based on a sandwich immunoassay and has a detection limit of 1.7 ppm almond. RIDA News has a new name! With the edition III 03 the name changes to "R-Biopharm News". RIDASCREEN Norwalk-like Virus The second generation ELISA - now available - worldwide for simultaneous detection of the geno-groups I and II in one specimen. RIDASCREEN Nitrofuran ELISAs nothing comparable exists R-Biopharm is launching new products:RIDASCREEN Nitrofuran (AOZ) and RIDASCREEN Nitrofuran (AMOZ). The quanitive analysis of AOZ and AMOZ is carried out with a competitive enzyme immunoassay. RIDASCREEN FAST Peanut: AOAC-RI Approval The RIDASCREENFAST Peanut (R6202) has been certified by the Association of Official Analytical Chemists International Research Institute (AOAC-RI Certificate No. 030404). Reliable Gliadin Gluten determination in wheat, barley and rye New RIDASCREEN RIDA test systems have been developed R-Biopharm AG. R-Biopharm has been awarded a major USDA contract CONTACT: Sean Tinkey R-Biopharm, Inc. (877) 789-3033 RIDA Quick Giardia R-Biopharm has expanded its panel of rapid assays regarding detection of Giardia lamblia in stool specimen. Hidden advantage of enzymatic test kits R-Biopharm would like to inform you that the enzymatic test kits produced from Roche (former Boehringer Mannheim) usually contain more determinations than indicated on the package and the test inserts as you can see from the product list. RIDA Quick Rotavirus and Adenovirus The RIDA Quick Rotavirus and Adenovirus tests are one step immuno-chomatographic assays for the antigen detection in stool samples. RIDA AllergyScreen, a new panel strip test for specific IgE RIDA AllergyScreen is an Immunoblot for the detection of specific IgE antibodies in human serum. RIDA X-Screen. POC Diagnostics Evaluation with RIDA X-Screen Intrument plus software for the evaluation and documentation of the RIDA AlleryScreen test strips. Anti - TSE - Antibodies R-Biopharm is launching new products: Two monoclonal antibodies directed against ruminant prion proteins. The RIDA Quick Histamin The RIDA Quick Histamin assay is the worldwide fastest test for the quantitative analysis (colorimetric) of histamine in fish and fishmeal BOEHRINGER MANNHEIM Oxalic Acid enzymatic test combination (UV test) available again The BOEHRINGER MANNHEIM Oxalic Acid test combination is of particular use in:breweries (oxalic acid makes the beer cloudy), honey processing companies (honeybee colonies are sprayed with oxalic acid), hospitals (oxalic acid contributes to the formation RIDASCREEN Chloramphenicol The RIDASCREEN Chloramphenicol test is an ELISA (Enzyme Linked Immunosorbent Assay), that allows detection of Chloramphenicol on a ppt (parts per trillion) level. EXPO PESCA from the 24th-26th of November, 2005 in Lima-Peru The event will take place in the Centro de Convenciones Jockey Plaza in Lima from 2:00 pm-9:00 pm. Sitevi 2005 Sitevi 2005 takes place in Montpellier FRANCE from the 29th-01th of December 2005. 2006 International Poultry Exposition in Atlanta USA from the 24th-27th of January 2006. Neue Ausgabe der R-Biopharm News Klinische Diagnostik Neuentwicklungen und weitere Aktivitten bei R-Biopharm: RIDASCREEN Norovirus ELISA Gastroenterologie NEU RIDA PentoCheck IHC Clostridium difcile Toxin A B-Nachweis Messen und Tagungen bis Mai 2006 Neueinfhrung des RIDASCREEN Campylobacter ELISA zum direkten und hochspezifischen Antigennachweis von C. jejuni und C. coli in Stuhlproben. !!FLLT AUS!! IV. Symposium - Gastroenterale Infektionen neuer Termin in 2006 wird noch bekanntgegeben! Ort:WISTA-Management GmbH Adlershof con.vent, Rudower Chaussee 17, 12489 Berlin R-Biopharm AG erneut fr den Preis Entrepreneur des Jahres 2005 nominiert Mit der Nominierung zum Finalisten in der Kategorie Industrie wrdigt Ernst Young die unternehmerische Leistung von R-Biopharm AG. Die Gewinner des Deloitte Technology Fast 50 des Jahres 2005 stehen fest Das Biotechnologieunternehmen R-Biopharm AG zhlt erneut, nach seiner Platzierung 2004, zu den am schnellsten wachsenden Technologieunternehmen Deutschlands 6. Fresenius Getrnke-Kongress Innovationen im Getrnkemarkt: Mythos oder Modeerscheinung? Schulungstermine Allergene in Lebensmitteln Am 1. Juni 2005 und am 7. September 2005 finden Schulungen fr den Nachweis von Allergenen in Lebensmitteln statt. Helicobacter Pylori Der RIDASCREEN FemtoLab H.pylori setzt Mastbe. Junior Regulatory Affairs Manager Diagnostik In dieser Funktion verstrken Sie unser Team im Bereich Regulatory Affairs. Sie bearbeiten internationale Registrierungsprojekte und Registrierungsnderungen. Trainee-Mitarbeiter Wir suchen zum Januar 2006 im Rahmen eines befristeten Arbeitsverhltnisses einen Trainee-Mitarbeiter Sales Manager International Wir suchen ab sofort Sales Manager International fr den Bereich klinische Diagnostik 2005 r-biopharm AG Gentra Systems DNA RNA purification equipment and methods. Offers manual and automated DNA, RNA purification and isolation products for clinical molecular diagnostics, gene discovery and pharmacogenetics. Home About Purification Kits Automated Instruments Order Contact Technical Assistance Meet your new lab assistant! Automated Nucleic Acid Purification System for genomic DNA and total RNA isolation. For more information Click Here Automated DNA Purification for Archival-Quality DNA click for info ___________________________ Serious Nucleic Acid Purification Convenient Kits Yield Pure DNA from up to 10 ml Blood 1 12 2005 MINNEAPOLIS, MN January 10, 2005 Gentra Systems is now offering V ersagene DNA Blood Purification Kits for isolating genomic DNA from whole blood. Kits come complete with all of the mini-columns and reagents needed to purify sample volumes ranging from 0.05 to 10.0 ml. V ersagene DNA produces exceptionally pure, double-stranded DNA with high molecular weights, typically 50 kb. Recovery rates are 60-90%. The DNA is free of RNA, protein and other contaminants, and is suitable for the most stringent downstream analyses including DNA microarrays, and Southern blotting. User-friendly kits contain no harsh organic reagents or guanidinium salts. The entire purification process can be completed on the laboratory bench, at room temperature, without a fume hood. Protocols do not require a cooled centrifuge, heat block or water bath. Samples of 0.4 ml or less can be purified in 30 minutes or less; 10 ml samples take 60 minutes or less. Kits are available in three sizes, for sample volumes ranging from 0.05 to 0.4 ml, 0.4 to 3 ml and 0.4 to 10 ml. Read more VERSAGENE Kits for 96-Well Plates Produce up to 100 g of RNA 12 13 2004 MINNEAPOLIS, MN December 13, 2004 Gentra Systems new V ersagene RNA 96-Well Cell Purification Kit produces pure, stable RNA, ready for downstream analyses requiring high-quality RNA, such as RT-PCR and microarrays. Kits accommodate cell densities of up to 10 million cells per well, resulting in total RNA yields of up to 100 g per well and 10 mg per plate. Versagene RNA 96- Well Cell kits, suitable for use with adherent and suspension cells, employ non-chaotropic chemistry to produce highly concentrated RNA. The 96-well protocol uses centrifugation to produce RNA that is essentially free of genomic DNA, protein and other enzymatic inhibitors. Kits come complete with all of the required reagents, including DNase, pre-mixed and ready to use. Disposable waste plates and sterile adhesive seals are also included. Because kits contain no harsh organic reagents or guanidinium salts, no fume hood is needed and no special waste disposal is required. Purifications can be completed on the lab bench at room temperature in as little as 90 minutes. Up to 192 samples can be processed in Read more Convenient Kits Yield Concentrated RNA from up to 10 ml Blood 12 13 2004 MINNEAPOLIS, MN December 3, 2004Gentra Systems is now offering V ersagene RNA Blood Purification Kits for fresh whole blood samples ranging in volume from 0.05 to 10.0 ml, and for blood samples drawn in PAXgene blood collection tubes. Versagene kits produce pure, stable RNA, free of genomic DNA, in concentrations as high as 1 g per 1 l, ready for downstream applications including RT-PCR and microarrays. V ersagene RNA blood kits come complete with pre-mixed, ready-to-use reagents, including DNase. Because kits contain no harsh organic reagents or guanidinium salts, no fume hood is needed and no special waste disposal is required. Purifications can be completed on the lab bench at room temperature in as little as 45 minutes. Three kits are offered, for samples ranging in size from 0.05 to 3.0 ml, samples from 3.0 to 10.0 ml, and for samples drawn in PAXgene collection Read more Quick Links Protocols Contact Tech Support Quick Tips Tip of the Month Distributors MSDS versaGene DNA Cell Purification Kit Purify ready-to-go DNA for CGH arrays, Allele discrimination arrays, SNP analysis and PCR-based diagnostics For more information, click here . 2005 Gentra Systems, Inc. | Contact Us | Privacy Policy Packard BioScience Manufactures instruments and related consumables, and services used in the life sciences research and nuclear industries. PerkinElmer Life and Analytical Sciences PerkinElmer Contact us Corporate Careers About us Life and Analytical Sciences My Account : Login Shopping cart Search Shop by product number USA: English Login Username Password Auto-login Register Forgot your password? Why login or register? Start shopping Shop by product number View my shopping cart View my favorites list Request a catalog My Account How to order online Order history status My Courses Favorites list Account profile Account number help E-mail preferences Support OneSource services Technical info MSDS Application notes Manuals Training Custom lab services What's new Promotions News Announcements Events New products Product categories Applications by industry Assay Platforms Atomic Spectroscopy Chromatography Consumables Accessories Elemental Analysis FTIR FTNIR Spectrometers Genetic Screening Diagnostics High Throughput Screening Lab Automation LIMS Software Microarrays SNPs Microscopy Imaging Proteomics Radioactivity Research Reagents Thermal Analysis UV Vis Spectrophotometers Product categories Applications by industry Academia Agriculture Clinical Environmental Food Beverage Forensics Geochemistry Homeland Security Life Sciences Petrochemical Pharmaceutical Plastics Polymers Semiconductor Materials Analysis Specialty Fine Chemicals Alphabetical product listing Promotions 40% Off All 125I Compounds and 3H Ligands and Lipids News PerkinElmer Introduces New Gold-Standard Spectrum 100 FT-IR and 100N FT-NIR Spectrometers Announcements Introducing the NEW EnVision Multilabel plate reader now with AlphaScreen technology! Events Newborn Screening Genetic Testing Symposium - Portland, OR, USA View more View more View more View more Contact us | Sitemap | Disclaimers | Privacy policy Copyright 1998-2005. PerkinElmer, Inc. All rights reserved Edge BioSystems Supplies DNA and PCR purification products, cDNA libraries and protein expression systems. Edge Biosystems Home Page Call Toll-Free 800-326-2685 Looking for a simple, economical, automatable, high-throughput PCR Purification Kit? I N T R O D U C I N G 96-Well UF PCR Purification Systems Proven Ultrafiltration technology is used to provide highly purified PCR products from 100bp- 48.5Kb Compatible with most vacuum manifolds Easily adapted for automated processing on standard liquid handling instruments Excellent removal of excess primers and primer-dimers Optimized for varying sample volumes, 50-300l Purified samples ready for your immediate use in your downstream applications NIH RESEARCHERS Visit us at the NIH IntraMall! Receive a 5% discount on all Edge products under NIH BPA 263-00046465 Promo Code: GO Transformation replication! Tube to plate, our chemically competent cells have a consistent edge giving you the same high transformation efficiencies in 96-well plates and single-use tubes. If youre searching for a high-quality, affordable strain to generate your large plasmid-based libraries, look no further! The ElectroEB10B electrocompetent cells are ideal for demanding cloning needs. High efficiency and affordability make these the cells of choice. IN THE NEWS... For the first time the biology, software and instrumentation required for protein expression have been combined on a fully integrated platform. NextGen Sciences Expressionfactory enables users to produce highly purified proteins automatically using Edge BioSystems Ultra BL21 (DE3) Competent Cells. ..more PUBLISHED? Have you published an article using Competent Cells from Edge BioSystems? If so, see how you can get a free kit! "The EB5Alpha Competent Cells are very nice. We routinely obtain our recombinant products on the first try, and the one-shot packaging is nicely cost-effective." Dr. Steve Hartson, Director of the DNA Protein Resource Facility, Oklahoma State University More Success Stories... Join Us! Edge is currently expanding its operations at all levels. Home | Site Map | Search Edge BioSystems | 201 Perry Parkway, Suite 5 | Gaithersburg, MD 20877 | 800-326-2685 2005 Edge BioSystems, All rights reserved. Hillside Books Books and equipment for entomologists for sale from a store in Canterbury, UK. index.html Insects Book and Equipment Books on insects: Entomological litterature: new, second-hand and old books Entomological equipment: Butterfly nets, Pooters, Continental insect pins, Beating tray, Tweezers, Mounting cards, ... Catalogue send free on request Hillside Books, Canterbury Lydie Rigout 1 Hillside Avenue Canterbury Kent CT2 8ET U.K. Texte franais phone: 01227 769924 (international: +44 1227 769924) fax: 01227 456013 (international: +44 1227 456013) e-mail: lr@insects.demon.co.uk Idaho Technology, Inc. Specialist in hybridization probes, thermocycling primers and custom oligo synthesis, with explanation, support and online ordering from Salt Lake City, Utah. Idaho Technology Inc. - Thermocyclers, Detection, High Res. Melters, Reagents, Probes and Primers All Idaho Technology Products R.A.P.I.D. System RAZOR System RapidCycler 2 Instrument LightScanner Instrument HR-1 Instrument LCGreen Melting Dye Freeze-Dried Reagents Wet Reagents Buffer IT BioChem Contact Us | About Us | Work With Us December 10 - 14 American Public Health Association Annual Meeting - APHA Philadelphia, PA, USA View Recent News and Events Legal Notices Privacy Policy Contact Webmaster 2001-2005Idaho Technology Inc. All Rights Reserved Idaho Technology Inc. Home HJ-Bioanalytik Presentation of a wide range of microtiterplates and additional equipment. HJ-Bioanalytik GmbH - Mikrotiterplatten Technologie, Deep-Well-Platten, Screening Korean Laboratory Equipment Collection Laboratory and pilot fermenters from Korea fermenter labkorea Home Korean products Home Fermenter Home Products range BioG-Micom BioG-Series Fermenter -Double Vessel 5L BioG-Series Fermenter -Single Vessel 10L BioG-Series Fermenter -Head Plate Accessories Bio S-80L Bio S-200L System Diagram Fermenter Send your inquiry E-mail: lab@labkorea.com ESEL TechTra Inc. Tel : +82 32 431 2371 Fax : +82-32-431-2372 1382-4, Kuweol-3dong, Namdongku, Incheon, Korea Copyright 2000 www.labkorea.com All right reserved Invitrogen Corporation Products and application areas include fluorescence polarization, drug metabolism, recombinant human proteins, PCR, molecular and cell biology, and contract manufacturing services. Develops, manufactures and markets research tools for use in gene cloning, gene expression and gene analysis as well as other molecular biology activities. (Nasdaq: IVGN). Invitrogen Welcome to Invitrogen Your country selection lets you view the most relevant content to help you accelerate your research. Please select your country from the list below. 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If you do not currently have a Flash enabled browser, you will be prompted to install Macromedia Flash Player to enhance your user experience. Copyright 2005 Invitrogen Corporation. All rights reserved. As a key partner in the global life science community, Invitrogen provides products and services that support academic and government research institutions as well as pharmaceutical and biotechnology companies. GenoVision Products and protocols for the direct isolation of DNA and RNA from a variety of sample sources, such as, dried blood, leucocytes, serum, buccal cells, cultured cells, biopsy samples, paraffin embedded tissue sections, animal tissue and yeast cells. GenoVision GenoVision offers customers high quality products that are user friendly, and give reliable results. GenoVision is proud to offer the new GenoM-6 Compact instrument, HaploPrep-Haplo Specific Extraction, and the OLERUP SSP HLA Products. ****Olerup SSP AB receives Conformity Certificate in accordance with the requirements of the In Vitro Diagnostic Directive 98 79 EC and the Medical Devices Regulations 2002:618. Quality Management System of Olerup SSP AB is ISO 9001:2000 and ISO 13485:2003 certified.**** GenoVision Inc. All Rights Reserved March 17, 2005 GenoVision AS is now known as QIAGEN AS Web site: www.qiagen.com (For more information about: GenoM-48 and GenoM-96 ) MD Biosciences Presents a broad range of RD biotechnology products. MD Biosciences - Drug development for inflammatory diseases Home About Us News Events Our Services Our Products Contact Us MD Biosciences is dedicated to providing the most advanced services and products for pre-clinical research in the area of inflammatory drug discovery. We provide in depth expertise as well as proprietary technologies to facilitate your research in developing anti-inflammatory drugs. We look forward to helping you make your research breakthroughs happen! MD Biosciences announces a novel in vitro assay for screening of Medical Devices Differentiating between contact dependent and contact independent inflammatory effects. Upcoming Events And Conferences You can visit MD Biosciences at the following conferences MD Biosciences announces expansion of current laboratory MDB expands it's laboratory to accommodate it's growing in-vitro services and research development program in St. Paul, MN. SIGN UP and be the first to know about our new products, the next trade show, latest research... click here for more Copyright 2005 Morwell Diagnostics GmbH. All rights reserved. Site Map Montreal Biotech Molecular biology equipment and cell culture products distributor. Montreal Biotech News: T3000 Thermocycler July 26, 2004 The T3000 Thermocycler represents the technological advancement of one of the most successful thermocyclers in Biometras history. Following the approved triple block concept, the new T3000 has been equipped with the latest in Peltier Technology to achieve excellent heating and cooling rates. Also the software has been completely revised for improved user friendliness. High performance on compact space together with unlimited flexibility, that is the new T3000 Thermocycler. RotorGene by Corbett Research - Real-time Quantitative Thermal Cycler The RotorGene is the first Real-time centrifugal thermal cycler using standard 0.2ml tube format! The samples are heated and cooled in an air chamber. The RotorGene collects fluorescent energy of each sample while spinning and is used to quantitate DNA and RNA copy number. The RotorGene detects point mutations using melt curve data. Rotor-Gene 3000, Four-Channel Multiplexing System Jun 6, 2002 Powerful and flexible real-time DNA amplification System, compatible with all real-time chemistries available on the market Rotor-Gene 3000A, Dual-Channel Multiplexing System July 15, 2004 High-performance and cost-effective real-time thermocycler. The Rotor-Gene 3000A is compatible with the most widely use real-time chemistries, including FAM, SYBR Green, HEX, JOE, VIC, TET, etc... Gene Disc System for Rotor-Gene Instruments J uly 15, 2004 72-well rotor shaped samples vessel that fit in the Rotor-Gene in a fast and single step. Designed for high-speed, high-throughput and automated process. Expert plus microplate reader J uly 15, 2004 The Expert Plus microplate reader is a stand alone product that combines a large graphics display with easy to use yet powerful on-board software, making it ideal for use in any laboratory performing ELISA and other microplate assays. BIS 303 PC J uly 15, 2004 The BIS 303 is an advanced bio-imaging solution ideal for low-light imaging applications such as chemiluminescence chemifluorescence, and fluorescence. The system fully automated, uses an advanced cooled CCD camera, a computerized image analysis, and a special printer. Brain-Mart Brain-related products including brain models and anatomical charts. Brain-Mart Online! Mail Order Form Corporate and School Orders International Shipping Track Your Order Home Page Human Brain Models Sensory Models Anatomical Charts Brain Books Brain Novelties Anatomy Software Kids Stuff - K8 NEW PRODUCTS Mail FAX Order Form Institutional and School Orders International Orders FAQ Privacy Policy Contact Us... Catalog Request Need help with Jury - Litigation exhibits? Advice on classroom models, charts, books? Click here to contact our consultants . Join our Mailing list for New Products and Specials of the Month! Subscribe Remove Read the latest news articles about the Brain... 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Principles of Psychobiology: Interactive Study Guide for the Allied Neurosciences Brainiac! Neuro Trainer Brain Atlas Screensaver Slideshow Brain Books Go to Books Books in the Brain Sciences... Need brain related books at great prices? Look no further! We give you one-stop shopping with the lowest overall prices on new books. See for yourself... Go to the brain book catalog page. Sheep Brains Go to Sheep Brains Sheep Brain Dissection Packages... Why not study a real brain? We sell preserved sheep brains and dissection manual packages for students that want hands-on experience with a real brain. Find out more by visiting our sheep brain product page. Brain Gifts and Novelties Brain Jello Molds and other Novelties Brain Novelties and Fun Stuff... All work and no play? Not at Brain-Mart...We sell brain novelty products that have both educational and entertainment value... Browse our novelty catalog page . 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New Brunswick Scientific - Home Page Home | Write Us | Site Index | NBS Offices | Order Status | Investor Relations NEW BRUNSWICK SCIENTIFIC CO., INC. Enter to Win an iPod! Take our 3-minute survey and you may win an iPod Mini! Click here for survey. In The News New Mini Innova CO2 Incubator is Ideal for Maintaining Sample Separation! New Innova Slim-Styled Freezer Fits Tight Spaces! New Innova Incubator Shakers with Refrigeration Option: Benchtop Console New Disposable Cell Culture System Saves Labor New Automated Agar Sterilizer Introduced New Brunswick Scientific (NBS) manufactures research through production-scale equipment for culture growth, detection and storage. Our products include biological and combinatorial-chemistry shakers , fermentors cell culture bioreactors , CO2 incubators , biological air samplers , automated plate preparation equipment and ultra-low temperature freezers . 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Molecula Research Laboratories, LLC Supplies high quality cost effective DNA RNA synthesis, dual labeled probes, various modifications and RNAi oligonucleotides. Specializes in design of siRNA and Antisense for gene function solutions. siRNA, antisense, RNAi, siRNA custom, siRNA design, antisense design, synthesis, transfection, IPTG, target, protein expression by Molecula Home | About | Online Store | Custom Oligos | RNAi Oligos | Antisense | Reagents | Technical Resources | Contact Us | Privacy | Legal Copyright MoleculA. All Rights Reserved R. Shadel Inc. Supplies for working with protein, RNA, DNA, radiation safety. Also Laboratory accessories and custom work. R. Shadel Inc. Welcome to R. Shadel, Inc.'s web site. R. Shadel, Inc. was established in 1976. Bob Shadel is the founder and chief designer of our products. His goal is to provide high quality products at affordable prices. 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Also, if an item that you have had for years, whether it is ours or a competitor breaks or needs some retooling, we can often restore the item inexpensively. R. Shadel, Inc. exists because we have loyal customers who have been buying our products for years. We take utmost pride in what we make. Thank you for placing confidence in our products. Darlene Shadel Chief Executive Officer Shandon, Inc. Equipment and consumables used in pathology applications, including cytology, histology, molecular biology, and immunochemistry, along with trade show listings and lab newsletter. Welcome to Thermo Electron Corporation and we are introducing a more comprehensive website. Please select one of the links below tobedirected tothe portion you want to visit.Upon arrival in the new site, we recommendupdating your bookmark. Anatomical Pathology visit Thermo's home page Incyte Pharmaceuticals A leading provider of integrated platforms of genomic technologies designed to aid in the understanding of the molecular basis of disease. Incyte: Home Learn About Dexelvucitabine (DFC) DFC (formerly Reverset) is currently in Phase II clinical trials.DFC shows promise in treating strains of HIV that are resistant to other treatments. Chemokine Receptor Antagonists Program Incyte's lead internal compound, INCB3284, is a proprietary, oral CCR2 antagonist in Phase II development that may have therapeutic value in a number of chronic inflammatory diseases. Drug Discovery Development Incyte is a Wilmington, Delaware-based drug discovery and development company with a growing pipeline of novel small molecule drugs to treat HIV, inflammation, cancer and diabetes. The company's most advanced product candidate, Dexelvucitabine (DFC), is an oral, once-a-day therapy in Phase II clinical trials to treat patients with HIV infections. Product Pipeline - Learn more aboutDexelvucitabine (DFC)and our internal drug discovery programs. Privacy Policy Legal Notices Feedback Copyright 2004 Incyte Corporation Kisker Supply laboratory products in the area of molecular biology. Kisker - Products for Biotechnology About us News Special offer Products Contact Order Sitemap Deutsch Copyright 1999-2005 Dipl.oec.troph.Gerlinde Kisker | Impressum | e-mail: contact | Newsletter Products for Biotechnology Our Product Range includes: Filter Tips Pipet Tip Gel Loading Tip PCR Tubes and Plates Centrifuge Tubes Rack Systems Cryoproducts Autoradiography LabelGuardTM Mikroliter Messzelle DNA-Workstation Hybridisation Thermal Cycler Dry block heat bath Mini Centrifuges Rotator Vortex Mixer Nylon Wool PAP PEN Microparticles Rainbow Scientific, Inc. Offers molecular cytogenetics, hematology, and clinical chemistry products. Includes a brief description of products, a listing of conference times and contact information. Rainbow Scientific Inc - molecular cytogenetics, hematology, and clinical chemistry products Welcome to Rainbow Scientific Rainbow Scientific offers state-of-the-art molecular cytogenetics, hematology, and clinical chemistry products that hospital clinical laboratories, biotechnology genomics companies, and both academic and government institutions need. We'd like to hear from you, so please feel free to call, write, fax, or email us. To contact us immediately, just click here . Rainbow Scientific, Inc. 83 Maple Avenue, Windsor, CT 06095 Tel: (860) 298-8382 Fax: (860) 298-8586 email: info@rainbowscientific.com Note: The contents of this web site are for informational purposes only and no further warranties are either expressed or implied. 2001-2003 Rainbow Scientific, Inc. All rights reserved. Designed and Hosted by Hosting Connecticut, LLC Jule Biotechnologies, Inc. Pre-cast, ready-made polyacrlamide gels in both mini and larger sizes, including tris-glycine, TBE, urea, and tricine gels, buffers, staining reagents, and gradient formers. Precast Gels , Jule Biotechnologies, Inc. Our web site has moved Our web site has moved, please follow the link to: www.precastgels.com * Please Note * If you have trouble with the link above, try here: http: site44042.dellhost.com (800) 648-1772 Fax: (203) 878-7448 precastgel@aol.com 185 Research Drive, 6 Milford, CT 06460 Imaging the Deaf Brain A research project exploring how British Sign Language (BSL) is processed by deaf people, with BSL translations of findings to date. Imaging The Deaf Brain Home Research The Team The Brain Volunteers Links Publications Contact Imaging the Deaf Brain Homepage Welcome to the Imaging the Deaf Brain website! Here you will find news and information about our project. The main aim of our project is to learn more about what happens in the brain when people watch a person sign or speak. Follow the links to find out more! Latest News Job opportunity posted 1 November 2005 Are you a recent psychology graduate with interests in deafness and the brain? We have a vacancy for a Research Assistant on this project. Please click here for further information. Volunteering updated 1 November 2005 New volunteers: click here to fill-in the on-line application form. Returning volunteers: if you took part in our previous research, you still need to fill-in the on-line form if you would like to be part of the new project. Please click here to go to the form. Or, contact us by email: deafbrain@ucl.ac.uk or by SMS: 07971 853273. Imaging the Deaf Brain on See Hear! posted 21 June 2005 On Saturday 18 June, the Imaging the Deaf Brain project was featured on See Hear , the BBC's weekly Saturday magazine programme for Deaf people. We had a lot to talk about but only seven minutes do it in. We'd like to thank everybody on the See Hear team for coming to chat with us. Extra special thanks to Seeta Manjeshwar for volunteering for the filming. For our current studies, we're scanning volunteers who learned BSL from birth from their Deaf parents. We hope to include volunteers who learned BSL later in life and those born to hearing parents in our future studies. If you've already completed our online volunteer form, thank you! We hope to contact you about joining our future studies as they develop. You don't need to fill the online volunteer application form again. But if you haven't filled out a form and would like to take part, please click here . New work with Sense posted 25 January 2005 We met recently with Sense , the UK's leading organisation for people who are deafblind. We are very excited that Sense is keen to help us with our research. With their support, we are hoping next year to be able to do some research with signers with Usher syndrome. We are interested to know how the brain processes sig n language received through touch (as opposed to through the eyes). We are also interested on how signing changes when Deaf people have Usher. If you know any signers who might like to take part, please pass this information on to them. Anyone who is interested should contact Cheryl Capek by email: deafbrain@ucl.ac.uk or by SMS: 07971 853273. Research Background information and what were trying to find out Links Other interesting websites The Team Some information about the research team Publications Our findings so far The Brain Find out about the brain Contact How to get in touch Volunteers Get involved in our research! Project FTP site: team members may contact Dafydd or Cheryl for FTP support Design : Remark! Internet 2004 www.remarkinternet.co.uk NINDS Neuron Fact Sheet Educational booklet about how neurons develop, function, and die, prepared by the National Institute of Neurological Disorders and Stroke. National Institute of Neurological Disorders and Stroke (NINDS) Accessible version Science for the Brain The nation's leading supporter of biomedical research on disorders of the brain and nervous system Disorder Quick Links Alzheimer's Disease Autism Cerebral Palsy Chronic Pain Epilepsy Headache Multiple Sclerosis Parkinson's Disease Stroke Traumatic Brain Injury Browse All Disorders Search NINDS... (help) Contact Us My Privacy NINDS is part of the National Institutes of Health You are here: Home Page Not Found We have redesigned our website and the page you are looking for has moved. Please visit the NINDS Home Page or, if you're looking for a particular person, please visit the NINDS Organizational Chart . National Institute of Neurological Disorders and Stroke Home | About NINDS | Disorders | Funding | News and Events | Find People | Jobs and Training | Accessibility The Myelin Group Research concerning the correct formation and maintenance of the myelin sheath. Includes publications, members, photo gallery, and views and opinions. University of Oulu. Site Overview Home University of Oulu The Myelin Group Refresh reload this page in your web browser to obtain the most recent information Project Overview The Myelin Group Members (past present) Publication List of The Myelin Group Who did what ? Other (mostly myelin-related) Publications of Tony Photo Gallery Reprint Requests Contact Info Positions Available in The Myelin Group ( updated 4th August 2004 ) (progradus can apply any time) Views and Opinions Collaborators Contributors The Myelination Myelin Disease Consortium Some other Links Brandi Ormerod Describes how neurogenesis in the adult brain is regulated by steroids and the immune system. Lists research, papers, talks, posters and awards. Phd from University of British Columbia. Currently doing post doctorate work at the Michael J. Fox Foundation. Brandi Ormerod's Website Welcome to My Webpage I obtained my PhD in Neuroscience in 2003, under the supervision of Dr. Liisa Galea in the Department of Psychology at the University of British Columbia . The work that I conducted for my dissertation characterized the effect of estradiol on neurogenesis (the proliferation of progenitor cells and the differentiation and survival of daughter cells) in the adult rodent hippocampus. I am currently a Michael J. Fox Foundation post-doctoral fellow working in Dr. Theo Palmers laboratory at Stanford University . I am pursuing my interest in discovering the cues that permit induce neurogenesis in some regions of the adult CNS while suppressing it in others using both in vitro and in vivo techniques to characterize the neurogenic microenvironment both in normal and disease states. Ultimately, I hope to be able generate neurons of the appropriate phenotype in the appropriate regions to alleviate the symptomology of Parkinsons and other neurodegenerative diseases. | HOME | RESEARCH | PAPERS | TALKS | POSTERS | TEACHING | FAVORITE LINKS | STANFORD | Dr. Brandi K. Ormerod Michael J. Fox Foundation Postdoctoral Fellow BSc Honors Psychology(Queens) PhD Neuroscience (UBC) Department of Neurosurgery MSLS P304 1201 Welch Road Stanford , CA 94305-5487 Phone (650) 498-7088 Fax (650) 736-0536 Email Me : Pietsch, Paul Neurophysiology, brain transplants (Indiana Univ., USA) shufflebrain ShuffleBrain (click for SAMPLES from popular science menu) --- How does a brain store a mind? -----A polycultural quest for the hidden treasures of the mental cosmos Paul Pietsch, PhD, Professor Emeritus, School of Optometry Indiana University to Main Menu to Neuroscience Audiotutorials pietsch@indiana.edu WEB SEARCH On the Web since July 1995.....Modified 04 November 2005 Requests (Hits): 10 Million+ supported in part by a grant to Emeritus Faculty from the Dean of the Faculties, Indiana University and backed up by the Technlogy Staff of the Indiana University School of Optometry MAIN MENU E-BOOKS (original) POPULAR SCIENCE SHORT SUBJECTS Being Mom Laura Hampson Shuffle Links OPTOSCOLIOSIS REGENERATION LOOKING FOR ZOEY EYES AND BRAINS: AQ's {asked questions} on diseases JOHN DEWEY Truth JOSEPH CONRAD sharing some gems AGENESIS OF THE CORPUS CALLOSUM (ACC) WEB AWARDS Regeneration and Memory PILOT AUDIOTUTORIAL LESSONS-- Your Own Eye Histology RESOURCES FOR BLIND AND VISUALLY IMPAIRED PERSONS NEUROSCIENCE AUDIOTUTORIALS (mp3 tapes) 1.Overview of the Brain 2. Brain Cells (in progress) 3. The Human Cerebrum, Introduction 4. Inside the Human Forebrain, Part 1 5. Inside the Human Forebrain, Part 2 6. INPUT TO THE HUMAN BRAIN, Part 1 7. THE BRAIN'S CONSCIOUS OUTPUT 8. ANATOMY OF VISION I: An Audiotutorial Overview of the Human Brain's Visual System 9. ANATOMY OF VISION II An audiotutorial introduction to the form and function of the human primary visual pathways 10. ANATOMY OF VISION III Some fine points about the primary visual pathways 11. ANATOMY OF VISION IV, Eye Movements and Pupillary Reflexes Supplements: Hemianopsia --and Neuroanatomy Popular Science Menu Shuffle Brain -- can a scrambled brain remember? The Beast's IQ -- hidden facets of intelligence Hologramic Mind --what's really real, anyway? Microminds -- can bacteria think? hurt? enjoy? Human Brain Shrinks, Yet Human Being Thinks Brain Swapping --excerpts from the book, Shufflebrain Holologic -- an Asa Zook dialog on the nature of holograms Split Human Brain -- our divided selves Musical Brain -- the gentler side Optics of Memory -- heck of an engineer! Short Subjects Gender and the Corpus Callosum Tiger salamander with an axolotl's eye THUMPER: Can the brain think without its head? The Tarantella Preparation Brainless -- the salamander with a blank cranium! Head Transplant -- are two heads better than one? The Human Corpus Callosum -- photojournalism inside the human skull Baboon Brain -- Picture! LIMBIC SYSTEM -- Cartoon TRUTH, what is it John Dewey? Scientific Works on Brains and Eyes Scrambled Brains Eyes and Eyes Frontal Lobotomy in the Salamander -- Wild Results Smart Skin Can a grafted eye work in the head of a different species? Skin Camouflage and Eyes How do we prove that a little salamander can really see? How does the salamander change its spots Gizmos for testing salamanders and fishes Brain Transplanting Fails to Demonstrate Memory Transfer eBooks SHUFFLEBRAIN: The Quest of Hologramic Mind, 2nd edition (nonfiction) -- an in-depth but non-technical look at experiments on the neural hologram: HTML VERSION PDF VERSION (for printing and downloading) 1st ed published by Houghton Mifflin Company, Boston, 1981 THE FIXED POINT OF ASA ZOOK --A novel about Asa Zook's quest of memory and regeneration: Aperu (Summary) BY CHAPTERS (in html) Entire eBook in PDF Format (recommended for printing or downloading) Literature searches prompted by readers' questions Agenesis of the Corpus Callosum (ACC) Introduction Set 01 Set 02 Set 03 Set 04 Set 05 (late 1995) Set 06 (1996) Set 07 (1997) Set 08 (1998) Set 09 (1999) Set 10 (2000) ACC 2001 Alien Hand Syndrome (AHS): 1994-1996 1996-1998 1999-2003 (Feb) ANDERMANN'S SYNDROME, the literature: 1996 1997 1998 1999 2000 2001 (October) Angiokeratoma AVM (arteriovenus malformation) Harvard's Neurosurgical Service (formerly the AVM Center) [recommended] Older Literature 2000 2001(sep) during pregnancy surgery with the gamma knife Asperger's Syndrome -- What is It? Autism and defects of the corpus callosum: any correlation? 1991-1996 1996-1998 AZOOR --Acute Zonal Ocult Outer Retinopathy 1991-1996 1996-1998 1998-2001 (August) Bannayan-Zonana Syndrome -- Literature 1997 (abstracts included) 1998 (abstracts included) 1999 (abstracts included) Best's macular dystrophy --1991-1997 1997 to early 1999 Coloboma of the Optic Nerve Coloboma, update (1998-early 1999) COMA, the literature: 1995-1997 1998-early 1999 Cortical (and Band) Heterotopia: 1997 1998 1999-July, 2000 CRI-DU-CHAT (CAT'S CRY) SYNDROME: 1998-1999 1999-2001 Dyscalculia (acalculia) -- problems handling math Eales Disease (bleeding from retinal veins) Encephalopathy: Drug Therapy Ellis-van Creveld Syndrome Literature (chrondro-ectodermal dysplasia) 01 -- 1991-1995 02 -- Update of 1995 03 -- 1996-1998 1999-2002 (sept.) Epiretinal Membranes -- The Recent Literature Update, 10 Feb 1997 Update, 31 July 1997 Update, 19 April 1999 Goldenhar Syndrome Hemihypertrophy Hippocampus (Human): Lesions. What's in the recent literature? 1991-1998 1999 Hydrocephalus and the Chromosomes and the recent literature on CSF [cerebrospinal fluid] Shunts Joubert's Syndrome (revised) Leigh's Disease (thru May, 2000) Lennox-Gastaut Syndrome Lesch-Nyhan Syndrome (Infantile self-mutilation) Music Therapy in Brain Damage -- Recent Literature Neuronal Migration Disorder (NMD) Opitz Syndrome 1997-1998 1999-2000 (summer) Pallister-Killian Syndrome ( PKS ), the recent literature: 1993-1999 2000-2001 PIRACETAM (aka nootropyl) older literature 1900-2000 2001-2002 2003-2004 Post-Polio Syndrome, the scientific literature, 1995-1998 Post-Polio Syndrome, the scientific literature, 1999-2001 (May) PTSD and Rape -- recent scientific literature Rhombencephalosynapsis -- fused cerebellum: 1991-1995 (with introduction) 1996-1999 (September) Ring Chromosome 13 Earlier literature Update, 1997-1999 Schizencephaly Septo-Optic Dysplasia (de Morsier's Syndrome): 1993-1998 1999-2000 (September) Sotos Syndrome (Infantile Giantism) SSPE (Subacute Sclerosing Panencephalitis) Sympathetic Reflex Dystrophy Syndrome (RSD) What's new in the biomedical literature? Sympathetic Reflex Dystrophy Syndrome (RSD) in Blunt Trauma Taurine and Epilepsy, a literature search Toriello-Carey Syndrome Trigonocephaly Williams Syndrome LOOKING FOR ZOEY Zo L. Langley, Contributing Editor Rickets, Seizures and Vitamin D EPILEPSY NEWS (Finding a Cure for Epilepsy and Seizures) : ---- EPILEPSY LECTURE SERIES --- For FACES home page click here! A letter to ShuffleBrain from Zoey Empathy -- a short story Zoey on Writing Two-Dog Night, another short story from Zoey Taurine and Epilepsy, a personal note (from Zoey) Floating Your Troubles Away Language Geometry MAYBE IT IS MORNING (Life After Stroke) MOZART as Mind Mender NEW APPROACHES TO SEIZURES: MEDICATIONS --- safely switching from multiple- to single-drug therapy YOGA for Epileptic Seizures Raising seizure thresholds Slow Cortical Potentials -- controlling with biofeedback Slow Cortical Potentials -- the recent scientific literature The Andrews Reiter Epilepsy Research Program: a comprehensive approach to the treatment of epileptic seizures SYNCOPE AND RAS: When seizures are NOT epilepsy CONTACTING ZOEY: zll51@hotmail.com BEING MOM by Laura Hampson It is in the moments before drifting off to sleep: Mother's Day 2005 ON MOTHER'S DAY Anniversaries, an essay Three Years ... a 2001 Mother's Day special OTHER ITEMS: Thank you, Qin Fong Paul Pietsch's Curriculum Vitae The Late Hiroharu Noda's Brain Research (cerebellar control of eye movements) . The Late Sir John Lorber: a list of some of his writings. pietsch@indiana.edu Brain Update "Science Friday" audio discussion with Martin Citron, Charles Gross, and Evan Snyder on the 1999 discovery that new neurons are continually being added to the brains of adult monkeys, even to parts of the brain responsible for very high-level functioning, and what this might mean for learning, memory and the treatment of neurological diseases. Features related links. October 22, 1999, Hour One: Brain Update THIS WEEK ON SCIENCE FRIDAY... Science Friday Archives 1999 October October 22, 1999: Hour One: Brain Update Last week, scientists at Princeton University made an announcement that goes counter to long-held wisdom about the brain. They discovered that new neurons are continually being added to the brains of adult monkeys, even to parts of the brain responsible for very high-level functioning. Once, it was believed that no new brain cells were created after adulthood. Later, it was found that some parts of the brain such as the hippocampus, could regrow cells. The work, reported in the October 15th issue of Science, means that neurogenisis may be much more common than previously thought. We'll talk about what the research might mean for learning, memory, and the treatment of neurological diseases. Other researchers have been trying to regrow brain cells in another way - by using generic "neural stem cells" that the body can develop into many different types of neural tissue We'll find out about efforts to clone theses neural stem cells, and how cells like these might be used in disease treatment. We'll also find out about a discovery announced this week by researchers at Amgen (Full disclosure: Amgen is one of Science Friday's funders on NPR.) The researchers, writing in this week's edition of the journal Science, report that they have located an enzyme that they believe is involved in the formation of "plaque" in the brains of people with Alzheimer's disease. While the existence of the enzyme has been assumed for a long time, it had never been actually isolated before. Might the discovery be of use someday for treating Alzheimer's? We'll find out. Listen to this program in RealAudio! Guests: Martin Citron Research Scientist Amgen Thousand Oaks, California Charles Gross Professor, Psychology Princeton Center for the Study of Mind, Brain, and Behavior Princeton University Princeton, New Jersey Evan Snyder Assistant Professor, Neurology Children's Hospital Harvard Medical School Boston, Massachusetts Books Articles Discussed: "Beta-Secretase Cleavage of Alzheimer's Amyloid Protein by the Transmembrane Aspartic Protease BACE" by Martin Citron et al. Science, 22 October 1999. "Neurogenisis in the Neocortex of Adult Primates" by E. Gould, A.J. Reeves, M.S.A Graziano, and C. G. Gross." Science, 15 October 1999. Search for books on: Related Links: Princeton - News - Scientists Discover Addition of New Brain Cells in Highest Brain Area American Academy of Neurology BrainWeb: Simulated Brain Database The Whole Brain Atlas Neuroscience for Kids Amgen Home Page Princeton - PWB 040599 - Do brain cells regenerate? Dana Foundation UPDATE 1999: New Connections Nerve Cell Clones Repair Brain Damage Alzheimer's Disease Education and Referral (ADEAR Center) Welcome to the Alzheimer's Association This segment produced by: Karin Vergoth Web producer: Charles Bergquist Have questions, comments, suggestions about the radio show? Contact us at scifri@npr.org . Send questions, comments, suggestions about the site to producer@sciencefriday.com . Science Friday and sciencefriday.com are produced by Samanna Productions, Inc. "Science Friday" is a registered service mark. Host Executive Producer Editor of Science Friday: Ira Flatow Senior Producer of Science Friday: Karin Vergoth 1998, 1999 ScienCentral, Inc. All Rights Reserved. The Science of Sleep Science Friday audio discussion of why we need sleep, with Clifford Saper, David White, and Craig Heller. March 22, 1996, Hour Two:The Science of Sleep THIS WEEK ON SCIENCE FRIDAY... Science Friday Archives 1996 March March 22, 1996 The Science of Sleep Harvard researchers recently identified a "slumber switch" that tells us when to go to sleep. But why do we even need sleep? In this hour of Science Friday, we'll find out what happens when we catch some Z's. Guests: Clifford Saper Chief of Neurology Beth Israel Hospital Boston, Mass. David White Professor of Medicine University of Colorado Health Sciences Center Denver, Colo. Craig Heller Professor of Biological Sciences Stanford University Palo Alto, Calif. Listen to this program in RealAudio! Books Articles Discussed: (find more SciFri Books here) Search for books on: Related Links: Have questions, comments, suggestions about the show? Contact us at scifri@npr.org . Send questions, comments, suggestions about the site to producer@sciencefriday.c om . Science Friday and sciencefriday.com are produced by Samanna Productions, Inc. "Science Friday" is a registered service mark. The Science Friday Web site is a production of ScienCentral, Inc . Executive web producer: Ira Flatow Web producer: Charles Bergquist Copyright ScienCentral, Inc., 1997, all rights reserved. Science Friday Home Microiontophoresis A practical guide to the art of microiontophoresis employed in neuroscience research. Kation Scientific Carbostar-3 Carbon Fiber Electrode Contact infomation E-mail us About Kation Pricelist and ordering Carbostar-4 Recording iontophoresis Carbostar-7S Recording iontophoresis Carbostar-1 Recording voltammetry Created: 10 17 96 Updated: 05 15 04 Our site is a practical guide to microiontophoresis and extracellular electrophysiology. These techniques are used in neuroscience research to test the effects of neuroactive substances on single nerve cells or to deposit dyes or tract-tracer materials in the nervous system for subsequent histological analysis. We hope to provide the interested with the knowledge and equipments crucial to such high quality experimentation. Tutorial themes: The art of microiontophoresis and extracellular electrophysiology Basic concepts An introduction to microiontophoresis. Experimental design The practice of microiontophoresis experiments. Pulling micropipettes Ins and outs of electrode making. Micropipettes and electrodes Carbon fiber-containing multibarrel pipettes. Action potential recording Extracellular amplifiers and spike recording techniques. Iontophoresis pumps Precision constant current sources for microiontophoresis. Ratemeter and timer software Software for iontophoresis and extracellular recording. Dyes and tracers Popularly used neural dyes and tract-tracing compounds. Neuroactive compounds Pipette concentration, pH, ejection polarity for some 150 drugs. Products for sale: Order from the US or from Europe Carbon fiber microelectrodes for: Extracellular recording with iontophoresis Singlebarrel recording voltammetry: Carbostar-1 Three-barrel recording iontophoresis: Carbostar-3 Four-barrel recording iontophoresis: Carbostar-4 Seven-barrel recording iontophoresis: Carbostar-7 Carbostar-7S Site marking by iontophoresis Electrophysiological instruments: Seldom seen recording quality Micropipette puller: Gravipull-2 New design! Microampere iontophoresis pump, 500V: BAB-500 High compliance voltage! Nanoampere iontophoresis pump, 36V: Union-36 Intra- or extracellular! ExAmp extracellular amplifiers: New: Probe and elecetrode holder in one! ExAmp-20KB ExAmp-20K ExAmp-20KD Battery operated! Direct electrode access! Dual channel! Accessories: Useful, hard to find items. BNC to BNC cables, 0.1" cable diameter: T20-X Reduce jungle of cables DC power cable, 2.1 mm x 5 mm plugs: T3006 Save money and space Gravipull-2 Micropipette puller Headstage probe and electrode holder in one! ExAmp-20KB Extracellular amplifier Sample recording Recording was taken from a brainstem neuron using an ExAmp-20KB in combination with a Carbostar-3 carbon fiber electrode. Cell firing was evoked by iontophoresed NMDA using a Union-36 iontophoresis pump. Back to top Kation Scientific, 2004 Telluride Workshop on Neuromorphic Engineering A three-week workshop focused on bringing together researchers from academia with their counterparts in industry, working on sensory systems and sensory-motor integration. Neuromorphic Engineering Workshop 2005 Workshop on Neuromorphic Engineering Contemporary Philosophy of Mind: An Annotated Bibliography Recent works in consciousness, philosophy of mind, and philosophy of artificial intelligence and psychology. Thousands of entries, categorized by subject matter. From David Chalmers. Contemporary Philosophy of Mind: An Annotated Bibliography Contemporary Philosophy of Mind: An Annotated Bibliography Compiled by David Chalmers , Philosophy, Australian National University. E-mail: chalmers at anu dot edu dot au. Technical support by David Bourget , University of Toronto. Last updated: November 12, 2005 Part 1: Consciousness and Qualia (1523 entries) Part 2: Mental Content (1348 entries) Part 3: Metaphysics of Mind (1465 entries) Part 4: Philosophy of Artificial Intelligence (639 entries) Part 5: Philosophy of Psychology (1087 entries) Part 6: Consciousness in the Sciences (2080 entries) Search by author's surname: Plain text search: Your browser is not configured for off-campus access. Click here to configure it. Your browser appears to be ready for off-campus access. Click here to change your configuration. Atlas of the Primate Brain Searchable database of stereotactic images of the primate brain for use as templates. BrainInfo Viewing this page requires a browser capable of displaying frames. Mitochondria and Neurons Innovative and speculative hypotheses on how mitochondria might act as flip-flop memory elements in the dendrites of neurons. Explanation of how mitochondria could trigger impulses and detect frequencies. .. .. Please Note: I do not choose the advertisements that appear with this webpage: Geocities (which provides me with free site hosting) chooses them. - Andrew Gyles Mitochondria _____________________________________ T R A C I N G . H U M A N . W A N D E R I N G S - MITOCHONDRIA and neurons - Y CHROMOSOME Andrew Gyles ___________________________ Return to main index page [Other page: Did the selective advantages of language drive a reduction in sequence variation in humans?] [Other page: Humans might have spoken two million years ago] C O N T E N T S CLICK ON TITLE TO GO STRAIGHT TO ARTICLE - MRI scans show higher oxygen levels in active fields of brain, consistent with mitochondria being drivers of information processing in neurons - Now we know: some dendrites in the brain are binary - Do the ATP enzymes in a mitochondrion rotate in phase? Can a mitochondrion act as a clock and a trigger in neurons? - The mitochondrion as a flip-flop memory element in neurons - Mitochondria as the motors of consciousness - The evolving mitochondrion as a killer of male embryos - The primitive mitochondrion as a fatal parasite - Miniature apoptosis in mussels - My hypothesis of a low mitochondrial mutation rate in humans - Five puzzles about mitochondria - A laboratory experiment to test the central assumption of the 'Out of Africa' theory - A possible reason for the smallness of the human Y chromosome ARTICLES ARE ARRANGED BELOW BY DATE OF PUBLICATION, NEWEST AT TOP ________________________________ CONTENTS MRI scans show higher oxygen levels in active fields of brain, consistent with mitochondria being drivers of information processing in neurons Neuronal activity in discrete fields of the brain associated with the performance of specific tasks can be detected by BOLD fMRI scans (Blood Oxygen Level Dependent functional Magnetic Resonance Imaging). The paradox revealed by these scans is that the oxygen level rises in active fields. Since neuronal activity consumes energy we should expect the oxygen level to fall. This is so because the energy is supplied in the form of ATP, and ATP is generated most efficiently by the aerobic, or oxygen-consuming, part of the long and complicated process of respiration. Aerobic respiration is done by mitochondria, which consume oxygen and generate ATP. There are hundreds or thousands of mitochondria in most cells. The standard explanation of this paradox is that the blood vessels in an active field dilate, bringing more oxygen into the field. Little of this extra oxygen is used. It is this higher oxygen level that is detected by the BOLD fMRI scan. A '50-50' mode in some mitochondria would reduce oxygen consumption I suggest that there is an alternative explanation for the rise in oxygen level in an active field: some of the mitochondria in its neurons switch to a (hypothetical) '50-50' mode of action, in which one side of a mitochondrion supplies ATP to the other side, which uses this supply of chemical energy to pump positively charged protons (in the form of hydronium ions: protons bonded with water molecules) across a narrow gap to the neuronal membrane. These positive ions trigger nerve impulses. In some cases a mitochondrion might act as a 'flip-flop' memory element in neurons as well as a trigger of nerve impulses. The oxygen consumption of mitochondria working in this '50-50' mode must be halved. One half of each mitochondrion maintains its oxygen consumption and generates ATP, but the rotary enzymes in the other half are driven in reverse, consuming the ATP and pumping out protons; this half does not consume oxygen. If extra ATP is needed in the active field (to drive ion pumps in the neuronal membrane, for example) it must be supplied through anaerobic respiration, which does not consume oxygen. The 'standard explanation' of the raised oxygen level makes the same assumption, at least in part. It has to do this, because if most of the extra oxygen brought to the active field by the postulated dilation of blood vessels were consumed it would not show up on the BOLD fMRI scan. Earlier articles describe possible roles of mitochondria in neurons I have written in some detail about the possible (hypothetical) roles of mitochondria in the information-processing and signalling activities of neurons (see articles below). One of the objections to such roles raised in scientific discussion groups was that protons were the active part of all acids, and in acting as a 'trigger' might damage the membrane of the neuron. My response to that objection is that protons drive the rotary enzymes in all mitochondria in multicellular animals while they are generating ATP. These enzymes are like molecular motors driven by a 'proton gradient' maintained by a chain of other enzymes in the mitochondrion. Obviously the protons do not damage the mitochondrion to an unsustainable degree. The neuronal membrane maintains gradients of various ions across itself; perhaps it would be no more damaged by protons than the mitochondrial membrane. It might depend on the number of protons involved. It is known that a small number of positive (metallic) ions can trigger a nerve impulse, so a small number of protons might be able to trigger an impulse. (I sent this article to the internet discussion group 'sci.bio.evolution' on 25 October 2001, where it was subsequently published.) Published on this site 25 October 2001. Andrew Gyles ________________________________ CONTENTS Now we know: some dendrites in the brain are binary In December 2000 there was some discussion in the newsgroup "bionet.neuroscience" of my hypothesis that mitochondria might act as flip-flop memory elements in neurons (see the article "The mitochondrion as a flip-flop memory element in neurons" below). One counter-argument ran as follows: "Why should neurons need a flip-flop memory element? There's no evidence they're digital". Well, perhaps there is some evidence now. In the 21 September 2001 issue of "Science" Dong-Sheng Wei et al report binary behaviour of some terminal apical dendrites of pyramidal neurons, which they characterised as "all-or-none responses that were subthreshold for somatic action potentials". They remarked that "Compartmentalized and binary behavior of parallel-connected terminal dendrites can greatly expand the computational power of a single neuron". Of course I am aware that the paper in "Science" neither proves nor disproves my hypothesis about a possible role of mitochondria as flip-flop memory elements. However, it does show that the behaviour of some dendrites is "digital" (binary behaviour is digital behaviour), and so opens the possibility that some neurons might need and use "flip-flop memory elements". Reference "Compartmentalized and binary behaviour of terminal dendrites in hippocampal pyramidal neurons", Dong-Sheng Wei et al, Science, volume 293, number 5538, 21 September 2001, pages 2272-2275. Published 25 September 2001. Andrew Gyles ________________________________ CONTENTS Do the ATP enzymes in a mitochondrion rotate in phase? Can a mitochondrion act as a clock and a trigger in neurons? In my hypotheses 'Mitochondria as the motors of consciousness' and 'The mitochondrion as a flip-flop memory element in neurons' (see below) I wrote about possible functions of mitochondria in neurons. Both hypotheses depend on my idea that the thousands of ATPsynthase ATPase enzymes in a mitochondrion might rotate in phase in at least some situations. Like a clock We know that the rotating enzyme is like a clock. It rotates about 20 times a second. As it rotates it passes a positively charged ion (a proton in most organisms, or a sodium ion in one species of bacterium) through itself at every 30 degrees of rotation. So we might think of it as passing a proton every time its motor and single 'hand' come to a 'numeral' on the dial of the 'clock'; that is, at 1 o'clock, 2 o'clock, 3 o'clock and so on through 12 o'clock. 60 'big steps' a second If it rotates 20 times a second it will pass a proton through itself 20 x 12 = 240 times a second. If it rotates in 'big steps' of 120 degrees, as some elegant work by a Japanese laboratory seems to have confirmed, it will pass four protons at each big step, and it will take 20 x 3 = 60 big steps a second. Protons could trigger nerve impulses When working 'in reverse' as ATPase, energised by ATP and pumping protons 'uphill' through the inner membrane of the mitochondrion, against the electrochemical gradient, the enzyme pumps protons into the cytoplasm of the cell. I argued in my hypotheses that these protons, being positively charged, could trigger a nerve impulse if some of them reached the inside of the membrane of a neuron. They could do this if the mitochondrion was inside the neuron and close to its membrane. 40,000 protons in each 'wave'? There must be thousands of identical ATPsynthase ATPase enzymes in each mitochondrion. Let us assume there are 10,000 (for all I know there might be 100,000). If they rotated in phase (or in phase plus or minus 120 degrees) at each 'big step' of 120 degrees they would pump a total of 10,000 x 4 = 40,000 protons into the cytoplasm. I argue that this might be more than enough positive ions to trigger a nerve impulse. (These numbers are illustrative only. I do not know what the actual numbers are. They might vary over a wide range, depending on the size of each mitochondrion.) I posted both of these hypotheses on various scientific discussion groups. One of the criticisms made by readers was that I had not shown how they might be experimentally tested. Response to a criticism In response I posted the following message on the discussion groups 'talk.origins' and 'sci.bio.evolution': ________________________________________________________ A preliminary experiment to test the hypothesis that a mitochondrion might function as a flip-flop memory element in neurons One experiment would be to search for some mitochondria that have their ATPsynthase ATPase enzymes rotating in phase. If none can be found the hypothesis fails. Everything in it depends on the enzymes running in phase, or in phase plus or minus 120 degrees. If this happened the electrochemical gradient across the inner membrane of the mitochondrion would oscillate at about 30-70 Hz. It does not seem an easy thing to do. The electrochemical gradient across the inner membrane of the mitochondrion is like the difference in potential across a capacitor. If the potential across a capacitor oscillated, how would you detect it except by connecting a potentiometer across its leads? There is no electric field outside a capacitor because the field extending from the positive charge on one side is cancelled by the field extending from the negative charge on the other side. If you brought a negatively charged plate close to the positively charged side of a capacitor you would set up an electric field between the two, and so could measure the oscillating potential of the capacitor, I think. But the probe would have to be negative in relation to what? Ideally you would insert an insulated probe with a bare tip inside the inner membrane of a mitochondrion, and then touch the outside of its inner membrane with the bare tip of another insulated probe. If the rotating enzymes were running in phase the potential across the probes would oscillate. (The outside of the inner membrane would always be positive and the inside would always be negative, but the potential difference would oscillate.) But a mitochondrion is about the same size as a bacterium! I might be able to find an electrical engineering laboratory in Japan that would be capable of doing this small-scale work. I am confident that Japanese workers could do it. One Japanese group has already done exquisite work on the rotating enzyme. This type of measurement was first done in 1939 in nerve fibres by Hodgkin and others. Later, glass micro-pipettes filled with a KCl solution were used as micro-electrodes. Andrew Gyles. (Posted on the discussion groups 'talk.origins' and 'sci.bio.evolution' on 21 December 2000.) ______________________________________ In retrospect I think that I might have exaggerated the difficulty of showing that the enzymes working in reverse as ATPase rotate in phase in some or all situations. It might not be necessary to insert an insulated electrical probe into the mitochondrion. The reason is that if the enzymes rotate in phase they will pump out protons in what I have called 'minor floods' or 'waves' about 60 times a second (60 Hz). But the electrons that counterbalance the positive charge of the protons will not be produced in 'minor floods' or 'waves' by the other enzymes in the respiratory chain; there is no reason to suppose that these electron-transferring enzymes will ever work in phase. A detectable oscillating electric current I therefore think that a mitochondrion with its ATPsynthase ATPase enzymes rotating in phase as ATPase might have a small oscillating electric current that could be detected by an external electric probe. This idea could be best explained by drawings. Detectable pressure waves I think too that a mitochondrion with its ATPsynthase ATPase enzymes rotating in phase would probably oscillate physically, slightly changing its shape and so generating pressure waves in the cytoplasm of the cell, at a frequency of about 60 Hz (the frequency range might be 20 - 80 hz, depending on the supply of energy-rich metabolites and oxygen, or of ATP). These waves could be detected by a tiny pressure-sensitive probe inserted into the cell and placed close the mitochondrion, but not inside the mitochondrion. Published on this site 28 December 2000. Andrew Gyles ________________________________ CONTENTS The mitochondrion as a flip-flop memory element in neurons I suggested in an earlier article that if certain mitochondria in neurons worked with all of their ATPsynthase ATPase enzymes rotating in phase or [to allow for geometric effects at the bends of cristae] in phase plus or minus 120 degrees, they would produce 'minor floods' of protons when working as ATPsynthase, which could trigger nerve impulses. Protons are positively charged. The arrival of positive charges at the negatively charged inner surface of a neuron membrane that is ready to 'fire' will trigger a nerve impulse. The triggering positive charge need only be very small; the main strength of a nerve impulse is contributed by the subsequent increase in permeability of the membrane to sodium ions, and the inrush of that ion into the neuron. Low mtDNA mutation rate in humans? This article, like the earlier one ('Mitochondria as the motors of consciousness'), is speculative. The validity of both models will depend on a detailed examination of the magnitudes of the various physical quantities involved. If the models are valid they will support the notion that the mutation rate in the mtDNA of humans might be very much lower than that in apes, for reasons I outlined in the earlier article. Triggering of 'gamma' waves of consciousness I have suggested that a mitochondrion close to a 'critical spot' on the inner surface of the membrane of a neuron might work sometimes with its ATPsynthase ATPase enzymes rotating in phase as ATPase, fuelled by a store of ATP in the matrix of the mitochondrion, and triggering nerve impulses in the neuron at three times the frequency of rotation of the ATPase enzymes. I proposed that this might be the origin of the 'gamma' waves observed in certain groups of neurons. These waves have been tentatively identified by some authors as the neural correlate of 'awareness' or 'consciousness' of particular aspects of objects. Waves with rhythm I suggested that the triggering of such waves by a mitochondrion might continue until the mitochondrion exhausted its store of ATP, when its rotating enzymes would have to reverse their direction of rotation and work as ATPsynthase, making ATP and storing it in the matrix (the inner hollow) of the mitochondrion. This reversing of mode of operation, from ATPase to ATPsynthase, and then back to ATPase and so on would, I suggested, produce the 'rhythmic' character of the 'gamma' waves that some researchers have observed. A more interesting mode of operation I now propose that a mitochondrion in a particular situation inside a neuron, with one of its sides pressed close to the inside of the membrane of the neuron, might operate in a more complex manner, and one more interesting to those workers trying to find parallels between the operation of a computer and the operation of the brain. The 'near' side and the 'far' side of the mitochondrion I shall call the side of the mitochondrion pressed close to the inside of the membrane of the neuron the 'near' side, and the opposite side of the mitochondrion the 'far' side. I suggest that the contact between mitochondrion and neuron might be rather like the contact of two neurons at a synapse, except of course that the mitochondrion is inside the neuron (not outside it), and is smaller than a typical synapse. There are cristae on the 'near' side of the mitochondrion and cristae on the 'far' side. These are infoldings of the inner membrane of the mitochondrion. Identical ATPsynthase ATPase enzymes are inserted in these cristae, close to each other (I assume) in a regular arrangement a bit like the molecules in a single layer of the lattice of a crystal. There may be millions of these identical enzymes, rotating like motors in phase, in the cristae of a single mitochondrion. 'Near' side has two stable states I propose that in particular mitochondria performing information storing and processing tasks in particular parts of a neuron the ATPsynthase ATPase enzymes in the cristae on the 'far' side work always as ATPsynthase. And I propose that the ATPsynthase ATPase enzymes in the cristae on the 'near' side work sometimes in phase as ATPsynthase and sometimes in phase in reverse as ATPase, in the latter case producing 'minor floods' of protons at three times the frequency of rotation of the central asymmetric 'axle' of the enzyme. From now on I shall refer to these 'minor floods' of protons as 'waves'. Switchable if volley phase is right Same phase If a volley of impulses passed through the neuron with the same frequency and phase as the waves of protons being produced on the near side of a mitochondrion with its enzymes working as ATPase the near side would 'see' high concentrations of positive charge at the peaks of the waves, and would (I propose) be 'pushed' into reverse by these high concentrations so that it worked as ATPsynthase and produced no waves of protons. I say 'pushed' because the positive charges appearing on the inside of the membrane of the neuron would repel the protons being produced by the near side of the mitochondrion. (A nerve impulse consists of a patch of positive charge appearing to travel along the inside of the membrane of the neuron in the direction of the impulse. After it has passed, the charge on the inside of the membrane becomes negative.) Opposite phase If a volley of impulses passed through a neuron with the same frequency as, but opposite phase to, the waves of ATP being produced on the near side of a mitochondrion with its enymes working as ATPsynthase the near side would 'see' high concentrations of negative charge at the peaks of the waves of ATP and would be 'pulled' into reverse so that its enzymes worked as ATPase and produced waves of protons. I say 'pulled' because the negative charges appearing on the inside of the membrane of the neuron would attract any protons in the near side of the mitochondrion and by drawing them outside it lower the concentrations of protons inside the mitochondrion. Switchable memory element The reader will, I think, immediately see the significance of the above two changes. In the first case the mode of operation of the enzymes in the near side of the mitochondrion is switched from a mode producing waves of positive charges to a mode producing no positive charges. In the second case the mode of operation is switched from one producing no waves of positive charges to one producing waves of positive charges. Unswitchable if phase is wrong If a volley of impulses passed through the neuron with the same frequency as, but opposite phase to, the waves of protons being produced on the near side of a mitochondrion with its enzymes working as ATPase the near side would 'see' low concentrations of protons (because the inside the of the neuron near the mitochondrion would be negative when each wave of protons reached its peak) and would therefore continue to work as ATPase. If a volley of impulses passed through a neuron with the same frequency and phase as the waves of ATP being produced on the near side of a mitochondrion with its enzymes working as ATPsynthase the near side would 'see' high concentrations of positive charge at the peaks of the waves of ATP and its enzymes would continue to work as ATPsynthase. The mitochondrion as a flip-flop In the four cases described above the near side of the mitochondrion can be seen as analogous to a 'flip-flop', a circuit defined in United States usage as 'a bistable pair of valves or transistors, two stable states being switched by pulses ... '. I do not push this analogy too far. Perhaps it would be better to regard such a mitochondrion as simply a binary cell, defined as 'An information storage element, which can have one or other of two stable states'. However, its current state does not have to be discovered: it is continually communicated by the mitochondrion itself. The near side of the mitochondrion has two stable states: enzymes working as ATPase or as ATPsynthase. It can be switched between these states by volleys of nerve impulses of particular frequency and phases, but not by volleys of the 'wrong' phase relative to the current stable state. Active memory The near side of the mitochondrion can be seen as an active memory store, in the sense that in one of its two modes of operation it continually triggers nerve impulses, which can be communicated to other neurons, and in the other mode it triggers no nerve impulses. In the appropriate context the lack of an impulse is a signal too. Thus it is not a passive memory store, like the patches of differing magnetic polarity on the surface of a computer hard drive, whose state has to be discovered by an actively interrogating reading head. Short-term memory I propose that mitochondria working as described above could be the basis of short-term memory. Binary arithmetic I propose that several, perhaps many, such mitochondria in the one neuron might enable it to do binary arithmetic and to process information. Perhaps it is relevant to note here that some neurons have many dendritic branches, and that a nerve impulse can travel in both directions along the membrane of a neuron. Switching different mitochondria in the one neuron A switching volley of nerve impulses must have a frequency three times the frequency of rotation of the enzymes in the near side of the mitochondrion. If each mitochondrion ran at its own frequency of rotation (governed, for example, by the supply and removal of metabolites in a particular situation) it could be switched only by a volley of nerve impulses of three times that frequency. Thus incoming volleys could switch different mitochondria in the one neuron, depending on the frequency of each volley. Andrew Gyles (I sent this article to the internet discussion group 'bionet.molbio.evolution' on 11 December 2000, where it was subsequently published.) Published on this site 12 December 2000. Andrew Gyles ________________________________ CONTENTS Mitochondria as the motors of consciousness Isuggest that the reason why mitochondria have retained some protein-coding genes is that these genes code for proteins that determine, indirectly or directly, the frequencies ofrotation of the ATPsynthase ATPase enzymes in the mitochondrial cristae. I propose here that thesefrequencies determine the characteristic singlefrequenciesof 'firing'ofvarious neurons that are important to particular aspects of consciousness. Alleles would confuse frequencies If these genes had been transferred to the nucleus each of them would have become paired (one on each homologous chromosome). Then they would probably have mutated into functional but non-identical alleles. These alleles couldbe variously expressedin the mitochondria of each cell. Each cell would then contain mitochondria thatrotated at different frequencies in the same circumstances. This could cause the neurons to be triggered at two or more frequencies,and so cause the loss of the aspect of consciousness for which each group of neurons was responsible. Biparental inheritance would confuse frequencies I propose that if mitochondrial DNA were inherited biparentally similar multi-frequency confusion would be caused in the neurons. ATPsynthase ATPase enzymes rotating in phase like dynamos In certain circumstances a mitochondrionwill oscillate (rather like the crystal oscillators used in electronic circuits)because 'hydraulic interference' between neighbouring F1 units of ATPsynthase ATPase arranged in almost crystalline fashion on the cristae will force all the units to rotate synchronously and in phase. They will therefore rotate like the dynamos of a national electricity generating network, which all run synchronously and in phase. Working in phase to avoid hydraulic interference As an example of strict'hydraulic interference' consider the actions of two divers reaching a completely flooded submarine and entering it, one from the stern and the other from the bow. They reach a central compartment with a door at each end. Each door can be opened inward or outward. They wish to enter this flooded compartment. If they try to open both doors inward simultaneously they will fail. If they try to open both doors outward simultaneously they will fail. But if one diver opens his door inward and the other diver opens his door outward they will succeed. This is because water is practically incompressible and inexpandable, except for the very small compressions and expansions involved in the transmission of sound. The divers must work together in phase so that they do not cause 'hydraulic interference'. Turbine-dynamos driven by electrochemical gradient Drawings and calculationselucidatingthe operation of the sodium ATPsynthase ATPase ofthe bacterium Propionigenium modestum have recently been published (1). This is a rotary enzyme driven by an electrochemical sodium gradient. The authors suggest that the same mechanism operates in other ATPsynthase ATPases, including the proton-drivenrotary enzymeof Escherichia coli. Much of the experimental work in this field has been done on the rotary enzymes of bacteria, the assumption being that they are similar to the rotary enzymes in the mitochondria of eukaryotes. I make the same assumption here. Like motor-pumps when going in reverse Rotary ATPsynthaseenzymes can be driven in reverse by the energy released when ATP is split into ADP and inorganic phosphate.They then pump sodium ions [or protons, as the case may be] 'uphill' against an electrochemical gradient. In this mode of operation the appropriate name for them is ATPase. Three pairs of double doors Other drawings (2) show the ATP-making (-cleaving) part of this class of enzyme to consist of three compartments. Each compartment has a catalytic site and has what looks to me like a 'double door'. Each pair of double doors opens and closes in sequence, separated by 120 degrees of phase angle, as a central asymmetric 'axle' is rotated by the passage of positive ions through the 12-segmented rotor in the bacterial (or mitochondrial inner) membrane. Three sites change states in sequence According to Boyer's binding exchange mechanism,each catalytic site passes through a cycle of three different states: open, loose and tight, corresponding to an empty state, a state with bound ADP and phosphate, and a state with tightly bound ATP; at any given moment the three sites are in a different state (3). ATPsynthase ATPase enzymes likely to rotate in synchrony It is reasonable to assume that theATPsynthase moleculesof a mitochondrion will rotate in synchrony because they are all identical and are all driven bythe sameelectrochemical gradient, which depends on the concentrations of protons inside and outside the inner membrane. These concentrations in turn depend on the activity of the other respiratory enzymes in the mitochondrion. Rotation in phase would minimise hydraulic interference I suggest that neighbouring rotatingATPsynthase ATPase enzymes on the cristae of a mitochondrion will fall into a phase relationship that minimises 'hydraulic interference' between neighbours as their opposed 'double doors' open and shut. There might be millions of these enzymes in a single mitochondrion. Frequency determined by supply of metabolites Thus all of the identical rotary enzymes at the end of the respiratory chain will rotatein phase at a frequency ultimately determined by thesupply of incoming metabolites and the metabolic activity of all of the 'earlier' enzymesin the respiratory chain. I suggestthat the full range of frequencies of rotation of the ATPsynthase ATPase mightturn out to be about 6 - 24 Hz. Typical frequencies of rotation The results of the calculations in (1) were that when the sodium-driven rotary enzymeoperated undera typical physiological electrochemical gradient it rotated at about 15-20Hz.It formed3 molecules of ATP per revolution. Twelve sodium ions passed through the rotary Fo part of the enzyme (the 'motor') for each revolution, corresponding to an average of 4sodium ions per ATP molecule formed. The authors remarked that the same operating principle could drive the proton-driven ATPsynthases, with slight changes to the design of the Fo motor. Other workers observing an isolated F1-ATPase unit by video microscopy (4) have shown thatit rotates in steps of 120 degrees. I conclude from these papers that it is likely that the proton-driven ATPsynthaseenzymes in the cristae of mitochondria rotate at about 15 - 20 Hz (the precise rate depending on the electrochemical gradient driving them). It is possible that when their movement is looked at in fine detail theywill beseen to advance in 12 small steps of 30 degreesper rotation (as shown in a figure of reference 1), at each step releasing one proton at the bottom of the gradient. However, the 30-degree steps shown in (1) are derived from theoretical calculation; they have not, as far as I am aware, been observed. Rotation in phase in 'big steps' of 120 degrees I assume that when the rotation of the ATPsynthase ATPaseenzymeis looked atmore broadlyit isseen to advance in three big steps of 120 degrees per rotation (as observed in reference 4), at each big step releasing one molecule of ATP and four protons at the bottom of the gradient. I propose that all of these enzymes in a mitochondrion rotate in phase, or in phaseplus or minus 120 degrees; that is, they all take a 120-degree step at precisely the same time. Frequency of 'big steps' same as gamma waves of consciousness The rate of the big steps will therefore be about 45 - 60 Hz. There is an important coincidence here: thisrate is about in the middle of the 'gamma' range of oscillation (20 - 70 Hz) ofcertain neurons that seem to play important roles invarious forms of perception, awareness, consciousness, and motor control. The precision of the timing of the cycling of these oscillations has been observed to be about a millisecond. Some workers have reported 'rhythmic' activity of neurons oscillating at gamma frequencies; I assume thatthey meanregular starting and stopping of the oscillations (5, 6, 7). As I suggested above, the full range of frequencies of rotation might turn out to be 6 - 24 Hz (at least while the enzyme is operating as ATPase); this would make the range of frequencies of the 'big steps'18 - 72 Hz and thus cover the full range of gamma oscillations. Enzymes in reverse pump 4 protons uphill at each big step If the ATPsynthase ATPase enzymes are driven in reverse as ATPase, utilising the energy released by the splitting of ATP, the same frequency relationships will hold, I assume. The rotation rate will be about 15 - 20 Hz (perhaps 6 - 24 Hz). One ATP molecule will be split for each big step of 120 degrees of rotation. Each enzyme will take 15 -60 (perhaps 18 - 72) big steps of rotationper second, precisely in phase with its neighbours,and in each big step 4 protons will be pumped up the electrochemical gradient to the outside of the inner membrane of the mitochondrion. How might a nerve impulse be triggered? How might the (hypothetical) oscillations in a mitochondrion caused bythe ATPsynthase enzymes rotating synchronously in phase in the cristae trigger oscillations of the same frequency in the 'firings' of a neuron? Possibility one: working as ATPsynthase One obvious possibility is that the mitochondrion will produce minor 'floods' of ATP molecules at frequencies in the range of 45 - 60 Hz. The neuronuses ATP to drive the enzymes in its membrane thatrepolarise the membrane after each 'firing'.Ifjust enoughATP molecules arrive at the membrane in minor 'floods' with a frequency of (say) 45 Hz, the membranecould be repolarised at that frequency and so could not fire at any higher frequency. However, it could fire at a lower frequency. And in any case, because ATP is made inside the inner membrane of the mitochondrion, and has to be carried outside by the ATP ADP translocators in that membrane, it is possible that an oscillation in its supply inside the mitochondrion will be almost completely 'smoothed out' or 'averaged' by the time the ATP arrives outside. Possibility two: working as ATPsynthase Another possibility is that the ATPsynthase enzymes rotating in phase will continually lower the concentration of protons outside the inner membrane of the mitochondrion at a frequency in the range of 45 - 60 Hz. When operating as ATPsynthase they are driven by the electrochemical gradient created by a high concentration of protons outside the inner membrane and a low concentration of protons inside it. (Other respiratory enzymes in the mitochondrion keep building up the concentration of protons outside the inner membrane.) Inside the membrane there may be a corresponding oscillating change in the concentration of protons as protons are released in minor 'floods' from the ATPsynthase enzymes. 'Minor floods' of protons as triggers If a sufficient number of excess protons passed through the outer membrane of the mitochondrion (which has VDAC pores that make it freely permeable to ions and most metabolites) (8) in minor 'floods' at frequencies in the range of 45 - 60 Hz and reached a critical spot on the membrane of the neuron they could depolarise the membrane at that spot and so trigger impulses at the same frequency. A neuron membrane ready to 'fire' The membrane of a neuron that is ready to fire is polarised by negative chargesinside it and positive charges outside it. Protons, which are positively charged, arriving at the inner surface would depolarise the membrane and socause the neuron to fire. Some doubts The question here is whether the ATPsynthase enzymes in a mitochondrion inside a neuron wouldallow minor floods ofexcess protons to leave the mitochondrion and cross a (small) gap to the inside of the membrane of the neuron. ATPsynthase might pass protons so quickly from outside the inner membrane of the mitochondrion to inside that no excess protons could pass from the mitochondrion to the membrane of the neuron. And it is possible that the positive charge of the protons outside the inner membrane of the mitochondrion is balanced, partly or wholly, by the negative charge of anions inside the inner membrane, so that the protons on the outside are 'tied' by the attractive force between them and the anions. (That is to say, the inner membrane of the mitochondrion might be partly or completely polarised when ATPsynthase ATPase is working as the synthase. I have no information on this.) Possibility three: working as ATPase and pumping protons in waves Because of the doubts outlined above I think it likely that, if mitochondria are indeed the motors of consciousness, they trigger the rhythmic firings of certain neurons at the gamma frequencies only when therotary enzymesare working as ATPases, fuelled by ATP and pumping protons from inside the inner membrane of the mitochondrion to outside it. 'Minor floods' or waves of protons I propose that when working thus they can produce'minor floods' or waves of excess protons that can quickly cross a small gap from the mitochondrion to the inside of the membrane of a neuron. The 'floods' of protons arrive at a gamma frequency and trigger firings of the neuron atthe same gammafrequency. As I explained above, the membrane of a neuron that is ready to fire is polarised by negative chargesinside it and positive charges outside it. Protons, which are positively charged, arriving at the inner surface would depolarise the membrane and socause the neuron to fire. Reversing enzymes give gamma waves their rhythm When the mitochondrion exhausts(or nearly exhausts) the supply of ATP inside it the ATPase has to stopusing ATP as a fuel; it then rotates in the reverse direction and is driven as ATPsynthase by the flow of protons from outside the inner membrane to inside. Thus the neuron will betriggered at a gamma frequency until the mitochondrion runs out of ATP. Then the triggering will stop for a while, while the mitochondrion 'recharges' its supply of ATP. This explains the rhythmicpattern observed in the gamma oscillations. Natural selection for a low mitochondrial DNA mutation rate If mitochondria are the motors of consciousness because they candrive certain neurons each at a single gamma frequency characteristic of that neuron at any one time (orof a group of neurons of which it is a member) it is possible that there has been natural selection for a lower mitochondrial mutation rate in humans than in other animals.Thisisso because higher consciousness (especially the ability to use language)gives humans many advantages in the struggle to survive and reproduce. Mutations (either maternally inherited or somatic) in mitochondrial DNA could produce populations of mitochondriathat oscillated at different frequencies in certain single neurons importantin the creation of an aspect of the conscious state. The driving of a single neuron at two or more different gamma frequencies wouldpresumably destroy the aspect of consciousness that its firing would normally help to create. Information systems in single-celled organisms I suggest that rotary enzymes might play important roles in the simple information systems of bacteria and single-celled eukaryotes. The slime mould thatextends itselfthrough the shortest path in a maze, for example, might depend on a sonar system driven by the oscillations of mitochondria.) References 1) Dimroth P et al (1999), Proceedings National Academy of Sciences 96(9): 4924-4929. 2) Scientific American, January 1998, p 9. 3) Saraste M (review) (1999) Science 283:1488-1493. 4) Noji H(essay with drawing) (1998) Science 282:1844, 1845. 5) Maldonado P E et al (2000) Cereb Cortex 10(11): 1117-1131. 6) Palva J M et al (2000) J Neurosci 20(3): 1170-1178. 7) Mima T et al (1999) Neurosci Lett 275(2): 77-80. 8) Green D R et al (1998) Science 281:1309-1312. Andrew Gyles (I sent this article to the internet discussion group 'bionet.molbio.evolution' on 30 November 2000, where it was subsequently published.) Published on this site 1 December 2000. Andrew Gyles ________________________________ CONTENTS The evolving mitochondrion as a killer of male embryos In any species of animal in which mitochondria are inherited only from the mother a conflict exists between the selfish interest of the mtDNA and the interest of the species. The selfish interest of the mitochondrion and its mtDNA is to be transmitted by every mature individual of the species to the next generation. But in the case of uniparental maternal inheritance of mtDNA half of the individuals, the males, do not transmit their mtDNA to the next generation. And in the more complex animals the mothers expend much energy and time in bearing each offspring. In this situation if a mitochondrion in a male embryo could think, and could detect the sex of the embryo, it would realise that the best chance of ensuring the transmission of its mtDNA to the next generation would be to kill the embryo. It has zero chance of beingtransmitted to the next generation if it is in a maleembryo. If it kills the male embryo the mother will soon have another chance to conceive, and there is a 50 per cent chance that her next offspring will be a female, which willtransmitthe same mtDNA to the next generation in the fullness of time.This is true because the mtDNA in themitochondrion in the male embryo is identical to the mtDNA in the mother. Of course mitochondria cannot think, but natural selection acting on random mutations of mtDNA (like throws of dice on the board of the conditions of existence) could produce the same effect. The mtDNA in an animal species inwhich inheritance of mtDNA is uniparental and maternal will evolveso that the mitochondria can detect the sex of anembryo and, if it be male, kill it. The killing mechanism would, I suggest, have been similar tothe"miniature apoptosis" thatdestroysmale-line (M type) mitochondria in female embryos in mussels. (I wrote aboutthis hypothetical miniature apoptosisin mussels inanother article.) In the present case the maternally inherited (F type) mitochondria would be destroyed, leaving the cell with no mitochondria. The embryo would die. The result of this evolution would be that most of the offspring born in each generation would be female. But thiswould not be good for the species as a whole. In the long run natural selection would favour those populations of individuals in whichthemtDNA genes coding for proteins that detected and killed male embryos hadbeen"consficated" by the nucleus of the cell and brought underthe control of the nucleus.I suggest that this is the reason why humans, for example, have only 13 protein-coding genes left in the mtDNA, all of them coding for respiratory enzymes. The mitochondria havebeen disarmed. In my hypothesis on miniature apoptosis in mussels I suggested that female-line (M type) mitochondria might have receptors in their outer membrane for a protein that was a receptor for thefemale-steroid molecule, and that in the abscence of the female-steroid molecule this protein fitted specifically into the receptor in the outer membrane and permeabilised it, thus destroying the mitochondrion. Such a mechanism might help the species by causing the death of any musselembryo, whether male of female,that did not quickly produce a typical level of female-steroid molecules. How could a mechanism like this in the ancestors of species that inherit all of their mtDNA maternally be modified by evolution to bring about the destruction of male embryos by miniature apoptosis? I think that the protein that was a receptor for the female-steroid molecule would have to evolve so that when it formed a specific complex with a male-steroid molecule it fitted specifically into the receptor in the outer membrane of the mitochondrion and permeabilised the membrane. Andrew Gyles (I sent this article to the internet discussion group 'bionet.molbio.evolution' on 2 November 2000, where it was subsequently published.) Published on this site 3 November 2000. Andrew Gyles ________________________________ CONTENTS A possible reason for the smallness of the human Y chromosome In humans the gamete contributed by the father determines the sex of the child. If the gamete has a Y chromosome the child is male. If the gamete has an X chromosome the child is a female. It would be in the selfish interest of the Y chromosome to get itself passed to much more than 50 per cent of the next generation. It is perhaps possible that more than once in the course of evolution of humans (and their non-human ancestors) mutations in the Y chromosome have resulted in genes that discriminate against the production of X- bearing gametes in spermatogenesis or sperm maturation. The most recent of such events might (for instance) have occurred in Africa 60,000 years ago. Such mutations would give the Y chromosome a tremendous evolutionary advantage. It might ensure that (for instance) four out of six of a man's offspring were males. This mutated chromosome could spread quickly through a widespread established population, generation by generation (assuming that a short-displacement wavelike movement of people, lasting a long time, was always possible). However, no other chromosomes would accompany it far on its journey. It would be a bit like the gene for 'hornlessness', which can be introduced into a herd of horned black Angus cattle by a cross with a hornless red Shorthorn bull and, under the artificial selection of the cattle-breeder, be spread throughout the herd. In about 20 years the herd consists of hornless black Angus cattle. It would be incorrect for a stranger to assume that the black cattle he or she sees in the field were of a breed that had been hornless for hundreds of years. Under natural selection a human population in which the males had the 'anti-X gamete' Y chromosome would suffer the disadvantages of a surplus of males and a scarcity of females. In the long run natural selection would favour subsequent mutants of the 'anti-X gamete' Y chromosome in which those mutant genes that discriminated against the production of X-bearing gametes in spermatogenesis or sperm maturation were deleted or rendered inactive. The result after many millenia of evolution of humans (and their evolutionary precursors) would be a human Y chromosome from which many genes had been deleted and in which many of the remaining DNA sequences were permanently inactivated. It would also be a Y chromosome that could give a misleading picture of the chronology and routes of human migration from Africa. Andrew Gyles (I sent this article to the internet discussion group 'bionet.molbio.evolution' on 1 November 2000, where it was subsequently published.) Published on this site 3 November 2000. Andrew Gyles ________________________________ CONTENTS Miniature apoptosis in mussels Mussels have two types of mitochondria and mtDNA: one that is transmitted from the mother to daughters and sons (the F type), and one that is transmitted from the father to daughters and sons (the M type). The female and male embryos receive M mtDNA through the sperm, but within 24 hours it is eliminated or drastically reduced in female embryos but is maintained in male embryos (1). I suggest that M mitochondria have in their outer membrane molecules that specifically fit a protein that acts as a male-steroid receptor.When this protein is present in the cytoplasm of the cell in the absence of male-steroid molecules it binds to the outer membrane of M mitochondria and permeabilises it, thus destroying the M mitochondria.I call thisaction 'miniature apoptosis' because the tiny organelles are destroyed, but not their host cell. When this protein forms a complex with a male-steroid molecule its conformation changes, so that it cannot permeabilise the outer membrane of M mitochondria. Thus M mitochondria are destroyed in female embryos, whose cells contain no, or few, male-steroid molecules. But M mitochondria are not destroyed in male embryos because their cells contain many male-steroid molecules. It is possible that F mitochondria have in their outer membrane molecules that specifically fit a protein that acts as a female-steroid receptor. When not complexed with a female-steroid molecule this protein can permeabilise the outer membrane of F mitochondria. When complexed with a female-steroid molecule the protein cannot permeabilise the F mitochondrial outer membrane. Ifthe cells of both female embryos and male embryos contain many female-steroid molecules the F mitochondria will be maintained in both sexes. This hypothesis is, I think, given somesupport by findings in a paper published last August. In human cellsa steroid receptor called TR3, normally present in the nucleus, translocates to mitochondria in response to apoptotic stimuli and permeabilises the mitochondrial membranes, releasing cytochrome c and triggering a series of events that cause apoptotic cell death. TR3 is called an 'orphan' receptor because the steroid with which it is assumed to form a specific complex has not yet been identified (2). Humans inherit mitochondria and mtDNA only from their mothers. I suggest that the evolutionary 'ancestor' of TR3 was like the (hypothetical) female-steroid receptor in mussels that permeabilises the outer membrane of F mitochondria in the absence of female-steroid molecules. I suggest that TR3 has evolved in such a way that it can no longer form a specific complex with a female-steroid molecule, and is therefore able to permeabilise mitochondria and trigger apoptosis in all human cells, whether male cells or female cells. It is a permanent 'orphan'. 1. Sutherland et al, Genetics 148: 341-347 (January, 1998). 2. Li et al, Science 289: 1159-1164 (18 August, 2000); and in the same issue the perspective by Brenner and Kroemer, pp 1150 and 1151. (I thank group members who provided information and references on mitochondrial inheritance.) Andrew Gyles (I sent this article to the internet discussion group 'bionet.molbio.evolution' on 30 October 2000, where it was subsequently published.) Published on this site 31 October 2000. Andrew Gyles ________________________________ CONTENTS The primitive mitochondrion as a fatal parasite The primitive mitochondrion might have been a parasite of primitive eucaryotic cells that preserved a free-living stage in its life cycle, gaining its freedom by lysing its host. Such an association would not have been disastrous for the host species if it were able to multiply more quickly with the parasite than without it, and if the parasite did not lyse a cell of its host too frequently. The great gain in metabolic efficiency conferred by the oxidative respiration of the primitive mitochondrionwould have helped the host cell to grow more quickly and multiply more quickly, and thereforea single-celled host species could survive the occasional lysing of some of its cells. Nonetheless,the host would gain a further advantage if it could stop the primitive mitochondrion from lysing the cell of its host.As the primitive single-celled eucaryotic cell evolved into separate species each species might have developedits ownways of 'disarming' its parasite. Oneway would have been to 'confiscate' those genes of the parasite that were involved in the lysing of the host and place themin the nucleus under the control of the host. Another way might have beenfor the host cell to interfere in the expression of the genes that remained functional in the mitochondrion by sending host-derived control proteins or RNA into the mitochondrion. The evolution of multicellularspecies couldnot have proceeded far ifoccasionally some of their cells were lysed at random. Such random lysing would disrupt the organisation upon which multicellularspecies depend for their success. Therefore we might expect to see in these organisms a more stringent control of lysing by mitochondria than insingle-celled species. However, controlled lysing of particular host cells might have been of great advantage in the evolution ofmulticellularspecies. Such an advantage might have beenachievedif the host gained control of the lysing activity ofits mitochondriaand applied itin a programmed way to achieve 'programmed cell death', or apoptosis. And indeed we know that mitochondria are the focus of many of the drastic processes involved in apoptosis. Thusthe simple assumption that the primitive mitochondrion was a parasite that occasionally lysed the cell of its host can explain whysome mitochondrial genes have been transferred to the nucleus in many species of eucaryotic cell, and why mitochondria are the focus of apoptotic activity invarious multicellular species. (Note: I have used the termslysing and lysein a general sense. I have used words such as disarming, confiscate, interfere, and so on as a concise way of expressing the results under natural selection of a few trillion dice throws on the board of the conditions of existence.) (I sent this article to the internet discussion group 'bionet.molbio.evolution' on 28 September 2000, where it was subsequently published.) Published on this site 29 September 2000. Andrew Gyles ________________________________ CONTENTS My hypothesis of a low mitochondrial mutation rate in humans There is a theoretical possibility that a mitochondrion could eliminate those mutations that cause a distortion of the double-stranded mtDNA, because such mutationsare physically detectable by a set of enzymes. The enzymes could then destroy the entire double-stranded copy of the circular mtDNA genome containing the distorted mtDNA, or alternatively tag it for 'export' and cause it to be ejected from the mitochondrion. (The ejecting of genetic material through a conjugation tube is a known bacterial behaviour. Mitochondria are thought to have a bacterial ancestor.) The destroyed or ejected copy of the mtDNA genome could be replaced, sooner or later, by the replication of an unmutated copy in the same mitochondrion. It is interesting to note that enzymes in the nucleus try to do the same thing. But of course, having detected a chromosome distorted by a mutation they cannot destroy the chromosome. If they did that they would not have an unmutated copy to replicate and so make good the loss. The homologous chromosome is not an identical copy. So the best they can do is to 're-pair' the distorted part of the double-stranded nuclear DNA. This is a chancey business because they cannot 'know' which base or bases to leave in and which to cut out. But it is better than doing nothing. Oxygen free radicals produced by the respiratory chain in mitochondria can damage mtDNA and thus increase the mutation rate. It is conceivable that an abnormally high mtDNA mutation rate in somatic cells is an indication that this hypothetical system for eliminating mutations that cause distortions in double-stranded mtDNA has failed in those cells. It is worth noting that if such a system is at work in the mitochondria of female germline cells it might have evolved to different degrees in different species of animal. For example, the development of higher intelligence and memoryand the acquisition of language in humans might havedepended on a simultaneous evolution of a lower mtDNA mutation rate inhuman brain cells in particular. However, the lower rate might have been achieved generally, in all cells. In that case it is possible that the mtDNA mutation rate in human female germline cells is much lower than has been assumed in studies of human evolution based on the 'mtDNA sequence divergence rate'. As far as I know this rate has never been objectively measured. Some indication of whether mitochondria do use the hypothetical system outlined above could perhaps be gained on cell cultures in vitro, using X-irradiation as a mutagenic agent to accelerate the mutation rate. (I published this summary on the 'message board' of the discussion group 'talk.origins' on 10 September 2000.) Published on this site 10 September 2000. Andrew Gyles ________________________________ CONTENTS Five puzzles about mitochondria The first puzzle is: Why does each mitochondrion have several copies of its chromosome? Each copy resembles a bacterial chromosome: it is circular and has no histones. But a bacterium has only one copy of its chromosome. I think that I have already solved this puzzle (see my letter to the Editor of 'Nature', sent on 2 August 2000, below). The mitochondrion has several copies of its chromosome so that it can destroy (or, alternatively, as I realised a day or two ago, eject from the mitochondrion) any copy in which a mutation has caused a physically detectable distortion, and then replace the destroyed or ejected copy by replicating an unmutated copy. As I remarked in my letter to the Editor of 'New Scientist' sent on 14 July 2000 (see below), conditions inside a mitochondrion are thought to be hostile to DNA; oxygen free radicals produced by the respiratory chain can damage DNA, causing mutations. Though mitochondria are thought to be descended from a bacterium (or from a common ancestor of bacteria, mitochondria and chloroplasts) the conditions inside a mitochondrion are likely to be much more hostile to DNA than those inside a bacterium. The mitochondrion is a highly specialised, hard-driven oxidiser of metabolites. Therefore, as I have suggested, it needs several copies of its chromosome. The second puzzle is: Why does the mitochondrial chromosome of most species of animal contain so few genes? For example, in humans it has 37 genes, of which only 13 code for proteins. The most 'primitive' mitochondrion yet discovered, in the flagellate Reclinomonas americana, has 92 genes (1). Of these, 27 code for ribosomal proteins, one codes for an elongation factor and four code for components of RNA polymerase. None of these 32 genes has been retained in the mitochondrion of humans. Many of them have been transferred to the nucleus. Why? One answer must be that it is safer to keep the genes in the 'mild' environment of the nucleus than in the 'hostile' environment of the mitochondrion (see the argument under 'first puzzle' above). However, of the 24 genes in the Reclinomonas americana mitochondrion that code for proteins involved in oxidative respiration the human mitochondrion has retained 13. Why? One author has written that the mammalian mitochondrial genome has been reduced in size in order to increase its replication rate. He wrote that many essential mitochondrial genes had been transferred to the nucleus of the cell, and 'The transfer of mtDNA sequences to the nucleus continues to this day' (2). I think that this is an over-simplification. The real question, in my view, is not 'Why have so many mitochondrial genes been transferred to the nucleus?' but 'Why have not all of the mitochondrial genes been transferred to the nucleus, and why were those coding for respiratory proteins nearly always retained ?' I argue that there has been plenty of time for all of the protein-coding genes of the mitochondrion to be transferred to the nucleus, but the cells that allowed this to happen have not been successful in the struggle for survival. The reason why remains the greatest mystery in the five puzzles. The third puzzle is: Why do the mitochondria in a cell occasionally fuse together? This behaviour is a bit like the way a bacterium sometimes donates a copy of some of its DNA to another bacterium through a conjugation tube. Has mitochondrial DNA been observed passing from one mitochondrion to another when the mitochondria are in the fused state? The fourth puzzle is: Why does only the female in multicellular animal species transmit mitochondrial DNA to the next generation? One answer is that the female's ovum is much bigger than the male's sperm and can therefore contain vastly more copies of the mitochondrial chromosome. Another is that the sperm has to work very hard in its voyage to the ovum and during this great physical effort many of the copies of its mitochondrial chromosome are damaged. I doubt that either of these is the main answer to the puzzle. I think it more likely that multicellular animals that allowed both sexes to transmit their mitochondria to the next generation did not succeed in the struggle for survival: only one sex could be allowed to do it, and the reasons given in the above two answers made it certain that the sex that was allowed to do it was the female. The reason why only one sex should be allowed to transmit copies of the mitochondrial chromosome to the next generation remains a mystery. The fifth puzzle is: Why do mitochondria play an important part in apoptosis, programmed cell death? This is sometimes called cell suicide. As I remarked above, I think that I have solved the first puzzle. I have spent some time thinking about the remaining four puzzles and consider that they are susceptible of solution, though not without imagination. References 1) Palmer, Jeffrey D., Nature, 387, 454-455 (1997). 2) Wallace, Douglas C., Science, 283, 1482-1487 (1999). Published 20 August 2000. Andrew Gyles ________________________________ CONTENTS A laboratory experiment to test the central assumption of the 'Out of Africa' theory I suggest that female chimpanzee germline cells be grown in a glass dish and female human germline cells be grown in another glass dish. (If it is not possible to grow germline cells somatic cells will have to be used instead.) The cells in both dishes should then be treated with equal doses of mutation-inducing radiation, such as X-rays, for a calculated period of time. This period should be long enough for the radiation to cause mutations in a few of the mitochondrial chromosomes of some of the cells but not long enough for it to cause mutations in the nuclear chromosomes of many of the cells. This should be possible because there are many more mitochondrial chromosomes than nuclear chromosomes in most cells. (For example, some cells contain thousands of mitochondria, and each mitochondrion contains several copies of the mitochondrial chromosome. I do not know typical figures for female chimpanzee and female human germline cells.) Many experiments have studied the mutagenic effects of irradiation with various doses of X-rays, so the choice of appropriate doses can be guided by a great reserve of experience. Alternatively, specialists in the experimental use of mutagenic agents might be able to suggest more suitable mutagens for this experiment. After the irradiation has been stopped the cultured cells in each dish should be allowed time to repair or destroy mutated mitochondrial chromosomes. Then their mitochondrial DNA (mtDNA) should be searched for permanently mutated sequences and the net rates of mutation of mtDNA in the chimpanzee cells and the humans cells should be calculated and compared. The central assumption of the 'Out of Africa' theory is that the sequence divergence rate in human mtDNA (determined by the mtDNA mutation rate) is about the same as that in chimpanzees. But I suggest that humans correct mutations to their mtDNA much more than do chimpanzees (see note below). If this experiment shows that the net sequence divergence rate in humans is about a tenth of that in chimpanzees it will remove the logical support for the 'Out of Africa' theory that this assumption has always provided. The experiment might be a laborious and difficult one. It is of course an artificial one that speeds up the process of mutation millions of times. There might be questions about the choice of cells to be used, the correct mutagenic treatments and the interpretation of the results. However, until such an experiment is done it remains true that the central assumption of the 'Out of Africa' theory has not been put to the acid test in the laboratory. (Note: A typical mammalian cell, whether somatic or in the female germline, contains hundreds or thousands of copies of the single mitochondrial chromosome. But no normal mammalian cell contains more than one copy of each nuclear chromosome except during replication: nuclear chromosomes are paired in somatic cells, but the members of the pairs are not identical. The simplest way for a mitochondrion to correct a mutation to its mtDNA would be for it detect any mitochondrial chromosome containing a mispaired region and destroy the entire chromosome. There are several chromosomes in each mitochondrion, and a new chromosome could be produced by the replication of an old one when required. Let me emphasise that this is not possible in the chromosomes of the nucleus. Another way for a mitochondrion to correct a mutation in its mtDNA would be for it to force its several chromosomes to swap strands, then repair the mispaired region that would be revealed as new pairs of DNA strands formed. There would always be a risk that the mutation might be spread by its being taken as the correct template to which to fit nucleotide bases during enzymatic repairing of the mismatch, but this would be numerically unlikely. It would be rendered virtually impossible if all of the mitochondria in a cell fused for a time and forced their chromosomes to swap DNA strands widely and then form new strand pairs. This would reveal mutated strands because they could not form a perfect pair with a normal strand. The cell could then either destroy the chromosomes containing mispaired bases, or repair the mismatched bases [the latter process being less than perfect because the repairing enzymes can hardly be expected to 'guess' correctly every time which is the correct base or sequence of bases to use as the template in performing the repairing. However, if the cell repeatedly forced the mitochondrial chromosomes to swap strands while the mitochondria were fused, and successively repaired mispaired strands, mutated strands would eventually be corrected]. The mitochondria in a cell do fuse from time to time. I suggest that they do indeed destroy or repair mutated mtDNA strands while fused. Fusing is perhaps a bacterial behaviour inherited from their bacterial ancestors, which swapped or donated sections of DNA through conjugation tubes. Nature is a great opportunist, and might have adapted the conjugating behaviour of the bacterial ancestor, in which one bacterium could donate a mutant gene to another bacterium, to similar behaviour in fused mitochondria, in which mutant mitochondrial DNA was not donated but revealed or exposed and got rid of. This [hypothetical] process of correcting mutations to mtDNA while the mitochondria of a cell are fused might interfere with the vital energy-converting function of the mitochondria. I suggest that an animal would evolve so that its cells did it only as often as necessary. And I suggest that something in the evolution of humans, perhaps the acquisition of language and abstract thought, and the great need that this created for perfect functioning of the brain cells over a period of many years, caused humans to correct mutations to their mtDNA much more effectively and rigorously than chimpanzees, and that this is done in all human cells, not just brain cells. Alternatively, the mitochondria might be involved in brain function in humans in a more complicated way than in other animals, and this might cause them to behave in the way I have outlined above. I shall write about this possibility in another article.) Published 19 June 2000. Andrew Gyles ________________________________ CONTENTS geovisit(); Computational Neuroscience Resources related in several area of brain. 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Ear and Brain Club Ear Brain Seminar* Berlin and Potsdam - - Hearing and vestibular research - - * Lehrveranstaltung 02 356 FS, FU Berlin Contact: Prof. Dr. Arne Ernst , FAX +49 (0)30 5681 2903 Priv.-Doz. Dr. Alfred H. Gitter , Please bookmark: www.medizin.fu-berlin.de klinphys ear Location 1: Universittsklinikum Benjamin Franklin, Hindenburgdamm 30, 12200 Berlin (Steglitz), elevator 17 or 18,5th floor,Dept. of Clinical Physiology, Room 5740 Subway (U-Bahn "U9") or local train (S-Bahn "S1") to "Rathaus Steglitz", then Bus line 283, bus stop "Klinikum", Street Map Location 2: Restaurant Hundekehle (Landhaus Dahlem), back room, Hundekehlestr. 33, 14199 Berlin (Schmargendorf), phone 823 4858 Bus stop Roseneck or S-Bhf. Hohenzollerndamm Next meeting: Wednesday July 03, 2002, 18 :00 s.t. Peter Florian Institut fr Klinsiche Physiologie, UKBF der FU Berlin "Tight junctions in der Cochlea" Location 1 : UKBF, Institut fr Klinische Physiologie Past meetings: Archive Members Prof. Dr. med. Arneborg Ernst HNO-Klinik Unfallkrankenhaus Berlin Voice: +49 30 5681 2901 Fax: +49 30 5681 2903 Ernst.ORL.UKBerlin@t-online.de Prof. Dr. phil. nat. Alfred H. Gitter Bereich Biophysik u. Bioinformatik(Raum 02.01.05) Fachbereich Medizintechnik Fachhochschule Jena Carl-Zeiss-Promenade 07745 Jena Voice: +49 (0)3641 205-665 Fax: +49 (0)3641 205-601 alfred.gitter@fh-jena.de Prof. Dr. med. Manfred Gross Klinik und Poliklinik fr Audiologie und Phoniatrie UKBF, FU Berlin Voice: +49 30 8445 6812 Fax: +49 30 8445 6855 phoniatrie@ukbf.fu-berlin.de Dr. med. Kai Helling HNO-Klinik und -Poliklinik UKBF, FU Berlin Voice: +49 30 8445 2440 Fax +49 30 8445 4460 kai.helling@medizin.fu-berlin.de Prof. Dr. med. Hans Scherer HNO-Klinik und -Poliklinik UKBF, FU Berlin Voice: +49 30 8445 2431 Fax +49 30 8445 4460 scherer@medizin.fu-berlin.de Prof. Dr. Marianne Vater Institut fr Biochemie und Biologie Universitt Potsdam Voice: +49 331 977 4893 Fax: +49 331 977 4861 vater@rz.uni-potsdam.de Peter Florian Institut fr Klinische Physiologie UKBF, FU Berlin Voice: +49 30 8445 4608 Fax: +49 30 8445 4239 pflorian@zedat.fu-berlin.de Dr. Ingo Scheffler Institut fr Biochemie und Biologie Universitt Potsdam Voice: +49 331 977 4883 Fax: +49 331 977 4861 ischeff@rz.uni-potsdam.de Dr. Dietmar Basta HNO-Klinik Unfallkrankenhaus Berlin Voice: +49 30 5681 3104 Fax: +49 30 5681 2903 dietmar.basta@ukb.de If interested in joining the seminar, please give your address to Alfred H. Gitter Links Acoustical Society of America AG Deutschspr. Audiol. und Neurootol. (ADANO) Association for Research in Otolaryngology (ARO) Deutsche Ges. fr Hals-Nasen-Ohren-Heilkunde Arbeitsgruppe Hrforschung, Uni Giessen Blockpraktikum Hrforschung, HNO Tbingen Prof. Scheich, IfN Magdeburg Processes in Animal Vision A new advanced text on all aspects of the visual system. Major sections on physiology, the photoreceptor cell, the neuron and the performance of the eye. The Neuron: Its processes and Mechanisms. Part of PROCESSES IN BIOLOGICAL VISION Main Home Page Synopsis Tutorial Table of Contents The fundamental neuron Top Level Block Circ. Diagram Standard Human Eye Performance Descriptors COMMUNICATIONS Questions Comments Download Files Links About Us HOMEPAGE of VISION CONCEPTS THE BASIS OF THE NEURAL SYSTEM from PROCESSES IN BIOLOGICAL VISION by JAMES T. FULTON Last date 15 Aug 03 Rhodonine and Activa: See Citation Page INTRODUCTION In developing the theory presented in PROCESSES IN BIOLOGICAL VISION , it was found that there was no satisfactory treatise on the BASIS OF THE NEURAL SYSTEM. The main work was stymied by this situation. It was necessary to overcome this problem and the result is presented here. Two fundamental finding and one major discovery resulted from this effort: The morphologically defined neuron is not the fundamental element of the neural system from a functional perspective. The functional aspects of the neural system are entirely electrolytic in operation. The chemical transport of simple ions, or heavy molecules, at the synapse separating neurons does not play a role in the signaling function of the neural system. The discovery of the active electrolytic semiconductor device, the Activa, provided the key to the understanding of the operation of the neural system. It placed the functional role of the various morphological structures in proper perspective and provided the correct interpretation of the operational phenomena involved. The Activa is a unique biologically based structure that exhibits "transistor action" The term "transistor action" is a term in the Patent lexicon to define a unique quantum mechanical mechanism. The Activa, US Patent 5,946,185, is the electrolytic (biological) equivalent of the man-made transistor. Go to INDEX for the NEURON PAGES Go to MAJOR CONCEPTUAL CHANGES introduced by the Electrolytic Theory of the neuron Go to CONTENTS OF PROCESSES IN BIOLOGICAL VISION related to the neurons. CONTENTS OF PROCESSES IN BIOLOGICAL VISION related to the neurons With the discovery of the Activa, it became possible to interpret the topography of the various neurons from a topological perspective. This led to the definition of the basic mechanisms and morphological forms found in the neural system. This material has been assembled into three Chapters within a PART of the main work: PART C ELECTROCHEMISTRY OF THE NEURON 8. The Basic Neuron of Vision 9. More Complex Neurons 10. The Morphology Electro-physiology of the Neuron Because of the unexpected success of this analysis, there has been considerable spill-over of new knowledge related to the cortical portion of the neural system. To tabulate this material in a preliminary manner, a Chapter 15 of PART D has been introduced to discuss the Higher Level Perceptual Functions. The theory presented here is far more complete and mathematically rigorous than any other presented to date. It takes issue with many concepts that have become dogma over the years through indiscriminate repetition in textbooks and journal articles. Many of these poorly defined dogmatic positions are compared with a more explicit position based on the theory. MAJOR CONCEPTUAL CHANGES The main work introduces three major paradigm shifts affecting concepts held true for the last 50 years, a super extended period considering the rate of changes in other scientific technologies. The second shift redefines the fundamental nature of the neuron. It calls for a extending the Neuron Doctrine of Cajol beyond the realm of morphology to include electrophysiology. A restated Neuron Doctrine [10.8.1] The neuron is the fundamental biologically sustainable unit of the nervous system. It is the minimum viable cellular structure. Each neuron contains one or more fundamental functional (signaling) units internally and one or more external fundamental units connecting it to an orthodromic structure. Each fundamental functional unit consists of an active electrolytic semiconductor device, an Activa, supported by its peripheral electrolytic components. Although the PARADIGM SHIFT related to the neuron is completely supported by the data in the literature, it is so significant that most of the hypotheses found in journal material must be considered obsolete until they are reinterpreted. Most neuron related hypotheses in current textbooks must also be considered obsolete. The PARADIGM SHIFTS, AS A GROUP , lead to a larger set of FUNDAMENTAL PREMISES that form the foundation of this work. The basic shift related to the neuron also leads to an entirely new description of the cytology and function of the specialized photoreceptor cell of the neural system. One premise that is fully documented in Chapter 8 [8.7]is that all known synapses are electrolytic in origin and contain an Activa. If the reader accepts the above premises and the shifts in thinking described, it is suggested that he will be amply rewarded. Many previously undefined phenomena become quantifiable and a large group of new performance descriptors become available. The descriptors are able to describe the vision process and the neural system to a totally new degree of accuracy and precision. A CAUTION Because of the revolutionary nature of some of the material presented, students are encouraged to review the Cautions Page before proceeding. It has been tailored separately for K-12 , lower university and higher level students. Continue to Content Summary on next page This site does not use Frames but is best viewed using version 4.0+ of AOL, Netscape, or Internet Explorer because it does use style sheets and tables. You must have Acrobat Reader on your system to download some of the documents. That program is available free from Acrobat Reader Get NEW TUTORIAL EXPLORE COLOR BLINDNESS EXPLORE HOW HUMANS READ A Beta release CD-ROM is available Copyright 2000 Vision Concepts Brain-Mind.com Everything you ever wanted to know about the brain and the mind, but were afraid to ask. Brain-Mind.com BrainMind.com BRAIN RESEARCH LABORATORY BrainMind.com Everything You Ever Wanted to Know about the Brain, Mind, Evolution, Emotion, Spirituality, Sexuality, NeuroTheology, Astrobiology and The Origin of Life... But Were Afraid To Ask Scientific American Frontiers Learn more about the fascinating human brain and uncover startling new evidence of our brain's ability to change, plus, take a virtual tour of the famous organ. PBS - Scientific American Frontiers:Changing Your Mind Behavioral Neuroscience Memorial to Shirley L. Buchanan and her contribution to behavioral neuroscience research. Includes information about her and other associated scientists, particularly journal publications. The Shirley L. Buchanan Neuroscience Project The Watership Down Behavioral Neuroscience Project In remembrance of Dr. Shirley L. Buchanan Current Research Researchers Donald A. Powell, Ph.D. Shirley L. Buchanan, Ph.D. Louisa Burris, Ph.D. Barbara B. Simon, Ph.D. Edwin Ayers, Ph.D. Jack Ginsberg, Ph.D. The Laboratory History of the Lab Pavlov's Biography Interesting Links Questions Comments Old Friends For thirty years the Shirley L Buchanan Neuroscience Laboratory has been seeking truths regarding the neural correlates of behavior. This page has several objectives in mind: (1) to emphasize Dr. Buchanan's contributions to the neuroscience community, (2) to give a brief history of the laboratory's work and the students and investigators who have been most involved in this lab's research, (3) to make this lab's most salient findings easily accessible, and (4) to provide information about behavioral neuroscience, and to provide well organized links for doing neuroscience research on the web. Exploratorium on Biological Bases of Behavior: Annotated links to sites in neuropsychology and brain science. Includes neuroanatomy, similations of neuron function, brain-based neurological disorders, gender differences in brain structure, and neurological bases of addiction. Exploratorium on Biological Bases of Behavior: Psyc Explorer Lab - Biological Bases of Behavior 2.1 THE NERVOUS SYSTEM AND BEHAVIOR - AMA Explore the American Medical Ass. tutorial site, Atlas of the Body 2.2 Basic Neural Processes Lab and Tutorial Experience a Tutorial by John Krantz on Neural Processes 2.3 The Nervous System Lab Explore the Inner Life of Neurons in this Psy Explorer Lab 2 .4 The Brain Lab and Tutorials Explore the Harvard Whole Brain Atlas and Internet Tutorials on the Brain 2.5 The Brain and Behavior lab Explore Connections between the Mind, Body, Emotions and Behavior 2.6 The Brain and Behavior Laboratory 2 Experience a Lab Simulation of Your Brain and Nervous System 2.7 Neurosciences on the Internet Explore Exceptional Neuroscience Sites and Colleges on the Web 2-8 Brain Research and Neuroscience News Keep Current with Neuroscience News and Research Briefings 2.9 Brain and Behavior : Neurological Disorders Learn about Neurological Disorders and Explore Brain Connections 2.10 Brain and Behavior: Gender Differences Research Brain Differences Between Males and Females 2.11 Fascinating Topics WebLinks: BRAIN AND BEHAVIOR Utilize Weblinks to Explore Links between the Brain and Behavior 2.12 University Brain Labs on the Web Explore Brain Research at University Laboratories 2.13 Forum: Brain, Drugs and Addictive Behavior Topical Exploratoria on Drugs, Addiction, Treatments 2.14 Psyc World Millenium Debate: "Your Brain on Drugs" Debate the Role Control of Drugs in the New Millenium Biological Bases of Behavior Use PsycExplorer to find fascinating links between our minds and bodies. Choose one of the topics and explore the web for exciting information about the biological foundations of behavior. Be sure to read at lea article from 2.8 on keeping current with neuroscience news. Visit a University Lab and explore interactive sites on the brain. Print out at least ten pages of information that you found particularly helpful or fascinating to document your exploration. Write at least a 100 word overview of your PsyExplorer journey. A. PsyExplorer 2.1 THE NERVOUS SYSTEM AND BEHAVIOR Explore Basic Neural Processes and their effect on behavior through interactive sites, tutorials and online original works of famous psychologists. American Medical Association Presents Atlas of the Body Use this interactive guide from Emory University to investigate neuroscience topics. Browse the brain, nervous system and see results of strokes on the brain. http: www.ama-assn.org ama pub category 7140.html The Nervous System Atlas Nervous System Atlas: Groups of Nerves: The Human Brain Lobes of the Brain Side View of the Brain Topic: The Effects of a Stroke on the Brain and Behavior Ever wonder why different people have differing effects of stroke? It all depends on where the brain damage was as is illustrated in this fascinating report on the effects of strokes on behavior. Your Endocrine System and Endocrine Glands Explore the Endocrine System and the network of glands that secrete hormones into your bloodstream, affecting your behavior in dynamic ways. 2.2 Basic Neural Processes Lab and Tutorial Excellent interactive teaching site by John Krantz for learning about the basics of neurological functioning. http: psych.hanover.edu Krantz neurotut.html How Nerve Cells Work Use this tutorial and watch the video of the "Flight of the Neuron" for a fascinating introduction to neurons, the basic structure underlying processes such as sensation, perception and thought http: www.epub.org.br cm n09 fundamentos transmissao voo_i.htm Neuroscience for Kids Exceptional interactive site for "big" kids to learn about the brain and behavior including "Explore the Brain and Spinal Cord" , drug effects and neurological and mental disorders . Explore " experiments and activities" and internet neuroscience resources . http: weber.u.washington.edu ~chudler neurok.html Neuroscience Art Gallery Open up this Art Gallery to "Fear and Defense" to see the response of neurons to the emotion of fear http: www.epub.org.br cm gallery all.htm A. PsycExplorer 2.3 THE NERVOUS SYSTEM A Guided Tour THE HUMAN NERVOUS SYSTEM LAB Take a guided tour of the Chudler Neuroscience Site to develop understanding of your nervous system http: faculty.washington.edu chudler introb.htmltn Introducing the Neuron Use this tutorial index to link to learning modules about your nervous system and neurons. Millions and Billions of Cells Learn about neurons, the basic building block for communication. What Do Neurons Look Like? The Gallery of Neurons Visit the Gallery of Neurons with pretty pictures of different types of neurons in your body. Action Potential Illustrated Neurons carry messages through action potential pathways. Discover the processes here Making Connections at the Synapse : The Art Gallery of Synapse Tour synapses. Like the Gallery of Neurons, this interactive site is fascinating! The Sounds of Neuroscience What do neurons sound like? Enter this audio exploratoria to discover the sounds of neurons at work! Explore Teaching Sites at Other Universities: The Function of the Neuron You are guaranteed to thoroughly enjoy this animnated introduction to the neuron and will marvel at the site as well as the functioning of your neurons! Site by neurologist, Dr. John. http: www.idiom.com ~drjohn neuron.html The Central Nervous System Introducing the Central Nervous System at the University of Rochester. http: www.rit.edu ~caa3045 cnv.html The Inner Life of Neurons Harvard brings you this article with beautiful photo focusing on the inner workings of neurons. http: www.med.harvard.edu publications On_The_Brain Volume4 Number2 SP95In.html End your exploration at this novel site: Neurons and their Growth Cones Watch neurons grow in movies and marvel at neurons at work PsycExplorer 2 .4 THE BRAIN AND BEHAVIOR tutorials Explore the fascinating relationship between the brain and behavior using these brain sites, tutorials and an online guided multimedia tour of the brain and nervous system. Study Tutorial for Structure and Function of the Brain Professor John Krantz of Hanover College has created this first tutorial of the brain to help college students understanding brain functioning. He uses slides from the Harvard Whole Brain Atlas below. http: psych.hanover.edu Krantz neural 021.html Frontal Section of the Brain: http: psych.hanover.edu Krantz neural 021.html Structure of the Brain: http: psych.hanover.edu Krantz neural 023.html Tutorial Quiz on Basic Brain Structure: http: psych.hanover.edu Krantz neural brain01.html Harvards Whole Brain Atlas Truly a phenomenal interactive site to learn about your brain and neural disorders http: www.med.harvard.edu AANLIB home.html See the interactive Normal Brain Structure Site http: www.med.harvard.edu AANLIB cases caseM mr1_t 027.html Unraveling the Mystery of the Frontal Lobes APA article on brain research findings about the frontal lobes and behavior http: www.apa.org psa sepoct96 sb.html PET Brain Atlas UCLA designed this interactive site that includes PET Scan images of the brain in a teaching format. Get your shockwave ready! http: www.crump.ucla.edu PBA A Laymans View Of Brain Chemistry End your study tutorial with this informative tutorial on brain chemistry and behavior. http: www.maui.net ~jms brainuse.html PsycExplorer 2.5 THE BRAIN AND BEHAVIOR lab- Mind-Body-Emotion Connections Mind-Brain Resources This is an excellent neuroscience compendium of resources that link the mind, brain and behavior http: mind.phil.vt.edu www mind.html Brain and Behavior These interactive tutorials on the mind will help you understand the amazing mind-body-emotion connection http: serendip.brynmawr.edu bb Serendip Lab The Brain and Behavior Enter this interactive lab with a free spirit to explore the many relationships between your brain and your behavior! Take a trip or two through options for interactive sites and games. http: serendip.brynmawr.edu bb Brain Facts and Figures Washington University educators developed this interactive teaching site that gives basic facts about the brain and nervous system (literally!). Did you know your brain weighs about 3 pounds! http: faculty.washington.edu chudler facts.html McConnell Brain Imaging Research Site Go to McGill University in Canada to link to brain imaging research http: www.bic.mni.mcgill.ca Syracuse Visible Human Viewer You can actually take a "slice" of a human to learn about contents and relationships at this Java Intensive Site http: library.advanced.org 10348 interact bodyviewer bodyviewer.html Mind-Body Link This short article from Brain Briefings, a publication of the Society for Neuroscience, sites recent evidence that the nervous, endocrine and immune systems are all intricately linked and important to our physical and mental health. http: www.sfn.org briefings mind.body.html 2.6 BRAIN AND BEHAVIOR LABORATORY A PsyExplorer Tour Explore the Brain and Nervous System Excellent tutorials written by professors at Washington. Explore the brain basics, neural system and topical areas such as drugs and mental disorders. http: faculty.washington.edu chudler introb.html BRAIN BASICS Brain Basics http: faculty.washington.edu chudler introb.htmlbb Divisions of the Brain: http: faculty.washington.edu chudler phylo.html Lobes of the Brain: http: faculty.washington.edu chudler lobe.html A Brain Slice: http: faculty.washington.edu chudler sagittal.html On Brain Weight and the Animal Kingdom! http: faculty.washington.edu chudler brainsize.html DO WE HAVE A "SPLIT-BRAIN"? Left-Hemisphere and Right Hemisphere "Brains" http: faculty.washington.edu chudler split.html Functional Divisions of the Cerebral Cortex: http: faculty.washington.edu chudler functional.html Which is your dominant side of your brain? a brain test! http: faculty.washington.edu chudler rightl.html THE SPINAL CORD Explore the Spinal Cord: http: faculty.washington.edu chudler spinal.html THE AUTONOMIC NERVOUS SYSTEM Learn about the sympathetic and parasympathetic systems: http: faculty.washington.edu chudler auto.html PsycExplorer 2.7 NEUROSCIENCES ON THE INTERNET Explore the fascinating growth of the interdisciplinary Neurosciences on the Internet. Explore the wide-ranging studies of the interaction between the mind and body as it applies to all areas of psychology. The Effect of the Internet on Neurosciences How has the Internet revolutionized the neurosciences? How can you find what you want in neuroscience news and how do the neuroscience connect to psychological topics such as sensation, memory, sleep, consciousness? Let the editor of online magazine Brain and Mind tell you from the Brazil center. http: www.epub.org.br cm n05 editori5_i.htm Brain and Mind Index of Online Journal Issues http: www.epub.org.br cm home_i.htm Neuroscience Connections Provides links for the biological foundations of psychology including topics such as sensation and perception, learning and memory, psychopharmacology, sleep and consciousness as well as mental and neurological disorders. http: www.jmu.edu psyc neuro index.html Neuroscience on the Internet Use this searchable index of neuroscience resources or view the latest neurology news. http: www.neuroguide.com Online Neuroscience Books and Articles Link to this up-to-date resource for neuroscience research using online articles http: faculty.washington.edu chudler booksh.html Neurosciences on the Internet Check for scientific information on the biological bases of mental disorders at this search site http: www.neuroguide.com neurodis.html PSYCHOBIOLOGY AND NEUROSCIENCE RESOURCES AT COLLEGE SITES Psychobiology Resources Wellesly College This student learning site offers a good introduction to psychobiology and offers exceptional resources for study. http: www.wellesley.edu Internet psychobio.html Neuropsychology Central Link to resources and college materials in the neurosciences. The "brain" map takes a while to load here! http: www.neuropsychologycentral.com Harvard Undergraduate Society for Neuroscience This society promotes the study of neuroscience and offers web resources, information and a newsletter. http: hcs.harvard.edu ~husn Washington and Lee Web Sources in Psychology, Cognitive Science and Neuroscience Washington and Lee supports cross-disciplinary study at this site and offers excellent resources. http: www.wlu.edu ~web neuro resources.html Biopsychology Indiana University http: www.indiana.edu ~iuepsyc Topics.htmlBiopsychology The Digital Anatomist Exploring The Brain Online Click on any part of this brain to learn more at this amazing site by the University of Washington Seattle. http: www9.biostr.washington.edu cgi-bin DA PageMaster?atlas:Neuroanatomy+ffpathIndex:Splash^Page+2 Neuroanatomy Interactive Syllabus Another interactive exploratory site to learn about neuroscience basics. Click on a part of your neuroanatomy. http: www9.biostr.washington.edu cgi-bin DA PageMaster?atlas:NeuroSyllabus+ffpathIndex:Splash^Page^Syllabus+2 2 - 8 Keeping Current with Mental Health News: 2-8 BRAIN RESEARCH AND NEUROSCIENCE news Keeping Up to Date on Brain Research NewsSources Brain News Search Feature Articles Search this interesting site to find how your brain affects your behavior in hundreds of ways. Choose an article of interest to share with your colleagues. http: www.dana.org dana brainews.htmlv6n8 Brain and Mind Electronic Magazine Keep up to date on brain research with this fascinating online magazine. http: www.epub.org.br cm Brain Briefings The Society for Neuroscience provides these "brain briefings" of the latest neuroscience research and news http: www.sfn.org briefings American Academy Of Neurology Search Engine Search for the latest in neurosciences from a medical perspective. http: www.aan.com search.html BrainWork News This bimonthly newsletter will keep you informed about brain research and psychobiology topics. http: www.dana.org dana brainwrk.html The AMA Health Insight Emory University provides Health Insight. Link to various disorders such as alcohol abuse, Alzheimers, depression . http: www.ama-assn.org consumer specond.htm Harvard Neuroscience Newletter Harvard Medical School publishes this online Neuroscience News and provides archived articles. http: www.med.harvard.edu publications On_The_Brain C. Biopsychology 2.9 Brain and Behavior - Neurological Disorders BIOPSYCHOLOGY TOPIC 1: NEUROLOGICAL DISORDERS Neurological Disorders Resources Exceptional links to information about various neurological disorders including Alzheimers, Parkinsons, Epilepsy, dementia as well as general topics such as sleep disorders, phobias and pain. http: faculty.washington.edu chudler disorders.html Neurological and Mental Disorders: http: faculty.washington.edu chudler introb.html This is an excellent starting place for basic information on neurological disorders and mental disorders with a brain connection. Learn about these interesting biopsychological disorders. Alzheimers Disease Attention Deficit Hyperactivity Disorder( ADHD ) "Brain Attack" - Stroke Schizophrenia Tourettes Syndrome Epilepsy Brain Injuries from Sports Contact Neurosciences on the Internet Human Neurological Disorders Search Engine Use this neuroguide to explore neurological and mental disorders and link to informative resources. This site is a college-level follow-up to the basic information provided in Dr. Chudlers site above and has a search engine that finds resources for over 50 neurological disorders including biopsychology of Autism and other mental disorders. http: www.neuroguide.com neurodis.html PsycExplorer 2.10 BRAIN AND BEHAVIOR- Gender Differences TOPIC: The Two Sexes: Male and Female Brains Are Male Brains and Female Brains the Same? You Guessed it! Read this article on He Brains and She Brains! It looks at the myth and the reality and links to interesting articles on this always popular topic for discussion. http: faculty.washington.edu chudler heshe.html Gender and the Brain The Society of Neuroscience offers these insights into the differing brains of men and women. http: faculty.washington.edu chudler heshe.html APA article on Biology, Sexual Orientation and Homosexuality What influences do biology and social learning have on our sexual orientation? Is homosexuality a mental or emotional problem? The American Psychological Association answers these questions and more for the public. http: www.apa.org pubinfo orient.html PsycExplorer 2.11 Fascinating Topics: WebLinks: BRAIN AND BEHAVIOR Explore the connections of mind and behavior to many interesting topics in the field of psychology. Topic 1: Simulations of Brain Activity and Thinking Computers Learn to Mimic Human Traits APA article A few years ago IBMs computer beat the world champion ches player making many nervous that computers could be programmed to "think" better than humans. Now they are adding perceptual qualities to the programming and more people are getting "nervous". Read this fascinating APA Monitor article : http: www.apa.org monitor mar97 computea.html Topic 2: Serotonin- The Neurotransmitter of the 90s Neurotransmitters excite or inhibit neuron firing and have been a key to the discovery of newer psychoactive drugs used to treat mental disorders. Serotonin is key to many brain-behavior connections in the treatment of depression. This is an example of a scientific article for professionals on the web. http: www.fairlite.com ocd articles ser90.shtml Topic 3: The Brain of Einstein Whatever Became of Einsteins Brain? How was it Different? You can actually link to pictures of Einsteins brain from this site and explore the brain of a genius! http: faculty.washington.edu chudler ein.html Topic 4: Are There Smart Drugs? Can herbs and common " drugs" like coffee (caffeine) increase our mental "strength" and power? Do herbs like Ginko Biloba increase our memory? This interesting introductory article links to other resources. http: faculty.washington.edu chudler smartd.html Topic 5: On Neurotoxins Ever wonder what happens when you get stung by a bee, bit by a spider etc.? This site is all about neurotoxins and how they attack your nervous system. Interesting educational site in case you meet up with a neurotoxin! http: faculty.washington.edu chudler toxin1.html Topic 6: Memory Loss, Aging and Alzheimers This special edition of the Harvard Brain Journal focuses on the neuroscience of memory http: www.med.harvard.edu publications On_The_Brain Volume2 Special SPAlz.html 2.12 University Brain Labs on the Web The Development of the Brain- University of Oregon The Department of Psychology Institute of Neurosciences sponsors this site. Fascinating research both past and present is presented here at this "live" lab. Check to see if anything is happening! Aarons brain also appears here to prove the site designer does have a brain!! http: bdl.uoregon.edu Visit their Brain Anatomy Gallery: http: bdl.uoregon.edu Galleries gallery.html Gross Anatomy Lab at University of Arkansas You can tour the body and get accurate labeled pictures of areas key to this unit such as the brain, eyes, ears etc. Excellent study aid and interesting tour of the body. http: www.science.wayne.edu ~wpoff memory.html PET Brain Atlas UCLA designed this interactive site that includes PET Scan images of the brain in a teaching format. Get your shockwave ready! http: www.crump.ucla.edu PBA Harvards Whole Brain Atlas Truly a phenomenal interactive site to learn about your brain and neural disorders http: www.med.harvard.edu AANLIB home.html See the interactive Normal Brain Structure Site http: www.med.harvard.edu AANLIB cases caseM mr1_t 027.html PsycExplorer 2.13 The BRAIN, DRUGS AND ADDICTIVE BEHAVIORS Explore the relationships between the brain, drugs and addictive behaviors. Explore the effects of drugs on the nervous system and brain and explore the path of addiction. Drugs, Brain and Behavior An Online Book Here is an entire online book. Choose a topic from the online chapter headings. http: www.rci.rutgers.edu ~lwh drugs Neurobiology of Drug Addiction The National Institute of Drug Abuse offers this teaching tutorial on drug addiction http: www.nida.nih.gov Teaching2 Teaching.html They also offer: Facts About Marijuana Society for Neuroscience What are the Effects of Nicotine on the Brain? http: www.sfn.org briefings nicotine.html Addictions Brain Path See the path of addiction, the neural reward system of the brain that is the neural root of all addictions. http: www.sfn.org briefings addiction.html Drug Watch International http: www.drugwatch.org Interesting non-profit organization with an international mission to reduce drug abuse and negative effects on societies worldwide. Includes handouts at: http: www.drugwatch.org dw1.html Links to the Interactive World of Drugs Site Click on any part of the World Map to see what the supply and demand of illicit drugs is in that region. http: www.lec.org WOD Drugs and the Brain The Harvard Neuroscience Newsletter interviews two physicians on the effect of drugs on the brain. http: www.med.harvard.edu publications On_The_Brain Volume2 Special SPAdd.html Effects of Drugs on the Nervous System: Use this guided tutorial to learn basic effects of ingestion of drugs on the nervous system. Learn basic facts about each drug and the extent of problem usage. http: faculty.washington.edu chudler introb.htmldrug Effect of Drugs on the Nervous System: A Grand Study Tour for Novices Alcohol Amphetamines Caffeine Cocaine Ecstasy Nicotine Marijuana LSD (Psychedelics) Heroin Inhalants Help for People Suffering From Addictions: The Web of Addictions Megasite The Web of Addictions is a self-help megasite with information, fact sheets, referral sources and mental health chats for those suffering from drug addictions including alcohol. http: www.well.com user woa Resources are at: http: www.well.com user woa sitesadi.htm Important Web Links for Addictions http: www.well.com user woa aodsites.htm Fact Sheet Links for Facts about Addictions http: www.well.com user woa facts.htm Rolodex for Locating National and Local Groups and Resources http: www.well.com user woa woarollo.htm Why do People Get Hooked on Drugs? This article looks at the neurotransmitter stimulation of each major class of drugs and describes the brain chemistry behind addiction. Dont miss the chart at the end depicting numbers addicted and neurotransmitters involved in each drug type. Some of the numbers of drug users are provided below. http: cgi.pathfinder.com time magazine 1997 dom 970505 medicine.addicted.html HIGH AND LOWS Number who used in the past month HEROIN 200,000 Triggers release of dopamine; acts on other neurotransmitters AMPHETAMINES 800,000 Stimulate excess release of dopamine COCAINE CRACK 1,500,000 Blocks dopamine absorption MARIJUANA 10,000,000 Binds to areas of brain involved in mood and memory; triggers release of dopamine ALCOHOL 11,000,000 abusers Triggers dopamine release: acts on other neurotransmitters NICOTINE 61,000,000 Triggers release of dopamine CAFFEINE 130,000,000* May trigger release of dopamine 2.14 Psyc World University Millenium Debate: "Your Brain on Drugs" Brain and Mind Online Topical Tour and Debate We offer this neuroscience-based tour of your brain on drugs. (not the fried egg TV ad tour!) This is guaranteed to delight and frighten you more as you enter the world of research on the effect of drugs on the mind and brain. We tip our Web hats to this A+ Online Journal, Brain and Mind from Brazil and to Sylvia Cardosa PH.D.and Renato Sabbatini, PH.D. The Pleasure System- Drugs, Behavior and Society This editorial prefaces the journal issue of Brain and Mind which includes fascinating articles on the search for pleasure through brain stimulation and what effects this drug use and abuse has on individuals and society. http: www.epub.org.br cm n08 editorial08-recompensa_i.htm Introduction to Issue by Silvia Helena Cardoso, PhD and Renato M.E. Sabbatini, PhD "We are constantly seeking pleasurable stimuli, such as tasteful foods, an ice-cold beer or the exciting sexual intercourse. This search is associated to a special "brain reward system", thus named by the American neurobiologist James Olds. It is a complex neural network which is activated every time we do something pleasurable, thus causing us to want to do the same thing again. Biologically, it has a very specific and essential function: to assure the survival of the individual and of the species, by giving motivation to behaviors such as feeding, drinking and sexual coupling. Unfortunately, not only normal physiological functions activate this system, but also alcohol and other substances of abuse, sometimes generating a much more intense pleasure than that of natural stimuli.. . As authors Cludio-da-Silva and Rocha-do-Amaral point out in their paper, Drug Abuse, "Whenever a person uses a drug and the effect it produces is somehow pleasant, this effect gets a rewarding quality for that person". In fact, recent studies have demonstrated that it is this brain reward system that underlies the action of drugs such as morphine, heroin, cocaine, alcohol, and even cigarette's nicotine. Although it can initially lead to euphoria and a sensation of well-being, wrongfully giving to the user the idea of a beneficial effect, the chronic influence of drugs on the reward system, by its repetitive use, gives rise to a powerful and inescapable cycle of addiction, many times damaging the brain and other organs. An impressive bit of information which has emerged from the innumerable investigations in this field is that the action of exceedingly small levels of drugs that reach the brain alter behavior in such a powerful manner; by interfering with the normal mechanisms of neurotransmission. A fundamental discovery made in the 60s, which was later confirmed for many other substances of abuse, is that our brain herarchical structures very similar to these very drugs (such as the endorphins, meaning, literally, endogenous morphines!) and chemical receptors in cell membranes which react specifically to these small levels of circulating drugs.. . Interesting focus on societal damage from drugs and on American life as seen through Brazilian eyes: "If we think better, this simple biological fact is behind an infinite number of personal and social dramas and of a probably irreversible damage to all societies which suffer, nowadays, from the heavy toll bring upon them by the illicit economic exploitation of drug addiction. In the USA, for example, it is estimated that at least 63% (1) of all criminal activities ranging from simple thefts to gang- and drug trafick-related assassinations, and an untold number of deaths and diseases, are directly or indirectly caused by the use of drugs of abuse by a relatively small parcel of the population. In countries such as Colombia, and in the great cities of Brazil, these statistics may be even worse. It is, undoubtedly, a scaring epidemic, the greatest tragedy of the end of this century." What will the new millenium bring to this exciting science of the mind and behavior? Will we learn to control our addictive behaviors or will we create more designer drugs to stimulate our brains? What will be the effects on society of our choices? What can we do about, as the Brazilians so aptly put it,"the greatest tragedy of the end of this century." Can we deal with the "irreversible damage to all societies and reverse the heavy toll of criminal activity, death and disease" discussed in this article? Do some exploring with the articles in the above section and resources from this article to answer these very serious questions!! The Pleasure System- Drugs, Behavior and Society This editorial prefaces the journal issue of Brain and Mind which includes fascinating articles on the search for pleasure through brain stimulation and what effects this drug use and abuse has on individuals and society. http: www.epub.org.br cm n08 editorial08-recompensa_i.htm Interactive Tutorial On Drug Abuse Why do people use drugs? What do they actually do to our minds and how do they affect our behavior? Enter this revealing documentary with video clips to see it live! http: www.epub.org.br cm n08 doencas drugs abuse_i.htm The Reward Deficiency Syndrome Watch videos of rats "addicted" to brain stimulation in the pleasure centers of the brain. Muse about the need we may have biologically to "feel good" and be rewarded by stimulation. This is a review of the classic experiment in brain stimulation and reward deficiency syndrome." http: www.epub.org.br cm n08 doencas drugs sindrome_i.html Electrical Stimulation of Brain Centers Often drug use results from a search for brain stimulation. Take a tour of various research clips from studies of electrical stimulation of the brain. http: www.epub.org.br cm n08 doencas drugs videorat_i.htm Effects of Cocaine on the Brain How does cocaine affect our neurotransmitters? See actual effects on this interactive site. http: www.epub.org.br cm n08 editorial08-recompensa_i.htm Action of Alcohol on the Brain Why do people become dependent on alcohol? How does it slow down mental proceses? Watch the effects on this animation but beware, you may not want to drink again when you see this! http: www.epub.org.br cm n08 doencas drugs alcool_i.htm Drugs and the Brain The Harvard Neuroscience Newsletter interviews two physicians on the effect of drugs on the brain. http: www.med.harvard.edu publications On_The_Brain Volume2 Special SPAdd.html Effects of Drugs on the Nervous System: Use this guided tutorial to learn basic effects of ingestion of drugs on the nervous system. Learn basic facts about each drug and the extent of problem usage. http: faculty.washington.edu chudler introb.htmldrug Effect of Drugs on the Nervous System: A Grand Study Tour for Novices Alcohol Amphetamines Caffeine Cocaine Ecstasy Nicotine Marijuana LSD (Psychedelics) Heroin Inhalants BESA Innovators in digital EEG and MEG software for research and clinical applications. BESA :: top frame This website requires Flash 5 for navigation. Please download the Flash plug-in 5 or higher at www.macromedia.com . For further questions please contact our support office at: support@besa.de ! MEGIS Software GmbHBahnhofstrae 9582166 Grfelfing - Germany Synapse Web Scientific resources for the study of synapse structure and function, including tutorials on neurocytology, software, 3D data, and reconstructions from serial electron microscopy. synapses.bu.edu synapses.bu.edu John C. Fiala | Links | Reconstructions | Software | Usage Synapses News: 11 15 05 Users Group gets v1.0.5.8 Members of the Reconstruct Users Group can download an updated version of Reconstruct from the group's Files section. 9 20 05 Spines don't have mitochondria Analysis using synapses.bu.edu software shows mitochondrial network in dendrites does not invade simple spines in the hippocampus. 9 18 05 Synapse speed depends on synapse shape Reconstruct used to show developmental speed-up of mEPSPs is due to increased compactness of postsynaptic receptors. 8 15 05 Run under WINE on Linux systems Users have verified WINE for running Reconstruct under Mandriva Linux w KDE 3.3.2. Get Reconstruct version v1.0.5.5 from the Users Group for proper cursor support. 7 1 05 Reconstruct v1.0.5.0 released! New version is available from synapses.bu.edu with an example series, or from the Reconstruct Users Group without the example data. 3 25 05 Reconstruct appears in J Microscopy Fiala JC (2005) Reconstruct: a free editor for serial section microscopy. J Microscopy 218:52-61. 2 16 05 New Reconstruct Developers Group Qualified developers can directly participate in open source development of Reconstruct. 1 26 05 Synapse size = Efficacy Reconstruct used in study showing synaptic area is directly related to the number of functional AMPA receptors in single synapses of cerebellum. Connect to Synapse Web Copyright 2004-2005 by John C. Fiala, Ph.D. Send comments or questions regarding content to: fiala@bu.edu Any use of materials should acknowledge the source as: synapses.bu.edu, Boston University Last Updated: 11 15 05 Evogen LC Offering a compilation of current research on: genetics, brain and mind. Biojuris Richard M. Lebovitz, 2005 The W.U.S.M. Neuroscience Tutorial Excellent tutorial for neuroscience. The W.U.S.M. Neuroscience Tutorial The Washington University School of Medicine Neuroscience Tutorial An illustrated guide to the essential basics of clinical neuroscience created in conjunction with the first-year course for medical students. Please select a section: Coronal and horizontal sections Basic visual pathway Basic somatosensory pathway Basic motor pathway Eye and retina Central visual pathways Auditory and vestibular systems Somatosensory pathways from the body Somatosensory pathways from the face Spinal motor structures Brainstem nuclei of cranial nerves Basal ganglia and cerebellum Hypothalamus and autonomic nervous system Medial temporal lobe and memory Sleep and language Where is...? Other interesting links created by Diana Weedman Molavi, PhD at the Washington University School of Medicine Photographs from the collections of Dr. Joel Price Dr. Harold Burton and Dr. David Van Essen, coursemaster Department of Anatomy and Neurobiology Comments: susan@pulvinar.wustl.edu Washington University Program in Neuroscience http: neuroscience.wustl.edu Copyright 1997 Hardin MD: Neurology Neurosciences Lists of Internet sources in neurology, neurosurgery, and neurosciences, and nervous system diseases. Hardin MD : Nervous System Neurology The Octopus Research Group Research group, at the Hebrew University of Jerusalem, working on the motor control of the cephalopod's (octopus vulgaris) flexible arm. The octopus research group at the Hebrew University of Jerusalem Copyright , 1997, The Hebrew University of Jerusalem. All Rights Reserved. - Last updated Aug 26, 2004. Advanced Brain Monitoring Develops portable brain monitoring devices that interpret the brain's electrical activity and identify levels of alertness or drowsiness, using patent-pending B-Alert software. Advanced Brain Monitoring, Inc. home about products research sleep apnea news resources contact Meeting the Challenge Head-on: Easy, accurate, and cost-effective systems for sleep apnea and safety What's New: Press Release Clinical Study Abstract October Newsletter Getting Started: Healthcare Providers Consumers Patients Downloads: Company Brochure Patient OSA Guide Advanced Brain Monitoring, Inc. has developed patented technologies to address sleep apnea, memory dysfunction, and alertness monitoring. Advanced Brain Monitoring products combine laboratory level accuracy with the portability, ease of use, and affordability of consumer electronics. The Apnea Risk Evaluation System (ARES) and EEG Technologies provide a synergistic approach to the assessment of sleep and neurological disorders, including diagnosis, measurement of treatment outcomes, and patient management. Advanced Brain Monitoring's enabling technologies can be integrated into numerous products with multiple applications and markets. Advanced Brain Monitoring offers physicians, dentists, industrial transportation companies, and consumers solutions to the problems of workplace fatigue, diagnosis of sleep and neurological disorders, and evaluation of pharmaceuticals. home | about | products | research | sleep apnea | news | resources | contact Copyright Advanced Brain Monitoring, Inc. NeuroDetective Contract research firm specializing in testing the functional efficacy of potential CNS therapeutics in animal models, with an additional focus on behavioural evaluation of genetically altered animals. Testing of CNS Therapeutics, Behavioural Phenotyping Brain and Behavior, from Serendip Interactive exhibits, forum, and links aimed at exploring the observational basis and significance of the assertion that the nervous system underlies all aspects of human behavior and experience. Brain Behavior Serendip Search BRAIN AND BEHAVIOR Who are you? Who are they? How did you get to be that way? How did they? What can you and they do about it? Lots of people wonder about these questions (whether they talk about it or not). And, over the centuries, people have thought of lots of different ways to try and answer them ... without, somehow, ever quite getting to the heart of the matter. Drawing by Rachel Grobstein The Brain - is wider than the Sky - For - put them side by side - The one the other will contain With ease - and You - beside- The Brain is deeper than the sea - For - hold them - Blue to Bue - The one the other will absorb - As sponges - Buckets - do The Brain is just the weight of God - For - Heft them - Pound for Pound - And they will differ - if they do - As syllable from Sound - Emily Dickinson (1830-1886) Over the past century, it has begun increasingly to look as if the heart of the matter might be ... the brain, as Emily Dickinson suggested nearly one hundred and fifty years ago. Or, more properly, that the heart of the matter might be the nervous system, of which the brain is a part. Is it possible that everything that one is, does, and experiences is a function of the brain? that one is who one is because of what one's brain is? that becoming something different means changing the brain? And, if so, what are the implications of this? Do we lose something, or is the brain actually big enough, as Dickinson suggested, to contain everything? If so, what might we be able to do that has never before been possible? What are the risks, the gains, the new landscapes which would be opened to explore? The interactive exhibits and other materials collected here are intended to make it possible for you to share some of the kinds of experiences which suggest that indeed the nervous system may be the heart of the matter. And to think with us about their implications, and the new questions they raise. Have some experiences, think about them, let us and others know what new thoughts and questions occur in your mind (brain?) in our Forum area, so we can all think together about these issues. Interactive Exhibits Time to Think? : Is brain = behavior? an experiment using reaction times, with capability of doing your own research, requires Shockwave plugin Pattern Detection and Serendipity : Can you find Serendip? a game with different searching strategies, uses CGI programing Competition and Cooperation , aka Prisoners' Dilemma: Cooperate or compete? a game studied by people in a variety of disciplines, including biology, sociology and public policy, uses CGI programing Blindsight: Seeing What You Don't See : Do you need to know you saw it to have seen it? a blindsight experiment, requires Java capable browser Seeing More Than Your Eye Does : Does your brain make up stories? a "blindspot" experiment Seeing More Than Your Eye Does, continued - Map your own blindspot (Java applet, requires Internet Explorer) Tricks of the Eyes, Wisdom of the Brain : Does your brain throw things away? a lateral inhibition network experiment, with optical illusions, requires Java capable browser Simple Networks, Simple Rules: Learning and Creating Categories : Can simple things learn? an experiment with a perceptron learning algorithm, requires Java capable browser The Free Will Problem : Can you control what you do? an experiment with ambiguous figures Comparative brain organization , exhibit under development Ambiguous Figures , exhibit under development Remember the Source : How is your memory? an experiment in human cognition and memory, requires Flash 6 plug-in Resources Serendip, Brain, and Behavior - an article on a neural uncertainty principle, published in The Encyclopedia of Human Behavior, Volume 4 (V.S. Ramachandran, editor), Academic Press, 1994 (pp 447-458) Genes, Brains, Behavior - resources and discussion Mind and Body: Ren Descartes to William James - an exhibit by Robert Wozniak Brain Matters , A question and answer forum for K-12 students Neurobiology and Behavior: A course and a conversation - Biology 202 at Bryn Mawr College Multiple reviews of Descartes' Error, by Antonio Damasio I began writing this book to propose that reason may not be as pure as most of us think it is or wish it were, that emotion and feelings may not be intruders in the bastion of reason at all: they may be enmeshed in its networks, for worse and for better. Notes for Talks Parallel Changes in Thinking About the Brain and About Education Genes, Networks, Behavior, and Beyond: Thinking Backwards About the Brain and Education Brain Size and Evolution Germinal Zones (places to look in search of new insights into brain and behavior) Brain and Behavior: Index of Topics Buddhist Meditation and Personal Construct Psychology The Gift of Saturn - Creativity and Psychopathology Music, The Brain, and Ecstacy, by Robert Jourdain (a book review) Exploring the Consciousness Problem: - a course and resource base Mental Health , an evolving resource base The "Nature" of Desire , a senior thesis on the neurobiology of love by Rachel Berman BMC '01 Measure for Measure: An Artistic Exploration of Eating Disorders, Body Image, and the Self , by Janna Stern The Novelist and the Neurobiologist: A Conversation About Story Telling Additional Resources Elsewhere Neurobiology at Serendip National Insitutes of Mental Health has excellent online booklets on a variety of topics including Learning Disabilities, and Attention Deficit Hyperactivity Disorder. Neuroscience for Kids , a nice set of activities and resources Neuroethics at Penn | Brain and Behavior Forum | Brain and Behavior | Serendip Home | Send us your comments at Serendip by Serendip 1994-2005 - Last Modified: Tuesday, 18-Oct-2005 12:03:17 EDT CNS Healthcare - Clinical Neuroscience Solutions Advanced evaluations, treatments, monitoring, education, for those with psychiatric and neurological diseases. CNS Healthcare - Leaders in psychiatric and neurological clinical research CNS Healthcare Leaders in psychiatric and neurological clinical research. Clinical trials for all ages... Alzheimer's Disease Attention Deficit Hyperactivity Disorder Bipolar Disorder Depression Generalized Anxiety Disorder Obsessive-Compulsive Disorder Panic Disorder Schizophrenia Sleep Disorders and more Clinical Neuroscience Solutions, Inc. Corporate Headquarters: CNS Healthcare 5401 South Kirkman Road Suite 480 Orlando, FL 32819 Toll Free: 1-866-CNS-HLTH 1-866-267-4584 Contact our webmaster at: webmaster@cnshealthcare.com Copyright 2002-2003, Clinical Neuroscience Solutions, Inc. All Rights Reserved. Ion Channels, Transmitters, Receptors, and Disease Extensive review of ion channel biology and related neuromuscular pathology - from Washington Univ.-St. Louis. Ion Channel Diseases Front , Search , Index , Links , Pathology , Molecules , Syndromes , Muscle , NMJ , Nerve , Spinal , Ataxia , Antibody Biopsy , Patient Info ION CHANNELS, TRANSMITTERS, RECEPTORS DISEASE Channels disorders Anions ATPase Calcium Chloride Concepts Cyclic nucleotide-gated Gap junctions Long QT Syndromes Magnesium Mitochondrial solute carriers Na+, K+, Cl- Co-transporters Potassium K+ H+ ATPase Proton-gated Sodium Na+ H+ exchangers Toxins Transient receptor potential Channel binding proteins Transmitters Receptors Acetylcholine ATP Capsaicin Catecholamines Dopamine Glutamine Glycine Purines Diagrams CHANNEL TYPES: General 9 Extracellular ligand-gated channels : Nicotinoid 5 Homologous polypeptide subunits Subunits have 4 membrane spanning regions Ligands: Neurotransmitters Specific receptors Nicotinic AChR GABAA GABAC Glycine 5-HT3 Glutamate activated anionic channels Types: NMDA; AMPA; Kainate 4 Homologous subunits Intracellular ligand-gated channels Ligands: cAMP, cGMP, Ca++, G-proteins, Phosphorylation Voltage-gated channels 4 domains Na+ Ca+ channels: In single polypeptide chain K+ channel: Tetramer of 4 similar subunits Each domain has 6 membrane spanning regions S4 sequence Contains + charged amino acids (lysine and or arginine) "Senses" voltage across membrane: Regulates pore opening Selective channel pore (Bacterial K+ channel model) Dimensions: 12 long; 3 wide Lined by main chain oxygen atoms Ion selectivity: Na+ , Ca++ or K+ Inward rectifier P domain: "Selectivity filter" 2 Flanking transmembrane region Homo- or heterooligomers in membrane Ion selectivity: K+ Gap junction channels 6 polypeptide subunits Each subunit has 4 membrane spanning regions ATP gated channels : 3 Homologous polypeptide subunits CHLORIDE CHANNELS Principles Disorders Chloride channels: Principles 14 Anion channels: General Classification schemes Localization: Plasma membrane vs. vesicular Single-channel conductance Mechanism of regulation Molecular structure Function Allow the passive diffusion of negatively charged ions along electrochemical gradient May conduct other anions (e.g., I- or NO3-) better than Cl- Often called Cl- channels because Cl- is the most abundant anion in organisms May perform functions in plasma membrane or in membranes of intracellular organelles Functions often related to transport of charge Cl- does not seem to play a role as intracellular messenger Cl- channel gating may depend on Transmembrane voltage: Voltage-gated channels Cell swelling Binding of signaling molecules: Ligand-gated anion channels of postsynaptic membranes Ions [e.g., Anions, H+ (pH), or Ca++]: Intracellular Cl- concentration may regulate channel activity Phosphorylation of intracellular residues by various protein kinases Binding or hydrolysis of ATP General function of Cl- channels in tissues Muscle: Contributes to resting conductance; Stabilizes resting potential; Loss produces myotonia Smooth muscle: Opening of Cl- channels leads to depolarization Structural classes of Cl- channels Extracellular ligand-gated Cl- channels (ELG) 4 transmembrane domains in each subunit Receptors function as pentamers Types Post synaptic GABA Glycine receptors Cystic fibrosis transmembrane conductance regulator (CFTR) Family: ATP-binding cassette (ABC) transporters Transmembrane domains: 2 Sets of 6 Sets separated by a cytoplasmic region with nucleotide binding fold (NBF1) regulatory R domain Channel opening is controlled by Intracellular ATP Phosphorylation by cAMP- or cGMP-dependent kinases Voltage-gated chloride channels (CLC) Membrane-associated part of CLC channels is composed of 17 -helices Helix A is not inserted into the membrane Most of the helices are not perpendicular to the membrane, but severely tilted Helices may not span the width of the bilayer Carboxy terminus of eukaryotic CLC proteins has two CBS domains Unspecified role in protein-protein interaction CLC channels are dimers: Each monomer has one pore (double-barreled channels) CLC-K proteins Associate with the -subunit barttin which spans the membrane twice CLC channel types CLC-1 Skeletal muscle, Placenta Voltage stabilization Mutation disorders: Myotonia ; Paramyotonia CLC-2 Ubiquitous Cell volume regulation Activated by hyperpolarization, cell swelling acidic pH Mutation disorders: Idiopathic generalized epilepsies CLC-3 Brain, Kidney (Type B intercalated cells), Skeletal muscle, Lung, Retina Intracellular Endosomes Synaptic vesicles Knockout: Degeneration of hippocampus retina CLC-4 Muscle, Brain, Heart, Kidney, Retina Vesicular channel CLC-5 Kidney (Type A intercalated cells) Endosomal channel Renal endocytosis ? Cl- reabsorption CLC-6 Ubiquitous Intracellular CLC-7 Brain; Testes; Skeletal muscle; Kidney Lysosomal Mutations: Osteopetrosis ClC-0: Torpedo electric organ Cl- channel ClC-K barttin channels: Transepithelial transport in kidney inner ear CLC-K1 (CLCN-KA) : Kidney Transepithelial Cl- transport Location: Thin ascending limb of Henle loop in renal inner medulla Plays role in urine concentration CLC-K2 (CLCN-KB) Kidney ? Cl- reabsorption Bartter syndrome types 3 4 Nucleotide sensitive chloride channel (CLNS1A) : Volume sensitive Chloride intracellular channels General Location: Nuclear or Plasma membrane No membrane spanning domains Found vacuolar organelles Function: Electrolyte composition Acidification of intravesicular spaces CLIC1 : Nuclear CLIC2 : Skeletal muscle; Fetal liver CLIC3 : Plasma membrane; Interacts with Erk7 CLIC4 : Brain, Heart, Placenta, Skeletal muscle CLIC5 : Heart; Skeletal muscle Calcium activated: Mediate a calcium-activated chloride conductance CLCA1 : Intestinal basal crypt epithelium goblet cells Lung-endothelial cell adhesion molecule-1 (Lu-ECAM-1) CLCA2 : Lung trachea Inhibitors: DIDS, Dithiothreitol, Niflumic acid, Tamoxifen CLCA3 : ? Does not function as a channel protein Also see Anion transporters Na+, K+, Cl- Co-transporters Chloride channels: Disorders Myotonia congenita (CLC-1) Dominant (Thompsen) Recessive (Becker) Myotonic Dystrophy ( DM1 ; DM2 ): Expanded CUG or CCUG repeats Retained in nucleus Disrupt splicing of chloride channel (ClC-1) pre-mRNA Epilepsy CLC-2 Absence epilepsy: Childhood Juvenile Myoclonic epilepsy, Juvenile Epilepsy with grand mal seizures on awakening Gamma-aminobutyric acid (GABA) receptors l GABA receptor, -2 subunit(GABRG2) ; Chromosome 5q31.1-q33.1; Dominant Generalized epilepsy with febrile seizures plus, type 3 Childhood absence epilepsy Febrile seizures Renal tubular disorders (CLC-5 ) Hypercalciuric nephrolithiasis X-linked recessive Nephrolithiasis Dent disease Nephrogenic diabetes insipidus (Mouse): (CLC-KA ) Bartter's syndrome (CLC-KB ) Cystic fibrosis (Epithelial chloride channel ) Osteopetrosis, infantile, malignant : CLC-7 Angleman or Prader-Willi: GABAAB3 receptor subunit SLC26A4: Transporter of chloride iodide Non-syndromic deafness, congenital Pendred syndrome Alcohol non-tolerant rat: GABA6 receptor subunit Glioma Cl- channels upregulated in glioma cells High grade (poorly differentiated) tumors also lose Na+ channels Toxin: Chlorotoxin (Scorpion) SODIUM CHANNELS Figure Principles: Na+ channels Exchangers Non-voltage-gated Voltage-gated Na+ channel disorders Sodium channels: Principles Types: Voltage-gated ; Non-voltage-gated ; Exchangers Voltage-gated Na+ channels Function Generate current to overcome membrane capacitance resistance Generate (Upstroke) Propagate self-regenerating action potential Associated proteins AnkyrinG Neurofascin Localization Clustered at axon initial segments, nodes of Ranvier Post-synaptic folds of NMJ AnkyrinG necessary for clustering Structure: Often 12 heterotrimer subunits Structure : 4 repeated domains; Each with 6 membrane spanning subunits; Glycosylated Function: Forms ion pore; May be sufficient for funtional Na+ channel Voltage sensor on 4th transmembrane domain Different subtypes: Specific tissue localization SCN1A (1; I) : Nav1.1 High levels in brain Blockers: Tetrodotoxin ; Saxitoxin SCN2A1 (2; II) : Nav1.2 Most abundant form in brain Peripheral nerve: Initial segment; Nodes of Ranvier Blockers: Tetrodotoxin ; Saxitoxin Mutations: Seizure disorder SCN2A2 High levels in brain SCN3A (3; III) : Nav1.3 High levels in brain Blockers: Tetrodotoxin; Saxitoxin Downregulated by: NGF; GDNF SCN4A (1) : Nav1.4 High levels in muscle Blockers: Tetrodotoxin; -conotoxins GIIIA, GIIIB, GIIIC Diseases : Hyperkalemic periodic paralysis, Paramyotonia, Myotonia, Myasthenia SCN5A : Nav1.5 Heart; Initial phase of upstroke on EKG Skeletal muscle: Denervated Tetrodotoxin Saxitoxin resistant Diseases Long QT syndrome 3 Progressive cardiac conduction defect (PCCD2) Congenital non-progressive heart block SCN7A : Nax Heart; Uterus; Skeletal muscle (Fetal Denervated) SCN8A (PN4) : Nav1.6 Brain Spinal cord Primary channel at nodes of Ranvier axon initial segments Physiology Currents: Fast transient; Smaller persistent (Contribute to intrinsic burst activity) Upregulation: Might produce hyperexcitability Diseases: motor endplate disease (med) mouse ; dmu mouse SCN9A (PN1) : Nav1.7 Similar to rat PN1: Dorsal root ganglia; Neuroendocrine (Adrenal Thyroid) Tetrodotoxin (TTX) sensitive Disease: Familial erythermalgia SCN10A (PN3; SNS) : Nav1.8 Depolarized activation potential Kinetics: Slow inactivation; Rapid repriming Tetrodotoxin resistant Location: Small sensory neurons in PNS Upregulated by: NGF; GDNF Clinical association: Pain sensitization SCN11A (NaN) : Nav1.9 Spinal sensory neurons: Dorsal root Trigeminal ganglia Tetrodotoxin resistant Upregulated by: NGF; GDNF Channel openining (rapid) stimulated by BDNF via BDNF binding to TrkB receptor Clinical association: Pain sensitization Other: Na-G (Glia); hNav (Heart) subunits General function: Regulate ion-conducting -subunits SCN1B (1) Binding to -subunit by non-covalent linkage Associates with different forms of -subunit in brain, heart skeletal muscle Provides inactivation kinetics to Na+ channel Disease: Generalized epilepsy with febrile seizures + SCN2B (2) Binding to -subunit by disulfide bond covalent linkage 1 transmembrane domain N-terminal similarity to contactin, a neural adhesion protein CNS localization SCN3B Location: Brain, especially hippocampus; Adrenal; Kidney Function Hyperpolarizing shift in voltage-dependence of inactivation Modulates subunit: Increases fraction of channels operating in fast-gating mode SCN3B inactivates channel opening more slowly than SCN1B SCN4B Alters channel properties of SCN2A Shifts the voltage dependence of activation in toward hyperpolarization No change in voltage dependence of inactivation Non-voltage-gated Na+ channels: Amiloride sensitive SCNN: Epithelial sodium channel Functions Control Na+ resorption Role in taste perception Heterotrimer: or Structure : 2 transmembrane domains Blockade: Amiloride Subunits SCNN1A () : Pseudohypoaldosteronism I SCNN1B () : Pseudohypoaldosteronism (Liddle syndrome) SCNN1D () SCNN1G () : Pseudohypoaldosteronism (Liddle syndrome) Degenerins: Epithelial Na+ channel family Characteristics Amiloride sensitive Neuronal: Brain; Spinal cord Function: Mechanosensory channels Permeable to Na+, K+ Li+ Mutations: Activate channels cause neurodegeneration in C. elegans Types: Acid-sensing ion channels BNAC1 (ACCN1) : Cation channel; Abundant in brain neurons BNAC2 (ACCN2) : Brain neurons BNAC4 : Expressed in pituitary gland See: Proton-gated ion channels Sodium Hydrogen exchangers Function: Eliminate acids from intracellular space Activation: Low intracellular pH Inhibition: Amiloride Types NAH1 (SLC9A1) Ubiquitous expression Functions: Regulation of intracellular pH cell volume Mouse mutant Slow wave epilepsy (3 Hz); Ataxia Pathology: Cerebellum (Deep nuclei) brainstem NAH2 (SLC9A2) Location: Intestine; Kidney Function: Na+ ion absorption into mitochondria NAH3 (SLC9A3) : Insensitive to amiloride NAH4 (SLC9A4) : Stomach NAH5 (SLC9A5) : Brain, Testis, Spleen, Skeletal muscle SLC9A6 : Location: Brain Skeletal muscle Other tissues Function: ? Mitochondrial SLC9A7 : 12 N-terminal alpha-helical hydrophobic membrane-spanning segments Location: Occipital lobe; Skeletal muscle; Secretory tissues Functions Amiloride-insensitive, benzamil-sensitive influx of Na+ or K+ for H+ Cation homeostasis function of the trans-Golgi network Other Na+ exchangers SLC5A Sodium-glucose transporters SLC5A1 : Glucose Galactose malabsorption SLC5A2 : Renal Sodium myoinositol cotransporter (SLC5A3) Na+ I- symporter (SLC5A5) : Congenital hypothyroidism Sodium-dependent multivitamin transporter (SLC5A6) SLC24 Sodium Potassium Calcium exchanger (SLC24A1) External link: UCLA anesthesia Sodium channels: Disorders Skeletal Muscle SCN4A, -subunit Hyperkalemic periodic paralysis Hypokalemic periodic paralysis Paramyotonia congenita Myotonia Fluctuans Myotonia Permanens Acetzolamide-responsive myotonia Malignant hyperthermia Myasthenic syndrome Monensin overdose: Rhabdomyolysis SCN8A (PN4) Diseases: motor endplate disease (med) mouse ; dmu mouse Peripheral nerve Localization of voltage-gated Na+ channels RI: Soma RII: Axonal initial segment nodes of Ranvier Hereditary SCN9A : Familial erythermalgia Immune Anti- GM1 ganglioside antibodies Multifocal Motor Neuropathy Acute motor axonal neuropathy ? Guillain-Barr CIDP Nerve injury Neuromas: Accumulation of Na+ channels on axons in neuromas Nerve transection Down regulation: SCN10A ; SCN11A Up regulation: SCN3A Contributes to hyperexcitability (Allodynia; Hyperesthesia) Na+ channel toxins Brain Spinal Cord subunit: SCN1A : Fever associated seizures Generalized epilepsy with febrile seizures plus, Type 2 (GEFS+2) Mutations Missense Location: S4 S5 transmembrane segments Mutation action: Disrupts channel inactivation Inheritance: Dominant Clinical: Mild seizure disorder Myoclonic Epilepsy of Infancy: Severe Most mutations De novo Truncating type Disease mechanism: ? Haploinsufficiency Clinical: Ataxia; Severe seizures (Onset 2 to 6 months); Mental retardation Infantile spasms subunit: SCN2A1 Seizure disorders Benign familial neonatal-infantile Febrile Afebrile Seizure disorder in mice Mutation action: Disrupts channel inactivation subunit: SCN8A Motor endplate disease (med) in mice subunit: SCN1B Generalized epilepsy with febrile seizures + (GEFS+1) Mutation action: Disrupts channel inactivation Cardiac - subunit: SCN5A Long QT Syndrome ( LQT3 ) Idiopathic ventricular fibrillation (IVF) Progressive cardiac conduction defect (PCCD2; Lenegre disease) Clinical syndrome: Syncope; Right bundle branch block Genetics DelG5280 Other locus: Chromosome 19q13.3 Non-progressive congenital heart block Epithelial, Nonvoltage-gated, subunits SCNN1A SCNN1B Pseudohypoaldosteronism (Liddle's syndrome; Hereditary hypertension) Thyroid Na+ I- symporter (SLC5A5) : Congenital hypothyroidism Endocrine Sodium-glucose transporter 1 (SLC5A1) : Glucose galactose malabsorption Neoplasms: Voltage gated Na+ channels Present in small cell lung cancer cell lines Associated with invasion by prostate cancer cells in vitro. Na+ channel Toxins 1 Guanidinium: Saxitoxin ; Tetrodotoxin Polypeptide Scorpion toxins ( ) Sea anemone toxins Conotoxins ( ) Lipophilic: Brevetoxins (Red tide), Veratridine Aconitine: Open Na+ channels Batrachotoxin; Ciguatoxin ; Grayanotoxin Drugs: Lidocaine ; Phenytoin CALCIUM CHANNELS Ca++ channel disorders Ca++ channel: Figures Types Voltage-gated Ca++ channels Classes Principles Ca++ sensors Intracellular activation : Ryanodine + Ligand gated Other Ca++ channels l Voltage-gated Ca++ entry channels: Principles Ca++ channels contain 4 or 5 distinct subunits -1 subunits Subtypes : Numerous; Different tissue peptide specificity 1A (CACNA1A; P Q type ; Cav2.1) : Brain, Motor neurons, Kidney 1B (CACNA1B; N-type ; Cav2.2) : CNS, PNS 1C (CACNA1C; L-type ; Cav1.2) : Heart, Fibroblasts, Lung, Smooth muscle 1D (CACNA1D; L-type ; Cav1.3) : Brain, Pancreas, Neuroendocrine 1E (CACNA1E; R-type ; Cav2.3) : Brain, Muscle (NMJ) 1F (CACNA1F; Cav1.4) : Retina 1G (CACNA1G; T-type ; Cav 3.1)) : Brain 1H (CACNA1H; T-type ; Cav3.2) : Kidney; Liver; D hair mechanoceptors 1I (CACNA1I; T-type ; Cav3.3) : Brain 1S (CACNA1S; L-type ; Cav1.1) : Skeletal muscle ; L-type DHP receptor Location: Transmembrane Functions Voltage sensor Ca++ selective pore: Conductance Structure: Consists of 4 internal repeated domains (I-IV) Domain I: responsible for channel activation kinetics Each domain contains 6 -helical transmembrane regions (S1-S6) S4: Positively charged; Forms part of the voltage sensor 2 additional domains between S5 S6: Form pore region of channel Verapamil nifedipine bind Helix 5 6 regions of domain III Sequence after helix 6 of domain 4 Non N-glycosylated Size: 160-273kD Lambert-Eaton myasthenic syndrome : IgG binds to domains II IV of 1A subunit Binding drugs: Dihydropyridines; Verapamil; Diltiazem Other subunits: Modulate channel functions 2 (CACNA2D1) Cell location: Membrane spanning Structure 2 : Derived from same gene Linked by disulfide bridges Glycosylated extensively on extracellular domains Size: 140-170kD Function: Regulatory Increases amplitude of Ca++ currents Binding drug: Gabapentin Skeletal muscle, Heart, Brain, Ileum Related subunit types CACNA2D2 : Lung Testis Brain, Heart, Pancreas CACNA2D3 CACNA2D4 Associated with coexpressed CACNA1C CACNB3 Expressed at high levels in heart skeletal muscle (CACNB) Location: Intracellular; Cytoplasmic Size: 52-78kD Subtypes 1 (CACNB1) : Skeletal muscle, Brain, Heart, Spleen 2 (CACNB2) : Brain, Heart, Lung, aorta 3 (CACNB3) : Many tissues 4 (CACNB4) : Brain, Kidney Subtypes associate with different 1 subunits in membrane 1 associates with 1S 1B associates with 1B 1E 4 associates with 1A Functions: Regulatory Has cAMP-dependent protein kinase phosphorylation sites Modifies current, voltage dependence activation inactivation (CACNG) Cell location: Membrane spanning; No cytoplasmic domain Size: 32kD Subtypes CACNG1 () : Skeletal muscle, Neuronal, Lung CACNG2 (2) : Neuronal CACNG3 CACNG4 CACNG5 CACNG6 CACNG7 CACNG8 Functions: Regulatory Produce small increase in peak Ca++ current activation rate Shift activation to more hyperpolarized membrane potentials Ca++ channel classes (Voltage-gated): Related to -1 subunit L-type (Long lasting) Ca++ channel Subunits : 1C, 1D, 1F, or 1S, 2, 3a Blockade Sensitive to dihydropyridine (DHP) agonists and antagonists Also blocked by phenylalkylamines (verapamil), benzothiazepines (diltiazem) calciseptine Activation: Strong depolarization Inactivation by depolarization: Little Localization Skeletal muscle: 1S Brain (Neuronal soma proximal dendrites): 1D Cardiac muscle: 1C Neuroendocrine: 1D Retina: 1F General function in muscle: Excitation-contraction coupling Cav 1.1 (A1S): Skeletal muscle; Also acts as voltage sensor Cav 1.2 (A1C): Heart Smooth muscle Diseases N-type Ca++ channel Subunits : 1B, 2, 1b Activation: Strong depolarization Inactivation: Slow Blockade: w- conotoxins GVIA (Strong; Irreversible) MVIIA DHP insensitive Neuronal localization: Presynaptic Constituents: No subunit; Novel 100 kd subunit Modulation 17 Enigma homolog (PKC binding protein) interacts with PKCe N-type Ca++ channels Allows modulation of Ca++ channel activity by PKCe Function: Transmitter release from presynaptic nerve terminals Diseases P-type Ca++ channel Subunits : 1A, 2, 4a Activation: Strong depolarization Inactivation: Slow Blockade: Funnel web spider venom; w-agatoxin IVA; w-conotoxin MVIIC Insensitive to DHP w-conotoxin GVIA Localization Neuronal presynaptic High concentration of 1A subunit in cerebellum: Purkinje cells Neuromuscular junctions Function: Transmitter release Diseases Q-type Ca++ channel Subunits : 1A, 2, 4a 1A subunit is splice variant of 1A in P-type channel Activation: Strong depolarization Inactivation: Slow Blockade: ? more sensitive to w-conotoxin MVIIC than P-type Location: Cerebellar granule cells; Hippocampal pyramidal neurons Function: Transmitter release R-type Ca++ channel Subunits : 1E (Cav2.3), 2, 1b Activation: High threshold, strong depolarization Inactivation: Voltage dependent; Rapid kinetics Blockade: SNX-482 peptide from African tarantula, Hysterocrates gigas Functions Transmitter release Insulin release: 2nd phase Associated protein: EFHC1 Increases R-type Ca++ channel currents Mutations: Cause Juvenile myoclonic epilepsy Location: Cerebellar granule neurons; Dendrites of hippocampal pyrimidal neurons Action: Provide transient surge of Ca++ influx T-type (Transient) Ca++ channel 18 Subunits May be formed by single 1 subunit 1G (Cav 3.1) Localization: Brain Currents generate burst mode firing of action potentials in thalamocortical relay neurons Generation of GABA-B receptor-mediated spike-and-wave discharges Fastest recovery from inactivation 1H (Cav 3.2) Highest expression in kidney and liver; Also cardiac, neural, endocrine Inhibition mediated by G protein -2 , -2 subunits Neural: D hair mechanoceptors ; Sympathetic ganglion neurons Skeletal muscle: Embryonic ; Associated with myoblast fusion Slowest recovery from inactivation Currents generate short burst firing Missense mutations associated with: Childhood Absence Epilepsy in Northern China 1I (Cav 3.3) Brain specific LVA currents: Activate and inactivate much more slowly than typical T-type channels Currents contribute to sustained electrical activities in neurons Activation By depolarization near resting potential Low voltage activation (LVA) threshhold Facilitated by strong depolarizing pulses Ca++ competes with protons for binding to channel selectivity filter Channels close slowly on repolarization of the membrane: Generates SD tail current Tiny equivalent single-channel conductance of Ba++ Ca++ Generates Low threshold calcium spikes (LTS) in brain Inactivation Rapid Steady-state inactivation occurs over a similar voltage range as activation Window current: Small range of voltages where T-type channels can open, but do not inactivate completely Rapid deinactivation Reactivation: Requires strong hyperpolarization T-type current regulation by G-protein coupled receptors Conductance: Low (~8pS) Blockade Nickel ions: Especially Cav 3.2 Mibefradil Kurtoxin: Peptide from South African scorpion, Parabuthus transvaalicus Ethosuximide: Not at therapeutically relevant concentrations Do not bind dihydropyridines Tissue localization: Cardiac vascular smooth muscle; Nervous system Function Rhythmic action (pacemaker) potentials in cardiac muscle neurons Burst firing mode of action potentials Regulate intracellular Ca++ concentrations Physiology of Ca++ channels Low threshhold: T-type High threshhold (Activated at membrane potentials nearer 0 than resting): L, N, P-type l Other Ca++ channels Ligand gated Ca++ entry channels Ca++ transporting ATPase ATP2A1 : Fast twitch skeletal muscle; Sarcoplasmic or endoplasmic reticulum ATP2A2 : Slow twitch; 2 isoforms SERCA2a: Heart Slow-twitch skeletal muscle SERCA2b: Smooth muscle Nonmuscle tissues ATP2B1 : Plasma membrane ATP2B2 : Plasma membrane ATP2B4 Disorders Capacitive Ca++ entry channels Intracellular activation channels General features Homotetrameric complexes Structure: 6 putative transmembrane sequences (TMSs) Putative channel lining region between TMSs 5 and 6 Covalently linked carbohydrate on extracytoplasmic loops of channel domains Ca++ release channels: Ryanodine receptors (RYR) Signalling system: Cyclic ADP-ribose (cADPR) Second messangers: cADPR-Ca++-Calmodulin Stimuli: Ca++; Caffeine; Ryanodine Inhibitors: Ryanodine Activated by activity of dihydropyridine-sensitive Ca++ channels Function: Signal amplifier Types RYR1 Location: Skeletal muscle Function: Involved in excitation-contraction coupling Disorders Malignant hyperthermia Central core disease Granulomatous myopathy : Antibodies vs RYR RYR2 : Cardiac Channel Structure: Tetramer comprised of 4 RYR2 polypeptides 4 FK506-binding proteins (FKBP1A) Location: Sarcoplasmic reticulum Function Major source of Ca++ needed for cardiac muscle excitation-contraction coupling Channel regulation by Protein kinase A (PKA) Phosphorylation of RYR2 Dissociates FKBP1A from RYR2 Regulates channel open probability RYR2 Macromolecular complex includes FKBP1A PKA Protein phosphatases PP1 PP2A Anchoring protein, AKAP6 Disorders ARVD2 Ventricular tachycardia, stress-induced polymorphic RYR3 : Brain Inositol-1,4,5-triphosphate (IP3) receptors Location: Brain cell endoplasmic reticular (ER) membranes Activated by increase intracellular levels of IP3 Structurally similar to ryanodine receptors Cause release of intracellular Ca++ stores after stimulation of cell surface receptors Function: Signal oscillation Other intracellular Ca++ channels 5 Nicotinic acid adenine dinucleotide phosphate (NAADP) receptor Signalling system: Cyclic ADP-ribose (cADPR) Releases Ca++ from a thapsigargin-insensitive store Second messenger Stimulus: Nanomolar NAADP Inhibition: High NAADP Function: Signal trigger Sphingolipid receptor (EDG1) Signalling system: Sphingolipid pathways Second messenger: ? Sphingosine-1-phosphate (S1P) or Sphingosyl-phosphorylcholine (SPC) l Ca++ sensors Type A: Expressed in photoreceptor cells; function Recoverin Visinin S-modulin Type B: Expressed in neurons VILIP Neuronal calcium sensor-1 (NCS1) : Associated with secretory granules l Ca++ channel disorders L-type Ca++ channel, voltage-gated; Skeletal muscle (CACNL1A3 1S) other subunits Hypokalemic periodic paralysis (CACNL1A3 1S subunit) Malignant Hyperthermia CACNL1A3 1S subunit ? 2 subunit Long QT syndrome with syndactyly (Timothy syndrome): CACNA1C X-linked congenital stationary night blindness: Incomplete form (CSNB2) Ca++ channel, voltage-gated; 1F subunit (CACNA1F) : Retina specific subunit Mouse models Muscular dysgenesis mouse : Absent 1S (CACNA1S) subunit Deafness: CACNA1D deficiency Toxins: Skeletal smooth muscle Polypeptides: Mamba snake (Calciseptine ) Dihydropyridines: Nifedipine...; Diltiazem; Verapamil Self-biting self-injurious behavior: Activation of CACNA1D containing L-type channels ((+ -)Bay K 8644) N-type Ca++ channel Toxins: Polypeptide w-conotoxin SVIA SNX-325 (Segestria spider toxin) P-type Ca++ channel, voltage-gated; Presynaptic terminal of motor axon Lambert-Eaton Myasthenic Syndrome w-agatoxins: Especially IVA IVB CACNA1A (CACNL1A4) 1A subunit 1 Episodic ataxia type-2 Truncating mutations in repeat domain III Probably produce non-functioning channel Haploinsufficiency mild cerebellar pathology Familial hemiplegic migraine Missense mutations in transmembrane segments Progressive ataxia: SCA 6 Trinucleotide repeat expansion in intracellular region near carboxy terminus Missense mutation: G293R Mouse mutations: Loss of both alleles prominent cerebellar degeneration Tottering leaner Recessive Ataxia Splicing mutation Produces truncated protein Physiology: Alteration in the whole-cell calcium current in Purkinje cells Tottering Recessive Ataxia; Absence seizures (spike-wave) Missense mutation in extracellular pore region of repeat domain II Physiology at neuromuscular junctions Greater Run-down of evoked acetylcholine release at high-rate stimulation Greater Spontaneous acetylcholine release from presynaptic terminals Rolling Nagoya CACNB4 4 subunit R482X: Juvenile myoclonic epilepsy 6 C104F: Generalized epilepsy praxis-induced seizures; Episodic ataxia R-type Ca++ channel, voltage-gated; 1E subunit ? Hemiplegic migraine T-type Ca++ channel, voltage-gated Greater current in reticular thalamic neurons in rat model of absence epilepsy Missense mutations of CACNA1H associated with: Childhood Absence Epilepsy in Northern China 19 Ca++ release channels (Ryanodine receptors) Ryanodine receptor 1 Malignant hyperthermia Central core disease Granulomatous myopathy : Antibodies vs RYR Ryanodine receptor 2 Ventricular tachycardia, stress-induced polymorphic Right ventricular dilated ( ARVD ) cardiomyopathy 2 Ca++ transporting ATPase ATP2A1 Brody myopathy ATP2A2 Darier-White disease: Keratosis follicularis ATP2B2 Deafwaddler (dfw) mouse: Deafness; Vestibular imbalance Mouse mutants: Other 1 null mutant mouse Lacks excitation-contraction coupling : Dies at birth Ca++ channel, voltage dependent, 4 subunit (CACNB4) Lethargic (lh) mouse: Seizures; Ataxia Ca++ channel, voltage dependent, 2 subunit (CACNG2) Stargazer: Absence epilepsy; Head tossing; Ataxia Waggler: Absence epilepsy; Head tossing; Ataxia CACNA2D2 : Ducky mouse; Ataxia Slow wave seizures POTASSIUM CHANNELS Figure K+ channel disorders Principles Structure Functions Subunits Types l Principles Types of K+ Channels Structure 4 K+ channel Inner Outer membrane face Layers of aromatic amino acids: Tryptophan; Tyrosine Form cuff around pore Pull pore opening like springs Selectivity filter Narrow region near outer face of membrane Contains glycine-tyrosine-glycine residues Lined by carbonyl backbone of conserved amino acids ? Carbonyl oxygens act as surrogate H2O: Coordinate 2 dehydrated K+ ions sitting in line in channel Ions travel through channel in single file Voltage gated K+ channels (Kv) 6 Transmembrane (TM) regions (S1-S6) 4 Subunits surround central pore (TM channel): S5 S6 regions of each subunit Selectivity filter (P region): Hydrophobic sequence between last 2 TM regions; Contains Gly-Tyr-Gly Voltage sensing: Multiple positively charged amino acids in 4th TM region (S4) Inwardly rectifying K+ channels (Kir) 2 Transmembrane regions (M1 M2): Correspond to last 2 TM regions (S5 S6) in Kv channels 4 Subunits surround central pore (TM channel) P region: Separates M1 M2 Non-conducting at positive membrane potentials K+ channel functions: Often voltage-sensitive Delayed rectifier K+ channels Delayed activation; Slow inactivation Allows efficient repolarization after action potential Blockers: 4-aminopyridine; Dendrotoxins; Phencyclidine; Phalloidin; 9-aminoacridine; Margatoxin; Imperator toxin; Charybdotoxin Structure: Tetramer of - subunits - subunit Inward rectifier K+ channels (Kir) General properties K+ channel: Greater tendancy to allow potassium to flow into cell rather than out Voltage dependance: Regulated by concentration of extracellular potassium Inward rectification mainly due to the blockage of outward current by internal magnesium Can be blocked by external Ba++ Subcellular location: Integral membrane protein Activity of Kir channels is dependent on interactions with phosphatidylinositol 4,5-bisphosphate (PIP2) Functions Maintain resting membrane potential near equilibrium potential for K+ ions Contribute to cell excitability Tissues: Excitable; Heart, Brain, Skeletal muscle Non-conducting at positive membrane potentials Typical Kir: Large family Roles in excitability resting conductance of muscle cells and neurons Some ATP-sensitive or GTP-activated Structure 2 membrane-spanning domains in each subunit (M1 M2) Correspond to last 2 TM regions (S5 S6) in Kv channels N-terminal domain: Intracellular C-terminal domain: Intracellular No voltage sensor in voltage-gated channels Homologous to regions in voltage-gated K+ channel Transmembrane regions 5 (M1) 6 (M2) P region Separates M1 M2 Pore helix Loop region: Major ion selectivity filter; Amino acid TVGYG core Subunit clustering Homotetramers or Heterotetramers 4 Subunits surround central pore (TM channel) Currents Large inward at potentials negative to K+ equilibrium potential Small outward currents at more positive potentials Blockers: LY97241; Gaboon viper venom; Sr++; Ba++; Cs+ Regulation: External K+; Internal Mg++; Intracellular polyamines, ATP or G-proteins Human ether-a-go-go ( HERG ; KCNH) : Atypical with 6 transmembrane domains See: Specific channel types ; Disorders Ca++ sensitive K+ channels: Generate membrane potential oscillations; Afterhyperpolarization General structure function 15 4 protein subunits Each subunit contributes one membrane-spanning segment (Helical structure) to the pore lining External surface: Contains selective K+ filter; Formed by backbone carbonyls Inner cavity: Accommodates a hydrated K+ ion Cytoplasmic side of channel Subunit helices form a bundle of RCK domains whch act as gate RCK domains have fixed flexible interaction domains 2 Ca++ ions bind to flexible RCK interaction domains regulate gate High conductance (BK) Gated by internal Ca++ and membrane potential Unit conductance: 100 to 220 picoSiemens (pS) Openers: NS004; NS1619; DHS-1 Blockers: Iberiotoxin; (+)-tubocurarine; Charybdotoxin; Noxiustoxin; Penitrem-A; TEA Intermediate conductance (IK) More sensitive to Ca++ than BK channels Gated only by internal Ca++ ions Unit conductance: 20 to 85 pS Blockers: Cetiedil; Trifluoroperazine; Haloperidol Small conductance (SK): Minimal voltage-gating ( KCNN ; ISK-family) More sensitive to Ca++ than BK channels Gated only by internal Ca++ ions Voltage independent Unit conductance: 2 to 20 pS Blockers: Apamin ; Leiurotoxin 1 ; (+)-tubocurarine ATP-sensitive K+ channels 25 General Inhibitory effect: ATP ATP acts from the cytoplasmic face of membrane ATP reduces K+ channel open probability Facilitation: Nucleoside diphosphate Components K+ pore: Kir6 subunits KCNJ8 KCNJ11 Regulatory subunits: Sulphonylurea receptors (SURs) Members of the ATP-binding cassette (ABC) family SURs: SUR1 SUR2 Properties Inwardly rectifying; pH sensitive Not voltage-dependent Openers: Levcromakalim; Diazoxide; Aprikalim; Pinacilil Blockers: Glibenclamide; Tolbutamide; Phentolamine: Ciclazindol; Lidocaine Structure: Tetramer of 2-transmembrane subunits Functions Couples membrane K+ conductance (membrane potential) of cell to metabolic state Senses intracellular nucleotide concentrations Role in many tissues: Response to metabolic changes such ashypoxia, ischaemia Glucose concentration sensor in -cells Underly insulin secretion due to increase in blood glucose concentration Heart Protective function: Response to hypoxia or ischaemia Underlie responses to metabolic or catecholamine stress Skeletal muscle Roles in fatigue glucose uptake Na+ activated K+ channels Voltage-insensitive Blockers: Mg++; Ba++ Cell volume sensitive K+ channels Activated by increased cell volume Blockers: Quinidine; Lidocaine; Cetiedil Type A K+ channels: Rapid activation inactivation Blockers: 4-aminopyridine; Quinidine; Mast cell degranulating peptide; Phencyclidine; Dendrotoxins ? Regulation of fast repolarizing phase of action potentials: Delay spiking Structure: Tetramer of -subunits + intracellular -subunits -subunits may confer rapid inactivation Receptor-coupled K+ channels Muscarinic-inactivated Slow activation; Non-inactivating; Non-rectifying Openers: Somatostatin; -adrenoceptor agonists Blockers: Ba++; Bradykinin Atrial muscarinic-activated Inward rectifying Blockers: Ba++; Cs+; 4-aminopyridine; TEA; Quinine Structure: Tetramer of KCNJ3 KCNJ5 Subunits: Molecular families Voltage-gated K+ channels (Kv) 6 transmembrane domains Activated by depolarization Present in both excitable and nonexcitable cells Functions Regulate resting membrane potential Control of the shape and frequency of action potentials subunits: 2 types Functional by themselves Electrically silent: Modulate activity of functional subunits Types KCNA (Shaker): KCNA 1, 5 6 genes located in cluster on Chromosome 12p13 KCNA1 (Kv1.1) Location: Presynaptic juxtanodal Delayed rectifier Disease: Episodic Ataxia Myokymia Syndrome (EA1) KCNA2 (Kv1.2) : Presynaptic juxtanodal; Delayed rectifier KCNA3 (Kv1.3) : Skeletal muscle Lymphocytes; Delayed rectifier KCNA4 (Kv1.4) : Presynaptic Axonal Fetal skeletal muscle; Type A rapidly inactivating KCNA4L KCNA5 (Kv1.5) : Heart Insulinoma; Delayed rectifier KCNA6 (Kv1.6) : Brain; Delayed rectifier KCNA7 KCNA8 KCNA9: see KCNQ1 KCNA10 KCNAB1 : 1 subunit (Kv--1.1) Modulates gating properties amplitudes of Shaker channels 3 subunit from alternate splicing of this gene KCNAB2 : 2 subunit (Kv--1.2) KCNAB3 External link: UCLA anesthesia KCNB (Shab) KCNB1 (Kv2.1) Locations: Soma; Proximal dendrite Associates with: KCNG3, KCNG4, KCNV2 KCNB2 (Kv2.2) KCNC (Shaw): Delayed rectifier KCNC1 (Kv3.1) : Brain, Skeletal muscle, Lymphocytes, Spleen KCNC2 (Kv3.2) : Brain KCNC3 (Kv3.3) : Brain, Liver KCNC4 (Kv3.4) : Brain, Skeletal muscle Function Kv3 channels regulate synaptic transmission at parallel fiber-Purkinje cell synapse in cerebellum Mice lacking Kv3.1 or Kv3.3 channels: Ataxic KCND (Shal): Molecular components of subthreshold-activating A-type K+ currents KCND1 (Kv4.1) : Brain KCND2 (Kv4.2) Locations: Brain (Distal dendritic; Post-synaptic), Heart, Aorta Modulated by Neuronal calcium sensor 1 Binds to Filamin C KCND3 (Kv4.3) : Cardiac ventricle transient outward potassium current I(to) KCNE General Components of slow voltage-gated channels Structure: Small, single transmembrane domain-containing proteins Channel function: Accessory subunits; Interact with regulate activity of Kv channels KCNE1 (minK protein) Epithelial cell apical membrane Codes for subunit Coassembles with KCNQ1 (KCNA8; KVLQT1) subunit: Causes increased current amplitude Forms slowly activating delayed rectifier K+ (IKs) channel Diseases: Jervell-Lange-Nielsen Syndrome ; Long QT Syndrome 5 KCNE2 (minK related peptide 1) Disease syndromes Long QT syndrome 6 Atrial fibrillation Ventricular fibrillation Clarithromycin-induced arrhythmia KCNE3 Interacts with -subunit KCNQ1 in intestine crypt cells KCNQ1 KCNE3 channel Related to cyclic AMP-stimulated intestinal Cl- secretion ? Involved in secretory diarrhea and cystic fibrosis Mutations may cause: Hypokalemic periodic paralysis KCNE4 High tissue levels: Heart, skeletal muscle kidney KCNE1L Expressed in heart, skeletal muscle, brain, spinal cord, and placenta Deleted in AMME contiguous gene syndrome KCNF KCNF 1 : Large transcript abundant in heart; Smaller one brain specific KCNG KCNG1 : Large transcript abundant in placenta brain; Smaller one in skeletal muscle KCNG2 Expressed in myocardium Subunits in delayed-rectifier type channels ? Contribute to cardiac action potential repolarization KCNG3 (Kv10.1) Functions as subunit: Modifies Kv2.1 channel activity Subcellular location: Plasma membrane KCNG4 (Kv6.3) Coexpressed with Kv2.1 Physiology Accelerates time course of activation Hyperpolarizes threshold for activation Hyperpolarizes voltage dependence of inactivation KCNQ family 10 General Express M-current properties Low-threshold, noninactivating, voltage-dependent K+ current Slowly opening closing: 100x slower than channels associated with action potentials Limits repetitive firing due to persistent depolarizing stimulus Interactions: Can couple to M1 muscarinic acetylcholine receptors M-channel activity Partially active in range of neuronal resting membrane potential Further activated by membrane depolarizations Inhibited by membrane receptors Muscarinic AChR activity; Dopamine; Serotonin; Glutamate; Peptides Receptors acting on G-protein receptors General actions Oppose epileptic activity: Restrain repetitive neuronal discahrges Mediate transient increases in activity after release of ACh and other transmitters Drug interactions Linopirdine: Blocker of M-channels; Promotes ACh release Retigabine: Opens M-channels BMS-204352: Activates KCNQ channels; May reduce infarct size Disorders KCNQ1 (KCNA8; KVLQT1) K+ current: Slow delayed rectifier Auxiliary subunit: KCNE1 Tissues: Heart, Pancreas, Cochlea (stria vascularis) Disorders LQT1 syndrome Jervell-Lange-Nielsen Syndrome Atrial fibrillation, Dominant Short QT syndrome 2 KCNQ2 Locations Brain: Somatodendritic pyramidal polymorphic neurons; Cortex Hippocampus Sympathetic ganglia Testis Form M-channels with KCNQ3 Calmodulin Diseases Benign neonatal epilepsy (EBN1) Myokymia Benign neonatal epilepsy KCNQ3 Locations Brain: Somatodendritic pyramidal polymorphic neurons; Cortex Hippocampus Sympathetic ganglia Spleen Cochlea Form M-channels with KCNQ2 Calmodulin Disease: Benign neonatal epilepsy (EBN2) KCNQ4 Locations Cochlea: Sensory outer, but not inner hair cells Vestibular organs Brainstem: Auditory nuclei Disorder: Nonsyndromic sensorineural hearing loss, Dominant (DFNA2) KCNQ5 Locations Brain Sympathetic ganglia Skeletal muscle Auxiliary subunit: KCNQ3 M-current KCNS family General Voltage-gated, Delayed rectifier Brain, Spinal cord, Retina No K+ channel activity Modulate activities of Kv2.1 (KCNB) Kv2.2 subunits KCNS1 (Kv9.1) Expressed in brain No potassium channel activity by itself Modulates activities of Kv2.1 (KCNB1) Kv2.2 KCNS2 (Kv9.2) Expressed in brain No potassium channel activity by itself Modulates activities of Kv2.1 (KCNB1) Kv2.2 KCNS3 (Kv9.3) Polymorphisms associated with airway hyperresponsiveness KCNV family KCNV1 (Kv8.1) Modifies kinetics of KCNB channels KCNV2 (Kv11.1) Coexpressed with Kv2.1 Brain cyclic nucleotide gated K+ channels (BCNG) 22 Types HCN1 : Expression in brain; Activate rapidly HCN2 : Expression in brain heart HCN3 HCN4 : Expression in heart, brain (thalamus) testis; Activate slowly Properties Permeability Cations K+ 4x Na+ Current carried by Na+ ions at typical membrane voltages None to anions Activation Hyperpolarized membrane potentials Slow time course Sensitive to intracellular cyclic nucleotides Modulated by: Cyclic nucleotides Blockade by Extracellular: Cesium; Capsazepine (Blocker of vanilloid receptors) Intracellular: QX-314 (Lidocaine derivative); ZD7288 Bradycardiac agent) Pacemakers: Generate rhythmic cellular activity h-currents (Ih) Allow cells to be rhythmically active over precise intervals of time Tissue location: Cardiac; Neuronal Other functions Dendritic integration Temporal summation of distal synaptic inputs Dampens cellular responses to inhibitory synaptic input Allows rapid resumption of tonic firing Synaptic release Can facilitate neurotransmitter release Response to repetitive action potentials Primary sensory reception Expressed in taste cells: Receptors for sour taste Thermoreception External link: UCLA anesthesia Potassium channels : Inwardly rectifying (Kir) General properties General families Kir2.0 Action: Strong rectification Function: Maintenance control of cell excitability Interactions: Among all Kir2 channels; SAP97 Kir3.0 (GIRK) KCNJ subtypes: 3, 5, 6, 9 G-protein gated Tetramers form KG channels Expressed throughout CNS Acetylcholine-responsive inward rectifier composed of Kir3.1 Kir3.4 Kir1.0 4.0: K+ transporters Kir5.1 Homomeric assembly with PSD-95 Related to PKA-mediated signalling Kir6 ATP sensitive Associates with sulfonylurea receptors Kir7 Very low single channel conductance Low sensitivity to block by external Ba++ and Cs+ No dependence of inward rectification properties on internal blocking Mg++ Helps to set membrane potential Kir Types: Large family KCNJ1 (Kir1.1): Highest tissue levels: Kidney Pancreas islets Activation: Internal ATP Blockade: External Ba++ Disease: Bartter syndrome (Antenatal) KCNJ2 (Kir2.1) Tissue localization: Brain, Heart, Skeletal muscle, Lung, Kidney, Placenta Strong inward rectifier Channel compositions Channels are often homotetramers Subunit associations: Other Kir2; SAP97 Polarized distribution: Enables channels to transport K+ ions to appropriate regions Role Generation of action potential waveform + Excitability in muscle neural tissue Prevents excessive loss of K+ during plateau phase of cardiac action potential Allows outward K+ flux during terminal repolarization diastole Development: Myoblast fusion; Bone morphogenesis G-protein enhanced current Blocked by Ba++ or Cs+ Diseases Andersen syndrome Short QT syndrome 3 KCNJ3 ( Kir3.1 ) Subunit associations KCNJ5, KCNJ6 KCNJ9 Homotetramers do not form functional channels Muscarinic G-protein linked Role: Heartbeat regulation KCNJ4 (Kir2.3) Subunit associations: Other Kir2; SAP97 Polarized distribution: Enables channels to transport K+ ions to appropriate regions Modulated by arachidonic acid Tissue localization: Heart; Skeletal muscle; Brain (Hippocampus) KCNJ5 ( Kir3.4 ) Subunit associations: KCNJ3, KCNJ6 Tissue localization: Pancreas; Heart Knockouts: Channel role in vagal regulation of heart rate Spatial memory KCNJ6 KCNJ7 ( Kir3.2 ) Localization: Cerebellum Associates with KCNJ9 Mediate inhibitory effects (outward currents) of opioids Disorders: Weaver mouse Knockouts: Seizures Ethanol-induced behaviors KCNJ8 (Kir6.1) Function: Regulation of vascular tone Controlled by G-proteins ATP Knockout: Sudden death; Spontaneous ST elevation; Atrioventricular block KCNJ9 ( Kir3.3 ) Associates with KCNJ6 Mediate inhibitory effects (outward currents) of opioids with Kir3.2 Knockouts: Neuron membrane depolarization KCNJ10 (Kir1.2; Kir4.1) Forms heterodimer with KCNJ16 ATP-dependent Location: Glial; Muller cells (Retina); Kidney; Gastric parietal cells Subcellular Polarized distribution: Enables channels to transport K+ ions to appropriate regions Subcellular clustering associated with Dystrophin isoform dp71 Predominantly expressed in membranes adjacent to basement membranes Laminin is necessary for surface expression of Kir4.1 Co-localizes with aquaporin-4 water channel in retinal glial cells Functions CO2 chemoreception ? Related to glial K+ buffering in brain Endocochlear potentials K+ secretion Knockout Spinal hypomyelination Loss of endocochlear potentials oligodendrocyte K+ conductance KCNJ11 (Kir6.2) Associates with sulfonylurea receptor (SUR1) Controlled by G-proteins ATP-sensitive Expression: Ubiquitous Function: Mediates glucose homeostasis; Glucose-stimulated insulin secretion Diseases Hyperinsulinemic hypoglycemia : Unregulated insulin secretion May contribute to Type 2 diabetes : E23K polymorphism Neonatal diabetes , transient or permanent KCNJ12 (Kir2.2) Channels formed by homotetramers or associations with other Kir2 ATP sensitive Role in action potential waveform and excitability of neurons muscle KCNJ13 (Kir7.1) Localization: GI; Neurons; Kidney; Retinal pigment epithelium Mild inwardly rectifying K+ current: Inverse dependence of conductance on [K+]o Function: K+ conductance of the Retinal pigment epithelium apical membrane KCNJ14 (Kir2.4) Cranial nerve motoneurons in general somatic special visceral motor cell columns KCNJ15 (Kir4.2) Localization: Kidney Forms heterodimer with KCNJ16 KCNJ16 (Kir5.1) Tissues: Brain, Kidney Pancreas Functional channels formed with: KCNJ15; PSD-95 Associated with CO2 chemoreception KCNJN1 Inhibitor of KCNJ12 (Kir2.2) Human ether-a-go-go (HERG; KCNH) : Related to cyclic nucleotide-gated cation channels KCNH1 Expressed at onset of human myoblast differentiation KCNH2 Channel activation accelerated by K+ Channel regulator 1 Diseases Long-QT 2 syndrome Short QT syndrome 1 KCNH3 Locations Cerebral cortex: Layer II to layer VI; Cell bodies of neurons with pyramidal shapes Hippocampus: CA1 CA3 pyramidal cell body layers; Granule cell layers of dentate gyrus Electrophysiology: Voltage-gated outward current with a fast inactivation component KCNH4 Locations: Brain specific Striatal regions: Putamen caudate nucleus Lower levels in cerebral cortex hippocampus Electrophysiology Voltage-gated outward current No fast inactivation component KCNH5 Adult brain tissue KCNH6 (HERG2) Time constant for deactivation: Voltage dependent; Decreased with more negative potentials Deactivation kinetics slower than KCNH7 KCNH7 (HERG3) Time constant for deactivation: Voltage dependent; Decreased with more negative potentials Fast deactivation kinetics KCNH8 Locations: Forebrain; Testis K+ current at depolarizing voltages Outward Slowly activating Noninactivating Slowly deactivating KCNK family: 4 transmembrane domains; 2 pore (P) (tandem pore) domains KCNK1 (TWIK) : Weakly inward-rectifying current Control of background K+ membrane conductances Expressed in CNS KCNK2 (TREK) : Outward rectifying Sensitive to extracellular K+ Na+ Expressed in CNS KCNK3 (TASK) : ? role in cell response to extracellular pH KCNK4 (TRAAK) Expressed in neural tissues Currents: K+ selective, instantaneous, noninactivating, outwardly rectifying Potentiated by polyunsaturated fatty acids, e.g. arachidonic acid KCNK5 (TASK2) : Renal KCNK6 (TWIK2; TOSS) : Many tissues; Eye ganglion cells inner nuclear layer KCNK7 (TWIK-1-like) Expressed in CNS No channel activity when expressed alone KCNK8 Expressed in eye, lung, stomach No channel activity when expressed alone KCNK9 (TASK3 protein) Expression: ? Selectively in cerebellum or Widely expressed Oncogenic: Over-expressed in human carcinomas Time-independent, noninactivating K+-selective current Current highly sensitive to changes in extracellular pH Blocked by barium, quinidine, and lidocaine KCNK10 (TREK2) Rapidly activating noninactivating outward rectifier K+ channel currents Stimulation Strongly by polyunsaturated fatty acids: Arachidonic acids Cell membrane stretch Intracellular acidification Inhalational general anesthetics Transiently activated by riluzole KCNK12 (THIK-2; Tandem pore domain Halothane Inhibited K+ channel) Expressed in brain kidney No functional current detected KCNK13 (THIK-1) Ubiquitous expression: High in olfactory, septal, hypothalamic thalamic nuclei of brain Weak inward rectification Current enhanced by arachidonic acid Current inhibited by halothane KCNK14 KCNK15 Expression in heart, skeletal muscle, testis, thyroid gland, adrenal gland, salivary gland, pancreas KCNK16 Channel properties K+ currents: Outward rectifying; Lost by elevation of extracellular K+ Activated at alkaline pH Current sensitive to barium, quinine volatile anesthetics Distribution: Pancreas KCNK17 Channel properties K+ currents: Outward rectifying; Lost by elevation of extracellular K+ Activated at alkaline pH Current sensitive to barium quinine volatile anesthetics Distribution: Liver, lung, placenta, pancreas, small intestine, aorta KCNM: Ca++ sensitive; Large conductance channels (MaxiK) General Respond to increased intracellular Ca++ ion concentrations -subunit: Pore forming -subunit: Modulatory Sensitive to peptide toxins: Charybdotoxin, Iberiotoxin; Bind to -subunit Functions Play a role in leukocyte-induced microbial death Translate Ca++ signals to vasoregulation KCNMA1 : Ca++ activated; Large conductance Mediates fast, Ca++-activated K+ current 17--estradiol binds to subunit May play role in cochlear frequency selectivity Fetal skeletal muscle Disease: Generalized epilepsy + Paroxysmal dyskinesia Null mice: Ataxia Vascular (smooth muscle) dysfunction KCNMB1 Smooth muscle, Skeletal muscle (Fetal), Brain (Hippocampus, Corpus calosum) KCNMB2 : Ca++ activated; Large conductance Subunit induces fast inactivating currents that can be increased by voltage intracellular Ca++ KCNMB3 KCNMB4 KCNN: Calcium-activated, Small Intermediate conductance KCNN1 (SK1) Brain, Heart Small conductance, Ca++ activated Apamin sensitive KCNN2 (SK2) Brain, Adrenal gland, Retinal ganglion cells neurons Apamin, Scyllatoxin Tubocurarine sensitive Charybdotoxin insensitive KCNN3 (SK3) Small conductance, Ca++ activated Intermediate apamin sensitivity Contains 2 CAG repeat sequences: Polymorphisms Long CAG sequences: Not causative but ? Associated with sporadic ataxia 13 Brain, Heart, Skeletal muscle (Embryonic), Liver KCNN4 (SK4) T-lymphocytes; Colon, Smooth muscles, RBCs, Neurons Intermediate conductance Ca++ activated Blocking agents: Clotrimazole; Charybdotoxin Major pathway for cell shrinkage via KCl and water loss in sickle cell disease KCNT family : Intermediate-conductance calcium-activated KCNT1 (Slack) Expression Moderate to high in all tissues Highest in liver brain Lowest in skeletal muscle Interacts with Slo subunits SUR (High-affinity sulfonylurea receptor) SUR1 ( ABCC8 ) : Pancreatic islets SUR2 ( ABCC9 ) 2A: Heart 2B: Brain, Liver, Skeletal Smooth muscle, Bladder Plasmolipin Brain ( myelin ) Kidney Forms K+ specific, voltage-dependent channels when added to lipid bilayers l Disorders of K+ Channels Toxins 1 Organic: 4-aminopyridine; Tetraethyl-ammonium Polypeptide Agitoxin-2 Apamin Charybdotoxin Dendrotoxin Tityus toxin K- Tarantula toxins Voltage sensor toxin 1 (VSTX1; Tarantula venom) Inhibits KvAP voltage dependent channel: Partitions in lipid membrane, then binds to receptor 20 Hanatoxin 1 : Binds to Kv2.1 Kv4.2; Alters gating energetics Hanatoxin 2 : Binds to Kv2.1; Blocks K+ currents Barium Aldosterone-like: Licorice (Glycyrrhizic acid); Carbenoxolone (Glycyrrhetinic acid) Volatile substances: Toluene Ethanol Cottonseed oil (with low dietary K+) Bergamot oil (Bergapten; 5-methoxypsoralen): Earl Grey tea Immune Neuromyotonia Cramp-fasciculation syndrome Morvan's fibrillary chorea Limbic encephalitis Hereditary Hypokalemic periodic paralysis : KCNE3 Andersen syndrome : KCNJ2 (Kir2.1) Bartter syndrome (Hypokalemic alkalosis with hypercalciuria), type 2 l Inward rectifing K+ channel, Subfamily J, Member 1 (KCNJ1) l Also caused by mutations in Na+ K+ Cl- transporter-2 (SLC12A1) and Cl- channel (CLC-Kb) Cardiac: Long-QT Syndromes KVLQT ( LQT1 syndrome): Voltage gated K+ channel ( KCNQ1 ) Jervell Lange-Nielsen Syndrome : Recessive Romano-Ward Syndrome : Dominant HERG ( LQT2 syndrome): Inward rectifying K+ channel (KCNH2) LQT4 : Chromosome 4q25-q27; ? gene Jervell Lange-Nielsen Syndrome : Recessive 2 genetic causes K+ Voltage gated channel, ISK-related subfamily, Member 1 ( KCNE1 ) KCNQ1 (KCNA8; KVLQT1) K+ channel Long-QT syndrome Congenital hearing loss Mechanism of arrhythmia Accelerate channel incativation Delays myocardial repolarization Long QT syndrome 5: KCNE1 Long QT syndrome 6: KCNE2 (minK related peptide 1) Ventricular fibrillation; Clarithromycin-induced arrhythmia Cardiac: Other Atrial fibrillation, Dominant : KCNQ1 Short QT syndrome 1 : KCNH2 Short QT syndrome 2 : KCNQ1 Short QT syndrome 3 : KCNJ2 Neural Episodic Ataxia Myokymia Syndrome : Voltage gated K+ channel ( KCNA1 ) Myokymia Benign neonatal epilepsy : KCNQ2 Benign neonatal epilepsy: KCNQ2 : KCNQ3 Mutations cause reductions in size of K+ currents Generalized epilepsy + Paroxysmal dyskinesia: KCNMA1 ?? Paroxysmal Choreoathetosis Spasticity Hyperinsulinemic hypoglycemia of infancy: Familial persistent Subunit of ATP-sensitive pancreatic -cell K+ channel (ABCC8) High-affinity sulfonylurea receptor (SUR1) Inwardly rectifying K+ channel: BIR subunit (KCNJ11) ; Pancreatic -cell Non-syndromic hearing loss, Dominant: KCNQ4 Weaver mouse: G-protein coupled, inward rectifing K+ channel (KCNJ6) Human homologue gene at Chromosome 21q22.1 HYPOMAGNESEMIA Clinical Seizures Tetany Paresthesias Weakness Genetic syndromes Primary hypomagnesemia l Claudin 18; Chromosome 3q; Recessive Hypomagnesemia with secondary hypocalcemia l Chromosome 9q12-q22.2; Recessive Magnesium Potassium depletion (Gitelman syndrome) l Na-Cl cotransporter ; Chromosome 16q13; Recessive Hypomagnesemia 2, Renal (HOMG2) l Chromosome 11q23; Recessive ANION CHANNELS, EXCHANGERS TRANSPORTERS Anion exchange proteins: SLC4A1 (AE1) : Erythrocyte band 3 protein Major integral glycoprotein in erythrocyte membrane Polymorphisms determine Diego blood group Diseases: Spherocytosis; Ovalocytosis; Renal tubular acidosis; Hypokalemic periodic paralysis Other SLC4A2 : Anion exchanger; ? Choroid plexus, GI Other SLC4A3 : Anion exchanger; Cardiac Brain SLC4A4 : Na Bicarbonate cotransporter; Renal; Renal tubular acidosis, glaucoma, cataracts, band keratopathy SLC4A5 : Na Bicarbonate cotransporter; Pancreas SLC4A6 : Na Bicarbonate cotransporter; Retina SLC17A5 (Sialin) : Salla syndrome (Sialic acid storage) SLC26A3: Down-regulated in adenoma (DRA) ? Sulfate transporter Congenital chloride diarrhea SLC26A4: Transporter of Chloride Iodide Non-syndromic deafness, congenital (DFNB4) Pendred syndrome Enlarged vestibular aqueduct syndrome Voltage dependent anion selective channel proteins: VDAC1 ; VDAC2 Outer mitochondrial membrane plasma membrane Channels for small hydrophilic molecules BCL2 proteins bind to VDAC: Regulate mitochondrial membrane potential release of cytochrome c during apoptosis VDAC1 Pathway for movement of adenine nucleotides through outer mitochondrial membrane Mitochondrial binding site for hexokinase and glycerol kinase Organic anion transporter (OATP) Na+-independent transport of organic anions, e.g. bile acids Canalicular multispecific organic anion transporter (cMOAT) Dubin-Johnson Syndrome Sulfate anion transporter CATION CHANNELS: CYCLIC NUCLEOTIDE-GATED CNG channels 1 subunit (CNGA1) Localization: Rod photoreceptors Integral membrane protein Mediates visual signal transduction Cyclic GMP is 2nd messenger: Activates cation channel Rod photoreceptor depolarization Polymerizes with CNGB1 Stimulation: Darkness opens channels to Na+ Depolarizes photoreceptors Inhibition: Light activates cGMP causing channel closure Hyperpolarizes photoreceptors Disease: Retinitis pigmentosa 2 subunit (CNGA2) : Olfactory Activated by 3 molecules of cATP Channel ions: Na+ Ca++ 3 subunit (CNGA3) Localization: Testis; Kidney; Heart; Eye Disease: Rod monochromacy (Total color blindness; Achromatopsia 2 ) 4 subunit (CNGA4) Olfactory signaling: Mediates negative feedback; Allows rapid adaptation 1 subunit (CNGB1) : Retina with CNGA1 3 subunit (CNGB3) : Achromatopsia 3 (Pingelapese blindness ) Brain CNG 1 2 : Voltage gated K+ channels Ca++ transporting ATPase ATP-gated Cation Channel (ACC) Family (P2X receptors) Cu++ transporting ATPase 7 Wilson's : polypeptide Menkes : polypeptide Occipital horn syndrome : polypeptide K+ H+ ATPase : B12 deficiency Hyperpolarization-activated cyclic nucleotide-gated K+ channels (HCN) PROTON-GATED ION CHANNELS: Neural General Two-transmembrane-domain proteins Related to putative mechanosensory DEG ENaC channels Gated by reductions in extracellular pH Most subtypes expressed in DRG: ASIC1b ASIC3 have preferential expression in sensory ganglia Types Dorsal root acidic sensing channel (DRASIC; ASIC-3) : Form hetermultimeric channels Location DRG neurons: Large-diameter mechanoreceptors; Unmyelinated small-diameter peptidergic nociceptors Sensory nerve terminals: Meissner corpuscles lanceolate fibers; Rapidly adapting low-threshold mechanoreceptors Free nerve endings: ? Nociceptors Low pH opens channel to Na+ Ca++ Curent: Biphasic; Rapidly inactivating Sustained components Inhibitor: Amiloride Functions: Related to Stimuli: Cutaneous touch; Acid Role for ASIC3 in tonic inhibition of high-intensity pain signals ASIC3-deficient mouse Reduced sensitivity of some mechanoreceptors to noxious pinch Enhanced sensitivity to light touch Enhanced behavioral responses to high-intensity nociceptive stimuli Acidic sensing ion channel (ASIC-1) 2 variants Alpha (ASIC-): Expressed widely in brain Beta (ASIC-): Expressed only on sensory neurons Inhibitor: Amiloride Ion permeability: Na+ Ca++ K+ Activation: Transient (Rapidly inactivating); By rapid extracellular acidification Disease Focal ischemia or acidosis: May play a role in cell injury ASIC1A H+-gated currents: May contribute to fear anxiety disorders Mammalian degenerin homologue (MDEG-1; ACCN1; BNC1) (ASIC-2) : Na+ channel Inhibitor: Amiloride Excited by: Hair movement; Acid, ASIC2b with ASIC-3 Physiologic function Role in: Mechanically stimulated graded potential in axonal receptors Nociception: Acid-induced cardiac pain Not related to detection of noxious mechanical stimuli Location Palisades of lanceolate nerve endings around hair follicles Dorsal root ganglion cells: Large Small ASIC-2 deficient mice Rapidly adapting mechanoreceptors: Reduced sensitivity to hair movement Some reduced sensitivity in response of slowly adapting mechanoceptors ASIC-4 (SPASIC) Expressed in pituitary brain Capsaicin receptor (VR1) Na-K-Cl CO-TRANSPORTERS (Solute carrier family (SLC) 12) General Integral membrane proteins Mediate coupled transport of Na+, K+, Cl- across plasma membrane KCC family members: Potassium-Chloride cotransporters Types SLC12A1 : Renal Mediates active reabsorption of NaCl Location: Thick ascending limb of the loop of Henle Site of action of diuretics: Furosemide; Bumetanide Disease: Bartter syndrome (Antenatal) SLC12A2 Expressed in many tissues: Secretory epithelia Mediates active Cl- secretion Mouse mutation Deafness; Shaker waltzer behavior, indicative of inner-ear defects Endolymph secretion: Reduced SLC12A3 : Renal Distal convoluted tubule: Principal mediator of Na+ Cl- in this segment Target of thiazide diuretics Disease: Bartter syndrome (Gitelman variant) SLC12A4 (KCC1) : Early erythroid maturation SLC12A5 (KCC2) Chloride extruder in brain Promotes fast hyperpolarizing postsynaptic inhibition SLC12A6 (KCC3) Tissues: Vascular endothelial; Brain; Heart; Skeletal muscle; Kidney Increased activity with cell swelling Disease: Andermann syndrome (HMSN Agenesis of Corpus Callosum) SLC12A7 (KCC4) : Highest expression in kidney, heart, lung, and liver Knockout mice Deafness: Outer hair cells of basal turns of the cochlea lost Renal tubular acidosis: Other causes are hydrogen ATPase AE1 (SLC4A1) anion exchanger Function: Potassium recycling into Deiters cells after exit from hair cells Stretch-activated non-selective cation channels (SA channels) Mechanism: Mechanically-gated channels Locations Ear Muscle spindles Vascular endothelial cells Neurosensory epithelia Types TRANSIENT RECEPTOR POTENTIAL (TRP) ION CHANNELS General Features Structure Subunits: Contain 6 membrane spanning domains Similarity Voltage gated K+ (Kv) Cyclic nucleotide gated (HCN CNG) Polycystic kidney disease proteins Form tetramers Pore lined by transmembrane domains 5 6 Location: Plasma membrane Functions Non-selective cation channel Act to shift membrane potential to 0 mV Depolarization from resting membrane potentials Allow Ca++ influx in non-excitable cells Some are temperature sensitive Channel opening: Linked to activation of 2nd messenger systems Activation of phospholipase C Generation of Inositol-1,4,5-triphosphate (Ins(1,4,5)P3) Opening of Ins(1,4,5)P3 receptor Response to depletion of intracellular calcium pools (Capacitative calcium entry) Some TRP play a role in phototransduction TRP families 12 TRPA receptors TRPA1 (ANKTM1) Stimuli Thermal stimulus: 17 C; Noxious cold Mechanoreceptors in hair cells Pharmacologic stimuli: May evoke burning sensation Icilin Pungent natural compounds in Cinnamon oil (cinnamaldehyde) Wintergreeen oil (methyl salicylate) Clove oil (eugenol) Mustard oil (allyl isothyocianate) Ginger (gingerol) Garlic (alllicin) Wasabi (allyl isothiocyanate) Channel properties: Non-selective cation currents Cell localization Dorsal root gangliaL Expressed in some cells that also express TRPV1 (heat-gated channel) May be up-regulated by NGF via p38 MAPK pathway Hair cells TRPC receptors (STrpC) TRPC1 : Expression widespread; Activated by diacylglycerol (DAG) Intracellular Ca++ depletion TRPC2 : Vomeronasal organ, Testes, Heart, Brain, Sperm; ? Pseudogene in humans TRPC3 : Brain, Placenta, Heart, Muscle; Activated by DAG InsP3R; Inward Outward rectifying TRPC4 : Brain cortex, Testes, Placenta, Adrenal, Endothelium; Receptor operated TRPC5 : Brain; Receptor operated TRPC6 Tissues: Lung, Brain, Muscle (Smooth) Activated by DAG Inward Outward rectifying Interacts with podocin nephrin Disease: Focal segmental glomerulosclerosis TRPC7 : Lung, Brain, Muscle (Smooth), Heart, Eye; Activated by DAG; Inward Outward rectifying TRPV receptors General: TRPV family contains many heat-sensitive channels TRPV1: Vanilloid receptor (VR1); Capsaicin receptor Location Brain Spinal cord: Laminae II III of dorsal horn Peripheral sensory neurons Location: DRG; Trigeminal; Nodose Size: Small to medium diameter Peptide Non-peptide releasing Other: Urinary bladder epithelium, Smooth muscle, Epidermal keratinocytes Subcellular location: Plasma membrane Physiology Outwardly rectifying Cation channel: Relatively selective for Ca++ Activated by Capsaicin : Sensory ganglion cells axons Resiniferatoxin (RTX): Highly potent analog Anandamide: Cannabinoid receptor ligand; Sensitized to anandamide by protein kinase C Temperature Heat to noxious range: 45 C (Lower after sensitization Steep temperature dependance Low pH (Acid) 2 effects of protons Activation of VR1 at room temperature: With extracellular pH 6 Currents resemble sustained component of proton-evoked responses in sensory neurons Potentiate responses of VR1 to capsaicin or heat Concentration range (pH 68) matches local acidosis associated with tissue injury More mediation of sustained than transient responses Inhibitors Capsazepine Ruthenium red Phosphatidylinositol (4,5)-bisphosphate Release of VR1 from inhibitory control: Bradykinin Nerve growth factor Functions Nociception Heat, Acid or Stretch induced Activation effects Releases neuropeptides (substance P) from nerve terminals Causes burning pain Inflammation Hypothermia Integrates effects of noxious heat, low pH vanilloid ligands on sensory neurons Experimental modification VR1 knockout mouse Severely deficient in moderate heat-evoked responses Few heat-sensitive C axons Reduced pain behavior at high temperatures ( 50C) No increased sensitivity to heat after tissue injury Anti-VR1 serum: Ameliorates thermal allodynia and hyperalgesia in diabetic mice TRPV2 : Vanilloid receptor-related (VRL-1) Location: Brain; Spinal cord; Spleen; Lung; Peripheral sensory neurons Physiology Outwardly rectifying Ions: Ca++ Na+ permeability Inhibition by ruthenium red Noxious heat sensation: Activated at 53 C TRPV3 : VRL-3 Location: Keratinocytes Activation Warm temperatures (25 to 40 C High response at noxious hot temperatures TRPV4 : VRL-2 Location: Brain; Liver; Kidney; Fat; Heart; Testes; Salivary gland; Trachea Outward rectifying Activation Reduced osmolarity Mediates sensitivity of nociceptive dorsal root ganglion neurons to hypoosmotic challenges Mechanosensitive: ? via 2nd messenger Warm temperatures (25C40C) TRPV5 : ECAC-1 Location: Intestine; Kidney; Placenta Inward rectification Ca++ selective Conductance increases in absence of divalent catiions Associated with 1,25 dihydroxyvitamin D3-dependent calbindin-D28K ? Role in Vitamin D responsive Ca++ uptake TRPV6 : ECAC-2 Location: Widespread Ca++ selective Inward rectification Passes most current at hyperpolarized potentials Activated by Ins(1,4,5)P3 thapsigargin-mediated store depletion TRPM (Long TRP, Melastatin) TRPM1 Eye (Melanocytes) Down-regulation prognostic marker for metastasis TRPM2 Brain (Fetal Adult), Placenta ADP-ribose regulation Non-selective channel TRPM3 TRPM4 : Highest levels: Heart; Prostate; Colon; Kidney (In fetus) Activated by intracellular Ca++ Conducts monovalent cations: Na+ K+ Modulates membrane potential TRPM5 Strong outward rectification Nonselective among monovalent cations Not permeable to divalent cations Regulated by Intracellular Ca++: Activates Desensitizes PIP2: Reverses desensitization Widely expressed Taste transduction channel Associated with Beckwith-Wiedemann syndrome TRPM6 Mutations in hypomagnesemia with secondary hypocalcemia (HSH) TRPM7 (TRP-PLIK) Kidney, Heart, Liver, Spleen, Lung, Brain Regulated by activity of carboxy terminal kinase Non-selective, whole cell current TRPM8 Voltage-dependent gating cold -sensitive channel Activation Initial activation: Cooling to 28 C Activity increases as temperature diminishes: Increased probability of channel opening Saturation: 10 C Menthol receptor on axons May also be activated by Icilin, eucalyptol WS-3 Nonselective outwardly rectifying channel Prostate, especially neoplasms Upregulated by NGF TRPN General features Contain ankyrin repeats in N-terminals Painless Stimulus: Heating (Noxious) to 41C Present in multidendritic neurons: CNS PNS no-mechanoreceptor-potential C (nompC) Stimulus: Mechanical (Hair) Ankyrin-like protein with transmembrane domains 1 (ANKTM1) Cold-activated channel: 17 C; Noxious Location: Nociceptive cold-sensitive sensory neurons Coexpressed with the capsaicin heat receptor Sensory neurons respond to capsaicin but not to menthol Pyrexia Gene encodes 2 proteins: PYX-PA PYX-PB Sequence homologies to other TRP proteins: ANKTM1; Painless Subunits form heteromeric channels Expressed along dendrites of a subset of peripheral nervous system neurons Opened by temperatures above 40 C More permeable to K+ than to Na+ Protects against high temperature stress PKD (Polycystin) family PKD Function PKD1 PKD 2 interact to produce Ca++-permeable nonselective cation currents Ion channel: Contributes to fluid-flow sensation by primary cilium in renal epithelium Activated by bending of the apical cilium in some epithelia Senses fluid flow parallel to the epithelial surface. PKD1 : Polycystic kidney disease, Dominant PKD2 : Polycystic kidney disease, Dominant Mucolipin 1 (MCOLN1) Cationic channel Functions Endocytic pathway Control of membrane trafficking of proteins and lipids ? Ca++ transport regulating lysosomal exocytosis Mucolipidosis IV Mucolipin 2 (MCOLN2) Mucolipin 3 (MCOLN3) Mouse disorder: varitint-waddler (Va) with tricolor hearing loss GAP JUNCTIONS 23 Gap junction External link: Expasy General Definition: Clusters of intercellular channels connecting cytoplasms of two cells Functions: Coupling Metabolic: Flow of metabolites between cells Electrical: Flow of ions between cells Signaling between neurons Especially prominent in developing nervous system May affect the dynamics of brain circuits: Synchronous firing of coupled neurons Patterns Symmetric Non-rectifying Voltage-sensitive Behavior independent of hyperpolarized side Asymmetric May depend on: Type of channel; Properties of coupled cells May be rectifying Formed by: Connexins (Vertebrates); Innexins (Invertebrates) Structure Each intercellular channel of a cluster comprises one multimeric hemichannel from each cell Each species contains a family of gap-junction monomers Each cell usually expresses more than one type of monomer Connexins General: Connexin properties association with gap junctions Multi-gene family Number: 21 in humans Sequence homology: 40% Molecular structure of connexins Membrane-spanning domains: Four; -helical Extracellular: 2 loops Cytoplasmic: Carboxy and amino terminal sequences; 1 Loop Connexon Formed by a hexameric array of connexins May be homomeric or heteromeric Gap junction structure Composition Pair of connexons joined end-to-end in extracellular space: Forms tight seal Connexons may be same (Homotypic) or different (Heterotypic) Forms a hydrophilic intercellular membrane channel Associated with 2 to 3 nm gap between neighboring cell membranes Gap junction channel function Allows diffusion of low molecular weight molecules ( 1kDa) between neighboring cells Molecule types: Ions; Amino acids; Nucleotides; Cyclic AMP; Glucose-6-phosphate; Tetrahydrofolic acid Gating: Controlled by multiple factors Calcium concentration Closed by high concentrations: Mediated by calmodulin pH: Closed at acid pH Transjunctional membrane potential: Closed by large transjunctional voltages Protein phosphorylation Gap junctions: Associated structures Cadherin-based adherens junctions Disease syndromes caused by connexin mutations Deafness Polyneuropathy Skin disorders Cataracts Types of connexins Connexin 26 (GJB2; CXB2) Diseases Non-syndromic deafness - Recessive Dominant (DFNA3) Vohwinkel syndrome Heterozygosity: Exacerbating factor for A1555G mitochondrial deafness (Aminoglycoside) Connexin 30 (GJB6) Diseases Deafness, Autosomal dominant, Nonsyndromic Sensorineural 3 (DFNA3) Ectodermal dysplasia 2, Hidrotic (Clouston syndrome) 21 Clinical: Strabismus, Mental deficiency, Finger clubbing, Palmar hyperkeratosis Mutant protein Forms functional hemichannels at cell surface Generates leakage of ATP into extracellular space Connexin 30.3 (GJB4) Disease: Erythrokeratodermia variabilis Connexin 31 (GJB3) Diseases Erythrokeratodermia variabilis Bilateral high-frequency hearing loss (AD) Hearing loss polyneuropathy Connexin 32 (GJB1; CXB1) Disease: CMT-X Connexin 36 (GJA9) : Formation of functional gap junctions in neocortex interneurons Connexin 40 (GJA5) : Cardiac; Intercalated disk regions of left ventricle Connexin 43 (CXA1; GJA1) Tissue: Heart Oculodentodigital Dysplasia Mouse knockout: Cardiac right ventricular outflow obstruction Connexin 46 (GJA3) Disease Cataract, Zonular Pulverulent, 3 Animal model: Nuclear cataracts with proteolysis of crystallins Connexin 46.6 (GJA12) Diseases: Pelizaeus-Merzbacher-like syndrome Connexin 50 (GJA8) Diseases: Cataract, Zonular pulverulent 1 Other connexins 31.1 (GJB5) : Skin 31.9 (GJC1) : Gated by cytoplasmic acidification or halothane 33 (GJA6) : Testis 37 (GJA4) : Multiple organs 45 (GJA7) Other cell junctions involved in intercellular adhesion include Desmosomes Large bundles: Anchor epithelial cells together Proteins: Desmocollins; Desmogleins; Plakoglobins ; Desmoplakins Diseases: Pemphigus; Congenital muscular dystrophy ; Naxos disease Tight junctions Leave little space ( 1 nm) between two plasma membranes Functions Selectively modulate paracellular permeability between extracellular compartments Act as boundary between apical basolateral plasma membrane: Maintain epithelial cell polarity Proteins: Cingulin; Zo-1, -2 -3; Claudins; Occludin, JAM, Symplekin, 7H6 antigen Diseases Claudin-11 : In oligodendrocytes; Mouse knockout ? CNS myelin abnormalities Claudin-14 : Deafness, Autosomal Recessive (DFNB29) Claudin-16 : Primary Hypomagnesemia ION CHANNEL-BINDING PROTEINS: INTRACELLULAR Ion channel Binding protein Mechanism Effect K+ channel , Voltage-gated Shaker type NMDA receptor NR2 subunit Chapsyns * : PSD-95 ; SAP97 ; Chapsyn-110 ; Sap102 ; Dlg Binding via PDZ ** domains 1st 2nd on PSD-95 Post-synaptic densities in CNS NMDA receptor NR1 subunit -actinin Actin binding protein Concentrated in dendritic spines Glycine receptor (GlyR) Gephyrin Binds to intracellular loop of GlyR tubulin AChR: Nicotinic Rapsyn 43K Neuromuscular junction localization Na+ channel Voltage-gated Ankyrin G Node of Ranvier localization AMPA receptor GluR2 subunit Glutamate receptor interacting protein (GRIP) Binding via PDZ domain Couples receptor to cytoskeletal signaling molecules Glutamate receptor Metabotropic Subunits: mGluR1a mGluR5 Homer Binding via PDZ-like domain Expression by synaptic activity * Belong to Membrane Associated Guanylate Kinase (MAGUK) family Chapsyn = Channel associated protein of synapse ** PDZ domains: Homologous 90 amino acid sequence repeats; Bind other proteins ACETYLCHOLINE RECEPTORS : Disorders Muscle Myasthenia Gravis Autoimmune : IgG vs 1 subunit Hereditary Subunits : Subunit : e Neuronal Immune neuropathies: Isaac's ; Subacute autonomic IgG antibody vs 3 subunit Paraneoplastic syndrome : Associated with small cell lung carcinoma Epilepsy Nocturnal frontal lobe, Type 1 l Neural nicotinic, 4 subunit ; Chromosome 20q13.2-q13.3; Dominant Nocturnal frontal lobe, Type 3 l Neural nicotinic, 2 subunit (CHRNB2) ; Chromosome 1p21; Dominant Schizophrenia: Attention disorder Lack of inhibition of P50 response to auditory stimulus Linked to dinucleotide polymorphism at 15q13-q14: Site of -7-nicotinic receptor Mouse knockouts Lethal: e-AChR subunit loss CNS neuronal loss with subunit knockout Neural nicotinic, 2 subunit of AChR (CHRNB2) Defects localized in CA1 and CA3 fields in hippocampus neocortex 7 subunit: Minimal phenotype 9 subunit: Altered innervation of cochlear hair cells Autonomic dysfunction Knockouts of neural nicotinic AChR subunits 3 : Bladder enlargement; Dilated, unresponsive pupils 2 Nicotine-elicited anti-nociception: Reduced Neurons in hippocampus neocortex: Reduced 4 Nicotine-elicited anti-nociception: Reduced Muscarinic IgG vs M3-muscarinic AChRs : Occur in both 1 2 Sjgren's Toxins Nicotinic agonists: Nicotine; Anatoxin A Nicotinic antagonists Peptides: -snake toxins ; -conotoxins Other: d-tubocurarine; Histrionicotoxin; Lophotoxin; Epibatidine Muscarinic agonists: Muscarine; Arecoline; Pilocarpine; Green mamba snake Muscarinic antagonists: Scopolamine; Atropine GLYCINE RECEPTORS Hyperekplexia (Startle disease) l Glycine receptor -1 subunit ( strychnine binding) ; Chromosome 5q33-q35; Dominant or Recessive Same mutation in Spasmodic mouse l subunit ; Chromosome 4q31.3; Sporadic or Recessive Also: Spastic mouse Toxins Picrotoxin: Non-competitive antagonist of glycine-activated Cl- channel Strychnine: Competitive antagonist of glycine-gated Cl- channel GLUTAMATE RECEPTORS Metabotropic glutamate receptor R1 (mGluR1): Paraneoplastic cerebellar degeneration Metabotropic glutamate receptor R1 (mGluR3): Rasmussen's encephalitis DOPAMINE RECEPTORS D4 subtype : Autonomic syndrome Long QT Syndromes 16 Cardiovascular disorder with tachyarrhythmias: Prolonged ventricular repolarization Ventricular fibrillation Torsade de pointes Fibrillation with waxing and waning Due to changing axis of depolarization General: Molecular features All LQT syndromes caused by K+ channel disorders except LQT3 Mechanisms: Current carried by defective potassium channels is impaired by reduced gating or modified channel kinetics Epidemiology Carriers: 1 in 10 000 persons Congenital long QT syndrome causes 3000 to 4000 sudden deaths in children young adults per year in US Onset: 50% by 12 years; 90% by 40 years Clinical syndromes Autosomal-dominant ( RomanoWard syndrome ): Pure cardiac phenotype Autosomal-recessive (Jervell and LangeNielsen syndrome): Association with congenital neuronal deafness Acquired long QT syndrome: Due to electrolyte disturbances or drug therapy Risk factors for syncope or sudden cardiac death Congenital deafness History of syncope Female: Cardiac events more common generally during pregnancy Males: Risk higher in childhood Documented torsade de pointes or ventricular fibrillation Age at first episode Duration of the corrected QT interval (QTc) Clinical features Syncope Seizures Sudden death Treatment: -blockers may reduce risk of cardiac events, especially LQT1 Types LQT1 syndrome: KVLQT voltage-gated K+ channel (KCNA8; KCNQ1 ) l KCNQ1 ;Chromosome 11p15.5 ; Dominant or Recessive Disease syndromes Jervell Lange-Nielsen Syndrome : Recessive Mutation suppresses dominant negative effect of truncated splice variant on full length isoform Heterzygotes: Some cardiac K+ current available for repolarization Romano-Ward (LQT1) : Dominant Dominant negative effect of truncated splice variant on full length isoform No delayed rectifier K+ current Disease mechanisms Mutants often cause dominant negative effect on wild type channels K+-selective outward (Repolarizing Iks) current: Reduced Prolongation of cardiac action potential: Produces predisposition to cardiac arrhythmias Prevalence: 42% of LQT syndromes Cardiac Stress-induced: Syncope; Palpitations; Torsade de pointe Frequency of cardiac events with mutation: 63% Risk of death from cardiac event: 4% Congenital hearing loss Onset: Earliest of common LQT syndromes Males: Before puberty Female: After puberty; Persisting cumulative risk Median age: 9 years Drugs provoking events Mefloquine Disopyramide Terfenadine Cisapride Rx: Opening K+ channels (Nicorandil); -blockers; Not mexilletine LQT2: HERG K+ channel (KCNH2; IKr) l Chromosome 7q35-q36; Dominant-negative Channel behavior: Inward rectifying Normal function may suppress arrhythmias Mutations: Several mechanisms of defect Defect in biosynthetic processing HERG channel retained in the endoplasmic reticulum No functional channels produced HERG current with altered gating properties Prevalence: 45% of LQT syndromes Onset: Median age 12 years Cardiac clinical events Precipitated by loud noise Syncope, Aborted cardiac arrest, Sudden death Frequency of cardiac events with mutation: 46% Risk of death from cardiac event: 4% Drugs provoking events Clarithromycin Quinidine Sulfamethoxazole Procainamide Oxatomide ? Rx by increasing serum K+ LQT3 : Cardiac Na+ channel - subunit; SCN5A l Chromosome 3p21-p24; Dominant Mechanisms Increased Na+ channel activity during plateau phase of the action potential Leads to extra component of inward current: Prolongs repolarization Prevalence: 8% of LQT syndromes Onset: Median age 16 years Cardiac clinical events Events occur at rest or during sleep Syncope, Aborted cardiac arrest, Sudden death Frequency of cardiac events with mutation: 18% Risk of death from cardiac event: 20% Cardiac events less frequent but more likely lethal than LQT1 or LQT2 Drugs provoking events: Halofantrine Rx: Mexilletine; ? by Na channel blockade Mutations also produce: Idiopathic ventricular fibrillation (Brugada syndrome ) LQT4 : Ankyrin-B (ANK2) l Chromosome 4q25-q27; Dominant Haploinsufficiency Disease mechanism: Defective targeting of calcium-handling proteins to transverse tubule membranes Inositol 1,4,5-trisphosphate receptor Sodium-calcium exchanger Sodium-potassium ATPase (Na+ K+ ATPase) Clinical Sinus node dysfunction: Onset in utero Bradycardia or Junctional escape rhythm Episodes of atrial fibrillation LQT5 : KCNE1 (minK protein) l Chromosome 21q22.1-q22.2; Dominant LQT6 : minK related peptide 1 l Chromosome 21q22.1; Dominant Long QT with congenital deafness (Jervell-Lange-Nielsen) l Chromosome 21q22.1-q22.2; Recessive K+ Voltage gated channel, ISK-related subfamily, Member 1 (KCNE1) Same phenotype as LQT1 l Chromosome 11p15.5; Recessive KCNQ1 (KCNA8; KVLQT1) Long QT syndrome with syndactyly (Timothy syndrome) l CACNA1C ; Chromosome 12p13.3; Dominant Long QT syndrome: Acquired HERG K+ channel blockade 2 Antiarrhythmic medications: Class IA or III Concepts in channelopathies What are the properties of the mutations in the chloride channel gene (CLC1) that determine whether a syndrome is inherited in a dominant or recessive pattern? The dominant or recessive nature of a mutation depends on the ability of the mutant chloride channel monomers to polymerize with normal channel monomers. Dominant mutations complex with normal monomers producing defective channels. For some mutations one abnormal monomer is sufficient to destroy the function of a tetramer complex (e.g. Pro480Leu). For other mutations (e.g. Gly230Glu) it requires two abnomal monomers to destroy the channel function of a tetramer. In either case, only a minority of tetramers remain functional and myotonia results. Recessive mutations do not complex with normal monomers. Normal monomers are then free to complex with other normal monomers. This produces enough functional tetramers in heterozygotes (50% of the usual amount) to preserve normal membrane excitablity and myotonia does not occur. What are the properties of the mutations in the sodium channel gene (SCN4A) that determine whether a syndrome presents with myotonia, paramyotonia, or weakness? Many mutations produce abnormal inactivation of the sodium channel. This results in increased sodium conductance and membrane depolarization. Mild depolarization is associated with increased membrane excitability and myotonia. Strong depolarization produces membrane inexcitability and weakness. Some mutations only reduce inactivation at low temperatures producing paramyotonic disorders (myotonia or weakness worse in the cold). Mutations in the inactivation gate (amino acid 1306) produce different degrees of disease severity depending on the size and charge of the side chain of the new amino acid. Alanine, with a short side chain produces mild myotonia fluctuans . Valine, with an intermediate side chain, produces paramyotonia congenita . Glutamic acid, with a long side chain and a negative charge, results in myotonia permanens . CHANNEL TOXINS Marine toxins Ciguatoxin Conotoxins Palytoxin (Clupeotoxism) Tetrodotoxin Shell fish Saxitoxin : Paralytic Domoic acid : Encephalopathic Brevetoxins : Neurotoxic Diarrheic Other Lidocaine Potassium channel Marine toxins: General 24 Clinical Syndromes occur after ingestion of toxins Systems involved Gastrointestinal Neurological: Peripheral nerves Differs from painful cardiovascular effects of marine venom toxins Toxin properties Heat and gastric-acid stable Low molecular-weight Affect voltage-gated Na+ channels: In myelinated unmyelinated nerves Ciguatera toxins 7 , 8 , 11 Epidemiology Toxicity Clinical Laboratory Epidemiology: Marine toxin Geographic distribution Caribbean Indo-Pacific Australia: Northeastern coast fish; Outbreaks in Sydney Incidence 10,000 to 50,000 annually Most common illness 2 finfish consumption Occurs in small clusters of patients who shared one, or a few, large fish Some Pacific Caribbean island nations up to 10% incidence Patient characteristics Males Females Age: 2nd 3rd decade Older individuals Symptomatic first poisoning more common Acute symptoms more severe Duration of symptoms longer Food chain Microalgae contaminated with Gamberdiscus: Benthic dinoflagellate on dead coral External link Herbiverous fish consume contaminated microalgae Carniverous fish eat contaminated herbivorous fish Toxin is concentrated in all tissues of carnivorous fish: Especially liver other viscera Human ciguatera disease: Caused by ingestion of fish with high concentration of toxin Toxic level: 0.1 ppb (0.1 g kg) Usually with ingestion of large fish: Rarely 2 kg; Especially 10 kg Reef fish types Barracuda (Sphyraena jello) Ephanids: Flowery (Epinephelus fuscoguttatus) spotted cod Moray eel (Lycodotis): Most toxic Serranids: Coral trout (Plectropomus leopardus) from Great Barrier reef; Grouper; Sea bass Lutjanids: Red bass snapper Amberjack Scombrids: Spanish mackerel (Scomberomorus commersom) tunas Carangids: Jacks Scads Lethrinids: Emperors Scavengers Toxicity Ingestion: Contaminated predatory fish Toxin Type: Lipophilic cyclic polyether Properties Heat-stable Lipid soluble: Long retention in neuronal lipid membranes Dinoflagellate toxins (Gambierdiscus toxicus) Associated with dead coral blue-green algae 20 different gambier- ciguatoxins Ciguatoxins bind to site 5 (transmembrane segment) on -subunit of Na+ channel Most prolong Na+ channel opening One blocks Na+ channels Produced in precursor form by Gamberdiscus toxicus Biotransformed to active more polar toxin in fish Ciguatoxin types Pacific: Pacific-ciguatoxin-1 (P-CTX-1); More toxic Caribbean: Caribbean-ciguatoxin-1 (C-CTX-1) Mechanisms of action Inactivation of voltage-gated Na+ channels Increases nerve membrane excitability P-CTX-1 TTX-sensitive Na+ channels open closer to normal resting membrane potential TTX-resistant Na+ channels recover from inactivation more quickly Clinical General Gastrointestinal: More common in Caribbean; Earliest onset (~12 hours) PNS: Indo-Pacific; Onset ~24 hours CNS (Hallucinations): Indian Ocean Rapid onset: 4 to 16 hours after ingestion GI: Vomiting; Diarrhea; Abdominal pain May produce electrolyte disturbances or dehydration: Especially children Course: Self limiting over 36 hours Cardiac Vasomotor: Bradycardia; Hypotension Discomfort: Myalgias; Cramping; Pruritis; Headache Longer term symptoms: Onset after 12 hours Most common: Weakness; Joint Muscle pain; Paresthesias Sensory Sensory loss Temperature (80%) Pin Vibration (50%) Paresthesias Pruritis: Intense Often presenting symptoms Especially in extremities Centrifugal spread from mouth tongue Duration: Days to Months "Reversal" of hot cold sensation Cold objects produce uncomfortable burning Warm: Fluids especially disturbing; Cold-sharp sensation Feelings of loose teeth Taste disturbance: Metallic Pain: Limbs; Skin; Joints; Dental; Urethral Muscle Pain Weakness May be related to neural involvement or inflammatory myopathy Diffuse Dysphagia Fatigue Autonomic Hypersalivation Bradycardia Laryngospasm Hypotension Pupils: Large or Small CNS Headache: May be presenting feature Depression Cerebellar: Often later onset (Up to 10 days); Ataxia; Tremor Short term memory loss Insomnia Coma in severe cases Death Frequency Mortality is region-specific: Up to 20% in occasional episodes Pacific 1% of patients Due to: Shock; Respiratory failure Occurs when more toxic parts of fish (liver, roe) ingested Recovery Time course: 6 to 24 months Most persistent symptoms: Pruritis; Arthralgia; Fatigue ? Toxin stored in adipose tissue Exacerbations with: Alcohol ingestion; Stress; Exercise; Weight loss Chronic syndrome Frequency: 3% to 20% of severe intoxications Fatigability Weakness Depression Hypersomnolence Subsequent attacks Often more severe than 1st attack Patients more sensitive to low doses of toxin Avoid eating fish for 6 months after initial attack Pregnancy ? Increased Fetal movements Newborn after exposure: Normal or transient weakness ? Breastfeeding may transmit toxin Treatment Symptomatic: Analgesics; Antihistamines Mannitol Not supported by controlled study In 1st 48 hours; 1g kg over 1 2 to 4 hours; May be repeated 1 or 2 times Laboratory Electrophysiology Slow NCV F-waves Prolonged refractory periods Repetitive axonal firing Mild cases Normal routine electrophysiology Latent tetany: Multiplets persisting 2 min after cessation of hyperventilation or ischemia Plasma cholinesterase: Reduced in 80% Diagnostic testing Mouse bioassay: Injection of fish extracts Immunoassay for Pacific-ciguatoxin -1 Confirmation by liquid chromatography tandem mass spectrometry Pathology: Schwann cell cytoplasm edema Differential diagnosis Clupeotoxism Other marine toxin syndromes Tetrodotoxin Shell fish intoxication: Saxitoxin ; Gonyautoxin Scombroid: 2 Histamine accumulation in spoiled fish Clupeotoxism From NCI Palytoxin Sources Plankton-eating fish: Sardines Herring (Clupeoid fish) Hawaiian spear toxin Probable producing organism: Ostreopsis siamensis (Benthic dinoflagellate) Chemical class: Polyether Active agent: Palytoxin Pore-forming toxin Converts Na+ K+ pumps into nonselective cation channels Increases H+ influx into cells: Increases intracellular Ca++ in cardiac myocytes Causes depolarization, Na+ accumulation Ca++ overload Causes contraction of smooth skeletal muscle May produce hemolysis Highly potent: Only botulinum tetanus toxins active at lower concentrations Clinical Produces a similar syndrome to ciguatera : May be mild or fatal Pain Cramps: Muscle Back Gastrointestinal: Nausea, Vomiting, Abdominal cramps diarrhoea Sensory Metallic taste Paresthesias Weakness Pupils: Dilated CNS: Ataxia; Coma Mortality rate: High Laboratory CK high Dark urine Conotoxins : Bind to AChRs Muscle nicotinic: GI , GIA , GII , MI, SI , SIA , SII , EI MI binds to - subunit interface EI binds to - subunit interface - Neuronal MII binds to 32 IMI binds to 7 : Bind to Na+ channels : Bind to Na+ channels w: Bind to Ca++ channels N-type: GVIA , MVIIA , SVIA N-, P- Q-type: MVIIC , MVIID Lidocaine Blocks voltage-gated Na+ channels Usage dependent Requires open Na+ channels Dosage effects Partial block: Slow NCV Higher dosage: Conduction block Very high dose: K+ channel block also Saxitoxin Toxicity Associated with "Red tides" Ingestion Contaminated bivalve shellfish (mussels, oysters clams) Filter feeding of shell fish concentrates toxins Origin of toxin: Dinoflagellates (Gonyaulax toxin) Alexandrium spp Pyrodinium bahamense var compressum Gymnodinium catenatum Xanthid crab External link Toxin type properties Guanidinium Heterocyclic Water soluble Heat stable Mechanism of action Binds to site 1 on voltage gated Na+ channel (Tetrodotoxin-sensitive channel) Blocks Na+ flux Clinical Onset Rapid: 1 2 to 3 hous after ingestion More rapid with increased severity of intoxication Paresthesias Numbness Early: Lips, tongue, extremities (distal) May become generalized Weakness: Extremities, bulbar, respiratory Tendon reflexes: Preserved early CNS: Coma; Most patients alert Systemic: Cardiac arrhythmias Other Headache Nausea vomiting Hypersalivation Diaphoresis Recovery: 2 to 7 days Death: Usually in first 12 hours External link: Epidemic report Laboratory Electrophysiology Slow NCV Long distal latencies Small motor sensory action potentials Conduction block Pathology: No morphologic changes Diagnosis Mouse bioassay HPLC Differential diagnosis: Similar clinical syndromes Tetrodotoxin Crab poisoning: External link External link: Neil Edwards Tetrodotoxin Toxicity Ingestion: Improperly prepared fish Species Tetraodontiformes (Bony fish): Fugu rubripes (puffer) Sheroides rubripes (globe) Other: Blue-ringed octopus bite Concentrated in organs: Liver Gonads (ovary) Intestine Skin Usual patterns of ingestion Served from October through March Served with enough toxin: Causes tingling of lips Toxin Type: Guanidinium; Heterocyclic Water soluble Produced by bacteria (Alteromas), not directly by fish Mechanism of action Binds to site 1 on voltage gated Na+ channel: Occludes outer pore Neutralization of negative amino acids 942 945 of S5-S6 loop reduces binding Puffer fish have Na+ channel mutation: Reduced toxin binding to own channels Blocks Na+ flux Guanidinium moiety enters channel Action independent of whether channel is open or closed Physiology Reduced action potential generation Reduced propagation of action potentials Tetrodotoxin Clinical Onset Rapid 15 minutes to 12 hours after toxin ingestion Sensory Numbness paresthesia Lips, tongue, extremities Loss: ? Reduced proprioception Weakness Extremities: Distal Proximal Bulbar Facial Respiratory Tendon reflexes: Preserved early CNS Dizziness Ataxia Coma Autonomic: With more severe intoxication Cardiac rhythm: Arrhythmias; Bradycardia Hypotension Pupils: Fixed, Dilated Consciousness: Normal Recovery: 4 to 5 days Laboratory Diagnosis: Toxin detection in urine Electrophysiology NCV: Slow Long distal latencies Conduction block Small motor sensory action potentials High threshold for stimulation Pathology: No morphologic changes Prognosis Mortality: High (50%) Good after survival for 24 hours External link: Jim Johnson Brevetoxins From FDA Epidemiology: Human poisoning reported in Florida: West coast North Carolina New Zealand Organism in shell fish: Marine dinoflagellate Gymnodinium brevis Chemistry Lipid-soluble polyether toxins Bind to voltage sensitive Na+ channels Bind at site 5 on Na+ channels Enhance Na+ entry into cells Neuroexcitatory effect: Cause nerve-cell depolarization spontaneous firing Clinical Gastrointestinal effects: Abdominal pain, Nausea Diarrhea Neurotoxic: Ciguatera-like Paraesthesia Temperature reversal Myalgia Vertigo Ataxia Other Rectal-burning pain Headache Bradycardia Mydriasis Severity: Usually mild Treatment: Supportive care Domoic Acid Epidemiology One human outbreak: Canada 1987; Mussels Mass deaths of marine mammals sea birds Pacific coast of Mexico, Washington Oregon Biology Ingestion of contaminated organisms Produced by microscopic algae: Nitzschia Chemistry Heat stable Water soluble Neuroexcitatory amino: Acts like glutamic acid Clinical: Amnesic syndrome Gastrointestinal Onset: 5 hours after exposure Vomiting, abdominal cramps diarrhea More common in younger patients Toxic encephalopathy: Severe memory loss confusion Onset: 48 hours Headache Eye movements: Disordered CNS excitability: Seizures; Myoclonus Mental status disorders Confusion Disorientation Short-term memory loss Coma Systemic features Hemodynamic instability Cardiac arrhythmias Respiratory secretions: Profuse Prognosis: Worse in older patients Pathology: Neuronal loss in amygdala and hippocampus Diarrheic shellfish poisoning (DSP) Caused by group of high molecular weight polyethers Toxins Okadaic acid Dinophysis toxins Pectenotoxins Yessotoxin Return to Myopathies Return to Neuromuscular Syndromes Return to Neuromuscular Home Page References 1. TINS Supplement: June 1996 2. Toxin illustrations from Ion Channel Research 3. Neurology 1997;49:1196-1199 br 4. Curr Opin Neurobiol 1999;9:267-273 5. Trends in Neurosciences 1999;22:488-495 6. Am J Hum Genet 2000;66 (May) 7. Medical Jourmal of Australia 2000;172:176-179 8. Medical Jourmal of Australia 2000;172:160-162 9. Physiol Rev 2000;79:1317-1372; Clin Neurophysiol 2001;112:2-18 10. TINS 2000;23:393-398, Arch Neurol 2003;60:496-500 11. Muscle Nerve 2000;23:1598-1603; JNNP 2001;70:4-8 12. Nature Reviews:Neuroscience 2001;2:387-396 13. Arch Neurol 2001;58:1649-1653 14. Physiol Rev 2002;82:503-568 15. Nature 2002;417;501-502 16. Ann Intern Med 2002;137:981-992 17. Nature Neuroscience 2003;6;468-475 18. Physiological Reviews 2003;83:117-161 19. Ann Neurol 2003;54:239-243 20. Nature 2004;430:232-235 21. Hum Mol Genet 2004;13:17031714 22. Molec Neurobiol 2004;30:279-305 23. Molec Neurobiol 2004;30:341-357 24. Lancet Neurology 2005;4:219-228 25. Current Pharmaceutical Design 2005;11:1915-1940 10 3 2005 Neurology and Neurosciences Journals Many useful links and information for neuroscientists, neurologists and fMRI researchers, such as funding opportunities, jobs, conferences, and brain atlas. functional MRI ( fMRI ) : links and information functional MRI ( fMRI ) links and information Research Network on Early Experience Brain Development Strives to be inter- and multi-disciplinary by drawing on experts from developmental psychology, developmental neurobiology, and developmental behavioral pediatrics. Research Network on Early Experience and Brain Development Network Researchers and Consultants Only OVERVIEW The Research Network on Early Experience and Brain Development was founded in 1998 to address questions of how the experiences of early childhood are incorporated into the structures of the developing brain, and how, in turn, those changes in the structures of the brain influence behavior. The network explores how knowledge of brain development can guide us in our understanding of behavioral development and vice versa. It focuses specifically on sensitive periods and neural plasticity, the reciprocal phenomena whereby (a) the brain is negatively affected if certain experiences fail to occur within a certain time period, and (b) the brain is altered by experience at virtually any point in the life span. Here we consider not only how the structure of experience is incorporated into the structure of the brain, but also how this knowledge can influence the decisions we make about intervening in the lives of children. The majority of the Network's research is conducted by Network members. We do not consider unsolicited proposals. Questions or comments about this site? Contact webmaster@macbrain.org Center for Consciousness Studies Interdisciplinary program promoting open, scientifically rigorous discussions of all phenomena related to the mind. Includes course, conference and workshop listings - from the Univ. of Arizona. Presents an outline of Consciousness research at the University of Arizona. Center for Consciousness Center . Tucson . Arizona Center Activities Consciousness Discussion Forum Fall 2005 Program now posted next talk Radu J. Bogdan (Tulane University) Self-Regulation and Self-Consciousness November 16, 6:30 Santa Cruz Room, Student Union Pre-registration and abstract submission "Tucson VII" Toward a Science of Consciousness 2006 Tucson Convention Center April 4-8, 2006 Abstract submission deadline Nov. 15, 2005 Pre-Conference Workshops Consciousness in Copenhagen Picture Slide Show by Robert van Gulick Moral Phenomenology Workshop November 4-6, 2005 Conferences Related Activities International Conference on Krishnamurti and Consciousness January 6-8, 2006 Hyderabad, India Music and Consciousness February 24-26, 2006 Sheffield, U.K. News "Encyclopedia of Nonlinear Science" by Alwyn Scott, CCS Co-Founder CCS and SCR Changes at the Center for Consciousness Studies About Tucson Articles Reviews The Memory Prediction Theatre Chris Carpenter Radiant Cool Book Review Global Workspace Theory An interview with Bernard Baars Breakthrough study on meditation Why subjective consciousness? Review by Allan Combs Pointing the Quest in the Proper Direction (Koch's book review continued) Stuart Hameroff Review of Jeffrey Gray's "Creeping up on the hard problem" by Nancy J. Woolf How we understand ourselves Review of "Cross-modal self-recognition" The Quest for Consciousness Response to Hameroff A 50-000-year-old blend A review of "The way we think" Heading in the wrong direction Review of Christof Koch's "The quest for consciousness" The quest for consciousness An interview with Christof Koch Exploding the 10 percent myth Levels of Consciousness Peeking into the conscious brain Review of "Human Brain Function" 2nd edition The Scientific Consciousness Community Mourns the loss of Francis Crick A specific drug for consciousness? How do you persist when your molecules don't? How children see desire and belief in others: humans vs God Latest Headlines Neuroethics and the 21st Century Brain An Intimate History of the Unconscious Discovering That Denial of Paralysis Is Not Just a Problem of the Mind Japanese develop 'female' android Blink and you miss it How visual salience wins the battle for awareness Making sense of another mind Theory of mind and moral cognition Psychophysical magic Gurwitsch's Relevancy for Cognitive Science The Psychopath Law and Human Behavior Consciousness: converging insights from connectionist modeling and neuroscience Cognition and Emotion Two neural correlates of consciousness? Psychobiology of Altered States of Consciousness The Rubber Hand Illusion Revisited Sustained Inattentional Blindness and the Capture of Awareness A general mechanism for decision-making in the human brain? fMRI reveals large-scale network activation in minimally conscious patients Microstimulation of the superior colliculus focuses attention without moving the eyes Examination of right- hemisphere hypothesis in lateralization of emotion Functional MRI changes before and after onset of reported emotions JCS Feb 2005, Vol. 12 No. 2 Experimental Psychology, Special Issue Do you hear what I hear? Do you see what I see Brain imaging could spot liars The clinical spectrum of musical hallucinations Cognition and Emotion, v18-8 Journal of Consciousness Studies, v11-12 Phenomenology and the Cognitive Sciences, v3-3 Phenomenology and the Cognitive Sciences, v3-4 Current Workshop No current workshops. See more workshops. Upcoming Conferences Dec 14 - 15 The International Conference on Cognitive Systems (ICCS) See more conferences . | Mission | People | Archives | Web Courses | Resources | Center for CONSCIOUSNESS STUDIES Department of Psychology University of Arizona Tucson, AZ 85721 USA phone: 520-621-9317 fax: 520-621-9306 email: center@email.arizona.edu Auditory Physiology and Biophysics Cellular basis of information processing in the auditory system. Potassium channels, modeling, synaptic transmission, and dendritic integration. Manis Lab - UNC Chapel Hill (USA) skip to: page content | links on this page | site navigation | footer (site information) UNC School of Medicine Dept. Otolaryngology Head and Neck Surgery UNC Curriculum in Neurobiology UNC Neuroscience Center Dept. of Cell and Molecular Physiology Home Research Grants Publications Lab Members Education Contact Cellular Mechanisms of Auditory Information Processing Research Grants Publications Lab Members Education Contact UNC Links UNCLE (library) The University of North Carolina at Chapel Hill Dept. of Otolarngology Head and Neck Surgery Dept. of Cell and Molecular Physiology Related Links Scientific Resources Links NIDCD To the immediate left is a schematic rendering of part of the circuit of the dorsal cochlear nucleus, looking en face at an isofrequency sheet (top), and looking down from the top of the nucleus at 3 such sheets (bottom). Pyramidal cells are blue, carwheel cells red, stellate cells grey, vertical cells green, and granule cells brown. The far left image is a dorsal cochlear nucleus pyramidal cell in a brain slice, filled with AlexaFluor 488, and digitally reconstructed. Electrical activity of the cell, and currents through channels are also shown. What do we do? Our laboratory is interested in the mechanisms that the nervous system uses to process sensory information. For example, what makes auditory neurons uniquely suited to the tasks that they must accomplish? What kinds of synaptic and ionic mechanisms normally operate, and what kinds of plasticity are present in the system? Other studies We recently have begun studying the effects of different forms of deafness on central auditory processing mechanisms. Cells in the nervous system sense their inputs and their own activity, and can respond by changing the proteins that they make and use. This can affect information processing. About Us | Site Map | Privacy Policy | Contact Us | 2004 Paul B. Manis Olfaction Current understanding of the physiological basis for olfaction (sense of smell) and the possible molecular interactions that specify odorant signaling. Olfaction - A Review Leffingwell Associates Olfaction - A Review Home Our Products Download Demos FF Companies FF Info FFTop Ten Chemoreception Chirality Odour Menthol Info FF Patents FFReviews Perfume Info Aromatherapy Food Science Herbs Botanical Molecular Modeling Alchemist WebPick Awarded by the webzine of ChemWeb.com Olfaction - Page 1 General Physiology of Olfaction Trigeminal Sense in the Olfactory Epithelium Olfaction - Page 2 The Odorant Binding Proteins Odorant receptors The Cellular Membrane Olfaction - Page 3 G-Protein Coupled Receptors G-Proteins The cAMP Transduction Cascade Ion Protein Channels Other Second Messengers in Olfaction - cGMP, IP3, NO, CO Olfaction - Page 4 Chemical Olfactory Stimulation - Theories on Olfaction The Steric Theory of Odor The Vibrational Theory of Odor Vibrational Induced Electron Tunneling Spectroscope Theory Ribonucleotides as the Odorant carrier? Olfaction - Page 5 Recent Events in Olfactory Understanding A Combinatorial Process for odor Interpretation Combinatorial Process Visualization Human Olfactory Receptor Genes Enantiomeric Specificity in the Olfactory bulb Download this paper as a pdf file Olfaction John C. Leffingwell, Ph.D. Leffingwell Associates The sense of smell is a primal sense for humans as well as animals. From an evolutionary standpoint it is one of the most ancient of senses. Smell (or Olfaction) allows vertebrates and other organisms with olfactory receptors to identify food, mates, predators, and provides both sensual pleasure (the odor of flowers and perfume) as well as warnings of danger (e.g., spoiled food, chemical dangers). For both humans and animals, it is one of the important means by which our environment communicates with us. This paper will explore the current status our understanding of olfaction and provide in some detail the possible molecular interactions that specify odorant signaling. General Physiology of Olfaction Odorants are volatile chemical compounds that are carried by inhaled air to the Regio olfactoria (olfactory epithelium) located in the roof of the two nasal cavities of the human nose, just below and between the eyes. The odorant must possess certain molecular properties in order to provide sensory properties. It must have some water solubility, a sufficiently high vapor pressure, low polarity, some ability to dissolve in fat (lipophilicity), and surface activity. And to date, no known odorant possesses a molecular weight greater than 294.1 The olfactory sense is able to distinguish among a practically infinite number of chemical compounds at very low concentrations.2 The olfactory region of each of the two nasal passages in humans is a small area of about 2.5 square centimeters containing in total approximately 50 million primary sensory receptor cells. The olfactory region consists of cilia projecting down out of the olfactory epithelium into a layer of mucous which is about 60 microns thick.2a This mucous layer is a lipid-rich secretion that bathes the surface of the receptors at the epithelium surface. The mucous layer is produced by the Bowmans glands which reside in the olfactory epithelium. The mucous lipids assist in transporting the odorant molecules as only volatile materials that are soluble in the mucous can interact with the olfactory receptors and produce the signals that our brain interprets as odor. Each olfactory receptor neuron has 8-20 cilia that are whip-like extensions 30-200 microns in length. The olfactory cilia are the sites where molecular reception with the odorant occurs and sensory transduction (i.e., transmission) starts. Above the mucous layer is the base olfactory epithelium which consists partially of basal cells located in the lowest cellular layer of the olfactory epithelium which are capable of mitotic cell division to form olfactory receptor neurons when functionally mature. The olfactory receptor neurons turnover approximately every 40 days. The epithelium also contains pigmented cells that are light yellow in humans and dark yellow to brown in dogs. The depth of color seems to be correlated with olfactory sensitivity. While the olfactory receptor neurons extend through the epithelium to contact odorants in the atmosphere, on the opposite side within the epithelium, the neuronal cells form axons that are bundled in groups of 10-100 to penetrate the ethmoidal cribriform plate of bone, reaching the olfactory bulb of the brain where they converge to terminate with post-synaptic cells to form synaptic structures called glomeruli. The glomeruli are connected in groups that converge into mitral cells. (Note that in the picture above this convergence is not clearly depicted). For example, in rabbits, there are 26,000 receptor neurons converging onto 200 glomeruli which then converge at 25:1 onto each mitral cell. The total convergence is estimated to be about 1000:1.3 Physiologically, this convergence increases the sensitivity of the olfactory signal sent to the brain. From the mitral cells the message is sent directly to the higher levels of the central nervous system in the corticomedial amygdala portion of the brain (via the olfactory nerve tract) where the signaling process is decoded and olfactory interpretation and response occurs. The Trigeminal Sense in the Olfactory Epithelium It must also be recognized that the olfactory epithelium contains another sensory system in the form of "Trigeminal Nerve" receptors. Whereas, the olfactory receptor system is highly localized in humans, the fifth cranial or trigeminal nerve (which is the largest cranial nerve and is the responsible sensory nerve of the face, teeth, mouth, most of the scalp, and the motor nerve of the muscles of mastication) provides a second set of nerve endings which are responsible for tactile, pressure, pain and temperature sensations in the areas of the mouth, eyes and nasal cavity. A number of chemical trigeminal stimulants produce effects described as hot, cold, tingling or irritating. For example, "leavo-menthol or (-)-menthol" produces the trigeminal feeling of cold at moderate concentrations and "hot" at high concentrations in the nasal cavity. This type of sensory "description" is often not just limited to the areas of the nose, mouth and eyes, but also occurs on skin areas not served by the 5th cranial nerve (especially, the genitalia) and thus such stimulants may effect a variety of nerve endings. Similarly "camphor" which possesses markedly more aroma than menthol, also produces the "cold" sensation via interaction with trigeminal receptors. Ohloff states that "About 70% of all odors are said to stimulate the trigemenal nerve although, in general, they may be several times less sensitive than olfactory receptors".4 Other commonly encountered trigeminal stimulants include the chemicals allyl isothiocyanate (mustard, mustard oil), capsiacin (hot Chile powder, mace spray) and Diallyl sulfide (onion). ......................................... ........... _____________ 1. Demole, E., H. Wuest, Synthses stroslectives de deux trioxydes C18H30O3 stroisomres, dambrinolide et sclarol-lactone a partir de derives du (+)-manool, Helv. Chem. Acta, 50: 1314 (1967). 2. Ohloff, G., Scent and Fragrances, Springer-Verlag, Berlin Heidelberg, 1994 3. http: www.cf.ac.uk uwcc momed jacob index.html 4. Ohloff, G., Scent and Fragrances, Springer-Verlag, Berlin Heidelberg, 1994, p. 6 _____________ Continue to Page 2 on Olfaction ......... Home Email: leffingwell@mindspring.com Other Subjects on the Leffingwell Associates Site The Product Offerings: Flavor-Base 2004 Additive-Master 2001 Juice-Master 2004 Beverage-Master 2004 VCF 2000 - Volatile Compounds in Foods ESO 2000 - Essential oils PMP 2001 - Perfumery Materials PFC - Perfume Fragrance Classification FRM 2001 - Flavor Raw Materials Odour Thresholds Other Interesting Places: In the News Welcome Page Guest Book Flavor Fragrance Links Herbs Botanical Links Food Science Links Chemoreception Links Search PubMed Phytochemical Ethnobotanical Search Page Chirality Odour Perception Odor Thesholds of GRAS Flavor Chemicals Olfaction - A Review Aldehydes - GRAS: Odor Properties and Molecular Visualization Alkenols: Odor Properties and Molecular Visualization Burnt Sugar Notes: Odor Properties and Molecular Visualization delta-Lactones - GRAS: Odor Properties and Molecular Visualization Esters - GRAS: Odor Properties and Molecular Visualization gamma-Lactones - GRAS: Odor Properties and Molecular Visualization Pyrazines - GRAS: Odor Properties and Molecular Visualization Carotenoids- Precursors of Important Fragrance Flavor Constituents Boronia - Aromas from Carotenoids Saffron - Aromas from Carotenoids Rose - Aromas from Carotenoids Osmanthus - Aromas from Carotenoids Tobacco - Aromas from Carotenoids Lycopene - The Ultimate Phytochemical Nutraceutical? Smoke Flavor I. -The Flavor of Hardwood Smoke Smoke Flavor II. - Dark Fire-Cured Tobacco .......August 23, 1999 Since April 3, 1999 FastCounter by LinkExchange Copyright 1999-2001 by Leffingwell Associates The Brain Page Eclectic collection of thought-provoking, quasi-scientific opinions on brain function. brainuse.html Jane's Brain Page Sponsored by Glossary Love impulse.mpeg music therapy Brain Graphic by John Sundsten, PH.D. Process - Biochemical basis of Behavior, Personality Perception Emotions - neuropeptides attaching to receptors stimulating an electrical charge on neurons . Joy, grief, love are all biochemical; each emotion involves the same peptides. Disorders - major shifts in mood, thoughts, or behavior that have a severe and continuous impact on all aspects of life. Heal Thy Self Altered States - Higher Consciousness , Self Destruction or a Tool for Mind Control? 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Busis, M.D. All rights reserved. Koch Lab Biophysics of Neuronal Computation The Koch Lab Neurophysiology of attention and awareness (Caltech) Using the detailed biophysics and microanatomy of cortical neurons to study their complexity from an information theory point of view - from the California Inst. of Technology. Research in biophysics, cortical circuits, psychophysics, visual illusions, neuronal correlate of consciousness. Home Page of the Koch Laboratory [Credits] [Directions to the lab] [Local use] [Home] [News] [Research] [People] [Papers] [Classes] [Jobs] Last modified: 2004-09-17 22:30:00 Principles of Psychobiology Interactive software study guide in psychobiology and neuroscience - for purchase from Red Reef Publications. Resources for the Brain Sciences Mail Order Form Institutional and School Orders International Shipping Brain Models Sensory Models Anatomy Software Anatomical Charts Books K- 8 Resources Brain Novelties Site Map Privacy Policy Catalog Request Contact Us Track Your Order 24 Hour Shipping for Most Products! Resources for the Brain Sciences Orders received in an average of 3 days* Product Search Search Join our Mailing list Human Brain Models for New Products and Specials of the Month! Subscribe Remove You're Safe! Read our Privacy Policy... Go to the Brain Model Page Go to Sensory and Spinal Models Budget Brain Models for as low as $29.95! We sell over 25 human brain models ranging from economy brain models to lecture-grade teaching models. Human brain models allow students to acquire fundamental knowledge about three-dimensional relationships in the human brain. To learn more about brain models visit the human brain model product page . 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Tree of Life Web Project Home Tree of Life Web Project Explore the Tree of Life Browse the Site Root of the Tree Popular Pages Sample Pages Recent Additions Random Page Treehouses Biographies Picture Sampler advanced News New data entry tools for ToL scientific contributors... read more about this picture Learn about ... Lophiiformes (anglerfishes) image info "The order Lophiiformes contains a highly diverse array of marine fishes that are primitively benthic shallow-water dwellers...." read more previously featured pages The Tree of Life Web Project (ToL) is a collaborative effort of biologists from around the world . On more than 4000 World Wide Web pages, the project provides information about the diversity of organisms on Earth, their evolutionary history ( phylogeny ), and characteristics. Each page contains information about a particular group of organisms (e.g., echinoderms , tyrannosaurs , phlox flowers , cephalopods , club fungi , or the salamanderfish of Western Australia ). ToL pages are linked one to another hierarchically, in the form of the evolutionary tree of life. Starting with the root of all Life on Earth and moving out along diverging branches to individual species, the structure of the ToL project thus illustrates the genetic connections between all living things. read more about the Tree of Life Web Project... "The affinities of all the beings of the same class have sometimes been represented by a great tree... As buds give rise by growth to fresh buds, and these if vigorous, branch out and overtop on all sides many a feebler branch, so by generation I believe it has been with the great Tree of Life, which fills with its dead and broken branches the crust of the earth, and covers the surface with its ever branching and beautiful ramifications." Charles Darwin, 1859 Browse Help Features Learning Contribute About Search Privacy Policy Copyright Policies Tree of Life design, images, and icons copyright 1995-2005 Tree of Life Web Project. All rights reserved. Image of rose 1999 Nick Kurzenko. Image of annelid worm 2001 Greg W. Rouse. The Tree of Life Web Project is hosted by The University of Arizona College of Agriculture and Life Sciences and The University of Arizona Library Site Navigation Browse Help Features Learning Contribute About Biognomen A Linnaean taxonomy arranged in hyperlinked evolutionary trees. One can navigate through the hierarchy vertically, or follow a lineage horizontally at a particular level of the hierarchy. Biognomen The Biognomen This is a Linnaean taxonomy arranged to show the evolutionary relationships among taxa. The evolutionary trees are mapped. Just click on the name of the group you want to see more detail on. Names in green are ancestor or descendant taxa. Clicking on a green name will keep you at the same level of the hierarchy. The names of extinct taxa are generally presented in gray. You can also go directly to a group by typing its scientific or common name in the search box. Be sure to use the singular form of common names. Criticism of cladistic taxonomy There are numerous good evolutionary trees on the web. I especially like the Tree of Life and the UCMP Phylogeny Wing . The problem is that they are all cladograms, not true evolutionary trees. While cladistics is a useful tool, for a general-purpose taxonomy the systematist should not stop there and merely use the cladogram as the final classification system. A classification system should indicate what an organism is like, without requiring one to trace its entire evolutionary history. The first problem with cladistic taxonomy is that many biologists are attempting to graft it onto the incompatible Linnaean system, insisting that each taxon should be a clade. This is possible if only living forms are considered, but it results in systems where primitive groups are excessively split, compared to the more advanced groups (such as four divisions of gymnosperms, only one division for the angiosperms). If extinct species are include, the method breaks down altogether. For example, if classes for mammals and reptiles are defined, the common ancestor of those two groups cannot be assigned to a class. Of course this same logic applies to the genus, so cladists need to either propose a new system of naming fossil species, or break their system and allow paraphyletic genera. Fortunately some cladists recognize this and don't try to assign Linnaean ranks to their clades. This practice is less objectionable for they are not rampaging through the traditional taxonomy, messing it up for no good reason, though they do have a tendency to hijack traditional terms that have passed into vernacular language, and try to convince people that birds are dinosaurs or whatnot. There are other problems with cladistic taxonomy though. They are tripped up by a frequent need to refer to paraphyletic groups that they are philosophically proscribed from naming. This leads to circumlocutions such as "stem reptiles" or "non-avian dinosaurs." In fact, in a comprehensive, multi-page cladogram, an individual page often forms a nice, useful, paraphyletic taxon plus anothergroup that doesn't fit and is probably hidden by some obscure name. One of the most ridiculous results of the cladistic system is that lungfish are grouped with human beings, rather than with salmon, even though the lungfish and salmon are both scaly, cold-blooded fish, while humans are hairy, warm-blooded bipeds that live on the land. 1999-2005 Brock Filer filerba@softhome.net Partnerships for Enhancing Expertise in Taxonomy National Science Foundation (USA) competition to support competitively reviewed research projects that target groups of poorly known organisms. NSF PEET Project Homepage The National Science Foundation (NSF) , in partnership with academic institutions, botanical gardens, freshwater and marine institutes, and natural history museums, seeks to enhance and stimulate taxonomic research and help prepare future generations of experts. NSF announces a special competition, Partnerships for Enhancing Expertise in Taxonomy (PEET), to support competitively reviewed research projects that target groups of poorly known organisms. This effort is designed to encourage the training of new generations of taxonomists and to translate current expertise into electronic databases and other formats with broad accessibility to the scientific community. News Conferences Workshops Awards PEET Products EMail List Related Sites New PEET Program Solicitation (NSF 04-606) NSF Supplement Opportunity for CETAF-NSF Cooperative Research Visits PEET V Announcement : "Spatial Temporal Issues in Taxonomy", 09 20-09 23 04 2003 PEET Awards posted. . PEET IV to be held at UC Berkeley June 1-5, 2002. NSF -- Assembling the Tree of Life Program Solicitation. NSF - Research Coordination Networks in Biological Sciences Program Announcement Biogeoinformatics of Hexacorallia Restructured and Modernized Scarab Beetles pages Postdoctoral Fellowship Available Symposium - Linnaean Taxonomy in the 21st Century , March 30-31, 2001 Symposium - Systematics and Biology of Aphelinidae and Trichogrammatidae, June 18-19, 2001 PDF Flyer - 2 Pages Don't miss the PEET-Bivalves website NSF announces solicitation for the Undergraduate Mentoring in Environmental Biology (UMEB) NSF announces (PEET): Special Competition in Systematic Biology (NSF 00-140) . Search the PEET Website Send technical comments or questions to robd@ku.edu . Send content related comments or questions to Steve Ashe . DELTA: Description Language for Taxonomy A flexible format for encoding taxonomic descriptions for computer processing. It can be used to produce natural-language descriptions, conventional or interactive keys, classifications, and information-retrieval systems. DELTA - DEscription Language for TAxonomy DELTA The DELTA format (DEscription Language for TAxonomy) is a flexible method for encoding taxonomic descriptions for computer processing. It has been adopted by the International Taxonomic Databases Working Group (TDWG) as a standard for data exchange. DELTA-format data can be used to produce natural-language descriptions, conventional or interactive keys, cladistic or phenetic classifications, and information-retrieval systems. Overview of the DELTA System Programs and documentation Support and discussion: the DELTA-L mailing list Data descriptions, illustrations, identification, information retrieval Methodology of interactive keys and descriptive databases References applications and documentation of the DELTA System Contacts, citation, acknowledgements Printing files obtained from this site Search WWW Search delta-intkey.com Biodiversity and Biological Collections Universal Biological Indexer and Organizer A networked information service for biological information resources, based upon the Taxonomic Name Server, a thesaurus of taxonomic information. uBio Home Page uBio is an initiative within the science library community to join international efforts to create and utilize a comprehensive and collaborative catalog of known names of all living (and once-living) organisms. The Taxonomic Name Server (TNS) catalogs names and classifications to enable tools that can help users find information on living things using any of the names that may be related to an organism. learn more Nomina si pereunt, perit et cognitio rerum If the names are lost the knowledge also disappears - J.C. Fabricius, 1778, Philosophia Entomologica VII,1 uBio News Sep. 22, 2005 - Volume 10 of Nomenclator Zoologicus online Aug. 5, 2005 - Name-string processing tools . July 1, 2005 - Name-aware Google Client June 7, 2005 Thanks to Charles Hussey for reviewing 100 pages of Nomenclator Zoologicus . May 23, 2005 - Dr. Adorian Ardelean starts new uBio position. More uBio NameBank Statistics NameBank records: 5,126,091 Scientific: 4,645,713 Vernacular: 480,378 Updated 11 17 05 10:00 am GMT Search TNS Ex. (" Elephant " or " Felis* ") MISSION STATEMENT | ADVISORY BOARD | PEOPLE | CONTACTUS uBio copyright 2004 by The Marine Biological Laboratory Systema Naturae 2000 An up-to-date historical cross-referenced classification of life based on original authorative scientific literature. Systema Naturae 2000 This page uses frames, but your browser doesn't support them. Curiosities of Biological Nomenclature Etymologies, puns and funny sounds and wordplay in taxonomy. Curiosities of Biological Nomenclature Curiosities of Biological Nomenclature Mark Isaak eciton@earthlink.net Scientific names of organisms are not usually known for their entertainment value. They are indispensable for clarity in communication, but most people skip over them with barely a glance. Here I collect those names that are worth a second look. Some names are interesting for what they are named after (for example, Arthurdactylus conandoylensis, Godzillius), some are puns (La cucaracha, Phthiria relativitae), and some show other kinds of wordplay (such as the palindromic Orizabus subaziro). Some have achieved notability through accident of history, and many show the sense of humor of taxonomists. The names which are recent additions to this collection will be shown in a brighter shade of red. (How recent depends on how often I update. I'll try to keep the newest names distinctive for about a month.) On This Page: The Rules We Play By Further Information Other Related Links The Rules We Play By Rules for assigning scientific names have become well codified in order to keep the names internationally unambiguous and understandable. The full set of rules is rather involved, but the most important parts are fairly simple: Binomens - A genus name is one word. A species name is binomial -- the genus plus a second word. Subspecies have a trinomial name (a "trinomen"). A subgenus is occasionally given in parentheses after the genus, thus: Bison (Bison) bison bison (Linne, 1758) Skinner Kaisen, 1947 (bison (what else?)) Authorship - The author's name and date of publication are typically given after the scientific name. If a name is later changed (e.g., moved to a new genus), The original author is given in parentheses. The names are often abbreviated; in particular, "L." is Linnaeus. Anonymous publication is invalid as of 1950, but was accepted before then. In botanical nomenclature, the authors are given in taxonomic monographs, and if a name is changed, both the original author (in parentheses) and the revising author are named. For example: Taphrina cerasi (Fuck.) Sad. The fungus Taphrina cerasi was originally described by Karl Wilhelm Gottlieb Leopold Fuckel and later redescribed by Richard Emil Benjamin Sadebeck, so this listing now appears in catalogs. Buettikoferella Stresemann, 1928 (buff-banded grassbird) This name was originally published in an obituary. Stresemann mentioned, in an obituary for Buettikofer, that a bird genus was named after him, but Stresemann realized that Buettikoferia was preoccupied, so he proposed this as a replacement. [Orn. Monatsb. 36: 40,note4] Description - After 1930, new names must come with a description (or reference to one) telling what the name means. Type specimen - Descriptions should refer to an actual specimen, available for examination in a museum or other collection. There are complicated rules for determining the type if the original is lost or if there was no type specimen with the original description. The taxonomy of types is rather complicated in itself; see this type dictionary . As of 1993, the paleontologist Edward Drinker Cope is the type specimen for Homo sapiens Linnaeus, 1758. Robert Bakker formally described his skull, and it was approved by the ICZN. Nessiteras rhombopteryx (Loch Ness monster) This proposed name is not a valid scientific name because there is no type specimen to go with it. Priority - The oldest valid published name is the one that gets used. This is true even if there is some error in the original name: Eschscholzia Chamisso, 1820 (California poppy) Named for zoologist Johann Eschscholtz, but the 't' was omitted from the publication. Haliaeetus Savigny, 1809 (bald eagle) This name is a misspelling; the original description had an extra 'e', which must now stay there. Wisteria Nuttall (woody vine) Named for Caspar Wistar, author of America's first anatomy textbook and successor of Thomas Jefferson as head of the American Philosophical Society. But Nuttall misspelled it with an "e", and the name is stuck. There are means of overruling priority, if the newer name has come into common use before the priority of the original name is recognized. Scrotum humanum Brookes, 1763 (Megalosaurus) Among the oldest dinosaur bones discovered. So named because the condyles had a testicular shape. Fortunately, the genus will continue to be known as Megalosaurus because that name came into common use before it was discovered that Scrotum was an earlier synonym. [Halstead Sargent, 1993, Modern Geol. 18:221-4] Sometimes the same name gets reused by people not aware of the original use: Argus Bohadsch, 1761 (gastropod) Argus Scopoli, 1763 (lycaenid) Argus Scopoli, 1777 (satyrid) Argus Poli, 1791 (mollusk) Argus Temminck, 1807 (bird) Argus Lamarck, 1817 (hesperiid) Argus Boisduval, 1832 (lycaenid) Argus Walckenaer, 1836 (arachnid) Argus Gray, 1847 (mollusk) Argus Gerhard, 1850 (lycaenid) Only the original name is valid; all the rest are homonyms. However, the same name can be used for a plant and an animal. There are many instances: Adonis L., 1753 (bird's-eye ranuncula) or Adonis Gronow, 1854 (fish) Andromeda L., 1753 (wild rosemary) or Andromeda Gistel, 1834 (bupestrid beetle) Arenaria Linnaeus 1753 (Caryophyllaceae plant) or Arenaria Brisson 1760 (bird) Aotus (pea, or monkey) Bartramia (moss, or sandpiper) Cannabis L. (hemp) or Cannabis Blyth, 1850 (bird) Cecropia (tree, or moth) Cereus (cactus, or sea anemone) Colocasia (taro, or tussock moth) Culcita (tree fern, or echinoderm) Darwiniella (orchid, or barnacle) Dracunculus (herb, or roundworm) Dugesia (composite, or flatworm) Ficus (fig, or gastropod) Iris (flower, or mantis) Lactarius (fungus or fish) Leptonia (toadstool (now usu. a subgenus of Entoloma), or rove beetle) Liparis Rich., 1818 (orchid) or Liparis Scopoli, 1777 (fish) Morus (mulberry, or gannet) Oenanthe (water celery, or bird) Pieris (Japanese andromeda, or butterfly) Prosopis (mesquite, or solitary bee) Prunella Linnaeus 1753 (Lamiaceae plant) or Prunella Vieillot 1816 (bird) Words and Letters - The names must be pronouncible words (preferably Latinized), using Latin letters, with no diacritics or punctuation (except hyphens can be used in some circumstances). Some names stretch the pronouncibility. Ekgmowechashala (early Miocene North American primate) The name means "small fox-man" in Lakota Lainodon orueetxebarriai Gheerbrant Astibia, 1994 (Upper Cretaceous mammal) Schtschurowskia Regel Schmalhausen, 1882 (Umbelliferae) Tahuantinsuyoa macantzatza Kullander, 1986 (Peruvian cichlid) The genus is a Quechuan name of the Incan empire; this page has a pronunciation. Exceptions - When an otherwise valid name would "disturb stability or universality or cause confusion," the International Commission on Zoological Nomenclature may choose another name instead. There are plenty of other rules; see the ICZN's code for the complete set. The rules above are for zoological nomenclature. The rules for botanical nomenclature are similar. One notable exception is that zoology allows tautonyms (genus and species repeating the same word, e.g. Bufo bufo), and botany does not. There is also a separate International Code of Nomenclature of Prokaryotes governed by the International Committee on Systematics of Prokaryotes (ICSP). It has published the Approved Lists of Bacterial Names, listing all names valid as of 1 January 1980; it serves as a starting point for adding new names. "(Approved Lists 1980)" may be used in place of an author citation for names on the lists. Other rules particular to prokaryotes are: Names must be published in International Journal of Systematic Bacteriology or International Journal of Systematic and Evolutionary Microbiology to be valid. Subgenus and subspecies names, when present, are labelled "subgen." and "subsp." Prokaryote names must avoid existing names of plants and animals. The Code recommends that if a species is named after a person, the person should in some way be connected with it. A name should be rejected "whose application is likely to lead to accidents endangering health or life or both or of serious economic consequences." top Further Information General For a collection of hundreds of related links, organized and annotated, see Zoological Record: Systematics, taxonomy, nomenclature . The All Species Toolkit , a database containing over 870,000 species. World Biodiversity Database , a taxonomic database and information system which aims to document all known species. In many cases, it includes information such as description, range, and genome. Species 2000 has the objective of enumerating all known species. NCBI's Taxonomy Resources , references and on-line resources used by the Taxonomy group at GenBank. International Plant Name Index Query Nomenclature For a good introduction to zoological nomenclature, see Gary Rosenberg's Naming Names . For a tutorial on botanical nomenclature, see A Guide to Botanical Nomenclature: A Tennessee Tutorial . Nomenclatural Glossary for Zoology . Perspectives on Binomial Names of Virus Species by M.H.V van Regenmortel. Other articles and collections of curious names Clever gene names . FlyNome , "A database of Drosophila nomenclature," tells the stories behind Drosophila gene names. Doug Yanega's home page . Arnold Menke's Funny or curious zoological names. Molecules with Silly or Unusual Names collects curiosities of chemical names. A Fly Called Iyaiyai , an article from Science News, May 26, 2001, by Susan Milius. Richard Conniff's "What's in a Name?," Smithsonian Magazine, December 1996. Its abstract is on the web. Warner Brother's pseudo-Latin names of Road Runner and Wile E. Coyote. Biological Etymologies Donald J. Borror's Dictionary of Word Roots and Combining Forms (Mayfield Publishing, Mountain View, CA, 1960) is quite a useful reference to many of the elements which make up more mundane scientific names. Biographical Etymology of Marine Organism Names (BEMON) gives biographies of people whom marine organisms are named after. Names of the Reptiles and Amphibians of North America has translations and etymologies for damn near all of them, with bibliographic and myth notes on the people and figures from mythology that are sources for names. Dictionary of Botanical Epithets . Etymologies of Bacteria Names (in French) top Other Related Links For an extensive and growing list and description of biodiversity, organized in the context of the evolutionary tree, see The Tree of Life . List of Bacterial Names with Standing in Nomenclature lists valid bacterial names. See also its Definitions and Abbreviations for an index of rules for bacterial nomenclature. Down with species , a brief article about a proposal to replace Linnaean taxonomy with one based on "Least-inclusive taxonomic units." Alroy, John, 2002. How many named species are valid? PNAS 99: 3706-3711. (". . . 24-31% of currently accepted names eventually will prove invalid. . . .") Biopat allows you to buy the privelege of naming a newly discovered species yourself. (The ICZN denounces it as a "striking departure from scientific tradition" that would "irreversibly obscure science and hinder conservation efforts.") Gazetteer of Planetary Nomenclature top Last modified: . 2002 Mark Isaak . All rights reserved. Back to Mark Isaak's Home Page Biodiversity and Biological Collection Databases Information of interest to systematists and other organismic biologists such as biological collections, taxonomic files, directories and ListServ archives, computer programs, reports by standards bodies (IOPI, ASC, and SA2000), and access to on-line journals. Biodiversity and Biological Collections Delta Intkey Taxacom Archives Morphometrics E-Pubs News Archives About Us Related Sites DigiMorph UMMZ NeoDat Site Currently Under Construction Supported by NSF Experimental Google sample searches -- Devoted to information of interest to systematists and other biologists of the organismic kind. Within these pages you will find information about specimens in biological collections, taxonomic authority files, directories of biologists, the Delta system and links for hundreds of biodiversity and collection resources. General Biodiversity (15) Natural History Museums (63) Biological Collections (82) Announcements and News (3) Conferences (22) Conservation (29) Collection Databases (53) Biological Societies (63) Directories Publications (49) Data Models and Standards (6) Ichthyology (47) Herpetology (38) Mammalogy (36) Ornithology (35) General Invertebrates (33) Entomology (63) Worms Botany (58) Mycology and Microbiology Paleontology (37) Top 10 Search Results for "Darwin's Finches" 0 results returned Nov 17, 2005 at 09:32 AM 2002 BioCollections.org Webmaster Integrated Taxonomic Information System Authoritative taxonomic information on plants, animals, fungi, and microbes of North America and the world. Integrated Taxonomic Information System Welcome to ITIS, the Integrated Taxonomic Information System! Here you will find authoritative taxonomic information on plants, animals, fungi, and microbes of North America and the world. We are a partnership of U.S., Canadian , and Mexican agencies ( ITIS-North America ); other organizations; and taxonomic specialists. ITIS is also a partner of Species 2000 and the Global Biodiversity Information Facility (GBIF) . Quick search on: Any Name or TSN* Common Name Scientific Name TSN* In: every Animal Plant Fungal Monera Protozoa Kingdom exactly for containing starting with ending with * Taxonomic Serial Number (TSN) Go to Advanced Search and Report Last Updated: 23-Nov-2004 Privacy statement and disclaimers http: www.itis.usda.gov index.html Treebase A relational database of phylogenetic trees and the data matrices used to generate them from published research papers. Includes animals, plants, and fungi. TreeBASE TreeBASE is a relational database of phylogenetic information hosted by the University at Buffalo . In previous years the database has been hosted by Harvard University Herbaria , Leiden University EEW , and the University of California, Davis . TreeBASE stores phylogenetic trees and the data matrices used to generate them from published research papers. We encourage biologists to submit phylogenetic data that are either published or in press, especially if these data were not fully presented in the publication due to space limitations. TreeBASE accepts all types of phylogenetic data (e.g., trees of species, trees of populations, trees of genes) representing all biotic taxa. For more information, see an introduction to TreeBASE, information on searching, the database schema, and a graphic presentation of the web site's internal structure. Also, check out some ideas on why you might want to use TreeBASE. TreeBASE is now a participant in CIPRes , the NSF-sponsored Cyberinfrastructure for Phylogenetic Research project. As such, it is being redesigned from the ground up through collaborative research among Computer Scientists, Biologists, and Programmers. Presently TreeBASE is being mirrored at the San Diego Supercomputer Center at UCSD . Eventually, the redesigned, new and improved CIPRes version of TreeBASE will take over. In the meantime, please send us suggestions of what kinds of features or functions would you like designed into the new database? Are there new or unusual data types , queries, and functions that are not already offered by the current version of TreeBASE? Please send your suggestions here . The WWW implementation of TreeBASE requires a forms-capable and frames-capable browser. We would be very grateful for any feedback on TreeBASE, including suggestions for improvement. In particular, if you encounter any errors please let us know. Glossary of Phylogenetic Systematics An annotated, extensive hypertext glossary of the terminology of Phylogenetic Systematics, with a discussion and criticsm of mainstream Computer Cladistics. weiterleitung ETI World Taxonomist Database Directory of specialists searchable by name, country, or specialization. ETI BioInformatics - World Taxonomist Database Search the database Submit your personal information Update your personal information Taxonomy and online databases Biodiversity Miscellaneous World Taxonomist Database Ever been looking for a colleague's address for a quick reference on his her latest publication? Or wanted to send an announcement to a group of specialists to inform them about a special workshop or symposium? Then connect with colleagues around the world using ETI's World Taxonomist Database, an online directory service with continuously updated information on thousands of taxonomists specialists worldwide. However, we depend on your cooperation to make it work. Please register and notify your colleagues of this service. It's also vital to keep your record up-to-date . If we all participate, this will continue to be a wonderful up-to-date taxonomist directory! Currently 4255 taxonomists specialists are registered in our World Taxonomist Database. You can search for a person, an institute, a specific country, a taxonomic group, or for a combination of these criteria if you need to narrow down your search. If you can't find who or what you are looking for, try an advanced search . Taxonomist Name: Who's new? Institute: Country: Select country... ---------------------- United States (926 records) Germany (216 records) United Kingdom (198 records) Australia (192 records) Brazil (173 records) India (143 records) Spain (141 records) France (136 records) Canada (132 records) Mexico (129 records) ---------------------- Algeria Angola Argentina Armenia Australia Austria Bangladesh Belarus Belgium Belize Benin Bermuda Bhutan Bolivia Brazil Brunei Darussalam Bulgaria Cameroon Canada Cape Verde Chile China Colombia Costa Rica Croatia (Hrvatska) Cuba Czech Republic Denmark Dominican Republic Ecuador Egypt Estonia Fiji Finland France French Guiana French Polynesia Gabon Georgia Germany Greece Greenland Guatemala Guyana Honduras Hong Kong Hungary Iceland India Indonesia Iran Ireland Israel Italy Jamaica Japan Kenya Korea, South Kyrgyzstan Laos Latvia Lebanon Libya Lithuania Luxembourg Malaysia Malta Mayotte Mexico Morocco Namibia Nepal Netherlands New Zealand Nicaragua Nigeria Norway Oman Pakistan Panama Papua New Guinea Paraguay Peru Philippines Poland Portugal Puerto Rico Romania Russian Federation Singapore Slovak Republic Slovenia South Africa Spain Sri Lanka Sudan Sweden Switzerland Syria Taiwan Thailand Trinidad and Tobago Tunisia Turkey Turkmenistan Ukraine United Kingdom United States Uruguay Uzbekistan Vanuatu Venezuela Viet Nam Yemen Yugoslavia Zimbabwe Specialization Enter a keyword that best describes your group of interest, either a vernacular or (preferably) a scientific name. You may also enter part of a word i.e., testu will retrieve records that contain Order Testudines as well as Family Testudinidae. Advanced search Scalenet - Glossary A short glossary explaining some of the terms used in taxonomy. From a site on scale insects. Glossary Glossary Terms Pertaining to Zoological Nomenclature Allotype A specimen designated from the type series that is the opposite sex of the holotype. Available name A name that is correctly proposed according to the International Code of Zoological Nomenclature. An available name is not necessarily the valid name. Category Any rank within the classification hierarchy, e.g., family, subfamily, subspecies. Change of rank When a name is moved from one level of the classification system to another, e.g., when De Lotto (1955) moved Ceroplastes destructor brevicauda from the subspecies to the species rank C. brevicauda this was a change of rank. Classification A system of nested hierarchical categories used to efficiently store information about the diversity of life. Classify To place a taxon in a classification system. Cotypes A term no longer recognized in the International Code of Zoological Nomenclature; synonymous with syntypes. Emendation An intentional change to a previously proposed name, e.g., Lindinger proposed the emendation Hemiberlesea for the armored scale Hemiberlesia indicating that it was originally improperly formed. Holotype A specimen that serves as the standard bearer of a species or subspecies name. Homonym One of two or more scientific names that are identical but pertain to different organisms, e.g., Eriococcus mancus Ferris, 1955 and Eriococcus mancus (Maskell, 1897); Onceropyga Ferris, 1955 and Onceropyga Turner, 1904. Incertae sedis A name of uncertain identity. Junior homonym If there are only two homonyms, the junior homonym is the most recently described homonym; if there are more than two homonyms, the junior homonyms are all but the oldest described homonym which is the senior homonym, e.g., Eriococcus mancus Ferris, 1955 is the junior homonym and Eriococcus mancus (Maskell, 1897) is the senior homonym. Junior synonym If there are only two synonyms, the most recently described one is the junior synonym; if there are more than two synonyms, the junior synonyms are all but the oldest described one which is the senior synonym, e.g., Apiomorpha nux Fuller, 1896 is the junior synonym and A. pharetrata Scharder, 1863 is the senior synonym. Justified emendation An emendation that is correct according to the International Code of Zoological Nomenclature, e.g., the name susani is proposed as a patronym for a woman named Susan; according to the Code the name must be changed to susanae and is a justified emendation. Lectotype A specimen chosen as the standard bearer of a species or subspecies and selected from the syntype series. Misidentification A citation of a name in the literature that used the incorrect name because the specimens were improperly determined. Misspelling A citation of a name in the literature that is incorrectly spelled. Neotype A specimen chosen as the standard bearer of a species or subspecies name for which none of the original type specimens exist. New combination When a species is transferred to a different genus for the first time. Nomen nudum A name that does not fulfill the criteria set by the International Code of Zoological Nomenclature as a legally described scientific name and therefore cannot be used unless it is subsequently proposed correctly. Paralectotype All of the specimens in the syntype series of a species or subspecies other than the lectotype. Paratype All of the specimens in the type series of a species or subspecies other than the holotype. Replacement name A name that is assigned to replace a name that is a junior homonym, e.g., Onceropyga Turner, 1904 is the valid name and Onceropyga Ferris, 1955 is the junior homonym and must be replaced; Hoy (1963) proposed the replacement name Oregmopyga. Senior homonym The oldest described homonym, e.g., Onceropyga Turner, 1904 is the senior homonym and Onceropyga Ferris, 1955 is the junior homonym. Senior synonym The oldest synonym, e.g., Apiomorpha pharetrata Scharder, 1863 is the senior synonym and A. nux Fuller, 1896 is the junior synonym. Synonym One of two or more scientific names that are spelled differently but refer to the same organism, e.g., Apiomorpha nux Fuller, 1896 and A. pharetrata Scharder, 1863 are names used for the same species of eriococcid and are synonyms. Synonymy A section of a systematic presentation about an organism that lists all of the names that have been used for the organism including synonyms, new combinations, misidentifications, etc. In some cases this section may include only true synonyms. Syntypes The series of specimens used to describe a species or subspecies when the author did not include a holotype. Systematics The field of science dealing with the diversity of life and the relationships of life's component organisms. Taxon One or more organisms that belong to the same taxonomic unit. Taxonomy The field of science that classifies life. Topotype One or more specimens collected at the same location as the type series regardless of whether they are part of the type series. Type A term used to describe the nomenclatural importance of various kinds of specimens. Type locality The geographic location where the primary type was collected. Type species A species that has been selected as the standard bearer of a genus or subgenus. Type genus A genus that has been selected as the standard bearer of a tribe, family, or superfamily and provides the stem of the family-group name. Unavailable name A name that is incorrectly proposed according to the International Code of Zoological Nomenclature. Unjustified emendation An emendation that is incorrect according to the International Code of Zoological Nomenclature, e.g., the generic name Hemiberlesea Lindinger is an incorrect change of Hemiberlesia Cockerell according to the Code and is an unjustified emendation. Valid name The correct name of an organism, e.g., if Apiomorpha nux Fuller, 1896 and A. pharetrata Scharder, 1863 apply to the same species (and therefore are synonyms), then by the law of priority (the oldest name prevails) A. pharetrata Scharder, 1863 is the valid name. Return to Background Information Page Return to ScaleNet Home Page Classification Lab A project examining the phylogenetic tree of life and all of its features, with information and pictures for every class and an interactive, dynamic hierarchy. Classification Lab [ Purpose | Organization of our Website | Interactive Diagram | Background on Classification | Procedure | Format for Classification | Links | Back to Labs Page ] Purpose: To gain a working knowledge and better understanding of the methods and taxonomic and systematic basis for the classification of organisms. To observe a number of different organisms from different domains, kingdoms, phyla, and classes, and to compare and contrast these organisms and understand their evolutionary relationships. A word about the organization of our website: The biological classification system uses taxa, or individual levels of organization, to classify all organisms. To navigate around this website, you can use one of the following: A diagram showing the domain and kingdom levels of classification on this page An interactive, dynamic hierarchy depicting our classification levels down from the domains* A comprehensive index of organisms with complete classification* *Click on any taxon (e.g. Eukarya ) and you will be pointed to the page for that taxon containing a comprehensive description, any applicable diagrams, and a list of all subordinate taxa. On the Conclusions page, there is a comprehensive essay detailing the radiation of the diversity of life as we know it, beginning at the lifeless Earth and proceeding through the evolution of humans. Diagram of the Modern Classification Scheme: The information for each kingdom refers to the questions in "Format for Classification," seen below. What is Classification?--A Brief Background: Classification is essentially an effort by scientists to discover, reconstruct, and clarify the phylogeny, or evolutionary history, of an organism or group of organisms. This effort is a part of systematics, or the study of biological diversity and organization. Organisms are classified in a number of different taxa, or levels. The number and depth of systematic taxa have changed significantly over the years. A two-kingdom system (plants and animals) was instituted in the mid-18th century by Carolus Linnaeus, who also proposed the binomial system for naming organisms (with the scientific name including the genus and species name). This system was prevalent and widely accepted for over two hundred years, but it obviously had several major problems, including the ambiguous classification of prokaryotes, protists, and fungi. In 1969, American ecologist Robert H. Whittaker instituted a five-kingdom system with Kingdoms Monera (the prokaryotes), Protista (unicellular, multicellular, and colonial protists), Plantae (the plants-multicellular photoautotrophs with cellulose cell walls and discrete organs), Fungi (multicellular non-motile chemoheterotrophs with a unique reproductive method and life cycle) and Animalia (the animals-multicellular motile chemoheterotrophs having cells lacking cell walls). This system has thrived for three decades, and indeed is still somewhat widely used. In this lab, however, we will utilize the system now considered generally to be the best. This new system institutes a taxon above kingdom--the domain. Under the new system, life consists of three domains--Bacteria, Archaea, and Eukarya. The Bacteria and Archaea are all the prokaryotes--confined to a single kingdom under Whittaker's system. There are a number of distinctions between the two domains, which are discussed on a separate page . These two domains are believed to have diverged very early in the evolution of life. Eukaryotes then diverged from Archaea, and they comprise the third domain, consisting of kingdoms of plants, animals, fungi, and several protist kingdoms (for simplicity in this lab, we refer to them comprehensively as Kingdom Protista). A great deal of scientific research continues to go toward discovering more about and supporting (or refuting) this system of classification. Classic systematics utilizes a number of methods to directly derive the classification of an organism. In addition to anatomical considerations (including homologous structures), molecular biology has become a powerful tool, and contributes to systematics by providing the means for protein comparisons and analysis of DNA and RNA. Beyond these direct classical methods, cladistic analysis has taken root rather recently (since the 1960s). It involves the use of classical methods to organize organisms into clades, or monophyletic taxa. Each clade shares a distinct feature. The study of these features in the context of an ingroup (organisms that have any of the features) and an outgroup (organisms that have none) has allowed the establishment of a number of effective classification schemes. In cladistic analysis, each feature, or character, is viewed as a primitive character (common to an entire group) or a derived character (that arose in the evolution within the group). Cladistic analysis tends to be more objective than classic analysis, and allows for testable hypotheses. Closely tied to cladistic analysis is parsimony, or the search for the simplest practical phylogeny for an organism. Keeping this primer in mind, you will be able to better understand the basis for the classification of our organisms. For more information about classification, we have found several excellent pages with focuses similar to ours at The University of Ohio , The University of Arizona , Yahoo! Directories , and Lycos Directories . Procedure: The general procedure for the Classification Lab was as follows: Observe, diagram, and label the organism (use dissecting microscope as necessary) Research the taxonomic classification of the organism Write a brief description of the organism, focusing on the characteristics that distinguish it as a member of its class (or other higher taxon, if not possible) Answer questions below (see Format for Classification) Format for Classification: For each organism, a brief biological description is given. In addition, four main questions are answered: Is the organism prokaryotic or eukaryotic? Is the organism unicellular, multicellular, or colonial? How does the organism reproduce, and how does it increase its genetic variability? What are the sources of energy and carbon for the organism? Links: INTERACTIVE "TREE OF LIFE" THE CONCLUSIONS ESSAY NUMERICAL LIST OF ORGANISMS THE PHYLOGENETIC TREE: STYLE OR SUBSTANCE? This page copyright 2000, The Bio-Web Group, Sidwell Friends School, Washington, D.C. If you have any questions or suggestions, please feel free to e-mail us , and please visit our homepage . Expert Center for Taxonomic Identification ETI is a non-governmental organisation in operational relations with UNESCO. Their mission is to develop scientific educational computer-aided information systems, to improve general access to, and to promote use of taxonomic and biodiversity knowledge worldwide. Aims to develop scientific and educational computer aided information systems, to improve the general access to, and to promote the broad use of taxonomic and biodiversity knowledge worldwide. ETI BioInformatics ETI BioInformatics develops and produces scientific and educational computer-aided information systems. We offer a wide range of products and services , including scientific and educational web applications; the Linnaeus II software package for biodiversity documentation; a series of scientific and popular titles on CD- and DVD-ROM and a 3D imaging studio. Examples of ETI's work in the past and present can be seen in our portfolio . Taxonomists and specialists are invited to become ETI partners and to sign up to the World Taxonomist Database , joining 4247 colleagues. The World Biodiversity Database currently includes 24514 extensively described and illustrated taxa. Latest news Latest releases How many taxonomists? ETI's World Taxonomist Database has played an important role in a recent survey by the Global Taxonomy Initiative (GTI). Bird collection website of the ZMA expanded Browse or search 450+ threatened or extinct bird species in the ZMA collection, each illustrated with a large picture. New project added to WBD The Diaspididae of the World project by G. Watson is the 17th project available in the World Biodiversity Database. Linnaeus II 2.5.1 update Linnaeus II 2.5 has received a maintenance update. More news European Multimedia Bioinformatics Educational Resource (EMBER) EMBER is an introductory bioinformatics tutorial. The CD-ROM includes exercises in protein sequence analysis, protein structure analysis and case studies (e.g., sickle cell anaemia, inositol phosphatases). More new releases Science at the Natural History Museum A world leader for research on taxonomy and biodiversity. Research and curation - Natural History Museum Skip to page content Skip to page content Research and curation Business centre About us Search Home Visit us Nature online Kids only Education Take part Buy online You are here: Home Research and curation Primary navigation Science Directorate Biodiversity research Science enquiries and NHM Consulting Research projects Collections and Library Science facilities Postgraduate learning Collaborations Departments Staff directory Research and curation Science at the Museum Stalagmitic malachite, polished to show banding, from Bwana Mkubwa Mine, Zambia. The Natural History Museum is an international leader in the scientific study of the natural world. Our science describes the present diversity of nature, promotes understanding of the critical importance of its past, and develops knowledge that supports anticipation and management of the impact of human activity on the environment. Read complete article Latest news Mass migration at the Museum Twenty eight million insects and spiders are on the move at the Natural History Museum before their current home is demolished to make way for a new 65.9 million extension. More... More news Research projects Research projects More than 300 scientists work at the Museum to tackle a diverse range of global problems, such as threats to the Earth's biodiversity, the maintenance of delicate ecosystems, environmental pollution and disease. Find out more Enquiries and NHM Consulting Enquiries From specimen identification to how to become a palaeontologist. NHM Consulting NHM Consulting draws upon the expertise, collections and facilities to support an established and expanding international consultancy service. Find out more Biodiversity UK Biodiversity Programme Find out more about how the Programme at the Museum is helping to conserve native wildlife. Find out more Contact and enquiries Accessibility Site Map Terms of use The Natural History Museum, London 2005. All Rights Reserved American Society of Plant Taxonomists Promotes research and teaching in the taxonomy, systematics, and phylogeny of vascular and nonvascular plants. Systematic Botany the Jornal of the American Society of Plant Taxonomists (ASPT) NCBI Taxonomy Homepage The NCBI Taxonomy Homepage NCBI Taxonomy Homepage PubMed Entrez BLAST OMIM Taxonomy Structure Search for As complete name wild card token set phonetic name taxonomy id lock Taxonomy browser Archaea Bacteria Eukaryota Viroids Viruses Taxonomy common tree Taxonomy information Taxonomy resources Taxonomic advisors Genetic codes Taxonomy Statistics Taxonomy Name Id Status Report Taxonomy FTP site FAQs How to reference the NCBI taxonomy database How to create links to the NCBI taxonomy How to create LinkOut links from the NCBI taxonomy Extinct organisms Recent changes to classification The NCBI Taxonomy Homepage Taxonomy Tip of the Day Change is good New scientific data can improve our understanding of the relationship among organisms. Consequently, the classification found in the NCBI GenBank taxonomy database will occasionally change to incorporate new systematic schemes. Some of the recent changes to our classification system are discussed here . These are direct links to some of the organisms commonly used in molecular research projects: Arabidopsis thaliana Escherichia coli Pneumocystis carinii Bos taurus Hepatitis C virus Rattus norvegicus Caenorhabditis elegans Homo sapiens Saccharomyces cerevisiae Chlamydomonas reinhardtii Mus musculus Schizosaccharomyces pombe Danio rerio (zebrafish) Mycoplasma pneumoniae Takifugu rubripes Dictyostelium discoideum Oryza sativa Xenopus laevis Drosophila melanogaster Plasmodium falciparum Zea mays Comments and questions to info@ncbi.nlm.nih.gov Credits: Joe Bischoff, Mikhail Domrachev, Scott Federhen, Carol Hotton, Detlef Leipe, Vladimir Soussov, Richard Sternberg, Sean Turner. [Help] [Search] [NLM NIH] [Disclaimer] BioNET - International A global network of country-owned collaborative LOOPs to support national programs for biosystematics to support goals in areas such as sustainable development and pest management. BioNET-INTERNATIONAL - Homepage Thursday 17 Nov 2005 Tue 1 Nov 05 BioNET-ANDINONET supports invasive alien species capacity building Work has started on several activities related to I3N (IABIN Invasives Information Ne... Mon 24 Oct 05 New BioNET-PACINET coordinator begins work in the Pacific Islands The University of the South Pacific (USP) in partnership with the Secretariat for the... Mon 22 Aug 05 BioNET-WAFRINET: Sierra Leone Crop Protection boosted by return of new taxonomist Supported by a BioNET-WAFRINET Fellowship, Dr. I. M. O. Shamie has been awarded a PhD... Mon 22 Aug 05 BioNET-EASIANET - WORKSHOP: THE IMPORTANCE OF TAXONOMY TO PLANT QUARANTINE The Mushroom Research Centre, Chiang Mai, will host a 10-day course aimed at strength... Tue 1 Nov 05 The 60th UN General Assembly, CBD and Science and technology for development Item 52 (h) is on the Convention on Biological Diversity, for which document A 60 171... Tue 1 Nov 05 Science 'should inform economic aid' Decisions on how to allocate international aid must take greater account of science, ... To place this newsfeed on your website click here . BioNET-INTERNATIONAL 1999-2005 | email In this website, the registered trademark BioNET-INTERNATIONAL has been abbreviated for presentational purposes to bionet* but all references should be taken to refer to the trademark in full. Fairchild Tropical Garden Virtual Herbarium Includes photos of more than 50,000 plant, palm, cycad and other cultivated tropical plants from Florida and taxonomic information on grasses, especially bamboos, and other economically important and interesting plants. Fairchild Tropical Garden Botanical Resource Center and Virtual Herbarium Please click here to enter the non-frames version Taxonomy and Systematics at Glasgow About taxonomy and systematics at the University of Glasgow, with links to other internet resources on these subjects. Page Lab Taxonomy, Systematics, and Bioinformatics at the University of Glasgow Home | People | Research | Data | Software | Publications | Services | Teaching | Links News May 2002 Bioinformatics Research Centr e launched at Glasgow February 19th 2002 Iowa State Supertree server November 20th 2001 RadCon 1.1.4 released. November 14th 2001 "Taxonomy at Glasgow" site relauched as "Page Lab" web site. Welcome to the Page lab web site! Our research interests include host-parasite cospeciation, phylogenetic inference, supertrees, genome evolution, RNA secondary structure and evolution, and louse phylogeny. Use the tabs above to browse the site. Some recent highlights PlaycentreatKelbourneStreet opens its doors 19 April 2004! Two PhD's available on phyloinformatics and supertrees . Start date October 2003. [These positions are now filled, 9 May 2003] MrBayes web form (create "mrbayes" blocks online) Daniel Huson's SplitsTree ported to Mac OS X Modified MinCut Supertrees presentation by Rod Page given at WABI 2002. TreeMap 2.0 is available for Mac OS. Page, Roderic D. M., editor Tangled Trees: Phylogeny, Cospeciation, and Coevolution Order now! ( University of Chicago Press ) Joe Thorley's supertree bibliography and links Technical report series launched to house unpublished (or unpublishable) manuscripts. RadCon 1.1.4 now available TreeView ported to Linux Unix. More... Reconciled tree analysis of 118 vertebrate genes supports a traditional view of vertebrate phylogeny. More... Mincut supertree server (experimental). More... Quick links Software: Circles COMPONENT GeneTree NDE RadCon Spectrum TreeMap TreeView TreeView X ------ Other software Search engines Google ResearchIndex Scirius Networked Computer Science Technical Reference Library Journals Electronic Journals at Glasgow Bioinformatics Cladistics International Journal for Parasitology Journal of Evolutionary Biology Mathematical Biosciences Molecular Biology and Evolution Molecular Phylogenetics and Evolution Nucleic Acids Research Systematic Biology Systematic Entomology Books Page, Roderic D. M., editor Tangled Trees: Phylogeny, Cospeciation, and Coevolution Order now! ( University of Chicago Press ) Molecular Evolution: A Phylogenetic Approach by Rod Page Eddie Holmes Blackwell Science ISBN 0865428891 Order now! ( Blackwell Science ) ( Amazon.com )( Amazon.co.uk ) EverythingBio.com: Life Science Glossary Glossary of genetic, molecular, cell and developmental biology definitions. Life Science Glossary Home | Glossary | Textbooks | Images | Tools | Protocols | PubMed | Images | Grad-school | Links Life Science Glossary: A B C D E F G H I J K L M N O P Q R S T U V W X Y Z Welcome to BioGlossary a life science glossary of over 3,700 definitions, and growing! Extensive collection in the following fields: Anatomy Biochemistry Biology Biophysics Cell biology Developmental biology Ecology Evolutionary biology Genetics Immunology Molecular biology Molecular genetics Ways to search glossary: Click on letter to get complete list of every word starting with that letter. Enter word in search box on the right. Enter part of a word in search box on the right to get every word that contains that part. Help make this a better resource for all by editing poorly rated definitions below: abiotic abiotic factors adaptation adenosine triphosphate (ATP) alcoholic fermentation allele anabolic anatomy aneuploidy apoptosis artificial selection assay astrocyte axon bacteria biochemistry biodiversity biosphere Biotechnology buffer C4 photosynthesis carbohydrase carbohydrate cDNA library cell cell cycle cell wall cellular respiration centromere Chargaff's rule chemical change chemical reaction chemistry chemoheterotroph chromatin chromoplast chromosome chromosome walking codominance codominant allele coimmunoprecipitation continuous variation control cosmid cytokinesis cytoplasm cytoskeleton Denaturing gradient gel electrophoresis (DGGE) density deoxyribonucleotide triphosphate diffusion discontinuous variation DNA fingerprint DNA gyrase DNA polymorphism DNA replication Ecology Ecosystem Efficacy endergonic reaction endoplasmic reticulum energy epidemiology eukaryote eukaryotic cell exergonic reaction fluid mosaic model Fluorescence in situ hybridization (FISH) formula unit gene cloning gene locus genetic engineering genetic polymorphism genetically modified organism genome genomic library Giemsa stain gliosis growth medium gymnosperm haplotype heterotroph heterozygosity histone homeostasis hypertonic solution hypothesis hypotonic solution in vivo independent assortment ionic bond kingdom lac operon law law of conservation of mass law of definite proportions law of multiple proportions Ligand Ligase chain reaction (LCR) linkage disequilibrium lysate Lysosome mass matter meiosis meroblastic cleavage metabolism Microarray mitosis mole MTHFR multiplicity of infection (moi) mutation NADP+ NADPH natural selection negative control nonsense mutation normality nucleoplasm nucleus Okazaki fragment open reading frame organelle organism orthologous genes osmosis phenotype photoheterotroph pKa plastid Pleiotrophy pleiotropy polar covalent bond polar molecule polarity polygenic inheritance polymerase chain reaction (PCR) Positional cloning positive control precipitate primer producer promoter Qualitative recessive allele reporter gene restriction enzyme RFLP ribosome RNA polymerase rough endoplasmic reticulum sex Sexual reproduction solute solvent substrate Supernatant transcription transgenic organism transposon Trihybrid cross vacuole variable variable-number-of-tandem-repeats (VNTR) locus vector virus SEARCH : Select Category: Glossary - word Glossary - def Textbooks Protocols Images Tools Forum PubMed Links Press Releases Products Whole Site Help About Us | Site Map | Privacy Policy | Disclaimer | Contact Us | 2005 EverythingBio.com Searching GenBank Text and similarity searching, provided by the National Center for Biotechnology Information (NCBI). Searching GenBank Searching GenBank PubMed Entrez BLAST OMIM Books Taxonomy Structure NCBI SITE MAP Text and Similarity Searching Entrez Browser GenBank (nucleotides and proteins), PubMed (MEDLINE), 3D structures, genomes, and PopSet databases. GenBank nucleotide records are found in the divisions CoreNucleotide, dbEST or dbGSS. Entrez queries can search these three databases together or separately. BLAST Sequence Similarity Searching Nucleotide or protein query sequences against the specified database using the BLAST suite of algorithms. GenBank nucleotide records are located in separate databases that must be searched independently. These include dbEST and dbGSS, plus multiple databases for the CoreNucleotide division, including nr, htgs, wgs and env_nt. See the BLAST info page for more information about the numerous BLAST databases. dbEST Searching dbEST (Database of Expressed Sequence Tags). dbSTS Searching dbSTS (Database of Sequence Tagged Sites). dbGSS Searching dbGSS (Database of Genome Survey Sequences). Information about Access to GenBank Network Client Server Applications Network BLAST. FTP Full release and daily updates of GenBank. Revised: November 7, 2005. Bioinformatics Glossary Alphabetical listing of terms defined related to gene sequencing, informatics and applied molecular biology. bioinfo_glossary.html Bioinformatics Glossary A B C D E F G H I J K L M N O P Q R S T U V W X Y Z Accession number An identifier supplied by the curators of the major biological databases upon submission of a novel entry that uniquely identifies that sequence (or other) entry. Active site The amino acid residues at the catalytic site of an enzyme. These residues provide the binding and activation energy needed to place the substrate into its transition state and bridge the energy barrier of the reaction undergoing catalysis Adenine A purine base found in DNA and RNA Agents Independent, autonomous, software modules that can search the Internet for data or content pertinent to a particular application, such as a gene, protein, or biological system. Agricultural biotechnology (AgBio) The application of rDNA technology to agriculturally important plants and organisms. Algorithm A series of steps defining a procedure or formula for solving a problem, that can be coded into a programming language and executed. Bioinformatics algorithms typically are used to process, store, analyze, visualize and make predictions from biological data. Alignment The result of a comparison of two or more gene or protein sequences in order to determine their degree of base or amino acid similarity. Sequence alignments are used to determine the similarity, homology, function or other degree of relatedness between two or more genes or gene products. Allele A given form of a gene that occupies a specific position or locus on a chromosome. Variant forms of genes occurring at the same locus are said to be alleles of one another. Alternative splicing One of the alternate combinations of a folded protein that are possible due to by recombination of multiple gene segments during mRNA splicing that occurs in higher organisms. Alternative splice-form One of the possible alternate combinations of exons into a folded protein that are possible by recombining multiple gene segments during mRNA splicing in higher organisms. Alu family A common set of dispersed DNA sequences found throughout the human genome; each is about 300 bases long and they are repeated at least 500,000 times. Alu sequences are speculated to have originated from viral RNA sequences that integrated into human DNA thousands of years ago. Amino acid One of the 20 chemical building blocks that are joined by amide (peptide) linkages to form a polypeptide chain of a protein Analogy Reasoning by which the function of a novel gene or protein sequence may be deduced from comparisons with other gene or protein sequences of known function. Identifying analogous or homologous genes via similarity searching and alignment is one of the chief uses of Bioinformatics. (See also alignment, similarity search.) Annotation A combination of comments, notations, references, and citations, either in free format or utilizing a controlled vocabulary, that together describe all the experimental and inferred information about a gene or protein. Annotations can also be applied to the description of other biological systems. Batch, automated annotation of bulk biological sequence is one of the key uses of Bioinformatics tools. Anticodon The triplet of contiguous bases on tRNA that binds to the codon sequence of nucleotides on mRNA. Example: GGG codes for Glycine. Antigen Any foreign molecule that stimulates an immune response in a vertebrate organism. Many antigens are proteins such as the surface proteins of foreign organisms. Antisense DNA or RNA composed of the complementary sequence to the target DNA RNA. Also used to describe a therapeutic strategy that uses antisense DNA or RNA sequences to target specific gene DNA sequences or mRNA implicated in disease, in order to bind and physically inhibit their expression by physically blocking them. Assay A method for measuring a biological activity. This may be enzyme activity, binding affinity, or protein turnover. Most assays utilize a measurable parameter such as color, fluorescence or radioactivity to correlate with the biological activity. Assembly Compilation of overlapping sequences from one or more related genes that have been clustered together based on their degree of sequence identity or similarity. Sequence assembly may be used to piece together "shotgun" sequencing fragments (see shotgun sequencing) based upon overlapping restriction enzyme digests, or may be used to identify and index novel genes from "single-pass" cDNA sequencing efforts. Autoradiography A method used to locate radioisotope-labeled materials which have been separated in gels or are present in blots. The location of the radiolabeled material is determined by overlaying the test material with a photographic film that is sensitive to the radioisotope. B back to top Bacterial artificial chromosome (BAC) Cloning vector that can incorporate large fragments of DNA. (see YACS) Bacteriophage A virus that infects bacteria. The bacteriophage DNA has served as a basis for cloning vectors, and is also utilized to create phage libraries containing human or other genes. Baculovirus An insect virus which forms the basis of a protein expression system Base pair A pair of nitrogenous bases (a purine and a pyrimidine), held together by hydrogen bonds, that form the core of DNA and RNA i.e the A:T, G:C and A:U interactions. Beta sheet A three dimensional arrangement taken up by polypeptide chains that consists of alternating strands linked by hydrogen bonds. The alternating strands together form a sheet that is frequently twisted. One of the secondary structural elements characteristic of proteins. Bioinformatics The field of endeavor that relates to the collection, organization and analysis of large amounts of biological data using networks of computers and databases (usually with reference to the genome project and DNA sequence information) Bivalent Having two binding sites; having 2 free electrons available for binding. Blunt-end (ligation) The joining of DNA fragments that contain no overhang at either end and consequently no DNA bases available for hybridization (cf. sticky-end ligation). C back to top Carboxyl group The -COOH functional group, acidic in nature, found in all amino acids cDNA (complementary DNA) A DNA strand copied from mRNA using reverse transcriptase. A cDNA library represents all of the expressed DNA in a cell. cDNA library A set of DNA fragments prepared from the total mRNA obtained from a selected cell, tissue or organism. Cell The basic unit of any living organism. Cell Cycle The life cycle of a cell which is marked by cell division which is separated into four phases: G1, S, G2, and M. DNA replication is confined to the S(synthesis) phase, and chromosomal separation in the M (mitotic) phase. Chimeric clone A cloning artifact created by a foreign gene being inserted into a vector in an incorrect orientation resulting in theexpression of a protein consisting of a fusion of two different gene products. Chromat Data file output from most popular DNA sequencers. Chromat files consist of the fluorescent traces generated by the sequencer for each of the four chemical bases, A, C, G, and T, together with the sequence and measures of the error in the traces at each sequence position. Chromatin The chromosome as it appears in its condensed state, composed of DNA and associated proteins (mainly histones). Chromosome The structure in the cell nucleus that contains all of the cellular DNA together with a number of proteins that compact and package the DNA. Clinical trials Research studies that involve patients. Biotechnology companies typically use clinical trials to assess the efficacy and safety of new therapies and to answer scientific questions. Typically, there are 3 phases during a clinical trial. Phase I is designed to evaluate the safety of the product in humans; phase II analyses the effects of dose escalation, and phase III definitively evaluates the clinical efficacy of the product. Clone A population of genetically identical cells or DNA molecules. Cloning The formation of clones or exact genetic replicas. Cluster The grouping of similar objects in a multidimensional space. Clustering is used for constructing new features which are abstractions of the existing features of those objects. The quality of the clustering depends crucially on the distance metric in the space. In bioinformatics, clustering is performed on sequences, high-throughput expression and other experimental data. Clusters of partial or complete gene sequences can be used to identify the complete (contiguous) sequence and to better identify its function. Clustering expression data enables the researcher to discern patterns of co-regulation in groups of genes. Coding regions (CDS) The portion of a genomic sequence bounded by start and stop codons that identifies the sequence of the protein being coded for by a particular gene. Codon A sequence of three adjacent nucleotides that designates a specific amino acid or start stop site for transcription. Combinatorial chemistry The use of chemical methods to generate all possible combinations of chemicals starting with a subset of compounds. The building blocks may be peptides, nucleic acids or small molecules. The libraries of compounds formed by this methodology are used to probe for new pharmaceutical reagents (see high-throughput screening). Complementary determining region (CDR) The hypervariable regions of an antibody molecule, consisting of three loops from the heavy chain and three from the light chain, that together form the antigen-binding site. Complexity (of gene sequence) The term "low complexity sequence" may be thought of as synonymous with regions of locally biased amino acid composition. In these regions, the sequence composition deviates from the random model thatunderlies the calculation of the statistical significance (P-value) of an alignment. Such alignments among low complexity sequences are statistically but not biologically significant, i.e., one cannot infer homology (common ancestry) or functional similarity. Configuration (in software) The complete ordering and description of all parts of a software or database system. Configuration management is the use of software to identify, inventory and maintain the component modules that together comprise one or more systems or products. Conformation The precise three-dimensional arrangement of atoms and bonds in a molecule describing its geometry and hence its molecular function. Consensus sequence A single sequence delineated from an alignment of multiple constituent sequences that represents a "best fit" for all those sequences. A "voting" or other selection procedure is used to determine which residue (nucleotide or amino acid) is placed at a given position in the event that not all of the constituent sequences have the identical residue at that position. Constitutive synthesis (expression) Synthesis of mRNA and protein at an unchanging or constant rate regardless of a cells requirements (see housekeeping genes). Contig A length of contiguous sequence assembled from partial, overlapping sequences, generated from a "shotgun" sequencing project. Contigs are typically created computationally, by comparing the overlapping ends of several sequencing reads generated by restriction enzyme digestion of a segment of genomic DNA. The creation of contigs in the presence of sequencing errors, ambiguities and the presence of repeats is one of the most computationally challenging aspects of the role of Bioinformatics in genome analysis. Convergence The end-point of any algorithm that uses iteration or recursion to guide a series of data processing steps. An algorithm is usually said to have reached convergence when the difference between the computed and observed steps falls below a pre-defined threshold. Cosmids DNA vectors that allow the insertion of long fragments of DNA (up to 50 kbases). Crystal structure Term used to describe the high resolution molecular structure derived by x- ray crytallographic analysis of protein or other biomolecular crystals. Cytoplasm The medium of the cell between the nucleus and the cell membrane. Cytosine A pyrimidine base found in DNA and RNA. D back to top Data Cleaning A process whereby automated or semi-automated algorithms are used to process experimental data, including noise, experimental errors and other artifacts, in order to generate and store high-quality data for use in subsequent analysis. Data cleaning is typically required in high-throughput sequencing where compression or other experimental artifacts limit the amount of sequence data generated from each sequencing run or "read." Data Mining The ability to query very large databases in order to satisfy a hypothesis ("top-down" data mining); or to interrogate a database in order to generate new hypotheses based on rigorous statistical correlations ("bottom-up" data mining). Data Processing Data processing is defined as the systematic performance of operations upon data such as handling, merging, sorting, and computing. The semantic content of the original data should not be changed, but the semantic content of the processed data may be changed. Data Warehouses Vast arrays of heterogeneous (biological) data, stored within a single logical data repository, that are accessible to different querying and manipulation methods. Database Any file system by which data gets stored following a logical process. (see also relational database) Deconvolution Mathematical procedure to separate out the overlapping effects of molecules such as mixtures of compounds in a high-throughput screen, or mixtures of cDNAs in a high density array. Deletion A chromosomal alteration in which a portion of the chromosome or the underlying DNA is lost. Deletion mapping Process in which different deletions in a region of DNA are created and used to map the functionally critical areas of that DNA. e.g the minimal region of DNA required for a test promoter can be ascertained by systematic deletions in the region of interest. Dendrogram A graphical procedure for representing the output of a hierarchical clustering method. A dendrogram is strictly defined as a binary tree with a distinguished root, that has all the data items at its leaves. Conventionally, all the leaves are shown at the same level of the drawing. The ordering of the leaves is arbitrary, as is their horizontal position. The heights of the internal nodes may be arbitrary, or may be related to the metric information used to form the clustering. Dimer A composite molecule formed by the binding of two molecules (see homo and heterodimers). Disulphide bond Covalent link formed between the sulphur atoms of two different cysteine residues in a protein. Important in maintaining the folded structure of a protein, and also for linking different proteins in a complex. DNA (deoxyribonucleic acid) The chemical that forms the basis of the genetic material in virtually all organisms. DNA is composed of the four nitrogenous bases Adenine, Cytosine, Guanine, and Thymine, which are covalently bonded to a backbone of deoxyribose-phosphate to form a DNA strand. Two complementary strands (where all Gs pair with Cs and As with Ts) form a double helical structure which is held together by hydrogen bonding between the cognate bases. DNA fingerprinting A technique for identifying human individuals based on a restriction enzyme digest of tandemly repeated DNA sequences that are scattered throughout the human genome, but are unique to each individual. DNA microarrays The deposition of oligonucleotides or cDNAs onto an inert substrate such as glass or silicon. Thousands of molecules may be organized spatially into a high-density matrix. These DNA chips may be probed to allow expression monitoring of many thousands of genes simultaneously. Uses include study of polymorphisms in genes, de novo sequencing or molecular diagnosis of disease. DNA polymerase An enzyme that catalyzes the synthesis of DNA from a DNA template given the deoxyribonucleotide precursors. DNA probes Short single stranded DNA molecules of specific base sequence, labeled either radioactively or immunologically, that are used to detect and identify the complementary base sequence in a gene or genome by hybridizing specifically to that gene or sequence. DNA sequencing The technique in which the specific sequence of bases forming a particular DNA region is deciphered. DNase (Deoxyribonuclease) One of a series of enzymes that can digest DNA. Domain (protein) A region of special biological interest within a single protein sequence. However, a domain may also be defined as a region within the three-dimensional structure of a protein that may encompass regions of several distinct protein sequences that accomplishes a specific function. A domain class is a group of domains that share a common set of well-defined properties or characteristics. Drug An agent that affects a biological process. Specifically, a molecule whose molecular structure can be correlated with its pharmacological activity. Drug discovery cycle The cycle of events required to develop a new drug. Typically this involves research, preclinical testing and clinical development, and can take from 5 to 12 years. E back to top Electronic Northerns The use of an electronic database of cDNA sequences (or probes derived from them) in order to measure the relative levels of mRNAs expressed in different cells or tissues. An example of the use of an electronic Northern might be to identify the differences in the genes expressed in prostate cancer and those in benign prostate hyperplasia, by subtracting the database of one from the other and seeing which cDNAs remain. Electrophoresis The use of an external electric field to separate large biomolecules on the basis of their charge by running them through acrylamide or agarose gels. Enhancers DNA sequences that can greatly increase the transcription rates of genes even though they may be far upstream or downstream from the promoter they stimulate. Enzyme A class of proteins that are capable of catalyzing chemical reactions (the making or breaking of chemical bonds). They do so by orienting their substrates into a suitable geometry in a particular location (the active site) where electrophilic or nucleophilic amino acid residues can participate in the reaction. Enzymes are protein catalyst that speeds up chemical reactions that would otherwise be prohibitively slow under physiological conditions. Epigenomics The study of complex expression networks or linkages both spatially (within the body) and temporally (at different times in development). Equilibrium constant Value that describes the equilibrium state of the reversible reaction between two molecular species. Eukaryote A cell or organism with a distinct membrane-bound nucleus as well as specialized membrane-based organelles (see also prokaryote). Exon The region of DNA within a gene that codes for a polypeptide chain or domain. Typically a mature protein is composed of several domains coded by different exons within a single gene. Expressed Sequence Tags (ESTs) A small sequence from an expressed gene that can be amplified by PCR. ESTs act as physical markers for cloning and full length sequencing of the cDNAs of expressed genes. Typically identified by purifying mRNAs, converting to cDNAs, and then sequencing a portion of the cDNAs. Expression (gene or protein) A measure of the presence, amount, and time-course of one or more gene products in a particular cell or tissue. Expression studies are typically performed at the RNA (mRNA) or protein level in order to determine the number, type, and level of genes that may be up-regulated or down-regulated during a cellular process, in response to an external stimulus, or in sickness or disease. Gene chips and proteomics now allow the study of expression profiles of sets of genes or even entire genomes. Expression profile The level and duration of expression of one or more genes, selected from a particular cell or tissue type, generally obtained by a variety of high-throughput methods, such as sample sequencing, serial analysis, or microarray-based detection. Expression vector A cloning vector that is engineered to allow the expression of protein from a cDNA. The expression vector provides an appropriate promoter and restriction sites that allow insertion of cDNA. F back to top Fingerprint A fingerprint is a set of motifs used to predict the occurrence of similar motifs, in either an individual sequence or in a database. Fingerprints are refined by iterative scanning of a composite protein sequence database. A composite or multiple-motif fingerprint contains a number of aligned motifs taken from different parts of a multiple alignment. True family members are then easy to identify by virtue of possessing all elements of the fingerprint, while subfamily members may be identified by possessing only part of it. Frameshift A deletion, substitution, or duplication of one or more bases that causes the reading-frame of a structural gene to shift from the normal series of triplets. Functional genomics The use of genomic information to delineate protein structure, function, pathways and networks. Function may be determined by "knocking out" or "knocking in" expressed genes in model organisms such as worm, fruitfly, yeast or mouse. Fusion protein The protein resulting from the genetic joining and expression of 2 different genes (see chimeric) G back to top Gaps (affine gaps) A gap is defined as any maximal, consecutive run of spaces in a single string of a given alignment. Gaps help create alignments that better conform to underlying biological models and more closely fit patterns that one expects to find in meaningful alignment. The idea is to take in account the number of continuous gaps and not only the number of spaces when calculating an alignment. Affine gaps contain a component for gap insertion and a component for gap extension, where the extension penalty is usually much lower than the insertion penalty. This mimics biological reality as multiple gaps would imply multiple mutations, but a single mutation can lead to a long gap quite easily. Gap penalties The penalty applied to a similarity score for the introduction of an insertion or deletion gap, the extension of a gap, or both. Gap penalties are usually subtracted from a cumulative score being determined for the comparison of two or more sequences via an optimization algorithm that attempts to maximize that score. Gel electrophoresis A technique by which molecules are separated by size or charge by passing them through a gel under the influence of an external electric field. Gene Index A listing of the number, type, label and sequence of all the genes identified within the genome of a given organism. Gene indices are usually created by assembling overlapping EST sequences into clusters, and then determining if each cluster corresponds to a unique gene. Methods by which a cluster can be identified as representing a unique gene include identification of long open reading frames (ORFs), comparison to genomic sequence, and detection of SNPs or other features in the cluster that are known to exist in the gene. GenBank Data bank of genetic sequences operated by a division of the National Institutes of Health. Gene Classically, a unit of inheritance. In practice, a gene is a segment of DNA on a chromosome that encodes a protein and all the regulatory sequences (promoter) required to control expression of that protein. Gene chips (also Gene arrays) The covalent attachment of oligonucleotides or cDNA directly onto a small glass or silicon chip in organized arrays. Over 50,000 different DNA fragments can be presented on a single chip providing a high throughput parallel method of probing gene expression, genotype or gene function. Gene expression The conversion of information from gene to protein via transcription and translation. Gene families Subsets of genes containing homologous sequences which usually correlate with a common function. Gene library A collection of cloned DNA fragments created by restriction endonuclease digestion that represent part or all of an organisms genome. Gene product The product, either RNA or protein, that results from expression of a gene. The amount of gene product reflects the activity of the gene. Gene therapy The use of genetic material for therapeutic purposes. The therapeutic gene is typically delivered using recombinant virus or liposome based delivery systems. Genetic code The mapping of all possible codons into the 20 amino acids including the start and stop codons. Genetic engineering (Recombinant DNA technology) The procedures used to isolate, splice and manipulate DNA outside the cell. Genetic Engineering allows a recombinantly engineered DNA segment to be introduced into a foreign cell or organism, and be able to replicate and function normally. Genetic marker Any gene that can be readily recognized by its phenotypic effect, and which can be used as a marker for a cell, chromosome, or individual carrying that gene. Also, any detectable polymorphism used to identify a specific gene. Genome The complete genetic content of an organism. Genomic DNA (sequence) DNA sequence typically obtained from mammalian or other higher-order species, which includes both intron and exon sequence (coding sequence), as well as non-coding regulatory sequences such as promoter, and enhancer sequences. Genomics The analysis of the entire genome of a chosen organism. Genotype Strictly, all of the genes possessed by an individual. In practice, the particular alleles present in a specific genetic locus. Glycosylation The addition of carbohydrate groups (sugars) e.g. to polypeptide chains Guanine (G) One of the nitrogenous purine bases found in DNA and RNA H back to top Hairpin A double-helical region in a single DNA or RNA strand formed by the hydrogen-bonding between adjacent inverse complementary sequences to form a hairpin shaped structure. Haploid A cell or organism containing only one set of chromsomes without the homologous pairs. (cf. diploid) Heterodimer Protein composed of 2 different chains or subunits. Heteroduplex Hybrid structure formed by the annealing of two DNA strands (or an RNA and DNA) that have sufficient complementarity in their sequence to allow hydrogen bonding. Hidden Markov model (HMM) A joint statistical model for an ordered sequence of variables. The result of stochastically perturbing the variables in a Markov chain (the original variables are thus "hidden"), where the Markov chain has discrete variables which select the "state" of the HMM at each step. The perturbed values can be continuous and are the "outputs" of the HMM. A Hidden Markov Model is equivalently a coupled mixture model where the joint distribution over states is a Markov chain. Hidden Markov models are valuable in bioinformatics because they allow a search or alignment algorithm to be trained using unaligned or unweighted input sequences; and because they allow position-dependent scoring parameters such as gap penalties, thus more accurately modeling the consequences of evolutionary events on sequence families. High-throughput screening The method by which very large numbers of compounds are screened against a putative drug target in either cell-free or whole-cell assays. Typically, these screenings are carried out in 96 well plates using automated, robotic station based technologies or in higher- density array ("chip") formats. HLA complex Another name for the MHC in humans; refers to the "Human Leukocyte Antigen" complex located on chromosome 6. Homeobox A highly conserved region in a homeotic gene composed of 180 bases (60 amino acids) that specifies a protein domain (the homeodomain) that serves as a master genetic regulatory element in cell differentiation during development in species as diverse as worms, fruitflies, and humans. Homeodomain A 60 amino-acid protein domain coded for by the homeobox region of a homeotic gene. Homeotic gene A gene that controls the activity of other genes involved in the development of a body plan. Homeotic genes have been found in organisms ranging from plants to humans. Homology (strict) Two or more biological species, systems or molecules that share a common evolutionary ancestor. (general) Two or more gene or protein sequences that share a significant degree of similarity, typically measured by the amount of identity (in the case of DNA), or conservative replacements (in the case of protein), that they register along their lengths. Sequence "homology" searches are typically performed with a query DNA or protein sequence to identify known genes or gene products that share significant similarity and hence might inform on the ancestry, heritage and possible function of the query gene. Housekeeping genes Genes that are always expressed (ie. they are said to be constitutively expressed) due to their constant requirement by the cell. Human Anti-Murine Antibody Response (HAMA) An immune response generated in humans to antibodies raised in murine (e.g. mouse or rat) cells. Hybridization The interaction of complementary nucleic acid strands. This can occur between two DNA strands or between DNA and RNA strands, and is the basis of many techniques such as Southern and northern blots. Hydrogen bond A weak chemical interaction between an electronegative atom (e.g. nitrogen or oxygen) and a hydrogen atom that is covalently attached to another atom. This bond maintains the two-helices of DNA together and is also the primary interaction between water molecules. Hydrophilicity (lit. water-loving) The degree to which a molecule is soluble in water. Hydrophilicity depends to a large degree on the charge and polarizability of the molecule and its ability to form transient hydrogen-bonds with (polar) water molecules. Hydrophobicity (lit. water-hating) The degree to which a molecule is insoluble in water, and hence is soluble in lipids. If a molecule lacking polar groups is placed in water, it will be entropically driven to finding a hyrdophobic environment (such as the interior of a protein or a membrane). I back to top Idiotype Antibody variants localized to the variable portion of an immunoglobulin that are recognised by their antigenic determinants. The determinants are composed from the antigen-combining site or CDRs. Every unique antigenic determinant has a specific antibody with its own unique idiotype. Immunoglobulin A member of the globulin protein family consisting of two light and two heavy chains linked by disulfide bonds. All antibodies are immunoglobulins. in silico (biology) (Lit. computer mediated). The use of computers to simulate, process, or analyse a biological experiment. in situ hybridization A variation of the DNA RNA hybridization procedure in which the denatured DNA is in place in the cell and is then challenged with RNA or DNA extracted from another source. (See also fluorescence in situ hybridization). Integration The physical insertion of DNA into the host cell genome. The process is used by retroviruses where a specific enzyme catalyses the process or can occur at random sites with other DNA (eg. transposons). Intracellular signalling The communication of a molecular message from the surface of the cell to the nucleus via the participation of a series of molecules, including receptors, enzymes, proteins, and small-molecules. The end result of the signalling process is the up- or down-regulation of a particular series of genes that may be involved in cell growth, division or differentiation. Introns Nucleotide sequences found in the structural genes of eukaryotes that are non-coding and interrupt the sequences containing information that codes for polypeptide chains. Intron sequences are spliced out of their RNA transcripts before maturation and protein synthesis. (cf. Exons) Isoschizomers Two different restriction enzymes which recognize and cut DNA at the same recognition site. e.g Sma I and Xma I both recognize and cut the sequence CCCGGG. Isozymes Two or more enzymes capable of catalyzing the same reaction but varying in their specificity due to differences in their structures and hence their efficiencies under different environmental conditions. Iteration A series of steps in an algorithm whereby the processing of data is performed repetitively until the result exceeds a particular threshold. Iteration is often used in multiple sequence alignments whereby each set of pairwise alignments are compared with every other, starting with the most similar pairs and progressing to the least similar, until there are no longer any sequence-pairs remaining to be aligned. J back to top Junk DNA Term used to describe the excess DNA that is present in the genome beyond that required to encode proteins. A misleading term since these regions are likely to be involved in gene regulation, and other as yet unidentified functions. K back to top Karyotype The constitution (typically number and size) of chromosomes in a cell or individual. Knockout mice (gene targeting) Mice which have been engineered to lack a chosen gene. The gene is inactivated in so called embryonic stem cells using the technique of homologous recombination. These cells are then introduced into a early stage embryo (blastocyst) and this is then transplanted into a recipient mouse. The subsequent progeny lack the targeted gene in some cells. This technique is used to determine the function of the chosen gene. L back to top "Lab on a chip" Term describing microdevices that allow rapid, microanalytical analysis of DNA or protein in a single, fully integrated system. Typically, these devices are miniature surfaces, made of silicon, glass or plastic, which carry the necessary microdevices (pumps, valves, microfluidic controllers, and detectors) that allow sample separation and analysis. These devices are used in drug discovery, genetic testing and separation science. Lead compound A candidate compound identified as the best "hit" (tight binder) after screening of a combinatorial (or other) compound library, that is then taken into further rounds of screening to determine its suitability as a drug. Lead optimization The process of converting a putative lead compound ("hit") into a therapeutic drug with maximal activity and minimal side affects, typically using a combination of computer-based drug design, medicinal chemistry and pharmacology. Leucine zipper Protein motif which binds DNA in which 4-5 Leucines are found at 7 amino acid intervals. This motif is present typically in transcription factors and other proteins that bind DNA. Lexicon In Bioinformatics, a lexicon refers to a pre-defined list of terms that together completely define the contents of a particular database. (strict.) The component in the grammar which is in bare form a list of words or lexical entries. Library A large collection of compounds, peptides, cDNAs or genes which may be screened in order to isolate cognate molecules. Ligand Any small molecule that binds to a protein or receptor; the cognate partner of many cellular proteins, enzymes, and receptors. Linkage The association of genes (or genetic loci) on the same chromosome. Genes that are linked together tend to be transmitted together. Linkage map A genetic map of a chromosome or genome delineated by mapping the positions of genes to their chromosomes by their linkage to readily identifiable genetic loci. Locus The specific position occupied by a gene on a chromosome. At a given locus, any one of the variant forms of a gene may be present. The variants are said to be alleles of that gene. M back to top Map unit A measure of genetic distance between two linked genes that corresponds to a recombination frequency of 1%. Markov chain Any multivariate probability density whose independence diagram is a chain.The variables are ordered, and each variable "depends" only on its neighbors in the sense of being conditionally independent of the others. Markov chains are an integral component of hidden Markov models. Meiosis A process within the cell nucleus that results in the reduction of the chromosome number from diploid (two copies of each chromosome) to haploid (a single copy) through two reductive divisions in germ cells. Melting (of DNA) The denaturation of double-stranded DNA into two single strands by the application of heat. (Denaturation breaks the hydrogen bonds holding the double-stranded DNA together). Messenger RNA (mRNA) The complementary RNA copy of DNA formed from a single-stranded DNA template during transcription that migrates from the nucleus to the cytoplasm where it is processed into a sequence carrying the information to code for a polypeptide domain. Methylation The addition of -CH3 (methyl) groups to a target site. Typically such addition occurs on to the cytosine bases of DNA. (see maternal imprinting). Microarray A 2D array, typically on a glass, filter, or silicon wafer, upon which genes or gene fragments are deposited or synthesized in a predetermined spatial order allowing them to be made available as probes in a high-throughput, parallel manner. Microfluidics The miniaturization of chemical reactions or pharmacalogical assays into microscopic tubes or vessels in order to greatly increase their throughput, by placing many of them side-by-side in an array. Mimetics Compounds that mimic the function of other molecules via their high degree of structural (conformational) similarity, and hence physio-chemical properties. Missense mutation A point mutation in which one codon (triplet of bases) is changed into another designating a different amino acid. Mitosis The nuclear division that results in the replication of the genetic material and its redistribution into each of the daughter cells during cell division. Modeling In bioinformatics, modeling usually refers to molecular modeling, a process whereby the three-dimensional architecture of biological molecules is interpreted (or predicted), visually represented, and manipulated in order to determine their molecular properties. (general) A series of mathematical equations or procedures which simulate a real-life process, given a set of assumptions, boundary parameters, and initial conditions. Monomer A single unit of any biological molecule or macromolecule, such as an amino acid, nucleic acid, polypeptide domain, or protein. Monovalent Having one binding site; strictly, an atom with only one free electron available for binding in its highest energy shell. Motif A conserved element of a protein sequence alignment that usually correlates with a particular function. Motifs are generated from a local multiple protein sequence alignment corresponding to a region whose function or structure is known. It is sufficient that it is conserved, and is hence likely to be predictive of any subsequent occurrence of such a structural functional region in any other novel protein sequence. Multigene family A set of genes derived by duplication of an ancestral gene, followed by independent mutational events resulting in a series of independent genes either clustered together on a chromosome or dispersed throughout the genome. Multiple (sequence) alignment A Multiple Alignment of k sequences is a rectangular array, consisting of characters taken from the alphabet A, that satisfies the following conditions: There are exactly k rows; ignoring the gap character, row number i is exactly the sequence sI; and each column contains at least one character different from "-". In practice multiple sequence alignments include a cost weight function, that defines the penalty for the insertion of gaps (the "-" character) and weights identities and conservative substitutions accordingly. Multiple alignment algorithms attempt to create the optimal alignment defined as the one with the lowest cost weight score. Multiplex sequencing Approach to high-throughput sequencing that uses several pooled DNA samples run through gels simultaneously and then separated and analyzed. Mutagen Any agent that can cause an increase in the rate of mutations in an organism. Mutation An inheritable alteration to the genome that includes genetic (point or single base) changes, or larger scale alterations such as chromosomal deletions or rearrangements. N back to top Naked DNA Pure, isolated DNA devoid of any proteins that may bind to it. NCEs (New Chemical Entity) Compounds identified as potential drugs that are sent from research and development into clinical trials to determine their suitability. Nested PCR The second round amplification of an already PCR-amplified sequence using a new pair of primers which are internal to the original primers. Typically done when a single PCR reaction generates insufficient amounts of product. Neural net A neural net is an interconnected assembly of simple processing elements, units or nodes, whose functionality is loosely based on the animal brain. The processing ability of the network is stored in the inter-unit connection strengths, or weights, obtained by a process of adaptation to, or learning from, a set of training patterns. Neural nets are used in bioinformatics to map data and make predictions, such as taking a multiple alignment of a protein family as a training set in order to identify novel members of the family from their sequence data alone. Nonsense mutation A point mutation in which a codon specific for an amino-acid is converted into a nonsense codon. Northern blotting A technique to identify RNA molecules by hybridization that is analogous to Southern blotting (see Southern blotting). Nuclease Any enzyme that can cleave the phosphodiester bonds of nucleic acid backbones. Nucleoside A five-carbon sugar covalently attached to a nitrogen base. Nucleotide A nucleic acid unit composed of a five carbon sugar joined to a phosphate group and a nitrogen base. O back to top Object-Relational Database Object databases combine the elements of object orientation and object-oriented programming languages with database capabilities. They provide more than persistent storage of programming language objects. Object databases extend the functionality of object programming languages (e.g., C++, Smalltalk, or Java) to provide full-featured database programming capability. The result is a high level of congruence between the data model for the application and the data model of the database. Object-relational databases are used in Bioinformatics to map molecular biological objects (such as sequences, structures, maps and pathways) to their underlying representations (typically within the rows and columns of relational database tables.) This enables the user to deal with the biological objects in a more intuitive manner, as they would in the laboratory, without having to worry about the underlying data model of their representation. Oligonucleotide A short molecule consisting of several linked nucleotides (typically between 10 and 60) covalently attached by phosphodiester bonds. Open reading frame (ORF) Any stretch of DNA that potentially encodes a protein. Open reading frames start with a start codon, and end with a termination codon. No termination codons may be present internally. The identification of an ORF is the first indication that a segment of DNA may be part of a functional gene. Operator A segment of DNA that interacts with the products of regulatory genes and facilitates the transcription of one or more structural genes. Operon A unit of transcription consisting of one or more structural genes, an operator, and a promoter. Ortholog Orthologs are genes in different species that evolved from a common ancestral gene by speciation. Normally, orthologs retain the same function in the course of evolution. Identification of orthologs is critical for reliable prediction of gene function in newly sequenced genomes. (See also Paralogs.) Overlapping clones Collection of cloned sequences made by generating randomly overlapping DNA fragments with infrequently cutting restriction enzymes. P back to top Palindrome A region of DNA with a symmetrical arrangement of bases occuring about a single point such that the base sequences on either side of that point are identical (if the strands are both read in the same direction) e.g 5 GAATTC 3 whose complementary sequence is 3 CTTAAG 5. Pattern Molecular biological patterns usually occur at the level of the characters making up the gene or protein sequence. A pattern language must be defined in order to apply different criteria to different positions of a sequence. In order to have position-specific comparison done by a computer, a pattern-matching algorithm must allow alternative residues at a given position, repetitions of a residue, exclusion of alternative residues, weighting, and ideally, combinatorial representation. Pathways Bioinformatics strives to define representations of key biological datatypes, algorithms and inference procedures, including sequences, structures, biological pathways and reactions. Representing and computing with biological pathways requires ontologies for representing pathway knowledge; User interfaces to these databases; Physico-chemical properties of enzymes and their substrates in pathways; And pathway analysis of whole genomes including identifying common patterns across species and species differences. Paralog Paralogs are genes related by duplication within a genome. Orthologs retain the same function in the course of evolution, whereas paralogs evolve new functions, even if these are related to the original one. Parameters Parameters are user-selectable values, typically experimentally determined, that govern the boundaries of an algorithm or program. For instance, selection of the appropriate input parameters governs the success of a search algorithm. Some of the most common search parameters in bioinformatics tools include the stringency of an alignment search tool, and the weights (penalties) provided for mismatches and gaps. Peptide A short stretch of amino acids each covalently coupled by a peptide (amide) bond. Peptide bond (amide bond) A covalent bond formed between two amino acids when the amino group of one is linked to the carboxy group of another (resulting in the elimination of one water molecule). Phage (Bacteriophage) A virus that infects bacterial cells and serves as a useful vector for introducing genes into bacteria for a number of purposes. Phage display A technique in which phage are engineered to fuse a foreign peptide or protein with their capsid (surface) proteins and hence display it on their cell surfaces. The immobilized phage may then be used as a screen to see what ligands bind to the expressed fusion protein exhibited (displayed) on the phage surface. Pharmacogenomics The use of (DNA-based) genotyping in order to target pharmaceutical agents to specific patient populations. Genetic differences are known to affect responses to many types of drug therapy, and pharmacogenomics analysis serves to customize the use of pharmaceuticals for specific subgroups of patients.The rationale for this approach is that observed gene expression differences may correlate with, and explain, the differences in side effects and efficacy to drugs in humans. Pharmacophore The three dimensional spatial arrangment of atoms, substituents, functional groups, or chemical features that together are sufficient to describe the pharmacologically active components of a drug molecule or molecule series. Phenotype Any observable feature of an organism that is the result of one or more genes. Phylum The segmentation of the animal kingdom into about 30 major groups collectively known as phyla. The members of each phylum share the same basic structure and organization. For instance, fish, birds, and human beings belong to one phylum - the Chordata - because all have spinal cords. Physical map A physical map consists of a linearly ordered set of DNA fragments encompassing the genome or region of interest. Physical maps are of two types, macro-restriction maps and ordered clone maps. The former consists of an ordered set of large DNA fragments generated by using restriction enzymes whose recognition sequences are infrequently represented in the genome. An ordered clone map consists of an overlapping collection of cloned DNA fragments. The DNA may be cloned into any one of the available vector systems--YACs, cosmids, phage, or even plasmids. Major advantages of ordered clone maps are that they are of high resolution and directly provide the clones for further study. Plasmid Any replicating DNA element that can exist in the cell independently of the chromosomes. Synthetic plasmids are used for DNA cloning. Most commonly found in bacterial cells. Pleitropy The multiple effects on an organisms phenotype due to a single gene or allele e.g the cytokines which can bind to multiple cellular receptors and effect growth and multiple immune pathways. Point mutation A mutation in which a single nucleotide in a DNA sequence is substituted by another nucleotide. Poly(A) tail The stretch of Adenine (A) residues at the 3 end of eukaryotic mRNA that is added to the pre-mRNA as it is processed, before its transport from the nucleus to the cytoplasm and subsequent translation at the ribosome. Polyadenylation site A site on the 3-end of messenger RNA (mRNA) that signals the addition of a series of Adenines during the RNA processing step and before the mRNA migrates to the cytoplasm. These so-called poly(A) "tails" increase mRNA stability andallow one to isolate mRNA from cells by PCR-amplification using poly(T) primers. Polygenic inheritance Inheritance involving alleles at many genetic loci. Polymerase chain reaction (PCR ) Technique used to amplify or generate large amounts of replica DNA of a segment of any DNA whose "flanking" sequences are known. Oligonucleotide primers which bind these flanking sequences are used by an enzyme (Taq polymerase) to copy the sequence in between the primers. Cycles of heat to break apart the DNA strands, cooling to allow the primers to bind, and heating again to allow the enzyme to copy the intervening sequence lead to a doubling of DNA at each cycle. The reactions are typically carried out on a regulated heating block and consist of 30-35 cycles of repeated amplification of all the DNA present. Single molecules of "target" DNA can be amplified to microgram amounts of DNA. The target DNA can be of any origin. Polymorphism (lit. many forms) The existence of a gene in a population in at least two different forms at a frequency far higher than that attributable to recurrent mutation alone. Variations in a population may be measured by determining the rate of mutation in polymorphic genes (see SNPs). Polypeptide A single chain of covalently attached amino acids joined by peptide bonds. Polypeptide chains usually fold into a compact, stable form (a domain) that is part (or all) of the final protein. Positional cloning Method used to define the location of a gene on a chromosome and use this information to identify and clone the gene. The location of the gene is determined by linkage analysis of DNA from a large family containing afflicted and normal members to identify linkages between the transmission of the disease gene and observable genetic markers. This information is then used to screen (by chromosomal jumping and walking) the location for putative genes. The disease gene must be compared between the afflicted and normal family members and be shown to be different in the two groups. The full sequencing of the gene will then provide information regarding the characteristics and function of the gene product, and a potential explanation for the cause of the disease. Post-transcriptional modification Alterations made to pre-mRNA before it leaves the nucleus and becomes mature mRNA. Post-translational modification Alterations made to a protein after its synthesis at the ribosome. These modifications, such as the addition of carbohydrate or fatty acid chains, may be critical to the function of the protein. Primary sequence (protein) The linear sequence of a polypeptide or protein. Primary structure (protein) see primary sequence. Primer A short oligonucleotide that provides a free 3 hydroxyl for DNA or RNA synthesis by the appropriate polymerase (DNA polymerase or RNA polymerase). Probe Any biochemical that is labelled or tagged in some way so that it can be used to identify or isolate a gene, RNA, or protein. Profile Sequence profiles are usually derived from multiple alignments of sequences with a known relationship, and consist of tables of position-specific scores and gap-penalties. Each position in the profile contains scores for all of the possible amino acids, as well as one penalty score for opening and one for continuing a gap at the specified position. Attempts have been made to further improve the sensitivity of the profile by refining the procedures to construct a profile starting from a given multiple alignment. Other representations for sequence domains or motifs do not necessarily require the presence of a correct and complete multiple alignment, such as hidden Markov models. Prokaryote An organism or cell that lacks a membrane-bounded nucleus. Bacteria and blue-green algae are the only surviving prokaryotes (cf. Eukaryote). Promoter (site) A promoter site is defined by its recognition by eukaryotic RNA polymerase II; its activity in a higher eukaryote; by experimentally evidence, or homology and sufficient similarity to an experimentally defined promoter; and by observed biological function. Protein families Sets of proteins that share a common evolutionary origin reflected by their relatedness in function which is usually reflected by similarities in sequence, or in primary, secondary or tertiary structure. Subsets of proteins with related structure and function. Proteome The entire protein complement of a given organism. Proteomics The study of the proteome. Typically, the cataloging of all the expressed proteins in a particular cell or tissue type, obtained by identifying the proteins from cell extracts using a combination of 2D gel electrophoresis and mass spectrometry. The large scale analysis of the protein composition and function. (cf genomics) Purine A nitrogen-containing compound with a double-ring structure. The parent compound of Adenine and Guanine. Pyrimidine A nitrogen-containing compound with a single six-membered ring structure. The parent compound of Thymidine and Cytosine. Q back to top Query (sequence) A DNA, RNA of protein sequence used to search a sequence database in order to identify close or remote family members (homologs) of known function, or sequences with similar active sites or regions (analogs), from whom the function of the query may be deduced. R back to top Rational drug design (Structure based drug design) The development of drugs based on the 3-dimensional molecular structure of a particular target. Reading frame A sequence of codons beginning with an intiation codon and ending with a termination codon, typically of at least 150 bases (50 amino acids) coding for a polypeptide or protein chain (see ORF and URF). Reagents Sources of biological or chemical material that can be used as the starting blocks in laboratory experiments. Reagents can range from chemicals needed to perform a particular chemical reaction, constituents of a laboratory protocol, or clones to be used in a large-scale gene expression study. Recessive Any trait that is expressed phenotypically only when present on both alleles of a gene (cf dominant). Recombinant DNA (rDNA) DNA molecules resulting from the fusion of DNA from different sources. The technology employed for splicing DNA from different sources and for amplifying the resultant heterogenous DNA. Recombination A new combination of alleles resulting from the rearrangement occuring by crossing-over or by independent assortment (see crossing over). Recursion An algorithmic procedure whereby an algorithm calls on itself to perform a calculation until the result exceeds a threshold, in which case the algorithm exits. Recursion is a powerful procedure with which to process data and is computationally quite efficient. Regulatory gene A DNA sequence that functions to control the expression of other genes by producing a protein that modulates the synthesis of their products (typically by binding to the gene promoter). (cf. Structural gene). Relational Database A database that follows E. F. Codds 11 rules, a series of mathematical and logical steps for the organization and systemization of data into a software system that allows easy retrieval, updating, and expansion. An RDBMS stores data in a database consisting of one or more tables of rows and columns. The rows correspond to a record (tuple); the columns correspond to attributes (fields) in the record. In an RDBMS, a view, defined as a subset of the database that is the result of the evaluation of a query, is a table. RDBMSs use Structured Query Language (SQL) for data definition, data management, and data access and retrieval. Relational and object-relational databases are used extensively in bioinformatics to store sequence and other biological data. Relational Database Management Systems (RDBMS) A software system that includes a database architecture, query language, and data loading and updating tools and other ancillary software that together allow the creation of a relational database application. Repeats (repeat sequences) Repeat sequences and approximate repeats occur throughout the DNA of higher organisms (mammals). For example, the Alu sequences of length about 300 characters, appear hundreds of thousands of times in Human DNA with about 87% homology to a consensus Alu string. Some short substrings such as TATA-boxes, poly-A and (TG)* also appear more often than by chance. Repeat sequences may also occur within genes, as mutations or alterations to those genes. Repetitive sequences, especially mobile elements, have many applications in genetic research. DNA transposons and retroposons are routinely used for insertional mutagenesis, gene mapping, gene tagging, and gene transfer in several model systems. Repetitive elements Repetitive elements provide important clues about chromosome dynamics, evolutionary forces, and mechanisms for exchange of genetic information between organisms The most ubiquitous class of repetitive elements in the DNA sequence in primate genomes is the Alu family of interspersed repeats which have arisen in the last 65 million years of evolution Alu repeats belong to a class of sequences defined as short interspersed elements (SINEs). Approximately 500,000 Alu SINEs exist within the human genome, representing about 5% of the genome by mass. Replication The synthesis of an informationally identical macromolecule (e.g. DNA) from a template molecule. Repressor The protein product of a regulatory gene that combines with a specific operator (regulatory DNA sequence) and hence blocks the transcription of genes in an operon. Restriction enzyme (restriction endonuclease) A type of enzyme that recognizes specific DNA sequences (usually palindromic sequences 4, 6, 8 or 16 base pairs in length) and produces cuts on both strands of DNA containing those sequences only. The "molecular scissors" of rDNA technology. Restriction fragment length polymorphisms (RFLPs) Variation within the DNA sequences of organisms of a given species that can be identified by fragmenting the sequences using restriction enzymes, since the variation lies within the restriction site. RFLPs can be used to measure the diversity of a gene in a population. Restriction map A physical map or depiction of a gene (or genome) derived by ordering overlapping restriction fragments produced by digestion of the DNA with a number of restriction enzymes. Reverse Genetics The use of protein information to elucidate the genetic sequence encoding that protein. Used to describe the process of gene isolation starting with a panel of afflicted patients (see positional cloning). Reverse transcriptase A DNA polymerase that can synthesise a complementary DNA (cDNA) strand using RNA as a template - a so-called RNA-dependent DNA polymerase. Reverse transcriptase-PCR (RT-PCR) Procedure in which PCR amplification is carried out on DNA that is first generated by the conversion of mRNA to cDNA using reverse transcriptase. Ribonucleic acid (RNA) A category of nucleic acids in which the component sugar is ribose and consisting of the four nucleotides Thymidine, Uracil, Guanine, and Adenine. The three types of RNA are messenger RNA (mRNA), transfer RNA (tRNA) and ribosomal RNA (rRNA). S back to top Secondary structure (protein) The organization of the peptide backbone of a protein that occurs as a result of hydrogen bonds e.g alpha helix, Beta pleated sheet. Selectivity Selectivity of bioinformatics similarity search algorithms is defined as the significance threshold for reporting database sequence matches. As an example, for BLAST searches, the parameter E is interpreted as the upper bound on the expected frequency of chance occurrence of a match within the context of the entire database search. E may be thought of as the number of matches one expects to observe by chance alone during the database search. Sense strand The strand of double-stranded DNA that acts as the template strand for RNA synthesis. Typically only one gene product is produced per gene, reading from the sense strand only. (Some viruses have open reading frames in both the sense and the antisense strands). Sensitivity Sensitivity of bioinformatics similarity search algorithms centers around two areas: First, how well can the method detect biologically meaningful relationships between two related sequences in the presence of mutations and sequencing errors; Secondly how does the heuristic nature of the algorithm affect the probability that a matching sequence will not be detected. At the user's discretion, the speed of most similarity search programs can be sacrificed in exchange for greater sensitivity - with an emphasis on detecting lower scoring matches. Sequence Tagged Site (STS) A unique sequence from a known chromosomal location that can be amplified by PCR. STSs act as physical markers for genomic mapping and cloning. Sexual PCR (Molecular Diversity) Sexual PCR is a form of PCR in which similar, but not identical, DNA sequences are reassembled to obtain novel juxtapositions, simulating the result of genetic recombination. The result is the creation of an array of related genes which may possess improved characteristics. By repeated rounds of recombination, selection and PCR-based amplification vastly improved gene-products, such as enzymes with greater activity, may be generated and selected. Shotgun cloning The cloning of an entire gene segment or genome by generating a random set of fragments using restriction endonucleases to create a gene library that can be subsequently mapped and sequenced to reconstruct the entire genome. Similarity (homology) search Given a newly sequenced gene, there are two main approaches to the prediction of structure and function from the amino acid sequence. Homology methods are the most powerful and are based on the detection of significant extended sequence similarity to a protein of known structure, or of a sequence pattern characteristic of a protein family. Statistical methods are less successful but more general and are based on the derivation of structural preference values for single residues, pairs of residues, short oligopeptides or short sequence patterns. The transfer of structure function information to a potentially homologous protein is straightforward when the sequence similarity is high and extended in length, but the assessment of the structural significance of sequence similarity can be difficult when sequence similarity is weak or restricted to a short region. Signal sequence (leader sequence) A short sequence added to the amino-terminal end of a polypeptide chain that forms an amphipathic helix allowing the nascent polypeptide to migrate through membranes such as the endoplasmic reticulum or the cell membrane. It is cleaved from the polypeptide after the protein has crossed the membrane. Single nucleotide polymorphisms (SNPs) Variations of single base pairs scattered throughout the human genome that serve as measures of the genetic diversity in humans. About 1 million SNPs are estimated to be present in the human genome, and SNPs are useful markers for gene mapping studies. Single-pass sequencing Rapid sequencing of large segments of the genome of an organism by isolating as many expressed (cDNA) sequences as possible and performing single sequencer runs on their 5 or 3 ends. Single-pass sequencing typically results in individual, error-prone sequencing reads of 400-700 bases, depending on the type of sequencer used. However, if many of these are generated from numerous clones from different tissues, they may be overlapped and assembled to remove the errors and generate a contiguous sequence for the entire expressed gene. Site Sites in sequences can be located either in DNA (e.g. binding sites, cleavage sites) or in proteins. In order to identify a site in DNA, ambiguity symbols are used to allow several different symbols at one position. Proteins, however, need a different mechanism (see Pattern). Restriction enzyme cleavage sites, for instance, have the following properties: limited length (typically, less than 20 base pairs); definition of the cleavage site and its appearance (3', 5' overhang or blunt); definition of the binding site. Southern blotting A procedure for the identification of DNA by transmitting a fragment isolated on an agarose gel to a nitrocellulose filter where it can be hybridized with a complementary "probe" sequence. Splice site The sequence found at the 5 and 3 region of exon intron boundaries, usually defined by a consensus sequence: Intron 5 CAGGTAAGT---------TNCAGG 3 A G C T N represents any nucleotide; the bottom line represents alternative nucleotides at the indicated positions. Splice form By using alternative splicing, a single message precursor from DNA can generate an entire family of mRNAs and proteins. This can be utilized to create specificity in cell-cell or cell-ligand interactions. A cell may produce a given protein, but it will be a different splice-form of the protein than that produced by an adjacent cell. In this manner, the two cells have the potential to interact differently with other cells or molecules. Two places where this has been extremely important is in the production of cell-surface specificity proteins in the immune and nervous systems. Splicing The joining together of separate DNA or RNA component parts. For example, RNA splicing in eukaryotes involves the removal of introns and the stitching together of the exons from the pre-mRNA transcript before maturation. Solvent accessibility The surface area (typically measured in square angstroms) of a biological molecule, usually a protein, that is exposed to solvent in its native, folded form. Determining the solvent accessibility of a protein helps define which amino acids in its molecular sequence are on the exterior of the molecule, and thus available to participate in interactions with other molecules. Structural gene Gene which encodes a structural protein (cf. Regulatory gene). Structure prediction Algorithms that predict the secondary, tertiary and sometimes even quarternary structure of proteins from their sequences. Determining protein structure from sequence has been dubbed "the second half of the Genetic Code" since it is the folded tertiary structure of a protein that governs how it functions as a gene product. As yet most structure prediction methods are only partially successful, and typically work best for certain well-defined classes of proteins. Substitution matrix A model of protein evolution at the sequence level resulting in the development of a set of widely used substitution matrices. These are frequently called Dayhoff, MDM (Mutation Data Matrix), BLOSUM or PAM (Percent Accepted Mutation) matrices. They are derived from global alignments of closely related sequences. Matrices for greater evolutionary distances are extrapolated from those for lesser ones. Subtraction library A cDNA library that only contains cDNAs uniquely expressed in a given cell or tissue. e.g T cells and B cells will express many common RNAs, as well as a very small percentage which will be unique for T cells and B cells respectively. To make a T cell subtraction library, the cDNA from a T cell library is hybridized with a vast excess of B cell RNA. The commonly expressed genes will result in RNA-cDNA hybrids which can be removed (or subtracted) to leave only T cell specific cDNAs. T back to top Tentative Consensus (TC) The identification of a sequence from an EST cluster that represents part or all of a complete gene. TCs are usually determined by clustering ESTs allowing for sequencing errors, artefacts such as chimeric clones, and naturally occuring biological phenomena such as alternative splicing. Creation of a cluster allows one to generate a consensus sequence and then identify a long open reading frame which would suggest the possibility of that consensus representing a bona fide gene. Tentative Human Consensus sequences (THCs) A consensus sequence generated from human EST fragments. THCs may be validated by comparison against databases of known human gene sequences, human genomic sequences, or by identification of the ORFs or other sequence features contained within the consensus as belonging to a known human gene product. Tertiary structure Folding of a protein chain via interactions of its sideschain molecules including formation of disulphide bonds between cysteine residues. Thymine A pyrimidine base found in DNA but not in RNA. Tissue Section of an organ that consists of a largely homogenous population of cell types. Since many organs are multifunctional, they have developed highly specialized cell types to perform different functions. Identifying the section of an organ that is homogenous for a particular cell type ensures that the gene expression profiles extracted from those cells will accurately resemble the class of cells that make up the tissue. Transcript The single-stranded mRNA chain that is assembled from a gene template. Transcription The assembly of complementary single-stranded RNA on a DNA template. Transcription factors A group of regulatory proteins that are required for transcription in eukaryotes. Transcription factors bind to the promoter region of a gene and facilitate transcription by RNA polymerase. Transfer RNA (tRNA) A small RNA molecule that recognizes a specific amino acid, transports it to a specific codon in the mRNA, and positions it properly in the nascent polypeptide chain. Transformation A genetic alteration to a cell as a result of the incorporation of DNA from a genetically diferent cell or virus; can also refer to the introduction of DNA into bacterial cells for genetic manipulation. Transgene A foreign gene that is introduced into a cell or whole organism (eg.transgenic mice) for therapeutic or experimental purposes. Translation The process of converting RNA to protein by the assembly of a polypeptide chain from an mRNA molecule at the ribosome. Transmembrane region The region of a transmembrane protein that actually spans the membrane. Transmembrane regions are usually hydrophobic in order to be thermodynamically compatible with the lipid bilayer portion of the membrane. They may consist of either alpha-helical or beta-strand secondary structure elements, but in either case the external residues (the ones facing the membrane) are invariably hydrophobic while the internal residues may be hydrophilic (as in the case of a pore or channel) or polar. One common transmembrane structural domain is the seven-helix bundle seen in numerous channel proteins. Tissue Section of an organ that consists of a largely homogenous population of cell types. Since many organs are multifunctional, they have developed highly specialized cell types to perform different functions. Identifying the section of an organ that is homogenous for a particular cell type ensures that the gene expression profiles extracted from those cells will accurately resemble the class of cells that make up the tissue. U back to top Unidentified reading frame (URF) An open reading frame encoding a protein of undefined function. Uracil Nitrogenous pyrimidine base found in RNA but not DNA. V back to top Variable numbers of tandem repeats (VNTRs) DNA sequence blocks of 2-60 base pairs which are repeated from two to more than 20 times in different individuals. This polymorphism makes VNTRs very useful DNA markers used in genomic mapping, linkage analysis and also DNA fingerprinting. Variation (genetic) Variation in genetic sequences and the detection of DNA sequence variants genome-wide allow studies relating the distribution of sequence variation to a population history. This in turn allows one to determine the density of SNPS or other markers needed for gene mapping studies. Quantitation of these variations together with analytical tools for studying sequence variation also relate genetic variations to phenotype. Vector Any agent that transfers material (typically DNA) from one host to another. Typically DNA vectors are autonomous DNA elements (such as plasmids) that can be manipulated and integrated into a hosts DNA or recombinant viruses. Virtual libraries The creation and storage of vast collections of molecular structures in an electronic database. These databases may be queried for subsets that exhibit specific physicochemical features, or may be "virtually screened" for their ability to bind a drug target. This process may be performed prior to the synthesis and testing of the molecules themselves. Visualization Visualization is the process of representing abstract scientific data as images that can aid in understanding the meaning of the data. W back to top Weight matrix The density of binding sites in a gene or sequence can be used to derive a ratio of density for each element in a pattern of interest. The combined individual density ratios of all elements are then collectively used to build a scoring profile known as a weight matrix. This profile can be used to test the prediction of the identification of the selected pattern and the ability of the algorithm to discriminate them from non-pattern sequences. Western blot Technique in which specific antibodies are used to identify their antigens from a mixture of proteins. Typically, these proteins mixtures are first separated by electrophoresis and then transfered onto nylon sheets by electrotransfer. Radiolabeled or enzyme-linked antibodies are incubated with the sheets and unbound antibodies washed away allowing the position of the bound antibody to be revealed by autoradiography or color which is formed upon addition of a substrate. Wild type Form of a gene or allele that is considered the "standard" or most common. X back to top X chromosome In mammals, the sex chromosome that is found in two copies in the homogametic sex (female in humans) and one copy in the hererogametic sex (male in humans). Y back to top Yeast 2-hybrid system A yeast-based method used to simultaneously identify, and clone the gene for, proteins interacting with a known protein. The basis of this method is a "transcriptional reporter assay" (see definition) in which reporter gene expression is dependent on two domains. The first domain is linked to the known protein. The second domain is genetically linked to a library. If the library is screened against the known protein the two domains will interact only if a protein from the library binds the known protein, resulting in transcription activation of the reporter gene, and a blue color. The "blue yeast clone" will contain the gene encoding the newly identified protein. Z back to top Z-DNA A conformation of DNA existing as a left-handed double helix (the phosphate-sugar backbone forms a left-handed zig-zag course), which may play a role in gene regulation. Zinc fingers A protein motif formed by the interaction of repeated cysteine and histidine residues with a zinc ion. The spacing of the repeats results in finger like arrangements of the protein loops formed from the interaction which interact with DNA. These motifs are typically found in transcription factors. Bioinformatics.ca resource directory features curated links to molecular resources, tools and databases. Bioinformatics Links Directory SITE MAP PRINT PAGE FRANCAIS Location: Home Bioinformatics Resources Links Links Home Suggest URL Acknowledgments NAR WEB 2005 NAR WEB 2004 Recently Added Links News Syndication Bioinformatics Links Directory The Bioinformatics Links Directory features curated links to molecular resources, tools and databases. All of the resources are free or available for a nominal fee. The links listed in this directory are selected on the basis of recommendations from bioinformatics experts in the field. We make every effort to list useful, well tested resources instead listing all tools. We also rely on input from our community of bioinformatics users for suggestions . Starting in 2004, we have also started listing all links contained in the NAR Webserver issue. These NAR links are indicated with a NAR Webserver icon in the directory. The UBC Bioinformatics Centre does not specifically endorse or support any of the links in the directory, nor are we responsible for the content of any of these external sites. Jump to: --------------------- ---------- COMPUTER RELATED Bio-* Programming Tools C C++ Databases Java Linux Unix PERL PHP Statistics Web Development Web Services ---------- DNA Annotations Comparative Genomics Gene Prediction Mapping and Assembly Phylogeny Reconstruction Sequence Feature Detection Sequence Polymorphisms Sequence Retrieval and Submission Tools For the Bench Utilities ---------- EDUCATION Bioinformatics Related News Sources Community Courses, Programs and Workshops Directories and Portals General Literature Goldmines Tutorials and Directed Learning Resources ---------- EXPRESSION cDNA, EST, SAGE Gene Regulation Microarrays Protein Expression Splicing ---------- HUMAN GENOME Annotations Comparative Genomics Ethics Genomics Health and Disease Other Resources Sequence Polymorphisms ---------- LITERATURE Goldmines Open Access Resources Search Tools Text Mining ---------- MODEL ORGANISMS Fish Fly General Resources Microbes Mouse and Rat Other Organisms Other Vertebrates Plants Worm Yeast ---------- OTHER MOLECULES Carbohydrates Small Molecules ---------- PROTEIN 2-D Structure Prediction 3-D Structure Prediction, Comparison 3-D Structure Retrieval, Viewing Biochemical Features Do-it-all Tools for Protein Domains and Motifs Function Interactions, Pathways, Enzymes Localization and Targeting Phylogeny Reconstruction Presentation and Format Protein Expression Proteomics Sequence Comparison Sequence Data Sequence Features Sequence Retrieval ---------- RNA Functional RNAs General Resources Motifs Sequence Retrieval Structure Prediction, Visualization, and Design ---------- SEQUENCE COMPARISON Alignment Editing and Visualization Analysis of Aligned Sequences Comparative Genomics Multiple Sequence Alignments Other Alignment Tools Pairwise Sequence Alignments Similarity Searching Computer Related (66) This category contains links to resources relating to programming languages often used in bioinformatics. Other tools of the trade, such as web development and database resources, are also included here. Model Organisms (135) Included in this category are links to resources for various model organisms ranging from mammals to microbes. These include databases and tools for genome scale analyses. DNA (201) This category contains links to useful resources for DNA sequence analyses such as tools for comparative sequence analysis and sequence assembly. Links to programs for sequence manipulation, primer design, and sequence retrieval and submission are also listed here. Other Molecules (4) Bioinformatics tools related to molecules other than DNA, RNA, and protein. This category will include resources for the bioinformatics of small molecules as well as for other biopolymers including carbohydrates. Education (68) Links to information about the techniques, materials, people, places, and events of the greater bioinformatics community. Included are current news headlines, literature sources, educational material and links to bioinformatics courses and workshops. Protein (286) This category contains links to useful resources for protein sequence and structure analyses. Resources for phylogenetic analyses, prediction of protein features, and analyses of interactions are also found here. Expression (111) Links to tools for predicting the expression, alternative splicing, and regulation of a gene sequence are found here. This section also contains links to databases, methods, and analysis tools for protein expression, SAGE, EST, and microarray data. RNA (48) Resources include links to sequence retrieval programs, structure prediction and visualization tools, motif search programs, and information on various functional RNAs. Human Genome (69) This section contains links to draft annotations of the human genome in addition to resources for sequence polymorphisms and genomics. Also included are links related to ethical discussions surrounding the study of the human genome. Sequence Comparison (82) Tools and resources for the comparison of sequences including sequence similarity searching, alignment tools, and general comparative genomics resources. Literature (15) Links to resources related to published literature, including tools to search for articles and through literature abstracts. Additional text mining resources, open access resources, and literature goldmines are also listed. ^ top CREDITS SITE MAP CONTACT PRIVACY POLICY AllExperts Biology QA Directory of scientists and scholars volunteering to answer questions in a variety of biological fields. Welcome to AllExperts.com AllExperts Search for Main menu Find out about volunteering! Question Archive About Us Feedback Expert Login Top Experts of the Month! Tell friends about us! Link to us! Disclaimer Ask any question! Allexperts.com is the oldest largest free QA service on the Internet Biology Biology Molecular Biology Careers: Biology Oceanography Chemistry (including Biochemistry) Pathology Computational Biology Bioinformatics Zoology Genetics Hematology Like our site? Recommend us to your friends! Newsletter Signup Subscribe to ExperTease. Enter name and email below! Name Email Search for Explore More on the AllExperts Network! Arts Humanities Autos Cities Towns Comedy Computing Technology Cultures Education Food Drink Gadgets Games Health Fitness Hobbies Home Garden Homework Help Industry Internet Online Jobs Careers Kids Money Movies Music Performing Arts News Issues Parenting Family People Relationships Pets Real Estate Recreation Outdoors Religion Spirituality Science Shopping Small Business Sports Style Teens Travel TV Radio Copyright 2000, AllExperts.com BelgoBiotech Educational biotech web site, selected links, biotech glossary, timeline, basic principles, and applications. BelgoBiotech The Book Page: Biology Classics Download obscure, antiquarian texts. Examples include Darwin, Huxley, Paley, Maunder, Russell, Haldane, Schrodinger, and Tyndall. The Book Page: Free online books Visit The AnswerSleuth FirstScience.com This site is a member of WebRing. To browse visit http: ss.webring.com navbar?f=ly=caimipgu=10007560 Virtual Library: Biosciences Directory of the Virtual Library, an expert-run catalog of sections of the web. Biosciences | The WWW Virtual Library Biosciences: en es fr zh The WWW Virtual Library Biosciences Quick search: Narrower Category : Model Organisms Animal Health, Wellbeing and Rights Animal Health, Wellbeing and Rights Links to online resources dealing with animal care and conservation. this resource in English is indexed under: Biosciences . Biochemistry and Cell Biology Biochemistry and Cell Biology A guide to major online resources in biochemistry, molecular and cell biology and related fields, indexed by subject with annotated links, with sections on angiogenesis, apoptosis, carbohydrates and glycosylation, cell adhesion and extracellular matrix, cell cycle and cytokinesis, cell senescence, chemical biology, cytoskeleton, cell motility and motors, development, enzymes, genes and gene expression, lipids and membranes, metabolism, cellular respiration and photosynthesis, microscopy, organelles, proteins, signal transduction, structural biology and systems biology. this resource in English is indexed under: Biosciences . Biotechnology Biotechnology This directory contains over 3000 links to companies, research institutes, universities, sources of information and other directories specific to biotechnology, pharmaceutical development and related fields. It places emphasis on product development and the delivery of products and services. this resource in English is indexed under: Biosciences , Engineering . Botany Botany Resources in plant biology with information categorized by provider and subject. this resource in English is indexed under: Biosciences . Developmental Biology Developmental Biology Subject pages on: gametogenesis and fertilization, early development, organogenesis and morphogenesis, pattern formation, gene regulation and genetics, cell lineage and fate maps, evolution and development, diseases, defects and development. Maintained by the Society for Developmental Biology. this resource in English is indexed under: Biosciences . Environmental History Environmental History The Environmental History section of the WWW Virtual Library is maintained by the European Society for Environmental History (ESEH). this resource in English is indexed under: Biosciences , History . Forest Genetics and Tree Breeding Forest Genetics and Tree Breeding Subdirectory of the WWW Virtual Library: Forestry. Courtesy of the Finnish Forest Research Institute. see also: Forestry . this resource in English is indexed under: Agriculture , Biosciences . Forestry Forestry This service is provided by the Library Information Services and Information Systems Services at the Finnish Forest Research Institute. It is part of the international World Wide Web Virtual Library of subject oriented link collections. It has two independent sub-sections: one for Forest Genetics and Tree Breeding and another for Forest Soils and Substrates. see also: Forest Genetics and Tree Breeding . this resource in English is indexed under: Agriculture , Biosciences . Genetics Genetics The Virtual Library of Genetics is sponsored by the U.S. Department of Energy Office of Science, Office of Biological and Environmental Research. this resource in English is indexed under: Biosciences . Microbiology Microbiology Note: non-compliant site (see http: vlib.org admin requirements). this resource in English is indexed under: Biosciences , Medicine and Health . Mycology Mycology summarizes Internet resources of interest to mycologists (biologists who study fungi). (fungus, mushroom) this resource in English is indexed under: Biosciences . Neurobiology Neurobiology Links to online resources in the neurosciences. this resource in English is indexed under: Biosciences . Parasitology Parasitology URLs taken from a poster on Internet Resources presented at the Spring Meeting of the British Society for Parasitology at Bangor, Wales, 1996. These have been subsequently updated and now total more than 620. this resource in English is indexed under: Biosciences . Physiology and Biophysics Physiology and Biophysics Links to online resources in physiology and biophysics. this resource in English is indexed under: Biosciences , Physics . Plant Microarrays Plant Microarrays this resource in English is indexed under: Biosciences . Whales Whale Watching Web Whale watching as a commercial activity began in 1955 in North America along the southern California coast. Today, whale watching is carried on in the waters of some 40 countries, plus Antarctica. All the large whale species and many dolphins and porpoises can be seen regularly on a wide range of tours, lasting from an hour to two weeks. Whale watching is a non-consumptive use of whales with economic, recreational, educational and scientific dimensions. The economic benefits occur in areas where whale watching has quickly become a significant aspect of a local tourism economy. this resource in English is indexed under: Biosciences . Broader Category : Natural Sciences and Mathematics See also : Agriculture This record is of type: category . Main Page Pages updated on Thursday, November 17, 2005 - 0:02:47 GMT . These pages are produced automatically from a topic map of the Virtual Library. These pages and the database WWW Virtual Library 1991-latest update. All rights reserved, including database rights . Arctic Theme Page Arctic sea ice ecology, organisms from bacteria, viruses, and unicellular algae to mammals (polar bears, reindeer, fox, whales) text, maps and photographs (current and historical). NOAA (National Oceanic and Atmospheric Administration) site provides access to widely distributed Arctic data and information for scientists, managers, decision makers and the general public on one of the last remaining frontiers. Organisms which thrive in Arctic sea ice - Krembs, Deming What do we know about organisms which thrive in the Arctic sea ice? Is there life in a desert of ice? Christopher Krembs Jody Deming University of Washington Arctic sea ice covers significant portions of the northern hemisphere ocean, forming and persisting at temperatures below the freezing point of seawater. That freezing point is generally around -1.9C when the salinity is 33 parts per thousand, however, the freezing point changes with the concentration of salt in the seawater. As ice crystals grow in the water during the autumn season, small ice platelets begin to accumulate at the ocean surface, inter-link, and form a porous structure of ice crystals filled with liquid, which is referred to as brine. The flourishing life within the briny habitat of sea ice. The ice specific ecosystem includes bacteria, viruses, unicellular algae, diatom chains, worms and crustaceans. Click on the image to see a magnified view of the brine channels containing these organisms. The flourishing life within the briny habitat of sea ice is intricately linked to physical processes. Temperature controls every physical and chemical aspect of ice, including the availability of light. The most notable effect of decreasing temperature, as winter progresses and the ice solidifies, is the reduction of pore space within the ice, and the concurrent increase in the salinity of the brine. Sea ice serves as habitat for an ice-specific food web ( sympagic foodweb ) [ 1 ] that includes bacteria, viruses, unicellular algae , which often form chains and filaments, and invertebrates sufficiently small to traverse the brine network. The brine network is comprised of passages in the ice, with diameters ranging from micrometers to several centimeters when the temperature remains above -5C. During the colder winter months, however, strong gradients of temperature persist throughout the ice, spanning from -2C at the bottom of the ice in contact with seawater to -35C at its wind-chilled surface. Here, connectivity of pore space is at a minimum, brine salinities reach 250 parts per thousand [ 2 ] and salts begin to precipitate as opaque minerals. Since the organisms have the same temperature as the ice, their survival depends on their ability to prevent the growth of ice crystals in their bodies. Many organisms accumulate large deposits of organic molecules, and fatlike material as a strategy to survive the harsh unproductive winter. Studying the capability of organisms to survive such extreme environments is an active research field of astrobiology , which is a branch of biology concerned with the effects of extraterrestrial environments on living organisms. Wintertime sea ice is used as an analogue for possible extraterrestrial habitats on the frozen surfaces of such solar bodies such as Europa, Ganymede, Mars and Titan. Single-celled (unicellular) algae, which develop in the lowermost sections of sea ice, often forming chains and filaments. Ice algae are an important component of the Arctic marine food web. Sea ice constitutes a thermal barrier against the cold winter atmosphere with the result that the interface between the ice and the seawater remains at the temperature of seawater. During spring, when light begins to be available for photosynthesis, and throughout the summer, a large biomass in the form of unicellular photosynthetic ice algae develops within the lowermost sections of the ice. They occasionally form long filaments that can extend several meters into the water column ( Melosira arctica ). Ice algae are a very important part of the marine food web, and contribute on average with 57% to the total Arctic marine primary production [ 3 ]. The interface between the ice and the seawater is therefore critical to the polar marine ecosystem. Organisms which eat zooplankton, called zooplankton grazers (such as Gammerus wilkitzkii), seek food in the ice and also protection from their predators. Arctic cod (Breogadus saida), which are an important food source for many marine mammals and birds ( Arctic marine food web ), use the same habitat as nursery grounds. Larger warm-blooded animals such as birds, seals, whales and polar bears use the ice for migration routes, hunting grounds, rookeries and protection for raising their young. Because sea ice is a diverse and constantly changing habitat, appearing in such varied forms as nilas pancake ice, several meter thick ridged first year and multi-year ice, and pack ice, animals have had to become very good navigators, using homing cues that are as yet not well understood. At the peak of algae production in spring, the solid ice cover transforms into pack ice with individual floes that transport organisms, sediment (see ice core photograph ) and, unfortunately, man-made pollutants over thousands of kilometers before they melt and discharge their contents into the water. It is the aim of scientists to understand how sea ice, its physics, extent and drift patterns affect polar marine populations and the food web in polar waters (the cryopelagic food web) that has formed the basis of sustenance for generations of native Inuit Eskimo peoples. References [1] Horner R. A., S. F. Ackley, G. S. Dieckmann, B. Gulliksen, T. Hoshiai, L. Legendre, I. A. Melnikov, W. S. Reeburgh, M. Spindler and C. W. Sullivan (1992). Ecology of sea ice biota. 1. Habitat, terminology, and methodology. Polar Biol. 12, 417-427. Return to article here . [2] Cox. G. F. N. and W. F. Weeks (1983). Equation for determining the gas and brine volumes in sea-ice samples, J Glaciol. 29, 306-316. Return to article here . [3] Gosselin M., M. Levasseur, P. A. Wheeler, R. A. Horner, B. C. Booth (1997). New measurements of phytoplankton and ice algal production in the Arctic Ocean. Deep-Sea Res. II, 44, 1623-1644. Return to article here . Sea Ice in the Bering Sea and the North Pacific Ocean Home Scientific General Interest Gallery Essays Faq Awards About the Arctic Theme Page | http: www.arctic.noaa.gov arctic.webmaster@noaa.gov Arctic Research Office, http: aro.arctic.noaa.gov Privacy Policy | Disclaimer Functional Genomics Resources Glossaries in genetics and genomics, molecular biology and biochemistry, post-genomics, biotechnology and bioinformatics (including proteomics)and medical genomics from Science Magazine Online. Science Functional Genomics Resources: Educational Resources Genomics Glossaries Genomic terminology defined and hierarchically related, from Cambridge Healthtech Institute. Emphasis is on biotechnology and pharmaceutical applications, proteomics, informatics, technologies, instrumentation and molecular biology. Genomics glossaries and taxonomies top.jpg Search This Site The Web Get a Free Search Engine for Your Web Site Term not found? tips BioPharmaceutical Glossary, Taxonomies and guide to 21st century therapeutics, technologies and trends Glossary last updated Oct. 31, 2005 Homepage last revised Oct. 12, 2005 4,500+ definitions Mary Chitty, Cambridge Healthtech Institute New Page 1 Please register for CHI's Genomics Glossaries Taxonomies website. This sign-in box with then disappear from each page, if you accept cookies. Use of this site will continue to be free, but better demographic data on who is accessing this material helps us to justify the expense of maintaining this resource. Registration policy has details . Registered users of the Genomics Glossaries Taxonomies will automatically be signed up for CHI's complimentary email monthly newsletter, GenomeLink, unless you choose to opt out of receiving it. Mr. Ms. Mrs. Dr. Prof. First: Last: Title: Dept.: Company: Address: City: State: Zip: Country: Email: Opt-out of Email YES NO Telephone: Fax: Pharmaceutical biotechnology terms ( definitions) not in most dictionaries About these glossaries taxonomies Site Map Contact us Tips FAQ What happened to the genomic glossaries? Basic genetics genomics; what are the differences? Concise Biopharmaceutical Glossary Ethics Business of biopharmaceuticals Alliances Financial Intellectual Property Drug discovery development Drug approvals Assays screening Combinatorial libraries synthesis Targets Molecular Medicine Biomarkers Cancer genomics Genetic genomic testing Pharmacogenomics Toxicogenomics Genomics Functional Genomics Metabolic Profiling Proteomics -Omes and -omics More... Applications Map Informatics Algorithms data analysis Bioinformatics Cheminformatics Computers computing Information management interpretation In silico molecular modeling Research More... Informatics Map Technologies Assays screening Biomaterials bioengineering Combinatorial libraries synthesis Gene amplification PCR Genetic manipulation disruption Mass spectrometry Microarrays protein chips Molecular Imaging NMR, synchrotrons crystallography Nanoscience miniaturization Sequencing Ultrasensitivity More... Tools Technologies Map Biology Biomarkers Biomolecules Chemistry biology DNA Expression, genes beyond Gene definitions Glycosciences Model other organisms Nomenclature Pharmaceutical biology chemistry Proteins Protein structures RNA SNPs other genetic variations More... Biology Chemistry Map Looking for unfamiliar terms Alphabetical glossaries index Bibliography Genomics Glossaries Taxonomies reviews New Scientist, Nov. 23, 2002 Weblinks: Genetics You're likely to find here definitions and information untouched by many other reference works. It doesn't get much better than this in terms of defining cutting edge biotech concepts and technologies. Honyaku Home Page: Medical 20 Aug 2002 Science Magazine Functional Genomics Resources "Finding the right word" A guide to some useful online glossaries Post-genomics, biotech and bioinformatics Extraordinary, one-of-a-kind site. The strong focus on, and lengthy treatment of, post-genomics topics makes this an invaluable resource Internet Scout Report, June 20, 2001 Because genomics is an interdisciplinary science that unites biology, chemistry, physics, and mathematics, its language is diverse and includes terms not always found in dictionaries. .. links to pages on nomenclature, a bibliography of Web and print resources, and a FAQ page are available at this fantastic Website "Omics, Schmomics" Jocelyn Kaiser ed. NetWatch Science 292 (5522): 1615, 1 June 2001 Everybody's talking about proteomics and structural genomics these days, but have you heard of transcriptomics? How about cellomics? One site trying to track the dizzying evolution of the postgenomics lexicon is Genomics Glossaries. More from Mary Chitty Chapter on genomics, proteomics and bioinformatics in Using the Pharmaceutical Literature , Sharon Srodin, editor, CRC Press, 2006 BioMedical Taxonomies Ontologies - Current Status, Ongoing Challenges Respondent, ASIST American Society for Information Science Technology Annual Meeting, Oct. 22, 2003, Long Beach CA Biomedical ontologies handout Special Libraries Association Annual Meeting, Pharmaceutical Health Technology Division sessions, New York, June 11, 2003 Biopharmaceutical Roundtable bibliography Return on Investment Breaking the Code: Proteomics in Drug Discovery bibliography Where's my stuff? Information overload, taxonomies and beyond Special Libraries Association Annual Meeting, Pharmaceutical Health Technology Division, June 10, 2002, Los Angeles, CA ABOUT THE LEXICOGRAPHER Mary Chitty, Library Director at Cambridge Healthtech Institute, is the author of Federal Information Sources in Health and Medicine ( Greenwood Press, 1988) and a number of book reviews. She was previously Head of Reference at the Library of the Massachusetts College of Pharmacy, Boston MA and supervised the Air Pollution Technical Information Center at the US EPA Library, Research Triangle Park, NC . Starting out as a picture researcher and fact- checker in the US and England, she has an MSLS from the University of North Carolina - Chapel Hill and a BA (Anthropology) from Yale. When not trying to keep up with the latest developments in molecular biology, she tries to keep up with her website about 19th century American theater and medical history . Functional Genomics All inclusive areas of functional genomics including analysis of mutagenesis and gene disruption, proteomics, microarrys, bioinformatics, SNP analysis, expression profiling, mutations detection, structural genomics,in silico methods, standardisation and benchmarking, data management and ontologies, and integration of data. Sponsored by the European Science Foundation FunctionalGenomics.org.uk - Welcome BioLink Links to about 30 web sites on biochemistry, cells, genetics, evolution, plants, animals, human anatomy, and ecology. RC Enterprises: BIOLINK Welcome to BioLink, where we provide you with the links in your biological explorations on the world wide web GENERAL ONLINE BIOLOGY BOOK Biology Labs Online BIOCHEMISTRY BioChemLinks THE CELL The Biology Project Cell Biology Cellupedia Mindquest Cell Biology GENETICS MendelWeb The Gene School Basic Genetics DNA and Chromatin Glossary of Genetics EVOLUTION The Origin of Species Talk Origins Evolution MICROBIOLOGY Journal of Bacteriology The Microbe Zoo The Bad Bug Book PLANTS Plants Our Environment Botanical Diversity Chemistry of Photosynthesis ANIMALS Animal Diversity Virtual Pig Dissection Endangered Species HUMAN ANATOMY Gray's Anatomy The Electric Heart Virtual Human Body ECOLOGY U.S. Environmental Protection Agency WhaleNet The Rainforest Report Card EnviroLink GOOGLE | YAHOO | HOTBOT | ALTAVISTA | ASK JEEVES | DOG PILE PLEASE EMAIL THE WEBMASTER ABOUT BROKEN OR NEW LINKS TO BE FIXED OR ADDED This page Copyright 2001-2003 RC Enterprises. All rights reserved. Glossary of Biotechnology and Genetic Engineering Food and Agriculture Organization (UN)'s consolidated yet comprehensive list of terms and acronyms in applied biotechnology, especially plant and animal genetic resources,food quality and plant protection. About 5000 terms. FAO RESEARCH AND TECHNOLOGY PAPER No. 7 Glossary of biotechnology and genetic engineering Note, in 2002, FAO published a revised,augmented version of this glossary. It is available at http: www.fao.org DOCREP 004 Y2775E Y2775E00.HTM or, as a searchable database, at http: www.fao.org biotech index_glossary.asp . Table of contents A. Zaid H.G. Hughes E. Porceddu F. Nicholas The designations employed and the presentation of the material in this document do not imply the expression of any opinion whatsoever on the part of the United Nations or the Food and Agriculture Organization of the United Nations concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. ISBN: 92-5-104369-8 ISSN: 1020-0541 All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying or otherwise, without the prior permission of the copyright owner. Applications for such permission, with a statement of the purpose and extent of the reproduction, should be addressed to the Director, Information Division, Food and Agriculture Organization of the United Nations, Viale delle Terme di Caracalla, 00100 Rome, Italy. Food and Agriculture Organization of the United Nations FAO 1999 Table of contents Preface Acknowledgements Abbreviations Notes on the structure of the glossary -A- -B- -C- -D- -E- -F- -G- -H- -I- -J- -K- -L- -M- -N- -O- -P- -Q- -R- -S- -T- -U- -V- -W- -X- -Y- -Z- Annex 1 Annex 2 Biology Online Dictionary, links and tutorials on cell biology, genetics, genetics and evolution, control of growth and development, regulation of biological systems, adaptation and freshwater ecology. Biology Online. Life Science Reference Forum Tutorials Dictionary Directory Biology Online - Information in the Life Sciences Biology Forum The biology forum is divided into different categories so that you can post and find answers with ease and also create biology related communities (or colonies if you wish). So, please register, post your questions, chat and enjoy this feature of Biology-Online.org. Latest Discussion Topic Replies Forum Views reproduction 0 Molecular Biology 1 mieosis and mitosis 0 Molecular Biology 6 TFPGA (tools for population genetic analysis) 0 Bioinformatics 7 'Twinning' 0 Human Biology 19 RNA contamination in spec analysis 0 Molecular Biology 24 Dictionary of Biology Check out the biology dictionary consisting of thousands of terms, working alongside the tutorials. Not sure of some terminology? Use the dictionary in conjunction with the tutorials to develop your understanding of the wording used. Search the dictionary Biology Tutorials The biology tutorials aim to give an introductory to intermediate understanding of various biological concepts and disciplines, split up into sections for ease of use. Within each tutorial are references to the biology dictionary, intending to give an easy reference to the terminology used. 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About Us | Contact Us | Link to Us | Science Partners: Chemistry | Equations | 2005 Biology-Online.org Disclaimer Privacy Amino Acid Repository Properties and images of amino acids, hydrophobicity scales, solvent accessibility of amino acids in known protein structures, mutation mass shifts, links to the NIST Chemistry WebBook for Amino Acids. IMB Jena Image Library: The Amino Acid Repository The Amino Acid Repository Individual properties of the 20 standard amino acids Properties and images Qualitative classification of the 20 standard amino acids (JPEG) Hydrophobicity scales All 20 Standard amino acids on one image (GIF) Properties of amino acids in proteins Postranslational modifications of amino acids in proteins Solvent accessibility of amino acids in protein structures Mutation mass shifts Graph of suggested amino acid substitutions (JPEG) Ramachandran plots for individual residue types (from Uppsala University) ( PostScript | GIF ) Individual properties and images of amino acids a Properties and images (name: NIST WebBook, three letter code: GIF, one letter code: VRML) amino acid mass surface b volume c pKa d pI e solubility e density e Alanine ALA A 71.09 115 88.6 - 6.107 16.65 1.401 Arginine ARG R 156.19 225 173.4 ~12 10.76 15 1.1 Aspartic Acid ASP D 114.11 150 111.1 4.5 2.98 0.778 1.66 Asparagine ASN N 115.09 160 114.1 - - 3.53 1.54 Cysteine CYS C 103.15 135 108.5 9.1-9.5 5.02 very high - Glutamic Acid GLU E 129.12 190 138.4 4.6 3.08 0.864 1.460 Glutamine GLN Q 128.14 180 143.8 - - 2.5 - Glycine GLY G 57.05 75 60.1 - 6.064 24.99 1.607 Histidine HIS H 137.14 195 153.2 6.2 7.64 4.19 - Isoleucine ILE I 113.16 175 166.7 - 6.038 4.117 - Leucine LEU L 113.16 170 166.7 - 6.036 2.426 1.191 Lysine LYS K 128.17 200 168.6 10.4 9.47 very high - Methionine MET M 131.19 185 162.9 - 5.74 3.381 1.340 Phenylalanine PHE F 147.18 210 189.9 - 5.91 2.965 - Proline PRO P 97.12 145 112.7 - 6.3 162.3 - Serine SER S 87.08 115 89.0 - 5.68 5.023 1.537 Threonine THR T 101.11 140 116.1 - - very high - Tryptophan TRP W 186.12 255 227.8 - 5.88 1.136 - Tyrosine TYR Y 163.18 230 193.6 9.7 5.63 0.0453 1.456 Valine VAL V 99.14 155 140.0 - 6.002 8.85 1.230 a mass [dalton], surface [2], volume [3], pKa [side chain], pI [at 25C], solubility [g 100g, 25C], density [crystal density, g ml], name: information from NIST Chemistry WebBook , three letter code: GIF, one letter code: VRML b C.Chothia, J. Mol. Biol., 105(1975)1-14 c A.A. Zamyatin, Prog. Biophys. Mol. Biol., 24(1972)107-123 d C. Tanford, Adv. Prot. Chem., 17(1962)69-165 e The Merck Index, Merck Co. Inc., Nahway, N.J., 11(1989); CRC Handbook of Chem. Phys., Cleveland, Ohio, 58(1977) back Hydrophobicity scales a Residue non-polar surface area b [A2] Estimated hydrophobic effect for residue burial [kcal mol] Estimated hydrophobic effect for side chain burial c [kcal mol] Gly 47 1.18 0.0 Ala 86 2.15 1.0 Val 135 3.38 2.2 Ile 155 3.88 2.7 Leu 164 4.10 2.9 Pro 124 3.10 1.9 Cys 48 1.20 0.0 Met 137 3.43 2.3 Phe 39+155 3.46 2.3 Trp 37+199 4.11 2.9 Tyr 38+116 2.81 1.6 His 43+86 2.45 1.3 Thr 90 2.25 1.1 Ser 56 1.40 0.2 Gln 66 1.65 0.5 Asn 42 1.05 -0.1 Glu 69 1.73 0.5 Asp 45 1.13 -0.1 Lys 122 3.05 1.9 Arg 89 2.23 1.1 a P.A.Karplus, Protein Science 6(1997)1302-1307 b All surfaces associated with main- and side-chain carbon atoms were included except for amide, carb- oxylate and guanidino carbons. For aromatic side chains, the aliphatic and aromatic surface areas are reported seperately. c The values are obtained from the previous column by substracting the value for Gly (1.18 kcal mol) from each residue. back Amino acids in proteins Postranslational modifications of amino acids in proteins Sulphydryls Disulfidebond -2.0159 Oxidation +15.9994 (C,M) Cysteinylation +119.1442 Glutathionylation +305.3117 Methylation +14.0269 Formylation +28.0104 Acetylation +42.0373 Lipoic acid +188.3147 Amines Farnesylation +204.3556 Myristoylation +210.3598 (K N) Biotinylation +226.2994 Palmitoylation +238.4136 Stearoylation +266.4674 Geranylation +272.4741 Acids Pyroglutamic acid (Q) -17.0306 Deamidation (Q,N) +0.9847 Amides(E D Q N) Carboxylation (E,D) +44.0098 Hydroxyl- Phosphorylation +79.9799 Sulphation +80.0642 groups (S T Y) Carbohydrates Pentoses +132.1161 Deoxyhexoses +146.1430 (S T N) Hexosamines +161.1577 Hexoses +162.1424 N-acetylhexosamines +203.1950 Sialic acid +291.2579 back Solvent accessibility of amino acids in known protein structures a SEA (Solvent Exposed Area) The solvent accessibility information was derived from (a). The data for this table was calculated from 55 proteins in the Brookhaven data base. The only clear trend in this table is that some residues, such as R and K, locate themselves so that they have access to the solvent. The hydrophobic residues, such as L and F, show no clear trend: they are found near the solvent as often as they are found buried. Amino Acid SEA 30 2 SEA 10 2 30 2 SEA 10 2 S 0.70 0.20 0.10 T 0.71 0.16 0.13 A 0.48 0.35 0.17 G 0.51 0.36 0.13 P 0.78 0.13 0.09 C 0.32 0.54 0.14 D 0.81 0.09 0.10 E 0.93 0.04 0.03 Q 0.81 0.10 0.09 N 0.82 0.10 0.08 L 0.41 0.49 0.10 I 0.39 0.47 0.14 V 0.40 0.50 0.10 M 0.44 0.20 0.36 F 0.42 0.42 0.16 Y 0.67 0.20 0.13 W 0.49 0.44 0.07 K 0.93 0.02 0.05 R 0.84 0.05 0.11 H 0.66 0.19 0.15 a D. Bordo and P. Argos, J. Mol. Biol. 217(1991)721-729 back Mutation mass shifts Residues DOWN the left indicate the EXPECTED residues Residues ACROSS the top indicate the MUTANT residues Gly Ala Ser Pro Val Thr Cys Ile Leu Asn Asp Gln Lys Glu Met His Phe Arg Tyr Trp Gly 14 30 40 42 44 46 56 57 58 71 72 74 80 90 99 106 129 Ala -14 16 26 28 30 32 42 43 44 57 58 60 66 76 85 92 115 Ser -30 -16 10 12 14 15 26 27 28 41 42 44 50 60 69 76 99 Pro -40 -126 -10 2 4 6 16 17 18 31 32 34 40 50 59 66 89 Val -42 -28 -12 -2 2 4 14 15 16 29 30 32 38 48 57 64 87 Thr -44 -30 -14 -4 -2 2 12 13 14 27 28 30 36 48 55 62 85 Cys -46 -32 -16 -6 -4 -2 10 11 12 25 26 28 34 44 53 60 83 Leu Ile -56 -42 -26 -16 -14 -12 -10 1 2 15 16 18 24 34 43 50 73 Asn -57 -43 -27 -17 -15 -13 -11 -1 1 14 15 17 23 33 42 49 72 Asp -58 -44 -28 -18 -16 -14 -12 -2 -1 13 14 16 22 32 41 48 71 Gln Lys -71 -57 -41 -31 -29 -27 -25 -15 -14 -13 1 3 9 19 28 35 58 Glu -72 -58 -42 -32 -30 -28 -26 -16 -15 -14 -1 2 8 18 27 34 57 Met -74 -60 -44 -34 -32 -30 -28 -18 -17 -16 -3 -2 6 16 25 32 55 His -80 -66 -50 -40 -38 -36 -34 -24 -23 -22 -9 -8 -6 10 19 26 49 Phe -90 -76 -60 -50 -48 -46 -44 -34 -33 -32 -19 -18 -16 -10 9 16 39 Arg -99 -85 -69 -59 -57 -55 -53 -43 -42 -41 -28 -27 -25 -19 -9 7 30 Tyr -106 -92 -76 -66 -64 -62 -60 -450 -49 -48 -35 -34 -32 -26 -16 -7 23 Trp -129 -115 -99 -89 -87 -85 -83 -73 -72 -71 -58 -57 -55 -49 -39 -30 -23 back Institute for Scientific Information Publishes scholarly research databases, including Current Contents, in the sciences, social sciences, and arts and humanities. Online access is available for most publications, usually by subscription. Publishes scholarly research databases in the sciences, social sciences, and arts and humanities. ISI - Thomson Scientific Thomson.com Advanced Search EN : JP : CN : KR Thomson Scientific, formerly known as Thomson ISI has been an established leader in providing access to high-value, essential information for researchers and scholars worldwide for over 45 years. Our goal is to increase the impact of research by empowering researchers with the information they need to accelerate discovery. You can keep up to date with all our product, events and training news via our new home page . ISI Web of Knowledge SM is a unique, fully integrated research environment that delivers a powerful combination of content, tools and technology. Built on a foundation that emphasizes quality, selectivity and objectivity, ISI Web of Knowledge delivers the essential data researchers seek. 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Follow this link to product specific journal lists such as SCIE, SSCI, AHCI etc. Disclaimer | Terms of Use Privacy Policy | Copyright Home | Contact Us | Products Services | Support | About Us | Press Room News | Knowledge Trends | Information Brands | Site Map Model Organisms WWW Virtual Library Guide to web resources for all major model organisms, including Drosophila (fly), C. elegans (worm), mouse, zebrafish, E. coli, Dictylostelium, and Arabidopsis. The WWW Virtual Library: Model Organisms The WWW Virtual Library: Model Organisms [ E. coli | S. cerevisiae | Dictyostelium | C.elegans | Drosophila | Arabidopsis | ZebraFish | Xenopus | Mouse | Others ] This site is a catalog of internet resources relating to biological model organisms, and is part of the Biosciences area of the Virtual Library project. Other organisms are listed under the Virtual Library sections for Genetics and Developmental Biology . To comment on the site or suggest links, please contact the maintainer . If you would like to take over responsibility for a specific Model Organism, please contact the Virtual Library. What is a Model Organism? Many aspects of biology are similar in most or all organisms, but it is frequently much easier to study particular aspects in particular organisms - for instance, genetics is easier in small organisms that breed quickly, and very difficult in humans! The most popular model organisms have strong advantages for experimental research, and become even more useful when other scientists have already worked on them, discovering techniques, genes and other useful information. General Model Organism Resources There is little on the web regarding model organisms in general, but some of the better resources are: Report of a 1998 NIH workshop on Model Organism databases Functional and Comparative Genomics from the Human Genome Project talks about the genomes of model organisms, and how they relate to the human genome. NIH reference site for model organisms, with links and information on grants and programs. The GenomeWeb has extensive links for genomics of various organisms. MEOW allows searches on genes of all major model organisms and human through a single interface. Use of model organisms in teaching biology. Comparative Genomics of model and other organisms With many genomes now sequenced, there are several efforts to functionally link genes in model organisms with their counterparts in humans and other models to expand their utility as models of human genes and processes. Some resources include The Gene Ontology Consortium (GO) aims to classify broad and specific functions of genes across several organisms. An oldish (1997) list of human disease genes and their model organism counterparts, at XREFDb , a project to link model organism genes to human homologs. What are the main Model Organisms? There are other excellent sections in the Virtual Library for these major Model Organisms: E. coli (bacterium) Yeasts (Saccharomyces cerevisiae, and other species) Dictyostelium discoideum (slime mold) Drosophila melanogaster (fruit fly) Xenopus laevis (African clawed frog) The following are the most popular web resources for other major model organisms. Caenorhabditis elegans (nematode worm) This tiny worm has a very fast life cycle, an invariant lineage (every animal has a specific number of cells) and is the first multicellular animal to have it's genome sequenced. An introduction to the worm, from the Riddle lab, and a more technical introduction from Mark Blaxter and another from the Minnesota Genetics Center . The C. elegans WWW server by Leon Avery at UTSMC is the best online reference for C. elegans, including an introduction, a list of worm labs and a search engine for worm literature. Wormbase is a large-scale database covering information on all worm genes. The full genome of has been sequenced ( Sanger Center and Washington University ) The C. elegans EST sequencing and expression mapping project ( NEXTDB ) from the Kohara lab. A consortium of labs aims to create knockouts of every worm gene. ACeDb is a complex but powerful database of C. elegans genetic information. A web interface is avaible from the USDA. The worm stock center (Caenorhabditis Genetics Center in Minnesota). WormAtlas is a database of structural and behavioral anatomy of the worm. Worm protocols from the Ambros lab. The bionet.celegans newsgroup, with an introduction and archive at the UTSMC site . Other nematodes are covered by Wormland . A good links page from the Ward lab . elegansNet : links on C. elegans and an eclectic variety of other biological topics. Heavy use of frames. Includes extensive introductory links ( ACekit ) Arabidopsis thaliana (mustard plant) This is now the main model plant system for genetics. Its small genome, and the recent application of classical genetics has put it far ahead of other models of agricultural importance (tomato, tobacco, corn etc.) It's genome is due to be fully sequenced in 2000. Arabidopsis thaliana database (AtDb): Major database on Arabidopsis genes and genomics efforts, with additional information on Arabidopsis researchers. cDNA sequencing project : Major EST sequencing project from the University of Minnesota and Michican State University. Arabidopsis database at TIGR : Genome and EST sequences from TIGR, including their "Gene Index" compilation of ESTs and genomic data into putative gene sequences. Stock Centres: Wild type and mutant stocks are available from Ohio State University and the University of Nottingham in England. See also the Lehle seeds company catalog. Extensive list of Arabidopsis labs on the web, from Lehle Seeds. News and information : Lots of up-to-date community information from arabidopsis.com. WeedsWorld , the Arabidopsis community newsletter is archived from 1994-97. Arabidopsis also has mailing lists and a newsgroup, bionet.genome.arabidopsis , which is archived . Arabinet at Harvard is a good collection of links. MIPS genome project in Germany offers sequences, annotations and functional classification. Zebrafish This small fish is a relatively new model. As a vertebrate, it is a good model for aspects of human biology, but is cheaper and easier to handle than mice, as well as having a transparent and readily accessible embryo for developmental biology work. FishNet at University of Oregon is an extensive resource site. The Zebrafish information server is another excellent general resource from the University of South Carolina. Washington University has a Zebrafish EST sequencing project underway. The ZebraFish Webserver at the Driever Lab covers anatomy, microsatellite maps and YAK libraries. Mouse The closest model organism to humans is especially used in development, genetic and immunology studies. The Whole Mouse Catalog has an extensive set of references to information throughout the web. Mouse Knockout Database (BioMedNet). Atlas of phenotypes and other information for mouse genes which have been disrupted (commercial). Genetic and Physical maps of the Mouse genome (MIT) The Mouse Atlas and Gene Expression Database Atlas of the Mouse Brain : scans through wild-type and mutant mouse brains. Mouse Genome Informatics : combination of databases at Jackson labs: the Mouse Genome Database (MGD), the Gene Expression Database , and the Encylopedia of the Mouse Genome , a Mac genome map viewer, which together give extensive coverage of mouse genetics and genomics. The TBASE database of transgenic mouse strains, from the Jackson lab. An article on Mice in Cancer Research . Human Mouse homology maps , from NCBI. Mouse Genome Resources from NCBI. Other model organisms Unicellular Chlamydomonas reinhardtii, a unicellular alga. Chlamydomonas internet resources from Wallace Marshall. Cyanobacteria, (photosynthetic bacteria). Cyanosite Plants Maize The Maize Page at Iowa State University. Maize Genetics sites of interest MaizeDB , the maize genome database. Trees The Virtual Library on Forest Genetics and Tree Breeding . Invertebrates Aplysia californica: a snail used in Neurobiology research The Aplysia hometank (Cornell) Ascidians: Primitive chordates used in developmental biology US Ascidian Home page (Fullerton) Cnidarians Coelenterates (jellyfish, corals, hydra etc.) Cnidaria home page Sea Urchin Urchin Web UrchiNet database Mosquito (Aedes sp.) Mosquito Genomics Server Vertebrates Fugu rubripes: Pufferfish with a very compact genome, used in genomics research. The genome is now largely sequenced and being assembled. Good Fugu site at the DOE JGI Fugu pages at the MRC in England. Medaka (ricefish; Oryzias latipes): another genetic model fish Medakafish Homepage Assorted mammals (mostly genomic resources) Roslin Institute : Mapping databases for Pig, Chicken, Sheep, Cattle, Horse, Cat and Tilapia (fish). The Dog Genome project at Berkeley. US Department of Agriculture genome mapping projects for Sheep, Pig and Cow. Other Model Organism Pages Sanger Center list of MO databases Another one at Caltech A nice review of model organism sites by Pam Gannon, for HMS Beagle (also available here ). Genomes and Organisms , an extensive list at Infobiogen. Cybergenome.com has links for model organisms and humans. Functional Genomics links from Science Genetics links from Nature. Finally, two personal links, one for a Bioinformatics Consultant and one for Bioinformatics on MacOS . http: ceolas.org VL mo By Gerard Manning Last update: Sep 23, 2002 Science Advisory Board Online panel of 5,000 life scientists and physicians who convene electronically to voice their opinions on emerging technologies. The Science Advisory Board Note: You are seeing this message either because your browser has not loaded our stylesheets, or because your browser does not support stylesheets (CSS). Please upgrade to a relatively modern browser to improve your experience. Not sure what to upgrade to? Try Firefox . Screen Name: Password: Lost password? 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Abzyme. See Catalytic antibody. Adaptive radiation. The evolution of new species or sub- species to fill unoccupied ecological niches. Aerobe. A microorganism that grows in the presence of oxygen. See Anaerobe. Agarose gel electrophoresis. A matrix composed of a highly purified form of agar that is used to separate larger DNA and RNA molecules ranging 20,000 nucleotides. (See Electrophoresis.) Alleles. Alternate forms of a gene or DNA sequence, which occur on either of two homologous chromosomes in a diploid organism. (See DNA polymorphism.) Alternative mRNA splicing. The inclusion or exclusion of different exons to form different mRNA transcripts. (See RNA.) Amino acid. Any of 20 basic building blocks of proteins-- composed of a free amino (NH2) end, a free carboxyl (COOH) end, and a side group (R). Ampicillin (beta-lactamase). An antibiotic derived from penicillin that prevents bacterial growth by interfering with cell wall synthesis. Amplify. To increase the number of copies of a DNA sequence, in vivo by inserting into a cloning vector that replicates within a host cell, or in vitro by polymerase chain reaction (PCR). Anaerobe. An organism that grows in the absence of oxygen. See Aerobe. Anneal. The pairing of complementary DNA or RNA sequences, via hydrogen bonding, to form a double-stranded polynucleotide. Most often used to describe the binding of a short primer or probe. Antibiotic. A class of natural and synthetic compounds that inhibit the growth of or kill other microorganisms. (See Antibiotic resistance, Bacteriocide, Bacteriostat.) Antibiotic resistance. The ability of a microorganism to produce a protein that disables an antibiotic or prevents transport of the antibiotic into the cell. Antibody. An immunoglobulin protein produced by B- lymphocytes of the immune system that binds to a specific antigen molecule. (See monoclonal antibodies, polyclonal antibodies.) Anticodon. A nucleotide base triplet in a transfer RNA molecule that pairs with a complementary base triplet, or codon, in a messenger RNA molecule. See Codon, Messenger RNA, RNA. Antigen. Any foreign substance, such as a virus, bacterium, or protein, that elicits an immune response by stimulating the production of antibodies. (See Antigenic determinant, antigenic switching.) Antigenic determinant. A surface feature of a microorganism or macromolecule, such as a glycoprotein, that elicits an immune response. Antigenic switching. The altering of a microorganism's surface antigens through genetic rearrangement, to elude detection by the host's immune system. Antimicrobial agent. Any chemical or biological agent that harms the growth of microorganisms. Anti-oncogene. See Recessive oncogene. Antisense RNA. A complementary RNA sequence that binds to a naturally occurring (sense) mRNA molecule, thus blocking its translation. (See RNA.) Asexual reproduction. Nonsexual means of reproduction which can include grafting and budding. Autosome. A chromosome that is not involved in sex de- termination. B beta-DNA. The normal form of DNA found in biological systems, which exists as a right-handed helix. beta-Lactamase. Ampicillin resistance gene. (See Selectable marker.) Bacillus. A rod-shaped bacterium. Bacillus thuringiensis (Bt). A bacterium that kills insects; a major component of the microbial pesticide industry. Backcross. Crossing an organism with one of its parent organisms. Bacteriocide. A class of antibiotics that kills bacterial cells. Bacteriophage (phage or phage particle). A virus that in- fects bacteria. Altered forms are used as vectors for cloning DNA. Bacteriostat. A class of antibiotics that prevents growth of bacterial cells. Bacterium. A single-celled, microscopic prokaryotic organism: a single cell organism without a distinct nucleus. Base pair (bp). A pair of complementary nitrogenous bases in a DNA molecule--adenine-thymine and guanine-cytosine. Also, the unit of measurement for DNA sequences. Bioaugmentation. Increasing the activity of bacteria that decompose pollutants; a technique used in bioremediation. Biodiversity. The wide diversity and interrelatedness of earth organisms based on genetic and environmental factors. Bioenrichment. Adding nutrients or oxygen to increase microbial breakdown of pollutants. Biofilms. See Microbial mats. Biologics. Agents, such as vaccines, that give immunity to diseases or harmful biotic stresses. Biomass. The total dry weight of all organisms in a particular sample, population, or area. Bioremediation. The use of microorganisms to remedy environmental problems. See Bioaugmentation, Bioenrichment. Biotechnology. The scientific manipulation of living organ- isms, especially at the molecular genetic level, to produce useful products. Gene splicing and use of recombinant DNA (rDNA) are major techniques used. Biotic stress. Living organisms which can harm plants , such as viruses, fungi, and bacteria, and harmful insects. See Abiotic stress. bP. See Base pair. Bt. See Bacillus thuringiensis. C Capsid. See Coat protein. Carcinogen. A substance that induces cancer. Carcinoma. A malignant tumor derived from epithelial tissue, which forms the skin and outer cell layers of internal organs. Catalyst. A substance that promotes a chemical reaction by lowering the activation energy of a chemical reaction, but which itself remains unaltered at the end of the reaction. (See Catalytic antibody, Catalytic RNA.) Catalytic antibody (abzyme). An antibody selected for its ability to catalyze a chemical reaction by binding to and stabilizing the transition state intermediate. Catalytic RNA (ribozyme). A natural or synthetic RNA molecule that cuts an RNA substrate. Cation. A positively charged ion. cDNA. DNA synthesized from an RNA template using reverse transcriptase. cDNA library. A library composed of complementary copies of cellular mRNAs. (See Library.) Cellular oncogene (proto-oncogene). A normal gene that when mutated or improperly expressed contributes to the development of cancer. (See Oncogene.) Centers of origin. Usually the location in the world where the oldest cultivation of a particular crop has been identified. Central dogma. Francis Crick's seminal concept that in nature genetic information generally flows from DNA to RNA to protein. Centrifugation. Separating molecules by size or density using centrifugal forces generated by a spinning rotor. G forces of several hundred thousand times gravity are generated in ultracentrifugation. (See Density gradient centrifugation.) Centromere. The central portion of the chromosome to which the spindle fibers attach during mitotic and meiotic division. Chemotherapy. A treatment for cancers that involves ad- ministering chemicals toxic to malignant cells. Chloramphenicol. An antibiotic that interferes with protein synthesis. Chromatid. Each of the two daughter strands of a duplicated chromosome joined at the centromere during mitosis and meiosis. Chromosome. A single DNA molecule, a tightly coiled strant of DNA, condensed into a compact structure in vivo by complexing with accessory histones or histone-like proteins. Chromosomes exist in pairs in higher eukaryotes. (See Chromosome walking.) Chromosome walking. Working from a flanking DNA marker, overlapping clones are successively identified that span a chromosomal region of interest. (See Chromosome.) Cistron. A DNA sequence that codes for a specific polypeptide; a gene. See DNA, Gene. Clone. An exact genetic replica of a specific gene or an entire organism. See Cloning. Cloning. The mitotic division of a progenitor cell to give rise to a population of identical daughter cells or clones. (See Directional cloning, Megabase cloning, Molecular cloning, Subcloning.) Coat protein (capsid). The coating of a protein that enclosed the nucleic acid core of a virus. Codon. A group of three nucleotides that specifies addition of one of the 20 amino acids during translation of an mRNA into a polypeptide. Strings of codons form genes and strings of genes form chromosomes. (See Initiation codon, Termination codon.) Coenzyme (cofactor). An organic molecule, such as a vitamin, that binds to an enzyme and is required for its catalytic activity. Cofactor. See Coenzyme. Colony. A group of identical cells (clones) derived from a single progenitor cell. Commensalism. The close association of two or more dissimilar organisms where the association is advantageous to one and doesn't affect the other(s). See Parasitism, Symbiosis. Competency. An ephemeral state, induced by treatment with cold cations, during which bacterial cells are capable of uptaking foreign DNA. Complementary DNA or RNA. The matching strand of a DNA or RNA molecule to which its bases pair. (See DNA, RNA.) Complementary nucleotides. Members of the pairs adenine-thymine, adenine-uracil, and guaninecytosine that have the ability to hydrogen bond to one another. (See nucleotide.) Concatemer. A DNA segment composed of repeated sequences linked end to end. Conjugation. The joining of two bacteria cells when genetic material is transferred from one bacterium to another. Constitutive promoter. An unregulated promoter that allows for continual transcription of its associated gene. (See Promoter.) Contiguous (contig) map. The alignment of sequence data from large, adjacent regions of the genome to produce a continuous nucleotide sequence across a chromosomal region. (See Mapping.) Copy DNA. See cDNA. Cross-hybridization. The hydrogen bonding of a single- stranded DNA sequence that is partially but not entirely complementary to a singlestranded substrate. Often, this involves hybridizing a DNA probe for a specific DNA sequence to the homologous sequences of different species. Cross-pollination. Fertilization of a plant from a plant with a different genetic makeup. Crossing-over. The exchange of DNA sequences between chromatids of homologous chromosomes during meiosis. Culture. A particular kind of organism growing in a laboratory medium. Cyclic AMP (cyclic adenosine monophosphate). A second messenger that regulates many intracellular reactions by transducing signals from extracellular growth factors to cellular metabolic pathways. Cytogenetics. Study that relates the appearance and behavior of chromosomes to genetic phenomenon. D Dalton. A unit of measurement equal to the mass of a hydrogen atom, 1.67 x 10E-24 gram L (Avogadro's number). Death phase. The final growth phase, during which nutrients have been depleted and cell number decreases. (See Growth phase. Denature. To induce structural alterations that disrupt the biological activity of a molecule. Often refers to breaking hydrogen bonds between base pairs in double-stranded nucleic acid molecules to produce in single-stranded polynucleotides or altering the secondary and tertiary structure of a protein, destroying its activity. Density gradient centrifugation. High-speed centrifugation in which molecules "float" at a point where their density equals that in a gradient of cesium chloride or sucrose. (See Centrifugation.) Deoxyribonucleic acid. See DNA, nuclease. Diabetes. A disease associated with the absence or reduced levels of insulin, a hormone essential for the transport of glucose to cells. Dideoxynucleotide (didN). A deoxynucleotide that lacks a 3' hydroxyl group, and is thus unable to form a 3'-5' phosphodiester bond necessary for chain elongation. Dideoxynucleotides are used in DNA sequencing and the treatment of viral diseases. (See Nucleotide.) didN. See Dideoxynucleotide. Digest. To cut DNA molecules with one or more restriction endonucleases. Diploid cell. A cell which contains two copies of each chromosome. See Haploid cell. Directional cloning. DNA insert and vector molecules are digested with two different restriction enzymes to create noncomplementary sticky ends at either end of each restriction fragment. This allows the insert to be ligated to the vector in a specific orientation and prevents the vector from recircularizing. (See Cloning.) DNA (Deoxyribonucleic acid). An organic acid and polymer composed of four nitrogenous bases--adenine, thymine, cytosine, and guanine linked via intervening units of phosphate and the pentose sugar deoxyribose. DNA is the genetic material of most organisms and usually exists as a double-stranded molecule in which two antiparallel strands are held together by hydrogen bonds between adeninethymine and cytosine-guanine. (See b-DNA, cDNA, Complementary DNA or RNA, DNA polymorphism, DNA sequencing, Double-stranded complementary DNA, Duplex DNA, Z-DNA.) DNA diagnosis. The use of DNA polymorphisms to detect the presence of a disease gene. DNA fingerprint. The unique pattern of DNA fragments identified by Southern hybridization (using a probe that binds to a polymorphic region of DNA) or by polymerase chain reaction (using primers flanking the polymorphic region). DNA ligase. See Ligase. DNA polymerase. See Polymerase. DNA polymorphism. One of two or more alternate forms (alleles) of a chromosomal locus that differ in nucleotide sequence or have variable numbers of repeated nucleotide units. (See Allele.) DNA polymerase. See Polymerase. DNA sequencing. Procedures for determining the nucleotide sequence of a DNA fragment. DNase (deoxyribonuclease). See Nuclease. Dominant. An allele is said to be dominant if it expresses its phenotype even in the presence of a recessive allele. See Allele, Phenotype, Recessive. Dominant gene. A gene whose phenotype is when it is present in a single copy. Dominant(-acting) oncogene. A gene that stimulates cell proliferation and contributes to oncogenesis when present in a single copy. (See Oncogene.) Dormancy. A period in which a plant does not grow, awaiting necessary environmental conditions such as temperature, moisture, nutrient availability. Double helix. Describes the coiling of the antiparallel strands of the DNA molecule, resembling a spiral staircase in which the paired bases form the steps and the sugar-phosphate backbones form the rails. Double-stranded complementary DNA (dscDNA). A duplex DNA molecule copied from a cDNA template. Downstream. The region extending in a 3' direction from a gene. dscDNA. See double-stranded complementary DNA. Duplex DNA. Double-stranded DNA. E Ecology. The study of the interactions of organisms with their environment and with each other. Ecosystem. The organisms in a plant population and the biotic and abiotic factors which impact on them. See abiotic factors; Biotic factors. Electrophoresis. The technique of separating charged mol- ecules in a matrix to which is applied an electrical field. (See Agarose gell electrophoresis, Polycrylamide gell electrophoresis.) Electroporation. A method for transforrning DNA, especially useful for plant cells, in which high voltage pulses of electricity are used to open pores in cell membranes, through which foreign DNA can pass. Encapsidation. Process by which a virus' nucleic acid is enclosed in a capsid. See Coat protein. Endonuclease. See Nuclease. Endophyte. An organism that lives inside another. Environmental Protection Agency (EPA). The U.S. regulatory agency for biotechnology of microbes. The major laws under which the agency has regulatory powers are the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA); and the Toxic Substances Control Act (TSCA). Enzymes. Proteins that control the various steps in all chemical reactions. EPA. See Environmental Protection Agency. Escherichia coli. A commensal bacterium inhabiting the human colon that is widely used in biology, both as a simple model of cell biochemical function and as a host for molecular cloning experiments. Ethidium bromide. A fluorescent dye used to stain DNA and RNA. The dye fluoresces when exposed to UV light. Eukaryote. An organism whose cells possess a nucleus and other membrane-bound vesicles, including all members of the protist, fungi, plant and animal kingdoms; and excluding viruses, bacteria, and blue-green algae. See Prokaryote. Evolution. The long-term process through which a population of organisms accumulats genetic changes that enable its members to successfully adapt to environmental conditions and to better exploit food resources. Exon. A DNA sequence that is ultimately translated into protein. See DNA. Exonuclease. See Nuclease. Express. To translate a gene's message into a molecular product. Expression library. (See Library.) F FDA. See Food and Drug Administration. Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA). See Environmental Protection Agency. Federal Plant Pest Act (PPA). See U.S. Department of Agriculture. Federal Seed Act. See U.S. Department of Agriculture. FIFRA. The Federal Insecticide, Fungicide, and Rodenticide Act. See Environmental Protection Agency. Flanking region. The DNA sequences extending on either side of a specific locus or gene. Food and Drug Administration (FDA). The U.S. agency responsible for regulation of biotechnology food products. The major laws under which the agency has regulatory powers include the Food, Drug, and Cosmetic Act; and the Public Health Service Act. Food, Drug, and Cosmetic Act. See Food and Drug Administration. Fungicide. An agent, such as a chemical, that kills fungi. Fungus. A microorganism that lacks chlorophyll. Fusion gene. A hybrid gene created by joining portions of two different genes (to produce a new protein) or by joining a gene to a different promoter (to alter or regulate gene transcription). G Gamete. A haploid sex cell, egg or sperm, that contains a single copy of each chromosome. GEM. A genetically engineered microorganism. Gene. A locus on a chromosome that encodes a specific protein or several related proteins. It is considered the functional unit of heredity. (See Dominant gene, Fusion gene, Gene amplification, Gene expression, Gene flow, Gene pool, Gene splicing, Gene translocation, Recessive gene, Regulatory gene.) Gene amplification. The presence of multiple genes. Amplification is one mechanism through which proto-oncogenes are activated in malignant cells. Gene cloning. The process of synthesizing multiple copies of a particular DNA sequence using a bacteria cell or another organism as a host. See DNA, Host. Gene expression. The process of producing a protein from its DNA- and mRNA-coding sequences. Gene flow. The exchange of genes between different but (usually) related populations. Gene frequency. The percentage of a given allele in a population of organisms. See Allele. Gene insertion. The addition of one or more copies of a normal gene into a defective chromosome. Gene linkage. The hereditary association of genes located on the same chromosome. Gene modification. The chemical repair of a gene's defective DNA sequence. See DNA. Gene pool. The totality of all alleles of all genes of all individuals in a particular population. Gene splicing. Combining genes from different organisms into one organism. See recombinant DNA. Gene translocation. The movement of a gene fragment from one chromosomal location to another, which often alters or abolishes expression. Genetic assimilation. Eventual extinction of a natural species as massive pollen flow occurs from another related species and the older crop becomes more like the new crop. See Gene flow. Genetic code. The three-letter code that translates nucleic acid sequence into protein sequence. The relationships between the nucleotide base-pair triplets of a messenger RNA molecule and the 20 amino acids that are the building blocks of proteins. See Base pair, Nucleic acid, Nucleotide. Genetic disease. A disease that has its origin in changes to the genetic material, DNA. Usually refers to diseases that are inherited in a Mendelian fashion, although noninherited forms of cancer also result from DNA mutation. Genetic drift. Random variation in gene frequency from one generation to another. Genetic engineering. The manipulation of an organism's genetic endowment by introducing or eliminating specific genes through modern molecular biology techniques. A broad definition of genetic engineering also includes selective breeding and other means of artificial selection. Genetic linkage map. A linear map of the relative positions of genes along a chromosome. Distances are established by linkage analysis, which determines the frequency at which two gene loci become separated during chromosomal recombination. (See Mapping.) Genetic marker. A gene or group of genes used to "mark" or track the action of microbes. Genome. The genetic complement contained in the chromosomes of a given organism, usually the haploid chromosome state. Genomic library. A library composed of fragments of genomic DNA. (See Library.) Genotype. The structure of DNA that determines the expression of a trait. See Phenotype. Genus. A category including closely related species. Interbreeding between organisms within the same category can occur. GEO. Genetically engineered organism. Germ cell. Reproductive cell. See Somatic cell. Germ cell (germ line) gene therapy. The repair or re- placement of a defective gene within the gamete-forming tissues, which produces a heritable change in an organism's genetic constitution. GMO. Genetically modified organism. Green revolution. Advances in genetics, petrochemicals, and machinery that culminated in a dramatic increase in crop productivity during the third quarter of the 20th century. Growth curve. See Growth phase. Growth factor. A serum protein that stimulates cell division when it binds to its cell-surface receptor. Growth phase (curve). The characteristic periods in the growth of a bacterial culture, as indicated by the shape of a graph of viable cell number versus time. (See Death phase, Lag phase, Logarithmic phase, Stationary phase.) H Haploid cell. A cell containing only one set, or half the usual (diploid) number, of chromosomes. Hemophilia. An X-linked recessive genetic disease, caused by a mutation in the gene for clotting factor VIII (hemophilia A) or clotting factor IX (hemophilia B), which leads to abnormal blood clotting. Herbicide. Any substance that is toxic to plants; usually used to kill specific unwanted plants. Heterochromatin. Dark-stained regions of chromosomes thought to be for the most part genetically inactive. Heteroduplex. A double-stranded DNA molecule or DNA-RNA hybrid, where each strand is of a different origin. Heterogeneous nuclear RNA (hnRNA). The name originally given to large RNA molecules found in the nucleus, which are now known to be unedited mRNA transcripts, or pre-mRNAs. (See RNA.) HGH. See Human growth hormone. hnRNA. See Heterogeneous nuclear RNA. Homologous chromosomes. Chromosomes that have the same linear arrangement of genes--a pair of matching chromosomes in a diploid organism. See Chromosomes. Homologous recombination. The exchange of DNA fragments between two DNA molecules or chromatids of paired chromosomes (during crossing over) at the site of identical nucleotide sequences. Homozygote. An organism whose genotype is characterized by two identical alleles of a gene. See Allele, Genotype. Host. An organism that contains another organism. Human Genome Project. A project coordinated by the National Institutes of Health (NIH) and the Department of Energy (DOE) to determine the entire nucleotide sequence of the human chromosomes. (See NIH.) Human growth hormone (HGH, somatotrophin). A protein produced in the pituitary gland that stimulates the liver to produce somatomedins, which stimulate growth of bone and muscle. Hybrid. The offspring of two parents differing in at least one genetic characteristic (trait). Also, a heteroduplex DNA or DNA-RNA molecule. Hybridization. The hydrogen bonding of complementary DNA and or RNA sequences to form a duplex molecule. (See Northern hybridization, Southern hybridization.) Hybridoma. A hybrid cell, composed of a B Iymphocyte fused to a tumor cell, which grows indefinitely in tissue culture and is selected for the secretion of a specific antibody of interest. Hydrogen bond. A relatively weak bond formed betwee n y. a hydrogen atom (which is covalently bound to a nitrogen or oxygen atom) and a nitrogen or oxygen with an unshared electron pair. Hydrolysis. A reaction in which a molecule of water is added at the site of cleavage of a molecule to two products. I Immortalizing oncogene. A gene that upon transfection enables a primary cell to grow indefinitely in culture. (See Oncogene.) Incomplete dominance. A condition where a heterozygous off- spring has a phenotype that is distinctly different from, and intermediate to, the parental phenotypes. See Heterozygote, Phenotype. Initiation codon. The mRNA sequence AUG, coding for methionine, which initiates translation of mRNA. Inositol lipid. A membrane-anchored phospholipid that transduces hormonal signals by stimulating the release of any of several chemical messengers. (See Phospholipid.) Insertion mutations. Changes in the base sequence of a DNA molecule resulting from the random integration of DNA from another source. See DNA, Mutation. In situ. Refers to performing assays or manipulations with intact tissues. Insulin. A peptide hormone secreted by the islets of Langerhans of the pancreas that regulates the level of sugar in the blood. Interferon. A family of small proteins that stimulate viral resistance in cells. Intergenic regions. DNA sequences located between genes that comprise a large percentage of the human genome with no known function. Introgression. Backcrossing of hybrids of two plant populations to introduce new genes into a wild population. Intron. A noncoding DNA sequence within a gene that is initially transcribed into messenger RNA but is later snipped out. See Coding, DNA, Messenger RNA, Transcription. Invasiveness. Ability of a plant to spread beyond its introduction site and become established in new locations where it may provide a deliterious effect on organisms already existing there. In vivo. Refers to biological processes that take place within a living organism or cell. Ion. A charged particle. Isotope. One of two or more forms of an element that have the same number of protons (atomic number) but differing numbers of neutrons (mass numbers). Radioactive isotopes are commonly used to make DNA probes and metabolic tracers. J Joining (J) segment. A small DNA segment that links genes to yield a functional gene encoding an immunogobulin. K Kanamycin. An antibiotic of the aminoglycoside family that poisons translation by binding to the ribosomes. See Kanamycin. kanr. Kanamycin resistance gene. (See Selectable marker.) Karyotype. All of the chromosomes in a cell or an individual organism, visible through a microsope during cell division. L Lag phase. The initial growth phase, during which cell number remains relatively constant prior to rapid growth. See growth phase. Lawn. A uniform and uninterrupted laver of bacterial growth, in which individual colonies cannot be observed. Legume. A member of the pea family that possesses root nodules containing nitrogen-fixing bacteria. Library. A collection of cells, usually bacteria or yeast, that have been transformed with recombinant vectors carrying DNA inserts from a single species. (See cDNA library, Expression library, Genomic library.) Ligase (DNA ligase). An enzyme that catalyzes a condensation reaction that links two DNA molecules via the formation of a phosphodiester bond between the 3' hydroxyl and 5' phosphate of adjacent nucleotides. Ligate. The process of joining two or more DNA fragments. Lineage. A chart that traces the flow of genetic information from generation to generation. Linkage. The frequency of coinheritance of a pair of genes and or genetic markers, which provides a measure of their physical proximity to one another on a chromosome. Linkage map. See Genetic linkage map. Linked genes markers. Genes and or markers that are so closely associated on the chromosome that they are coinherited in 80% or more of cases. Linker. A short, double-stranded oligonucleotide containing a restriction endonuclease recognition site, which is ligated to the ends of a DNA fragment. Liposomes. Membrane-bound vesicles constructed in the laboratory to transport biological molecules. Locus (plural = loci). A specific location or site on a chromosome. Log phase. See Logarithmic phase. Logarithmic phase (log or exponential growth phase). The steepest slope of the growth curve--the phase of vigorous growth during which cell number doubles every 20-30 minutes. (See Growth phase.) Lysis. The destruction of the cell membrane. Lysogen. A bacterial cell whose chromosome contains in- tegrated viral DNA. Lysogenic. A type or phase of the virus life cycle during which the virus integrates into the host chromosome of the infected cell, often remaining essentially dormant for some period of time. See Lysogen. Lytic. A phase of the virus life cycle during which the vi- rus replicates within the host cell, releasing a new generation of viruses when the infected cell lyses. M Malignant. Having the properties of cancerous growth. Mapping. Determining the physical location of a gene or genetic marker on a chromosome. (See Continuous map, Genetic map, Physical map.) Megabase cloning. The cloning of very large DNA fragments. (See Cloning.) Meiosis. The reduction division process by which haploid gametes and spores are formed, consisting of a single duplication of the genetic material followed by two mitotic divisions. Messenger RNA (mRNA). The class of RNA molecules that copies the genetic information from DNA, in the nucleus, and carries it to ribosomes, in the cytoplasm, where it is translated into protein. (See RNA.) Metabolism. The biochemical processes that sustain a living cell or organism. Metallothionein. A protective protein that binds heavy metals, such as cadmium and lead. Microbe. A microorganism. Microbial mats (biofilms). Layered groups or communities of microbial populations. Microinjection. A means to introduce a solution of DNA, protein, or other soluble material into a cell using a fine microcapillary pipet. Mitosis. The replication of a cell to form two daughter cells with identical sets of chromosomes. Molecular biology. The study of the biochemical and mo- lecular interactions within living cells. Molecular cloning. The biological amplification of a specific DNA sequence through mitotic division of a host cell into which it has been transformed or transfected. (See Cloning.) Molecular genetics. The study of the flow and regulation of genetic information between DNA, RNA, and protein molecules. Monoclonal antibodies. Immunoglobulin molecules of single- epitope specificity that are secreted by a clone of B cells. Monoculture. The agricultural practice of cultivating crops consisting of genetically similar organisms. Monogenic. Controlled by or associated with a single gene. Movable genetic element. (See Transposon.) mRNA. See Messenger RNA. Multi-locus probe. A probe that hybridizes to a number of different sites in the genome of an organism. (See Probe.) Mutagen. Any agent or process that can cause mutations. See Mutation. Mutation. An alteration in DNA structure or sequence of a gene. (See Point mutation.) Mutualism. See Symbiosis. Mycorrhizae. Fungi that form symbiotic relationships with roots of more developed plants. N National Institutions of Health (NIH). A nonregulatory agency which has oversight of research activities that the agency funds. National Science Foundation (NSF). A nonregulatory agency which has oversight of biotechnology research activities that the agency funds. Natural selection. The differential survival and reproduc- tion of organisms with genetic characteristics that enable them to better utilize environmental resources. Nick translation. A procedure for making a DNA probe in which a DNA fragment is treated with DNase to produce single-stranded nicks, followed by incorporation of radioactive nucleotides from the nicked sites by DNA polymerase I. Nicked circle (relaxed circle). During extraction of plasmid DNA from the bacterial cell, one strand of the DNA becomes nicked. This relaxes the torsional strain needed to maintain supercoiling, producing the familiar form of plasmid. (See Plasmid.) NIH. See National Institutes of Health. Nitrocellulose. A membrane used to immobilize DNA, RNA, or protein, which can then be probed with a labeled sequence or antibody. Nitrogen fixation. The conversion of atmospheric nitrogen to biologically usable nitrates. Nitrogenous bases. The purines (adenine and guanine) and pyrimidines (thymine, cytosine, and uracil) that comprise DNA and RNA molecules. Nodule. The enlargement or swelling on roots of nitrogen- fixing plants. The nodules contain symbiotic nitrogen- fixing bacteria. See Nitrogen fixation. Nontarget organism. An organism which is affected by an interaction for which it was not the intended recipient. Northern blotting. See Northern hybridization. Northern hybridization. (Northern blotting). A procedure in which RNA fragments are transferred from an agarose gel to a nitrocellulose filter, where the RNA is then hybridized to a radioactive probe. (See Hybridization.) NSF. See National Science Foundation. Nuclease. A class of enzymes that degrades DNA and or RNA molecules by cleaving the phosphodiester bonds that link adjacent nucleotides. In deoxyribonuclease (DNase), the substrate is DNA. In endonuclease, it cleaves at internal sites in the substrate molecule. Exonuclease progressively cleaves from the end of the substrate molecule. In ribonuclease (RNase), the substrate is RNA. In the S1 nuclease, the substrate is single-stranded DNA or RNA. Nucleic acids. The two nucleic acids, deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), are made up of long chains of molecules called nucleotides. See DNA, RNA, Nucleotides. Nuclein. The term used by Friedrich Miescher to describe the nuclear material he discovered in 1869, which today is known as DNA. Nucleoside. A building block of DNA and RNA, consisting of a nitrogenous base linked to a five carbon sugar. (See Nucleoside analog.) Nucleoside analog. A synthetic molecule that resembles a naturally occuring nucleoside, but that lacks a bond site needed to link it to an adjacent nucleotide. (See Nucleoside.) Nucleotide. A building block of DNA and RNA, consisting of a nitrogenous base, a five-carbon sugar, and a phosphate group. Together, the nucleotides form codons, which when strung together form genes, which in turn link to form chromosomes. (See Chromosome, Codon, Complementary nucleotides, Dideoxynucleotide, DNA, Gene, Oligonucleotide, RNA.) Nucleus. The membrane-bound region of a eukaryotic cell that contains the chromosomes. O Occupational Safety and Health Act. See Occupational Safety and Health Administration. Occupational Safety and Health Administration (OSHA). One of the U.S. agencies responsible for regulation of biotechnology. The major law under which the agency has regulatory powers is the Occupational Safety and Health Act. Oligonucleotide. A DNA polymer composed of only a few nucleotides. (See Nucleotide.) Oncogene. A gene that contributes to cancer formation when mutated or inappropriately expressed. (See Cellular oncogene, Dominant oncogene, Immortalizing oncogene, Recessive oncogene.) Oncogenesis. The progression of cytological, genetic, and cellular changes that culminate in a malignant tumor. Open pollination. Pollination by wind, insects, or other natural mechanisms. Open reading frame. A long DNA sequence that is unin- terrupted by a stop codon and encodes part or all of a protein. (See Reading frame.) Operator. A prokaryotic regulatory element that interacts with a repressor to control the transcription of adjacent structural genes. Organelle. A cell structure that carries out a specialized function in the life of a cell. Origin of replication. The nucleotide sequence at which DNA synthesis is initiated. OSHA. See Occupational Safety and Health Administration. Overlapping reading frames. Start codons in different reading frames generate different polypeptides from the same DNA sequence. (See Reading frame.) Ovum. A female gamete. P Paleontology. The study of the fossil record of past geo- logical periods and of the phylogenetic relationships between ancient and contemporary plant and animal species. Palindrome. See Palindromic sequence. Palindromic sequence. A DNA locus whose 5'-to-3' sequence is identical on each DNA strand. The sequence is the same when one strand is read left to right and the other strand is read right to left. Recognition sites of many restriction enzymes are palindromic. See DNA. pAMP. Ampicillin-resistant plasmid developed for this laboratory course. (See Plasmid.) Parasitism. The closee association of two or more dissimilar organisms where the association is harmful to at least one. See Commensalism, Parasitism, Symbiosis. Pathogen. Organism which can cause disease in another organism. pBR322. A derivation of ColE1, one of the first plasmid vectors widely used. (See Plasmid.) PCR. See Polymerase chain reaction. Pedigree. A diagram mapping the genetic history of a par- ticular family. Persistence. Ability of an organism to remain in a particular setting for a period of time after it is introduced. Pesticide. A substance that kills harmful organisms (for example, an insecticide or fungicide). Phage (particle). See Bacteriophage. Phenotype. The observable characteristics of an organism, the expression of gene alleles (genotype) as an observable physical or biochemical trait. See Genotype. Pheromone. A hormone-like substance that is secreted into the environment. Phosphatase. An enzyme that hydrolyzes esters of phosphoric acid, removing a phosphate group. Phosphodiester bond. A bond in which a phosphate group joins adjacent carbons through ester linkages. A condensation reaction between adjacent nucleotides results in a phosphodiester bond between 3' and 5' carbons in DNA and RNA. Phospholipid. A class of lipid molecules in which a phos- phate group is linked to glycerol and two fatty acyl groups. A chief component of biological membranes. (See Inositol phospholipid.) Phosphorylation. The addition of a phosphate group to a compound. Physical map. A map showing physical locations on a DNA molecule, such as restriction sites, and sequence-tagged sites. (See Mapping.) Plant Pest Act (PPA). See U.S. Department of Agriculture. Plant Variety Act (PVA). See U.S. Department of Agriculture. Plaque. A clear spot on a lawn of bacteria or cultured cells where cells have been Iysed by viral infection. Plasmid (p). A circular DNA molecule, capable of autonomous replication, which typically carries one or more genes encoding antibiotic resistance proteins. Plasmids can transfer genes between bacteria and are important tools of transformation for genetic engineers. (See Nicked circle, pAMP, Relaxed plasmid, Stringent plasmid, Supercoiled plasmid.) Pleiotrophy. The effect of a particular gene on several different traits. Point mutation. A change in a single base pair of a DNA sequence in a gene. (See Mutation.) Poly(A) polymerase. Catalyzes the addition of adenine residues to the 3' end of pre-mRNAs to form the poly(A) tail. (See Polymerase.) Polyacrylamide gel electrophoresis. Electrophoresis through a matrix composed of a synthetic polymer, used to separate proteins, small DNA, or RNA molecules of up to 1000 nucleotides. Used in DNA sequencing. (See Electrophoresis.) Polyclonal antibodies. A mixture of immunoglobulin molecules secreted against a specific antigen, each recognizing a different epitope. Polygenic. Controlled by or associated with more than one gene. Polylinker. A short DNA sequence containing several re- striction enzyme recognition sites that is contained in cloning vectors. Polymer. A molecule composed of repeated subunits. Polymerase (DNA). Synthesizes a double-stranded DNA molecule using a primer and DNA as a template. (See Poly(A) polymerase, Polymerase chain reaction, RNA polymerase, Taq polymerase.) Polymorphisms. Variant forms of a particular gene that occur simultaneously in a population. Polynucleotide. A DNA polymer composed of multiple nucleotides. (See Nucleotide.) polymerase chain reaction (PCR). A procedure that en- zymatically amplifies a DNA polymerase. (See Polymerase.) Polypeptide (protein). A polymer composed of multiple amino acid units linked by peptide bonds. Polyploid. A multiple of the haploid chromosome number that results from chromosome replication without nuclear division. Polysaccharide. A polymer composed of multiple units of monosaccharide (simple sugar). Polyvalent vaccine. A recombinant organism into which has been cloned antigenic determinants from a number of different disease-causing organisms. (See Vaccine.) Population. A local group of organisms belonging to the same species and capable of interbreeding. PPA. See U.S. Department of Agriculture. Prion. See Proteinaceous infectious particle. Probe. A sequence of DNA or RNA, labeled or marked with a radioactive isotope, used to detect the presence of complementary nucleotide sequences. See Nucleotide. Prokaryote. A bacterial cell lacking a true nucleus; its DNA is usually in one long strand. See Eukaryote. Proto-oncogene. See oncogene. Primary cell. A cell or cell line taken directly from a living organism, which is not immortalized. Primer. A short DNA or RNA fragment annealed to single-stranded DNA, from which DNA polymerase extends a new DNA strand to produce a duplex molecule. Probe. A single-stranded DNA that has been radioactively labeled and is used to identify complementary sequences in genes or DNA fragments of interest. (See Multilocus probe.) Promoter. A region of DNA extending 150-300 bp upstream from the transcription start site that contains binding sites for RNA polymerase and a number of proteins that regulate the rate of transcription of the adjacent gene. (See Constitutive promoter.) Pronucleus. Either of the two haploid gamete nuclei just prior to their fusion in the fertilized ovum. Protease. An enzyme that cleaves peptide bonds that link amino acids in protein molecules. Protein. A polymer of amino acids linked via peptide bonds and which may be composed of two or more polypeptide chains. (See Polypeptide.) Proteinaceous infectious particle (prion). A proposed pathogen composed only of protein with no detectable nucleic acid and which is responsible for Creutzfeldt-Jakob disease and kuru in humans and scrapie in sheep. Protein kinase. An enzyme that adds phosphate groups to a protein molecule at serine, threonine, or tyrosine residues. Proteolytic. The ability to break down protein molecules. Provirus. See virus. Public Health Service Act. See Food and Drug Administration. pUC. A widely used expression plasmid containing a -galactosidase gene. (See Plasmid.) PVA. The Plant Variety Act. See U.S. Department of Agriculture. R Reading frame. A series of triplet codons beginning from a specific nucleotide. Depending on where one begins, each DNA strand contains three different reading frames. (See Open reading frame, Overlapping reading frames.) Recessive(-acting) oncogene, (anti-oncogene). A single copy of this gene is sufficient to suppress cell proliferation; the loss of both copies of the gene contributes to cancer formation. (See Oncogene.) Recessive gene. Characterized as having a phenotype expressed only when both copies of the gene are mutated or missing. Recognition sequence (site). A nucleotide sequence--composed typically of 4, 6, or 8 nucleotides--that is recognized by a restriction endonuclease. Type II enzyrnes cut (and their corresponding modification enzymes methylate) within or very near the recognition sequence. Recombinant. A cell that results from recombination of genes. Recombinant DNA. The process of cutting and recombining DNA fragments from different sources as a means to isolate genes or to alter their structure and function. Recombination frequency. The frequency at which crossing over occurs between two chromosomal loci--the probability that two loci will become unlinked during meiosis. Regulatory gene. A gene whose protein controls the activity of other genes or metabolic pathways. Relaxed circle plasmid. See Plasmid. Relaxed plasmid. A plasmid that replicates independently of the main bacterial chromosome and is present in 10-500 copies per cell. (See Plasmid.) Renature. The reannealing (hydrogen bonding) of single- stranded DNA and or RNA to form a duplex molecule. Replicon. A chromosomal region containing the DNA sequences necessary to initiate DNA replication processes. Repressor. A DNA-binding protein in prokaryotes that blocks gene transcription by binding to the operator. Restriction endonuclease (enzyme). A class of endonucleases that cleaves DNA after recognizing a specific sequence, such as BamH1 (GGATCC), EcoRI (GAATTC), and HindIII (AAGCTT). Type I. Cuts nonspecifically a distance greater than 1000 bp from its recognition sequence and contains both restriction and methylation activities. Type II. Cuts at or near a short, and often symmetrical, recognition sequence. A separate enzyme methylates the same recognition sequence. Type III. Cuts 24-26 bp downstream from a short, asymmetrical recognition sequence. Requires ATP and contains both restriction and methylation activities. Restriction-fragment-length polymorphism (RFLP). Differences in nucleotide sequence between alleles at a chromosomal locus result in restriction fragments of varying lengths detected by Southern analysis. Restriction map. See Mapping. Retrovirus. A member of a class of RNA viruses that utilizes the enzyme reverse transcriptase to reverse copy its genome into a DNA intermediate, which integrates into the hostcell chromosome. Many naturally occurring cancers of vertebrate animals are caused by retroviruses. Reverse genetics. Using linkage analysis and polymorphic markers to isolate a disease gene in the absence of a known metabolic defect, then using the DNA sequence of the cloned gene to predict the amino acid sequence of its encoded protein. Reverse transcriptase (RNA-dependent DNA polymerase). An enzyme isolated from retrovirus-infected cells that synthesizes a complementary (c)DNA strand from an RNA template. RFLP. See Restriction-fragment-length polymorphism. Rhizobia. Bacteria in a symbiotic relationship with leguminous plants that results in nitrogen fixation. See Nitrogen fixation. Rhizosphere. The soils region on and around plant roots. Ribozyme. See Catalytic RNA. Ribosomal RNA (rRNA). The RNA component of the ribosome. (See RNA.) Ribosome. Cellular organelle that is the site of protein synthesis during translation. See Organelle, Translation. Ribosome-binding site. The region of an mRNA molecule that binds the ribosome to initiate translation. RNA (ribonucleic acid). An organic acid composed of re- peating nucleotide units of adenine, guanine, cytosine, and uracil, whose ribose components are linked by phosphodiester bonds. (See Antisense RNA, Heterogeneous nuclear RNA, Messenger RNA, Ribosomal RNA, RNA polymerase, Small nuclear RNA, Transfer RNA.) RNA polymerase. Transcribes RNA from a DNA template. (See Polymerase, RNA.) rRNA. See Ribosomal RNA. S Salmonella. A genus of rod-shaped, gram-negative bacteria that are a common cause of food poisoning. Satellite RNA (viroids). A small, self-splicing RNA molecule that accompanies several plant viruses, including tobacco ringspot virus. SE. See U.S. Department of Agriculture. Self-pollination. Pollen of one plant is transferred to the female part of the same plant or another plant with the same genetic makeup. Selectable marker. A gene whose expression allows one to identify cells that have been transforrned or transfected with a vector containing the marker gene. (See B-Lactamase, Kanr.) Semiconservative replication. During DNA duplication, each strand of a parent DNA molecule is a template for the synthesis of its new complementary strand. Thus, one half of a preexisting DNA molecule is conserved during each round of replication. Sequence hypothesis. Francis Crick's seminal concept that genetic information exists as a linear DNA code; DNA and protein sequence are colinear. Sequence-tagged site (STS). A unique (single-copy) DNA sequence used as a mapping landmark on a chromosome. Sexual reproduction. The process where two cells (gametes) fuse to form one hybrid, fertilized cell. See Asexual reproduction, Gamete, Hybrid. Signal transduction. The biochemical events that conduct the signal of a hormone or growth factor from the cell exterior, through the cell membrane, and into the cytoplasm. This involves a number of molecules, including receptors, pro- teins, and messengers. Site-directed mutagenesis. The process of introducing spe- cific base-pair mutations into a gene. Small nuclear RNA (snRNA). Short RNA transcripts of 100-300 bp that associate with proteins to form small nuclear ribonucleoprotein particles (snRNPs), which participate in RNA processing. (See RNA.) snRNA. See Small nuclear RNA. Somatic cell. Any nongerm cell that composes the body of an organism and which possesses a set of multiploid chromosomes (diploid in most organisms). (See Gamete, Somatic cell gene therapy.) Somatic cell gene therapy. The repair or replacement of a defective gene within somatic tissue. (See Somatic cell.) Somatotrophin. See Human growth hormone. Southern blotting. See Southern hybridization. Southern hybridization (Southern blotting). A procedure in which DNA restriction fragments are transferred from an agarose gel to a nitrocellulose filter, where the denatured DNA is then hybridized to a radioactive probe (blotting). (See Hybridization.) Species. A classification of related organisms that can freely interbreed. Spore. A form taken by certain microbes that enables them to exist in a dormant stage. It is an asexual reproductive cell. See Asexual reproduction, Dormant. Stationary phase. The plateau of the growth curve after log growth, during which cell number remains constant. New cells are produced at the same rate as older cells die. (See Growth phase.) Sticky end. A protruding, single-stranded nucleotide se- quence produced when a restriction endonuclease cleaves off center in its recognition sequence. Stringency. Reaction conditions--notably temperature, salt, and pH--that dictate the annealing of single-stranded DNA DNA, DNA RNA, and RNA RNA hybrids. At high stringency, duplexes form only between strands with perfect one-to-one complementarity; lower stringency allows annealing between strands with some degree of mismatch between bases. Stringent plasmid. A plasmid that only replicates along with the main bacterial chromosome and is present as a single copy, or at most several copies, per cell. (See plasmid.) STS. See Sequence-tagged site. Stop codon. See Termination codon. Structure-functionalism. The scientific tradition that stresses the relationship between a physical structure and its function, for example, the related disciplines of anatomy and physiology. Subcloning. The process of tranferring a cloned DNA fragment from one vector to another. (See Cloning.) Subunit vaccine. A vaccine composed of a purified antigenic determinant that is separated from the virulent organism. (See Vaccine, Enzyme.) Supercoiled plasmid. The predominant in vivo form of plasmid, in which the plasmid is coiled around histone-like proteins. Supporting proteins are stripped away during extraction from the bacterial cell, causing the plasmid molecule to supercoil around itself in vitro. (See Plasmid.) Supergene. A group of neighboring genes on a chromosome that tend to be inherited together and sometimes are functionally related. Supernatant. The soluble liquid action of a sample after centrifugation or precipitation of insoluble solids. Symbiosis. The close association of two or more dissimilar organisms where both receive an advantage from the association. See Commensalism, Parasitism. Synapsis. The pairing of homologous chromosome pairs during prophase of the first meiotic division, when crossing over occurs. T Taq polymerase. A heat-stable DNA polymerase isolated from the bacterium Therrnus aquaticus, used in PCR. (See Polymerase.) TATA box. An adenine- and thymine-rich promoter sequence located 25-30 bp upstream of a gene, which is the binding site of RNA polymerase. T-DNA (transfer DNA, tumor-DNA). The transforming region of DNA in the Ti plasmid of Agrobacterium tumefaciens. Telomere. The end of a chromosome. Template. An RNA or single-stranded DNA molecule upon which a complementary nucleotide strand is synthesized. Termination codon. Any of three mRNA sequences (UGA, UAG, UAA) that do not code for an amino acid and thus signal the end of protein synthesis. Also known as stop codon. (See Codon.) Terminator region. A DNA sequence that signals the end of transcription. Tetracycline. An antibiotic that interferes with protein synthesis in prokaryotes. Thymidine kinase (tk). An enzyme that allows a cell to utilize an alternate metabolic pathway for incorporating thymidine into DNA. Used as a selectable marker to identify transfected eukaryotic cells. Ti (tumor-inducing) plasmid. A giant plasmid of Agrobac- terium tumefaciens that is responsible for tumor formation in infected plants. Ti plasmids are used as vectors to introduce foreign DNA into plant cells. Toxic Substances Control Act (TSCA). See Environmental Protection Agency. Trait. See Phenotype. Transcapsidation. The partial of full coating of the nucleic acid of one virus with a coat protein of a differing virus. See Coat protein. Transcription. The process of creating a complementary RNA copy of DNA. Transducing phage. See Transduction. Transduction. The transfer of DNA sequences from one bacterium to another via lysogenic infection by a bacteriophage (transducing phage). Transfection. The uptake and expression of a foreign DNA sequence by cultured eukaryotic cells. Transfer DNA. See T-DNA. Transfer RNA (tRNA). See tRNA. Transformant. In prokaryotes, a cell that has been ge- netically altered through the uptake of foreign DNA. In higher eukaryotes, a cultured cell that has acquired a malignant phenotype. (See Transformation.) Transformation. In prokaryotes, the natural or induced uptake and expression of a foreign DNA sequence--typically a recombinant plasmid in experimental systems. In higher eukaryotes, the conversion of cultured cells to a malignant phenotype--typically through infection by a tumor virus or transfection with an oncogene. (See Transformant, Transformation efficiency.) Transformation efficiency. The number of bacterial cells that uptake and express plasmid DNA divided by the mass of plasmid used (in transformants microgram). (See Transformation.) Transforming oncogene. A gene that upon transfection converts a previously immortalized cell to the malignant phenotype. (See Oncogene.) Transgene. See Transgenic. Transgenic. An organism in which a foreign DNA gene (a transgene) is incorporated into its genome early in de- velopment. The transgene is present in both somatic and germ cells, is expressed in one or more tissues, and is inherited by offspring in a Mendelian fashion. See Transgenic animal, Transgenic plant. Transgenic animal. Genetically enginnered animal or offspring of genetically engineered animals. The transgenic animal usually contains material from at lease one unrelated organism, such as from a virus, plant, or other animal. See Transgenic. Transgenic plant. Genetically engineered plant or offspring of genetically engineered plants. The transgenic plant usually contains material from at least one unrelated organisms, such as from a virus, animal, or other plant. See Transgenic. Transition-state intermediate. In a chemical reaction, an unstable and high-energy configuration assumed by reactants on the way to making products. Enzymes are thought to bind and stabilize the transition state, thus lowering the energy of activation needed to drive the reaction to completion. Translation. The process of converting the genetic infor- mation of an mRNA on ribosomes into a polypeptide. Transfer RNA molecules carry the appropriate amino acids to the ribosome, where they are joined by peptide bonds. Translocation. The movement or reciprocal exchange of large-chromosomal segments, typically between two different chromosomes. Transposable genetic element. See Transposon. Transposition. The movement of a DNA segment within the genome of an organism. Transposon (transposable, or movable genetic element). A relatively small DNA segment that has the ability to move from one chromosomal position to another. tRNA (transfer RNA). The class of small RNA molecules that transfer amino acids to the ribosome during protein synthesis. See Transfer RNA. Trypsin. A proteolytic enzyme that hydrolyzes peptide bonds on the carboxyl side of the amino acids arginine and lysine. TSCA. The Toxic Substances Control Act. See Environmental Protection Agency. Tumor DNA. See T-DNA. Tumor-inducing plasmid. See Ti plasmid. Tumor virus. A virus capable of transforming a cell to a malignant phenotype. (See Virus.) U Upstream. The region extending in a 5' direction from a gene. USDA. See The U.S. Department of Agriculture. U.S. Department of Agriculture. The U.S. agency responsible for regulation of biotechnology products in plants and animals. The major laws under which the agency has regulatory powers include the Federal Plant Pest Act (PPA), the Federal Seed Act, and the Plant Variety Act (PVA). In addition, the Science and Education (SE) division has nonregulatory oversight of research activities that the agency funds. V Vaccine. A preparation of dead or weakened pathogen, or of derived antigenic determinants, that is used to induce formation of antibodies or immunity against the pathogen. (See Polyvalent vaccine, Subunit vaccine.) Vaccinia. The cowpox virus used to vaccinate against smallpox and, experimentally, as a carrier of genes for antigenic determinants cloned from other disease organisms. Variable surface glycoprotein (VSG). One of a battery of antigenic determinants expressed by a microorganism to elude immune detection. Variation. Differences in the frequency of genes and traits among individual organisms within a population. Vector. An autonomously replicating DNA molecule into which foreign DNA fragments are inserted and then propagated in a host cell. Also living carriers of genetic material (such as pollen) from plant to plant, such as insects. Viral oncogene. A viral gene that contributes to malig- nancies in vertebrate hosts. (See Oncogene.) Viroid. A plant pathogen that consists of a naked RNA molecule of approximately 250-350 nucleotides, whose extensive base pairing results in a nearly correct double helix. (See Satellite RNA.) Virulence. The degree of ability of an organism to cause disease. Virus. An infectious particle composed of a protein capsule and a nucleic acid core, which is dependent on a host organism for replication. A double-stranded DNA copy of an RNA virus genome that is integrated into the host chromosome during lysogenic infection. (See Coat protein, DNA, Genome, Host, Nucleic acid, RNA, Tumor virus.) VSG. See Variable surface glycoprotein. W Weed. An undesirable plant. Weediness. Unwanted effects of a plant. Wild type. An organism as found in nature; the organism before it is genetically engineered. X X-linked disease. A genetic disease caused by a mutation on the X chromosome. In X-linked recessive conditions, a normal female "carrier" passes on the mutated X chromosome to an affected son. X-ray crystallography. The diffraction pattern of X-rays passing through a pure crystal of a substance. Z Z-DNA. A region of DNA that is "flipped" into a lefthanded helix, characterized by alternating purines and pyrimidines, and which may be the target of a DNA-binding protein. The partial biology dictionary is made available to you by Susan A. Hagedorn. One of the best online biology dictionaries. Back to previous Go to the Bio-Informer Home Page Community of Science Network of scientists and their institutions geared toward publicizing research, collaboration, funding opportunities - from Johns Hopkins Univ. Community of Science (COS) - Funding resource, expertise database and abstract management system Home Services Join About COS Press Contact COS Workbench Username: Save My Login Password: Forgot Your Password? Submit an NIH Grant Faster Community of Science (COS) is the leading global resource for hard-to-find information critical to scientific research and other projects across all disciplines. We aggregate valuable information so you spend less precious time and money searching for the information you need, leaving more time and money for your projects. 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Promote your research with a COS Profile : showcase your research and expertise among researchers and scholars from universities, corporations and nonprofits in more than 170 countries. Use convenient tools to keep your CV updated and accessible. Copyright 2005 Community of Science, Inc. | Privacy Policy | Site Map BIOSIS A not-for-profit organization serving the life science community by providing researchers, students, and librarians with references to research published around the world. BIOSIS - Thomson Scientific Thomson.com Advanced Search EN : JP : CN : KR BIOSIS information solutions for the global life sciences community are now provided by Thomson Scientific. You can keep up to date with all our product news via our new home page . Our databases are the most complete resource for finding life sciences information quickly and efficiently. We select documents from thousands of sources worldwide, index and abstract them into citations which describe their content, and maintain databases for searching citations adding more than 600,000 new entries each year. BIOSIS Previews, Biological Abstracts and Zoological Record are available on several leading information platforms including ISI Web of Knowledge SM, the powerful web-based platform that delivers a powerful combination of content, tools and technology. Interdisciplinary - BIOSIS databases integrate important subjects from many different fields all across biology. International - More than 90 nations are represented in BIOSIS databases. Easy to Search - BIOSIS databases use a unique indexing system that allows flexible, efficient searching. Informed by Diverse Sources - You can find citations for articles, meetings, patents, book chapters, and more in BIOSIS databases. Products BIOSIS Previews Zoological Record Biological Abstracts Biological Abstracts RRM Abstracts of Entomology Abstracts of Mycology BasicBIOSIS BIOSIS Serial Sources BIOSIS Search Guide Highlights BiologyBrowser - links to science news stories, evaluated web sites, and more Search strategies Product updates Product update archive Case studies Back Years Relational Indexing Disclaimer | Terms of Use Privacy Policy | Copyright Home | Contact Us | Products Services | Support | About Us | Press Room News | Knowledge Trends | Information Brands | Site Map The SNP Consortium Ltd. A non-profit foundation organized to develop up to 300,000 single nucleotide polymorphisms (SNPs) distributed evenly throughout the human genome and to make the information related to these SNPs available to the public without intellectual property restrictions. TSC: The SNP Consortium website Home :: Frequency Genotype :: Linkage Maps :: Protocols Search :: News :: About :: Help :: Download data :: Feedback Single Nucleotide Polymorphisms for Biomedical Research Search: ( advanced | help ) Single nucleotide polymorphisms (SNPs) are common DNA sequence variations among individuals. They promise to significantly advance our ability to understand and treat human disease. The SNP Consortium (TSC) is a public private collaboration that has to date discovered and characterized nearly 1.8 million SNPs ( more ) New ATTENTIONThe GBrowse installation on this site is no longer maintained and has been deactivated. Users are advised to use the GBrowse SNP resource on the HapMap website ( http: www.hapmap.org cgi-perl gbrowse gbrowse ) which is currently maintained by our group [September 21st, 2003] Final data release, consisting of frequency genotype data, as well as full MySQL database text table dump (see Downloads ). July 2003The HapMap project, in which The SNP Consortium is a participant, is now underway. The project website is at http: www.hapmap.org . [January 28th, 2003] Website updates: chromosome locations in GBrowse back end database updated to NCBI genome assembly build31 (NB SNP gene-function classes are disabled temporarily, sorry). CMap viewer will have build31 sequence map soon as well. Also added batch query for SNP identifiers: users can now paste in a list of IDs on the Search page . Miscellaneous fixes in scripts and HTML-content. [January 23rd, 2003] Added link to mini-article about TSC website (NAR 2003 database issue) to About page [November 28th, 2002] New allele frequency datafiles finally released. See README in FTP-directory for details. [November 24th, 2002] Database updated: recently released SNPs have been assigned ss and rs by dbSNP in their current release. The TSC database has been updated with this information, so now ALL released TSC SNPs have both ss and rsand can be queried by those. However, genomic map locations have yet to be released for these SNPs in a form that we can use, but as soon as such data are available the TSC genome browser database will be updated. [October 24th, 2002] Database updated: final ~400.000 previously unreleased TSC SNPs made available via website, bringing the total up to ~1.8 million SNPs. These SNPs have also been submitted to dbSNP. Most of those will turn out to be non-unique in the genome (the reason for withholding them until now), though the genome assembly has changed much since two years ago. dbSNP is now in the process of building a new set of reference SNP clusters (rs), during which all of these new TSC SNPs will be either assigned to existing clusters, or put in their own cluster and subsequently mapped to the genome. Hopefully some of these new SNPs will turn out to be unique SNPs and thus useful to the community, but until their genome positions are known they will only be accessible via their TSC IDs (example: TSC1268304 ) [October 18th, 2002] Website updated, chromosome locations updated to genome assembly build30, updated Comparative map viewer and updated TSC linkage map data release [ more ]. Sponsors (more) GlaxoSmithKline Last updated on Tuesday, 10-Aug-2004 12:37:44 EDT Comments on website are welcome BioABACUS Biotechnology ABbreviation and ACronym Uncovering Service - Searchable database of biotechnology and bioinformatics abbreviations and acronyms for biological and computer science terminology, journals, and organizations (about 6000 terms). BioABACUS Search BioABACUS is a searchable database of abbreviations and acronyms in Biotechnology that contains terms in such categories as: Biochemistry, Cell Biology, Computers and Internet, Diseases, Grants, Journals, Laboratories, Medicine, Molecular Biology Genetics, Neuroscience, Other Organizations, Professional Societies and US Government. The data provided include the name of the term, its meaning, the category in which it is mostly used and, when available, a link in which additional information for the term can be found. 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BioTech's Life Science Dictionary Welcome to BioTech's life science dictionary!Please read the Search Instructions first. Search Terms: AND OR Search Definitions: Contains this word letter fragment Begins with this word letter fragment Find terms that contain the entered word in their definitions Looking for a chemical acronym? Try searching BioTech's Chemical Acronyms Database . This free resource was developed by our staff members and contributors and is still very much under construction. Currently, most of our 8300+ terms deal with biochemistry, biotechnology, botany, cell biology and genetics. We also have some terms relating to ecology, limnology, pharmacology, toxicology and medicine. Don't expect to find common or exotic animals here; there are far too many species to cover even a fraction in a resource like this. However, we've included medically- and biotechnologically-relevant organisms such as bacteria, worms, fungi, and some plants. 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Pedro's BioMolecular Research Tools Pedro's BioMolecular Research Tools A Collection of WWW Links to Information and Services Useful to Molecular Biologists !Under Revision! This Collection is mirrored in the U.S. , Germany , Switzerland and Japan . For your convenience use the nearest connection!. To install a local copy you can now get the June 16th, 1995 Version Part 1: Molecular Biology Search and Analysis (96 06 15 - 64k) Part 2: Bibliographic, Text and WWW Searches (95 06 15 - 25k) Part 3: Guides, Tutorials and Help Tools (96 10 13 - 28k) All: Parts 1, 2 and 3 (!No Pictures!) (95 02 23 - 69k) - Old! Journals: Bio Chemical Journals and Newsletters (95 06 15 - 67k) Extras: List of Pedro's Biological Resources Personal Classification of Links: - Hot Very Useful Tools * - Good Useful Tools * - Other Tools * - Journal Links * - Local Pages * - Email Search * - More Recent Additions Changes * - Less Recent Additions Changes * W3 - WWW Server Gopher - Gopher Server FTP - FTP Server Telnet - Telnet Port I welcome any comments or suggestions ! Last Modified: 96 03 15 USA: pedro@iastate.edu Germany: michael@alpha.biophys.uni-duesseldorf.de Switzerland: nager@fmi.ch Japan: denis@ala.peri.co.jp Cell and Molecular Biology Online An all-around reference site for the field with educational, technical, and professional net resources. Cell and Molecular Biology Online An Informational Resource for Cell and Molecular Biologists Research We Recommend... Online Publications Protocols and Methods Current Research Education General Resources Courses and Texts Images and Videos Cool Bio Stuff Communication Career Resources Professional Societies Conferences Grant Information Random New Content FAQ About CMBO Awards Perspective Biomaterials - The Technology of the Future Online Career Resources for Bioscientists Genes on the Web : A Report from the Internet Society 2000 Conference Welcome to the CMBO site! I am planning major revisions this fall and winter -- I apologize that this has taken so long! If you have any link recommendations, please let me know. Thanks! Please sign the Guest Book ! CMBO Site Map This web site is maintained by Pamela Gannon Copyright 1995-2004 Pamela M. Gannon Table of Standard Genetic Code Translation table of nucleotide codon sequences to amino acids. Table of Standard Genetic Code Table of Standard Genetic Code T C A G T TTT Phe (F) TTC " TTA Leu (L) TTG " TCT Ser (S) TCC " TCA " TCG " TAT Tyr (Y) TAC TAA Ter TAG Ter TGT Cys (C) TGC TGA Ter TGG Trp (W) C CTT Leu (L) CTC " CTA " CTG " CCT Pro (P) CCC " CCA " CCG " CAT His (H) CAC " CAA Gln (Q) CAG " CGT Arg (R) CGC " CGA " CGG " A ATT Ile (I) ATC " ATA " ATG Met (M) ACT Thr (T) ACC " ACA " ACG " AAT Asn (N) AAC " AAA Lys (K) AAG " AGT Ser (S) AGC " AGA Arg (R) AGG " G GTT Val (V) GTC " GTA " GTG " GCT Ala (A) GCC " GCA " GCG " GAT Asp (D) GAC " GAA Glu (E) GAG " GGT Gly (G) GGC " GGA " GGG " 1st European Congress on Conservation Biology Includes general information. Eger, Hungary. ECCB 2006 - 1st European Congress of Conservation Biology (Eger, Hungary) Home Venue Information News About the congress General Information Scientific Programme Call For Papers List of Symposium and Workshops Exhibitors Sponsors Registration Accommodation Social Programme Field trips Excursion Pictures FAQ Contacts Are you interested in the congress? Contact us! (Please, avoid using national characters.) Name:* Affiliation (Institute Company):* Department: Fax number:* E-mail address:* Comment:* *required fields 1st European Congress of Conservation Biology 22-26 August 2006 Eger, Hungary The European Section of the Society for Conservation Biology is determined to promote the development and use of science for the conservation of European species and ecosystems, and to make sure that conservation policy is firmly underpinned by the best available scientific evidence. The European Section needs to grow in number and capacity to make sure that the voice of conservation science informs the many European policies that impact on our biodiversity. We also need to increase the awareness of European policy-makers and scientists of conservation issues and the complex mix of scientific disciplines required to properly manage them. Europe is where humans and natural resources have been coexisting for millenia and we have developed unique solutions to mitigate the conflicts and move toward sustainability. We are till far from having solved all problems but we have good lessons for the rest of the world. We need your support to help the Society assume a prominent role in the development of European conservation science and policy. For these reasons, we are inviting all of you, policy makers, scientists, students and managers of biodiversity to the first European Congress of Conservation Biology and we hope to see you in great number in Hungary in 2006. Luigi Boitani, President European Section of SCB Hungary is in the heart of Europe, has a unique and diverse wildlife, and the home of famous wines, drinks and cuisine. Just some of the many reasons to attend the congress in Eger, 2006! We will keep registration fees as low as possible and intend to fund colleagues and students with limited resources. So save the dates in your calendar, and see the two slide shows on the website to get more information on Hungary and the congress! Andrs Bldi, Chair Local Organising Committee 'Call for Papers' has been announced on the congress website 'Call for Papers' has been announced on the congress website. 'Online Abstract Submission' will be open on 30 November 2005. Web submission is strongly encouraged. 2005-11-03 | Read 2nd meeting of the Scientific Committee of ECCB The Scientific Committee of the 1st ECCB had its second meeting in Hatfield, U.K. in September 2005. 2005-10-26 | Read More than 500 persons have already expressed interest in ECCB 2006! More than 500 persons have already subscribed to ECCB 2006 Congress mailing list. 2005-10-19 | Read Home Information News About the congress Sitemap FAQ Contacts Copyright 2004 eccb2006.org Site build online marketing: Xpedient 6th International Conference on Systems Biology Includes event information and registration. Boston, Massachusetts, U.S. ICSB 2005 Conference skip to: page content | links on this page | site navigation | footer (site information) home program registration abstract submission tutorials workshops committees sponsors information contact us search Sixth International Conference on Systems Biology Home Program Registration Abstract Submission Tutorials Workshops Committees Sponsors Information Host Institutions CSBi at MIT Bauer Center at Harvard Broad Institute Appl. Biodynamics at BU Systems Biology at HMS Major Sponsors Bristol-Myers Squibb Eli Lilly and Company Merck and Company Conference Sponsors Affymetrix CombinatoRX Genentech Novartis Pfizer October 19-24, 2005 in Boston, Massachusetts Hosted by The Conference Center at Harvard Medical 77 Avenue Louis Pasteur, Boston, MA 02115 The 6 th International Conference on Systems Biology continues an annual series of conferences initiated by Hiroaki Kitano in Tokyo in 2000. Subsequent conferences were held at Caltech in Pasadena, and at the Karolinska Institute in Stockholm. In 2003, the ICSB was held at Washington University in St. Louis, Missouri and in 2004 in Heidelberg, Germany. October 19 - Tutorials October 19-22 - Conference October 23 24 - Workshops Announcements The ICSB 2005 presentations will be available on the web before the end of the year. If you would like to be notified by email when they are available, please enter your email address on this page. To receive e-mail notification of conference information updates, enter your e-mail address below: E-mail updates from ICSB 2005 | Privacy Policy | Contact Us | 2005 CSBi FASEB Office of Scientific Meetings and Conferences Information on approximately 12 meetings and 24 Conferences organized by the Federation of American Societies for Experimental Biology. FASEB Office of Scientific Meetings The FASEB Office of Scientific Meetings and Conferences manages approximately 12 meetings and 24 FASEB Conferences. The services provided include site selection, facility arrangements, personnel and equipment arrangements, exhibit management, advertising and promotion hospitality, assistance with abstract processing and programming, registration processing and CME credits. Geri Swindle Director Jean Lash Exhibit Manager Pauline Minhinnett , CMP Senior Meeting Manager Nancy Copen , CMP Meetings Manager FASEB Summer Research Conferences Julie Levin Manager Please send any comments or suggestions concerning this web site to: OSMC Webmaster Soft Condensed Matter Physics in Molecular and Cell Biology Contains lecture slides and program. Edinburgh, Scotland. NATO ASI SUSSP 59: Soft Condensed Matter Physics in Molecular and Cell Biology SOFT CONDENSED MATTER PHYSICS IN MOLECULAR AND CELL BIOLOGY NATO ASI SUSSP 59 EDINBURGH, SCOTLAND, UK 29th March - 8th April 2004 Latest: I now have most of the notes from the lectures and am making arrangements for a password protected area of the site. I should be able to mail you all the password during the week and you should be prepared for the protected area to become active not too long afterwards, certainly before Monday 3rd May 2004. Also, I am in the middle of making up certificates of participation. This should not take too long and I should be able to email them to those people who want them in the near future -- Daniel. Lecturers D. Andelman (Tel Aviv) D. Bensimon (Paris) S. U. Egelhaaf (Edinburgh) R. Elber (Cornell) D. Frenkel (Amsterdam) J. F. Joanny (Paris) M. Kozlov(Tel Aviv) F. C. Mackintosh (Amsterdam) T. C. B. McLeish (Leeds) P. D. Olmsted (Leeds) R. Podgornik (Ljubljana) W. Poon (Edinburgh) M. Rief (Munich) C. F. Schmidt (Amsterdam) C. A. M. Seidel (MPI, Goettingen) P. B. Warren (Unilever) Biology is living soft matter biological surfactants (lipids) make up the membranes, while proteins and DNA are biological polymers. Brownian motion has a dominant role diffusion on structures with reduced spatial dimensionality (2-dimensional on membranes and 1-dimensional on various filamentous structures such a microtubules) play a crucial role in transport and other processes, while diffusion in a very-high-dimensional free-energy landscape underlies protein folding. The new insights into soft matter gained by physicists over the last few decades can therefore be expected to have significant impact on the understanding of biological systems, from single biomolecules through to cells and (perhaps) beyond. In particular, the increasing attention paid by soft condensed matter physicists to non-equilibrium phenomena and dynamics are crucial to the interaction between the two fields the two italicised words being almost synonymous with life itself! The purpose of this ASI SUSSP is to gather together some of the principal scientists responsible for pushing back the frontiers of the application of soft matter physics to the understanding of biological systems and give them the opportunity to present the tools of their trade and some of the latest results to junior researchers. International Organizing Committee: W. C. K. Poon (Director) D. Andelman (Director), F. C. Mackintosh, T. C. B. McLeish Local Organizing Committee: W. C. K. Poon, S. U. Egelhaaf, D. T. F. Dryden, P. D. Berry Ceilidh Time Table City and Travel Information Location and Accommodation Information Application Information. Posters The ASI SUSSP is receiving additional sponsorship from: The Biotechnology and Biological Sciences Research Council (BBSRC) The Engineering and Physical Sciences Research Council (EPSRC) This ASI SUSSP is an official satellite of the Isaac Newton Institute for Mathematical Sciences (Cambridge) programme: 'Statistical Physics of Biomolecules and Cells.' (19th Jan - 9 Jul 2004) for further details please mail softbioasi@ph.ed.ac.uk Australian Marine Sciences Association Annual Conference 2004 Range of themes including ecosystem change, biophysical oceanography, aquaculture and fisheries, and management. Includes program, registration, paper and poster information, and related links. Tasmania, Australia. AMSA Annual Conferences Home About Students Members Publications Around Australia Annual Conference Contact Login Register Print Friendly AMSA Annual Conferences AMSA ANNUAL CONFERENCES The AMSA Conference is AMSA's primary event of the year, and is held each July (usually in the AVCC week) and each year is hosted in a different state, with the conference each fourth year being a combined one with AMS New Zealand. AMSA encourages students to attend and present at the AMSA Conference and provides incentives by way of registration concessions, prizes and travel subsidies. FUTURE AMSA CONFERENCE VENUES 2006 Cairns Convention Centre (in conjunction with the Society of Wetland Scientists) 9-14 July Proposed Draft AMSA Program 2007 Coffs Harbour, NSW (supported by Council - to be confirmed) 2008 Christchurch, New Zealand 2009 Melbourne 2010 Adelaide (tentative) PAST AMSA CONFERENCES 2005 Darwin, 11-13th July 2005 NOMINATION FORM FOR ELECTION OF AMSA COUNCILLORS (to be submitted at least 21 days prior to the AGM, to the AMSA Secretary) Application for Membership and Renewals Application Form . Please use this if, on login, the online renewal is unavailable. AMSA2006 Conference 9-13th July 2006 (AVCC week) Catchment to Coast A joint conference with the Society for Wetland Scientists. Conference details coming soon... Copyright Australian Marine Sciences Association Inc. 2005 | Privacy | Disclaimer Powered by RegionalNet 10th Invertebrate Reproduction and Development Conference Includes registration, accommodation, and tours. Newcastle, U.K. 10th INTERNATIONAL CONGRESS OF INVERTEBRATE REPRODUCTION AND DEVELOPMENT HOME NEWS NOTICE BOARD REGISTRATION PROGRAMME ACCOMMODATION CONFERENCE TOURS TRAVEL Sunday 18th July 2004 to Friday 23rd July 2004 Newcastle upon Tyne, UNITED KINGDOM ENTER 10th ICIRD (2004) School of Marine Science Technology Ridley Building Newcastle upon Tyne University Newcastle upon Tyne, NE1 7RU UNITED KINGDOM EMAIL: ICIRD.2004@NCL.AC.UK FAX:(0044)+191 222 7891 3rd Conference on High Pressure Bioscience and Biotechnology Circular and general information. Rio de Janeiro, Brazil. http: www.hpbb2004.org 3rd International Conference on High Pressure Bioscience and Biotechnology September 27 30, 2004 Rio de Janeiro, Brazil (last update: 09 16 2004) hpbb2004@bioqmed.ufrj.br hpbb2004 Proceedings of the hpbb2004 - As first directed in the hpbb2004 circular , authors that attended and presented their work in the hpbb2004 (both as Lecture, Oral contribution or Poster) can submitt a cientific article to be published in the Brazilian Journal of Medical and Biological Research ( BJMBR ), which will characterize the Proceeding of the hpbb2004; - The categories of articles (for the Proceedings of the hpbb2004) can be both Full-length Papers and Review Articles; - Final deadline for submission: December 20, 2004 (we have extended the deadline due to the request of some hpbb2004 participants); - All submitted articles will be peer reviewed; - Author submissions must follow BJMBR instructions ( html and pdf ). - According to BJMBR, all accepted manuscrits will be charged . - All manuscripts should be send to BOTH email: hpbb2004@bioqmed.ufrj.br AND bjournal@fmrp.usp.br . - Please contact us ( hpbb2004@bioqmed.ufrj.br ) if you have any questions concerning the Proceedings of the hpbb2004. hpbb2004: complete program folder second circular call for abstracts LOCAL ORGANIZING COMMITTEE OF THE CONFERENCE - Jerson Lima Silva , Full Professor Medical Biochemistry Department , ICB, Rio de Janeiro Federal University, Brazil - Julio A. Mignaco , Associate Professor Medical Biochemistry Department , ICB, Rio de Janeiro Federal University, Brazil - Lus Maurcio T. R. Lima , Associate Professor School of Pharmacy , Rio de Janeiro Federal University, Brazil - Debora Foguel , Associate Professor Medical Biochemistry Department , ICB, Rio de Janeiro Federal University, Brazil - Amauri Rosenthal , Associate Researcher Director CTAA EMBRAPA Food Technology , Rio de Janeiro, Brazil LINKS UFRJ Faculdade de Farmcia UFRJ Pestana Rio Atlantica Hotel (The Conference Hotel) Sbbq EMBRATUR - official site of the Brazilian Ministry of Tourism Hotels, tourism and other information concerning Rio de Janeiro City hpbb2004 on Jornal da Cincia online EHPRG European High Pressure Research Group AIRAPT International Association for the Advancement of High Pressure Science and Technology LAST AND UP-COMING EVENTS IN THE HIGH PRESSURE FIELD - 1st HPBB - Kyoto, Japan, 2000 - 2rd International Conference on High Pressure Bioscience and Biotechnology (2002) , Dortmund, Germany - Hydration Forces in Protein Folding and Protein Interactions - Hydrostatic and Osmotic Pressure Approaches - Rio de Janeiro, Brazil, 2002 - Gordon Research Conference (2002), Meriden , New Hampshire - EHPRG Meeting (2002), Edinburgh, UK - Joint AIRAPT-EHPRG Conference, High Pressure Science and Technology (2003), Bordeaux, France - 3rd International Conference on High Pressure Bioscience and Biotechnology (2002) - Gordon Research Conference (2004), Meriden, New Hampshire - EHPRG Meeting (2004), Lausanne, CH (to be confirmed) - Joint AIRAPT-EHPRG Conference (2005), Karlsruhe, Germany Keystone Symposia Scientific Conferences Organizes molecular and cellular biology meetings in Alberta, California, Colorado, New Mexico and Utah, U.S. Contains list of symposia with scientific programs, registration and abstract submission forms. Keystone Symposia | Scientific Conferences on Biomedical and Life Science Topics 0 Keystone Symposia, a non-profit organization dedicated to Connecting the Scientific Community for the benefit of society, conducts scientific conferences on biomedical and life science topics in relaxing environments that catalyze information exchange and networking. View Meetings on: Biochemistry Cancer Cardiovascular CellBiology Development DrugDiscovery Genetics Genomics Immunology InfectiousDiseases MetabolicDiseases MolecularBiology Neurobiology PlantBiology StructuralBiology Meeting Series: Global Health Series Translational Medicine Series Search meetings Include PAST Meetings or View All 2006 Meetings Keystone Symposia is a 501(c)(3)non-profitorganization directed and managed by the scientific community. Register ContactUs Account Login User Name: Password: New User? Keystone Symposia is a 501(c)(3) non-profit organization directed and supported by the scientific community. Phone: (800) 253-0685 or (970) 262-1230 Fax: (970) 262-1525 info@keystonesymposia.org Canadian Federation of Biological Societies 46th Annual Meeting Cardiovascular and metabolic disease theme. Contains program, presentation guidelines, abstract submission form, and registration information and form. Ottawa, Canada. CFBS | Canadian Federation of Biological Societies 48th Annual Meeting Registrants Exhibitors Online Forms President's Letter LOC Letter Program Information By Theme By Date Program Summary Accommodation Sponsors Exhibitor List Local Committee Constituent Societies The Canadian Federation of Biological Societies invites you to attend : CFBS 48th Annual Meeting, "Second Northern Lights Summer Conference" June 21 - 24, 2005 University of Guelph, Guelph, ON The main theme is: LIFESTYLE MOLECULAR BASES OF HEALTH DISEASE CARDIOVASCULAR HEALTH, DIABETES, EXERCISE, NUTRITION, OBESITY Health Canada will be participating in the exhibits and will be collecting resumes. Hours for Non- Registrants are Wednesday, June 22 from 10:00 AM - 12:00 PM and Thursday, June 23 from 2:00 - 4:30 PM Second Northern Lights Summer Conference Poster Transportation Information All abstracts have been scheduled for Poster Presentation Registrants Information Exhibitors Information The theme is composed of seven symposia chaired by recognized leaders in the field. The Scientific Program is being organized by: Dr. Arend Bonen, University of Guelph. Dr. Janis Randall, University of Guelph, is the Local Organizing Committee Chair. The 48th CFBS Annual Meeting (2nd Northern Lights Summer Conference) offers: Scientific Exhibits Door Prizes Poster and Oral Presentations Students Activities Travel Awards Science Policy Forum Societies Award Lectures and Banquets CFBS Award Lectures Social Events Updated: May 10, 2005 Online Forms Attendee Registration Abstract Exhibitor Meeting Registration Exhibitors and Sponsors Home | About CFBS | Annual Meeting | Grants Awards | Science Policy News | Job Postings | Publications | Advertising | Contact Us Canadian Federation of Biological Societies, Federation canadienne des societies de biologie 4th International Conference on Systems Biology Includes program, registration and local information. Missouri, U.S. ICSB 2003 - 4th International Conference on Systems Biology BioVision: World Life Sciences Forum Annual event dedicated to linking life sciences with news, society and industry. Contains newsletters and details about upcoming and previous conferences. The World Life Sciences Forum: BioVision, international platform The World Life Sciences Forum BioVision - Lyon-France, is a unique international platform, bringing together representatives from society, science, and industry in equal numbers, to discuss, debate and put forth proposals on the major international issues concerning the future of health, food and the environment. A growing international success Since its inception in 1999, the BioVision Forum has brought together the top decision makers and stakeholders from the global Life Sciences community. Held every two years, the Forum and its associated events has grown from 1,200 participants in BioVision 1999 to an anticipated 4,500 participants in BioVision 2005. With the availability of a newly expanded Lyon Convention Center, this number is expected to reach 6,000 for BioVision 2007 The World Life Sciences Forum: BioVision, international platform Biovision,The World Life Sciences Forum,BioVision.nxt,NGOs Life Sciences,Nobel Laureates Day,Biotech conference,Biotech News,business,Agbiotech,environment,health,Biocluster,GMOs,healthcare,conference,EuroBioClusters,Alexandria,BioIndustry,Cluster,convention,plenary session,parallel conference,Ag Food,nutrition,agriculture,developping countries,ethics,NGO,Ag Developments,polio vaccination,vaccins,experts,Academy of Sciences,immunology,vaccination,disease,Nobel Prize,food, sustainability,humankind,Vital Issues,Policy Makers,Decision makers,Opinion leaders BioVision : The World Life Sciences Forum is a unique international platform, bringing together representatives from society, science, and industry in equal numbers, to discuss, debate and put forth proposals on the major international issues concerning the future of health, food and the environment In April 2003, 1,500 experts from over 50 countries attended The World Life Sciences Forum BioVision, with, as guest speakers, many of the most prominent scientists, society and industry leaders involved in the development of Healthcare, Agriculture and Environment Discover the members the intitutions which composes the International steering committee of Biovision like Mr.Raymond Barre, European Parliament, European Commission, UNESCO, UNEP, OECD, EuropaBio Discover the members the intitutions which composes the International scientific commitee of Biovision like Prof. Franois Gros, Acadmie des Sciences de lInstitut de France, National Academy of Sciences Discover the Chair College Members which composes the Chair College Members Science, the Chair College Members Society and the Chair College Members Industry Discover the BioVision Network : European Commission, UNESCO, Acadmie des Sciences de lInstitut de France, European Federation of Biotechnology, European Platform Patient Organisations, Sciences Industries The Bibliotheca Alexandrina is proud to host BioVision Alexandria, a milestone gathering of BioSciences experts, in partnership with The World Life Sciences Forum, BioVision conference - platform Biosquare 2005 : Bringing the Global Life Sciences Community Together. The International Partnering Conference combined with The World Life Sciences Forum BioVision Synopsis of The World Life Sciences Forum and Associated Events : BioVision.Nxt Day, Networks' Day and the BioVision Nobel Laureates' Day Discover the BioVision Working Sessions : Plenary Sessions, Parallel Conferences and The Ministers Plenary Session BioVision Working Sessions the Wednesday April 13 : Plenary Session and Parallel Conferences about Health for All, Agriculture Nutrition and Industrial BioSciences the Environment BioVision Working Sessions the Thursday April 14: Parallel Conferences Plenary Session about Health for All, Bioethics, Agriculture Nutrition and BioIndustry Environment, New Energy Development BioVision Nobel LaureatesDay 2005 : The breaking news that spread on April 12, 1955 confirming that the Salk Polio Vaccine had proven safe and effective was a landmark in 20th century history BioVision.Nxt 2005 will take place within the context of The World Life Sciences Forum BioVision, and will bring together Tomorrows BioLeaders NGOs Life Sciences Day : On the occasion of the next World Life Sciences Forum, BioVision 2005, a special day will be dedicated to the NGOs and their perceptions of the Life Sciences NGOs Life Sciences Day : This special day representing the official start of the World Life Sciences Forum 2005. The Monday morning is being organised around nine workshops The Plenary Session of the NGOs Life Sciences Day will be dedicated to sharing and debating the workshops conclusion with the general public China Europe Colloquium Latin America Colloquium EAGLES Special Event Lyon Life Sciences Discovery Day List of Speakers BioVision 2005, invited Keynote Speakers List of Speakers BioVision 2003 Clik here to access the Registration Process or click here if I cannot attend The World Life Sciences Forum in 2005 but I am interested in acquiring the Proceedings of the Conferences The World Life Sciences Forum BioVision 2005 is organised with the efficient support of the following Regional Government Authorities Lyon Rhne-Alpes like Ville de Lyon, Conseil Gnral du Rhne, Le Grand Lyon, Conseil Rgional Rhne-Alpes Discover the Official Sponsors Partners of BioVision 2003 : Global Partner like Cap Gemini; Major Sponsors like Aventis, Merial; Country Pavilions like Holand Regular Sponsors like 3M, FranceTelecom Global Partner, Major Sponsors, Country Pavilions Regular Sponsors Discover the Sponsor's Logistic Information for The World Life Sciences Forum Biovision The World Life Sciences Forum BioVision is a unique international platform, bringing together representatives from society, science, and industry in equal numbers, to discuss, debate and put forth proposals on the major international issues concerning the future of health, food and the environment The World Life Sciences Forum BioVision offers a unique opportunity for Science, Society-at-large and Industry to share views on a wide range of issues related to Life Sciences Press Contacts for The World Life Sciences Forum BioVision : Mr. Andr de Marco; for Ruder Finn : Emilie Geoffroy, Frdrique Impennati, Frdrique Galloudec Rus; for Kalia : Virginie Palpacuer Discover the documentation about The World Life Sciences Forum BioVision 2005 : Save The Date, Second Announcement, BioVision Nobel Laureates'Day, International Committees Discover the documentation about The World Life Sciences Forum BioVision 2003 : Final Programme 2003 Contact The World Life Sciences Forum BioVision, a unique international platform, bringing together representatives from society, science, and industry Home Save The Date The World Life Sciences Forum BioVision 2006 - Alexandria, April 26-29 BioVision 2007 - Lyon, March 11-14 BioVision 2005 Conclusions Health for All? Agriculture Nutrition BioIndustry Environment Newsletter Newsletter BioVision 2005, 6 BioVision NobelLaureates'Day "Of Microbes, Science and Mankind" Polio Vaccine 50th Anniversary Tuesday April 12, 2005 Press Release:Society Life Sciences Day BioVision Working Sessions Plenary Sessions, Parallel Conferences... BioVision.Nxt 2005 Credits | Site map | Powered by Add Online 4th International Plant Biomechanics Conference Includes program, online paper submission, and general information. East Lansing, Michigan, U.S. 4th Plant Biomechanics Conference 3rd International Conference of Comparative Physiology and Biochemistry in Africa Includes scientific program, presentation instructions, registration form and venue information. KwaZulu-Natal, South Africa. 4th ICCPB in Africa Fourth ICCPB in Africa: 2008 Maasai Mara National Reserve, Kenya Mara Simba Lodge July 19-25: 2008 Follow this link to www.natural-events.com mara link to home page for the recent meeting Ithala 2004 Natural Events Safaris Home Page Much of the funds provided by Natural Events to support the ICCPB in Africa come from modest profits on N.E. Safari operations. Please help maintain this support by clicking through to this link and using N.E. for bookings Materials from the 2nd ICCPB in Africa Chobe 2001 refereed papers: Comparative Biochemistry and Physiology, Part A Volume Issue 133 3 Direct link to PDF files at www.sciencedirect.com Download PDF file of program or Download PDF file of abstracts from Chobe 2001 List including papers from the 1st ICCPB in Africa Skukuza 1997 refereed papers: list only For Vacation Safaris Tours go to http: www.natural-events.com or http: naturalsafaris.kwando.co.za Designed for 1024 x 768 resolution The 4th International Symposium on Serpin Structure, Function and Biology Includes pre-registration form. Cairns, Australia. serpins2005.org Welcome to serpins2005.org Why am I seeing this web site? Vacation Technology Health Beauty Gifts Personal Finance Home Pin Set Pin Set Software Computer Books Desktops Wireless Internet Online Chat Job Search Part Time Jobs Employment Opportunities Direct Education College Grants Featured Directory Televisions Consumer Electronics DVD Camcorders DVD Players Calculators International Airlines World Travel Cruise Reviews Inclusive Cruises Cheap Motels Stock Prices Home Designs Web Directory Vacation Cruise , Hotel , Cheap Flight , Travel Agent , Golf Vacations Technology Digital Camera , Plasma Television , Mobile Phone , Laptop , Web Hosting Health Beauty Weight Loss , Fitness , Plastic Surgery , Skin Care , Pregnancy Gifts Books , DVD , Engagement Ring , Chocolate , CD Personal Finance Credit Cards , Debt Consolidation , Financial Advisor , Loans , Credit Report Home Home Improvement , Recipe , Family , Home Decorating , Pets BECON Nanoscience and Nanotechnology Symposium Aimed at achieving a better understanding, for biologists, of nanoscience and nanotechnology, identifying possible applications relevant to biology and medicine, and exploring future research possibilities. Bethesda, Maryland, US. Reparative Medicine BECON 2001 Reparative Medicine: Growing Tissues and Organs THE DEADLINE FOR POSTER ABSTRACTS AND EXHIBIT ABSTRACTS HAS BEEN EXTENDED TO TUESDAY, MAY 15, 2001. Welcome to the BECON 2001 Symposium Website June 25-26, 2001 Natcher Conference Center National Institutes of Health Bethesda, Maryland 13th International Conference on Invertebrate Dioxygen Binding Proteins Contains topics, program, registration form and venue details. Mainz, Germany. IO2BIP 2003 Mainz, Germany This document contains frames , but your browser is not configured to display frame websites XIIIth International Conference on Invertebrate Dioxygen Binding Proteins Mainz , Germany September 7 - 12, 2003 link to INDEX for not using frames Contact: io2bip@uni-mainz.de This document contains frames , but your browser is not configured to display frame websites Plant and Microbe Adaptations to Cold Meeting Winter survival of agricultural and forest plants, as well as the functioning of microbes at low temperatures. Includes program, registration information, accommodations, transportation, and tourist information. Quebec City, Canada. Congrs Adaptation au froid des plantes et des microorganismes Plant and Microbe Adaptations to Cold Meeting Avis importants Important Notices Plant Species-Level Systematics Symposium Topics covered include species radiations, molecular evolution, multiple genomes, and identification and diagnostics. Contains program, online registration, tourist information, and related links. Leiden, The Netherlands. NHN symposium 2002 The Linnean Society of London Plant species-level systematics: patterns, processes and new applications A 3-day international symposium from 13 to 15 November 2002 in Leiden, The Netherlands Home Organisation Programme Abstracts Venue Registration Accommodation Tourist information Nationaal Herbarium Nederland Contact information Links Plant systematics has seen some dramatic changes over the past decades, mainly due to the application of molecular markers in phylogenetic reconstruction at the generic level and above. In contrast, species-level patterns and processes in plants are still generally less well understood, partly because of limited resolution of commonly used phylogenetic markers. This symposium seeks to review current insights from the fields of molecular biosystematics and speciation, focussing on the following selected topics of particular importance: - Plant species radiations - Molecular evolution in time and space - Multiple genomes: plant hybrids, polyploids and systematics - Identification and diagnostics This symposium brings together a panel of internationally known experts, as well as scientists from within the Nationaal Herbarium Nederland . There will be invited papers, but the symposium is also open for contributed papers by anyone with an interest in species-level systematics and plant evolution, especially research students and post-doctoral fellows. Nationaal Herbarium Nederland Last update on Monday October 21, 2002 by P.B. Pelser International Conference on Magnetic Resonance in Biological Systems Contains program, online registration, abstract submission, presenter guidelines, and links of interest. Toronto, Canada. ICMRBS - Home Sorry, your browser doesn't support Java. I nternational C onferences on M agnetic R esonance in B iological S ystems Background: The International Conferences on Magnetic Resonance in Biological Systems (ICMRBS) is a series of biennial conferences that has grown substantially in both size and scope over the past 30 years. Besides covering important new developments in the use of EPR and in vivo NMR, the meeting is widely considered one of the premier meetings in the rapidly growing field of protein and nucleic acid structure determination by multi-dimensional NMR techniques. From its inception in 1964, this conference initially alternated in locale between North America and Europe, but in more recent years it has been held in Japan, India and Israel, as well. The ICMRBS typically brings together a broad spectrum of magnetic resonance experts. It is aimed at developing an in-depth evaluation of the current status of the field and at determining the directions where magnetic resonance could have the greatest impact on addressing biologically important problems. Since its inception in 1964, the biennial ICMRBS has been held in 12 countries, with each meeting organized by a national committee, supported by an International Advisory Committee. Overall coordination of the series is provided by the ICMRBS Council , composed of the organizers of previous conferences. Information: This website will maintain information of current interest to the ICMRBS and it will provide links to upcoming meetings. Please bookmark and return to this site whenever you need information regarding the ICMRBS. If you need to contact the ICMRBS Council, please send email to info@icmrbs.org Founders Medal: The ICMRBS Founders Medal is presented at the conference and recognizes exceptional contributions to developments and or progress in the area of magnetic resonance in biological systems. The first recipient was Lewis E. Kay, Univ. of Toronto, Canada, awarded in 2004. Founders Medal Awarded: Nico Tjandra , National Institutes of Health, Bethesda, MD, received the award and his award lecture. For further information, including the citation, click here . Recent Meetings: The XXth ICMRBS meeting was held in Toronto, Canada, August 25-30, 2002. The XXIst ICMRBS was held in Hyderabad, India, January 16-21, 2005. Prof. Chary and his colleagues organized an excellent meeting, and their efforts are greatly apprcieated. The program featured highlights in all areas of biological magnetic resonance. The website is still active for those who wish to review the topics. Next Meetings: The XXIInd ICMRBS will be held in Goettingen, Germany, August 20-25, 2006. The website is active and will be the site of information, including the scientific program and registration, for the upcoming meeting. Please check that site frequently as the date approaches. The XXIIIrd ICMRBS will be held in San Diego, California, USA, August 24-29, 2008. The meeting will be organized by Drs. Jane Dyson, Peter Wright, and others in the San Diego-La Jolla community. Please check back to this site for future details including the launch of a website for this meeting.. Future Meeting Proposals: The Council of the ICMRBS will be soliciting proposals for meetings in 2010. Further information is provided here . _________________________________________ Home Council ICMRBS Founders Medal Future Meetings Comparative Physiology and Biochemistry in Africa Conference Papers on animal physiology and biochemistry relating to the African environment or species will be presented. Includes scientific program, presentation instructions, abstracts, list of delegates, registration and venue information, and tourist links. Chobe National Park, Botswana. Chobe 2001 18-24 August 2001 Chobe National Park Botswana - Calling for papers Chobe 2001, Second International onference of Comparative Physiology and Biochemistry in Africa, Botswana 18-24 August, 2001 Designed for 1024 * 768 pixel resolution and 24-bit True Colour Links in this site open separate browser windows. If a window seems not to appear check the button panel at the bottom of the window to see if extra web browsers are open but not expanded SIXTH ( FINAL GENERAL) ANNOUNCEMENT SECOND INTERNATIONAL CONFERENCE OF COMPARATIVE PHYSIOLOGY BIOCHEMISTRY IN AFRICA HOW ANIMALS WORK CHOBE NATIONAL PARK, BOTSWANA: 18-24 AUGUST 2001 On November 16, 2001 there were available places for further: ORAL PAPERS - 0 POSTER PAPERS - 0 This is the second conference of its nature to be held in southern Africa. This meeting follows on the first and very successful conference held at Skukuza in Kruger National Park in 1997, and the chosen theme for 2001 is: How animals work. The meeting will present papers on any aspects of animal physiology and biochemistry including especially papers relating to the African environment or species. DIRECTORY Use Links Below Chobe 2001 - meeting Safari shirt offers - click on banner for details! Registration,Venue and Program Accommodation Travel Social Activities Conference Safaris Program of Papers and events Accommodation Information Getting to Kasane ( away) Self-Driving? see below General Overview Program and Abstracts in PDF download format Chobe Safari Lodge Weather Climate in Kasane, Vic Falls and N. Botswana Social Program - details Travel options Registration Information The Garden Lodge Charter Flights Afternoon Game Drives Venue Information Mowana Safari Lodge Immigration visa information Afternoon Chobe River Cruises How to PAY KASANE MARINA LODGE Hotel at Johannesburg International Airport Night Drives information only for first 80 registered delegates List of Registered Delegates Camping Tips and advice for travel to Botswana Nature Walk and Village Visit in Zambia limited to 16 people per day (long format Sunday) Abstracts Online Lodges in Kasane Location Map Tips Self-drive: Jo'burg Pretoria to Kasane Sunday - full day part day activities Submission of Abstracts Manuscripts NO Email facility Flight advisory if you plan to safari in Botwsana Safari Botswana - pre- and post-conference Safari Zimbabwe - pre-conference What to take on Safari? or your Lodge visits? Preparation of papers posters FLIGHT PLANNER - CHOBE 2001 to IUPS First aid and medical concerns? Important Dates 1) For dates and flight transfer information for International Theriological Congress, South Africa and IUPS, New Zealand - see bottom of page Pre Post-Conference Safaris no secured packages prior to 20% deposit 2) If you plan a pre or post-conference safari tour please consult the appropriate pages before reserving your flights Natural Events Safaris Registration Accommodation booking forms Registration wait list now open Registration Accommodation booking forms Registration wait list now open Charter Flight Reservation Form Full payment: June 1, 2001(April 26 by credit card) CLOSED - TICKETS ISSUED Game drives, Cruises Activities Information Booking Form Pre-booking CLOSED bookings on arrival To receive more information, contact the Executive Commitee at the address below. See you in Chobe! Executive Commitee Steve Morris (scientific programme and venue coordinator) School of Biological Sciences, University of Bristol, UK Steve.Morris@bristol.ac.uk Willie van Aardt and Andr Volsoo (local planning and organising) School of Environmental Science Development, Potchefstroom University for CHE, South Africa drkwjva@puknet.puk.ac.za drkav@puknet.puk.ac.za International Organising Panel Michael Castellini Aline Fiala Horst Felbeck Charles Gerday Moe Burg Hamid Habibi Klaus Hoffman Ian Hume Harvey Lillywhite Tom Miller Gnther Pass Bernd Pelster Berry Pinshow Hans-Otto Prtner Ken Storey Mike Thompson Ian van Tets Johan van Vuren Sjoerd Wendelaar Bonga Paul Yancey Snail mail enquiries to: Dr Andr Vosloo School of Environmental Sciences and Development (Zoology) Potchefstroom University for Christian Higher Education Private Bag X6001 Potchefstroom 2520 Republic of South Africa FAX: +27 18 299 2368 SPONSORS CORNER The Company of Biologists Ltd. The University of Bristol, UK Other Meetings IF YOU WOULD LIKE A LINK TO YOUR MEETING PLEASE EMAIL STEVE MORRIS SEB Annual main meeting, Canterbury, April 2-6, 2001 Zoological Society of Southern Africa Symposium 2001: A Southern African Odyssey University of Port Elizabeth, South Africa, 9-12 July, 2001 International Theriological Congress, S. Africa. 12-17, August 2001 Delegates attending the Theriological Congress will need to transfer to Chobe from Jo'burg on Saturday 18, August - the day after the ITC concludes. Please see section on Charter Flights IUPS 2001, Christchurch, New Zealand, 26-31, August 2001 Delegates attending the IUPS meeting in New Zealand will need to transfer to Jo'burg from Chobe on the afternoon of August 24, 2001and should book a connecting flight leaving Jo'burg that evening to arrive in New Zealand on the 25 August - the day before the IUPS, 2001 starts. If you plan a Pre-conference Safari please plan your flights carefully. Please see section on Charter Flights and on Pre-Conference Safaris FLIGHT PLANNER - CHOBE 2001 to IUPS ANZSCPB - Annual meeting, Adelaide University, Australia. 6-9 December 2001 4th Eurasian Congress on Raptors, Seville, Spain. 25-29 September 2001 The Roles of Experimental Biology in the Protection of Biodiversity and of the Control of Exotic Species, University of California, Los Angeles. 12-14 September , 2001 Note: 'around the world' flights represent large cost savings and from Jo'burg via Christchurch head for L.A. IUBS 6th ICCPB Australia-2003-Call for Symposia The Sixth International Congress of Comparative Physiology and Biochemistry will be held in Australia in early February 2003. The site we have chosen is The Mount Buller Campus of La Trobe University . The area is a ski resort in Winter and in summer provides bush walking,chair lifts, mountain cycling and many other sporting activities. It is an easy bus ride from Melbourne, but can also be reached from Sydney or Canberra. The Campus is located in the Victorian high country in an area of mountain ranges, snowgums and rivers. It is three hours from Melbourne and free from the hassles of down-town campuses. A range of accommodation from backpacker-style rooms to 4 star suites is available. Dining facilities also cover this range. Your proposal should be discussed with and submitted to the International Representative of your IUBS member society. In your IUBS symposia proposal, please include the following: 1. Title 2. List of speakers, and their approximate topics (about 5 in the final version). 3. Rationale for the focus and timeliness of the symposia 4. Contact information for symposia organizers Visitor Number since September 25, 1999 ICCPB Chobe, Botswana 2001; Main Page Info (6.1) Last revised: November 16, 2001 Page Maintained By: Steve Morris Steve.Morris@bristol.ac.uk http: www.bio.bris.ac.uk research smorris stevemorris.htm 2nd International Conference on Systems Biology Application of experimental, theoretical and modeling techniques to the study of biological organisms at all scales. Keynote speakers, schedule, presentation guidelines, registration form, and travel information. Pasadena, California, U.S. ICSB2001: The 2nd International Conference on Systems Biology .The Future of Biology in the 21st Century November 4-7, 2001 California Institute of Technology Order a copy of the Proceedings on-line! Keynote Speakers: Dr. Al Gilman, UT Southwestern, AFCS . Dr. David Botstein, Stanford University . Dr. Adam Arkin, UC Berkeley Session Speakers: R. Aebersold, ISB A. Murray, Harvard University U. Alon, Weizmann Institute M. Savageau, U Michigan D. Bray, Cambridge University B. Schoeberl, MIT P. Devreotes, Johns Hopkins L. Shapiro, Stanford University D. Eisenberg, UCLA J. Stelling, Max Panck Inst. J. Hofmeyr, Stellenbosch J. Stiles, PSC L. Hood, ISB S. Teichmann, MRC P. Iglesias, Johns Hopkins J. Tyson, Virginia Tech H. Kitano, Sony H. Westerhoff, Amsterdam D. Lauffenburger, MIT D. Wild, Keck Graduate Inst. T. Meyer, Stanford University S. Wodak, EBI E. Mjolsness, JPL . Session Topics: Signal Transduction . Cellular Physiology . Genomics . Experinemtal Technologies . Theory Computation Registration: Limited to 300 Poster Abstract Deadline: September 2, 2001 The ICSB2001 Organizing Committee is: Mel Simon California Institute of Technology John Doyle California Institute of Technology Hiroaki Kitano ERATO Kitano Symbiotic Systems Project, JST, and The Systems Biology Institute Premier Sponsors: AstraZeneca Leading Sponsors: Arcturus: Systems for Microgenomics Physiome Sciences Supporting Sponsors: Affymetrix Biacore Gene Network Sciences Inpharmatica Japan Science and Technology Corporation Lion Bioscience The Karolinska Institute in Stockholm, Sweden, will be the host for next year's ICSB2002 (the Third International Conference on Systems Biology) . We are seeking a host for 2003's conference; please refer to the call for site proposal (pdf) . top . 6th International Congress of Systematic and Evolutionary Biology Covers ten major themes relating to biodiversity in the information age. Scientific program, registration form, excursions and tours, list of committees, venue information, and tourist links. Patras, Greece. VI International Congress of Systematic and Evolutionary Biology This page uses frames, but your browser doesn't support them. 43rd International Conference on the Bioscience of Lipids Covering biochemical, biophysical, molecular biological and cell biological aspects of lipids. Contains program (scientific and social), presentation guidelines, online registration, tours, and general information. Graz, Austria. ICBL 2002 Graz - welcome Histology World Links, books, mnemonics and information about histology for undergraduate and graduate anatomy, medical, dental, and other health professional students. Includes reviews and recommendations. Histology-World! Histology-World! Home Histology CD Roms Histology Textbooks Histology Atlases Histology Review Books Histology Slide Shop Histology Greeting Cards Histology Art Histology Crosswords Histology Quiz Show Cool Histology Effects Histology Concentration Histology Hangman Histology Puzzles Histology Wordsearch Quotes Dumb Definitions Histology Trivia Daily Joke Audio Histology Slides Histology Quiz Master Histology Test Bank Histology Image Quiz Histology Word-of-the-Day Histology Slide Show Web Histology Quizzes Articles Shopping Guest Book Histology Links Histology Can be Fun? You bet! Watch an animated flash video intro, so you know just what kind of adventure you are in for here at Histology-World! Histology Quiz Show (1 , 2 ) , histology crosswords (1 , 2 , 3 ) and histology puzzles (1 , 2 , 3 ) are a great way to have fun with histology! How about playing a game of histology hangman or histology concentration right now? Or test your skill at a histology wordsearch game. You can see (and hear) some really cool histology effects that you can bet you won't see with a microscope! There are fun and humorous quotes and definitions relating to histology, anatomy and medicine. You can vote on an important histology issue. Read the daily joke about histology, anatomy and medicine. Come back from time to time since there are new histology mnemonics daily. If you like mnemonics, you can buy anatomy mnemonic merchandise . How about downloading a histology screensaver ? You can even send a virtual histology greeting card or real histology greeting card to all of your friends! Click here to add Histology-World! to your favorites so that you can come back often and explore! NEW!!! Listen to me describe histology slides Can I Learn Any Histology Here? Absolutely! Histology-World! is more than just histology fun and games. Listen to me discuss the key features of some histology slides . Improve your histology vocabulary every day with a histology word-of-the-day . Test your histology knowledge with random histology quiz questions in histology quiz master (1 , 2 ). Want more histology test questions? Then check out the multiple choice histology questions in the histology test bank . There is also a fun and educational histology image quiz . If you want even more histology quizzes, links to histology quizzes from all over the world-wide-web are brought together and sorted by category here. View the histology slide show full of beautiful histology slides. Read some interesting histology trivia . Histology can be tough; learn how to get an A in histology . There are recommendations and links for histology books , histology software , and histology atlases . You can read current articles about general health , health news , cancer , HIV , and hepatitis C . There are some general interest health articles posted here. There are also links to some other great histology sites (1 , 2 ) for you to explore. Help build Histology-World! Some of the histology artwork and histology images used on this site was anonymously donated and other histology images are from the Education Interactive, Human Histology Photo CD . Copyright 2005 Histology-World! All rights reserved. Histology - Biol 305 Includes class notes, course objectives and old exams. Also, has related resource links. Written by Craig S. Hood from Loyola University in Louisiana, USA. BIOLOGY 305 -- Histology Histology BIOL 305 A Biology Elective Course Dr. Craig S. Hood Department of Biological Sciences Monroe Rm 358 Office phone: 865-2193 Biology Office 865-2288 email: chood@loyno.edu Course Description This course seeks to lead the student to an understanding of the normal microscopic form and function of human tissues through lectures, discussions, and laboratories. The lab and lecture portions of the course are strongly integrated; the lab requires extensive microscope work and viewing of video-projected slides. For more information, link to the Course Syllabus . Course materials and assignments Class Notes from your instructor Lecture Objectives (to study and prep for exams) Laboratory Objectives (to study prep for practicals) Old exams Web sites to explore ! ! The Tree of Life Evolution Entrance at Berkeley Smithsonian Natural History Museum Links for Study of Evolution Animal WWW links Other Organisms Last updated February 12th, 1998 Send me a message concerning the class or this page = chood@loyno.edu Return to Biological Sciences Department Home Page Return to Arts Sciences Departmental Home Pages List Vanderbilt University Medical School Cell and Tissue Biology Lesson plans for blood, epithelium, nervous tissues, salivary glands, and exocrine pancreas tissues. Cell Biology Spring, 2005 Course Information Home Introduction Course Director Grades Evaluation Method Time And Location Course Materials Faculty Listing Dr. Cathleen Pettepher Dr. Wayne Lambert Dr. Lillian Nanney Dr. Art Dalley Dr. Roy Zent Dr. Jay Jerome Lecture Schedule Calendar Lecture Notes List of Topics Powerpoint Files Word Files Internet Resources Helpful Sites Interactive Atlas Update Lecture Comments Handout Corrections Tools Image Console (Log in required!) mammary3 A higher magnification light micrograph of a terminal duct-lobular units (TDLU) within the breast tissue of a non-pregnant women of reproductive age. The extensive branching duct system is surrounded by relatively dense fibrous interlobular tissue. The translucent spaces surrounded the extensive arborization of the duct system of the breast is the loose connective tissue, which immediately surrounds these branches. Webmaster | Contact Course Director | Comments | Disclaimer Martindale's Health Science Guide: Anatomy Histology Center Histology section includes exams, courses, techniques and procedures, and tissue preservation resources. Martindale's Anatomy Histology Center MARTINDALE'S THE "VIRTUAL" ~ MEDICAL CENTER ANATOMY HISTOLOGY CENTER US Pacific: Wednesday, November 16, 2005 Sydney, Australia: Thursday, November 17, 2005 File Download Time Calculator World Daily Reports (Weather, Time, Ships, Ports, Museums, Orchestras etc.) Author, E-Mail, Privacy Policy Disclaimer ANATOMY ATLASES, COURSES, IMAGE DATABASES, TEACHING FILES, MOVIES EMBRYOLOGY REPRODUCTION DEVELOPMENTAL ANATOMY Reproduction ~ Embryology ANATOMY Anatomy Dictionaries Glossaries Basic Interactive Anatomy Browsers: Ages 5 to 135 Intermediate Advance Interactive Anatomy Browsers Anatomy Atlases Image Databases Anatomy Courses Image Databases Combined Anatomy Teaching Modules, Lectures Image Databases Combined Anatomy the Aging Process Radiology Anatomy ~ Osteology ANATOMY EXAMS Gross Anatomy ~ Brain Skull ~ Neuroanatomy Anatomy Dissection Laboratory Step-by-Step Whole Body Anatomy Dissection (Pathology Center) Neuroanatomy (Brain Neuro Center) Anatomy Associations ANATOMY ATLASES, COURSES, IMAGE DATABASES, TEACHING FILES, MOVIES BY SUBJECT ANATOMY BY SUBJECT: SECTION I ABDOMEN - DIGESTIVE SYSTEM (Kidney, Liver, Stomach Spleen, Colonoscopy, Endoscopy) BRAIN BRAINSTEM ~ BREAST ~ CHEST, CARDIOTHORACIC ANATOMY BY SUBJECT: SECTION II ENT (Head Neck Ear - Cochlear Fluids, Hearing Balance Larynx - Vocal Chords Nose Paranasal Sinuses - Smell - Olfaction Taste - Gustation) EYE ENDOCRINE SYSTEM (Hypothalamus, Pituitary, Thyroid) MUSCLE, MUSCULOSKELETAL ~ FOOT ANKLE ~ KNEE ~ SPINAL CORD ORAL TEMPOROMANDIBULAR JOINT ~ SKIN HISTOLOGY MICROANATOMY ATLASES, COURSES, IMAGE DATABASES, TEACHING FILES, MOVIES HISTOLOGY MICROANATOMY Dental Histology ~ Medical Histology Microanatomy Dental Medical Histology Exams ~ Histology Associations LABORATORY DIAGNOSTICS PROTOCOLS LABORATORY DIAGNOSTICS Clinical Lab Tests, Pathology Laboratory Tests, Diagnostic Techniques Procedures, Lab Techniques Genetic Laboratory Tests ~ Neuromuscular Laboratory Testing Medical Tests (Infants, Children Adults): Consumers Patient Education CHEMISTRY LABORATORY TECHNIQUES CHEMICAL EXPERIMENTS BIO LABORATORY PROTOCOLS, METHODS TECHNIQUES Apoptosis Protocols ~ Histology Protocols, Methods Techniques HPLC, HPLC Columns, Spin Columns, Electrophoresis Gels Microbiological Methods: Microbiological Analyses of Foods Cosmetics Microfluidics: Lab-on-a-Chip Technology Molecular Biology Protocols C. elegans Protocals MICROSCOPY TECHNIQUES PROTOCOLS Microscopy, Photomicrography Digital Imaging Techniques Transmission Electron Microscopy TEM, Cryosectioning, Immunocytochemistry, etc. Chemistry Center - Analytical Chemistry ~ Chemistry Calculators Center ANATOMY HISTOLOGY OVERVIEW Virtual Hospital's Complete Curriculum ~ Medical Schools Complete Curriculum Medical Dental Dictionaries ~ Literature Search ~ Medical Calculators ~ Radiation Calculations Language Dictionaries Translation ~ Patents, Trademark Copyright Chemical Biochemical Databases ~ Periodic Tables Laboratory Diagnostics Protocols ~ Chemical Biochemical Safety Guidelines International Travel, Passport Information, World Disease Outbreaks Immunization Guidelines for Medical Information ~ Human Subjects Guidelines ~ Medical Conferences Doctors Physicians ~ Dentist, Orthodontist, Oral Maxillofacial Surgeons Clinical Trials ~ CME ~ Hospital Beds Available ~ Hospitals World Wide Blood Groups, Blood Chemistry, Blood Banks Transfusion Health Science Guide ~ Medical Center Home Page E-Mail Jim Martindale Copyright 1994-2005, All Rights Reserved, Jim Martindale The Biological Stain Commission Quality control organization for biological dyes and stains. Publications, services, histology links, and protocols are provided. The Biological Stain Commission Welcome to the official Web Site of the Biological Stain Commission The BSC will be Sponsoring the International Lecture at the NSH Meeting - click here for more info. USE THE "FAVORITES" ICON ON YOUR BROWSER TO MAKE THIS WEBSITE READILY AVAILABLE TO YOU IN THE FUTURE. Test your knowledge. Identify the sections and the stain at the bottom of each page.Click on picture to see larger view, then use your browsers back button. Image 1 Solutions are provided by clicking here [Home] [ Services ] [ CertifiedStains ] [ PublicationsoftheBSC ] [ Solutions ] [ Links ] [ AnnualConference ] [ AbouttheBSC ] Webmaster: mfrank@biostains.org This page was last modified 08 10 05. Histology on the WWW Contains links to sites with images, protocols and techniques, and general histology resources. Histology Techniques (Microscopy Imaging, Cellular Imaging Core, SWEHSC) SWEHSC Facility Cores Cellular Imaging Microscopy Imaging Resources on the WWW Histology See also: Fluorescence Techniques , Light Microscopy This page: Histo-technique , Immuno Histo Cyto-chemistry , Internet Resources , On-line Images , Safety , Menu General Histo-technique Histotechnology Tutorials If you are unfamiliar with the practice of histotechnology, this is an excellent place to start. This series of pages includes a tutorial on general Histotechnique (fixation, tissue processing, sectioning, general staining and slide making information), Special Stains (listed by what types of molecules tissues that they stain) and examples from their Procedure manuals (note: you will need the free Adobe Acrobat reader to view the procedure manuals). (WebPath, University of Utah, College of Medicine) Histopathology Laboratory Protocols This site has a wealth of technical information about histologic technique.(The University of Nottingham and the Queens Medical Centre, United Kingdom). Histologic Special Stains Using a Microwave This page written by Joyce Moore, of the Jefferson Regional Medical Center Histo-Path Laboratories, outlines the use of Microwaves in histologic staining. Other interesting pages at this site (WWW site courtesy of EBSciences): Microwave Antigen Retrieval Technique , Working Procedures in Microwave Histology and Microwave Processing Techniques for Microscopy Histology . Laboratory Protocols An excellent resource with information about: cryostat sectioning , histologic fixatives , histologic stains , peroxidase techniques , treating slides for "stickiness" , tissue processing and specimen collection (Veterinary Pathology, University of Bristol, UK). Protocols On-Line - Immunology Histological Techniques StainsFile: A Resource for Histotechnologists This site, developed by Bryan D. Llewellyn, is primarily about histologic staining techniques and dyes. The Histology Page Includes extracts from Woods and Ellis, "Laboratory Histopathology: A Complete Reference" (1994 Churchill Livingstone). Topics include: Cryotechniques , Fixation , Haematoxylin and Counterstains , Microtomy , Mountants , Resin Processing and Tissue Processing . Techniques Manual From the House Ear Institute (Paul Webster, Ph.D.). This site has electron microscopy techniques as well as cytochemical and immuno staining techniques. Tissue Preparation for Histology: The WWW pages Use and Misuse of Formaldehyde Fixatives and Bouins Fixatives were developed for this site in response to some local concerns. Immuno Histo Cyto-chemistry Immunohistochemistry Home Page A listing of immunohistochemistry resources on the Internet (Mahmood Aijazi, MD). Another resource is the Immunohistochemistry page of Roy Ellis, which includes suggestions for control tissues for different stains and a sample protocol that is in an ISO 9000 compliant format. Journal of Histochemistry Cytochemistry "The official Journal of the Histochemical Society, publishes papers that report the development of new histochemical and cytochemical methods, significant modifications of existing techniques, or original research in which histochemical and cytochemical methods make a significant contribution." Many excellent full-text articles are available on-line. Fluorescence Techniques A web resource from this site with information about fluorescent dyes, antibodies and sample preparation. Miscellaneous Protocol Resource Sites BioVisa.net - Cell Biology Microscopy Histochemistry Cell Labeling BioVisa.net - Biotechnology In-situ hybridization Silverman Lab protocols (Children's Hospital, Boston) NIEHS Laboratory of Experimental Pathology - Immunohistochemistry , In-Situ ImmunoPortal.com - Immunohistochemistry In-Situ Hybridization (Hogne Red Nilsen) Internet Resources The HistoTech's Home Page This list of Internet resources is intended to be used as a browser home page for Histotechnologists. (The National Society for Histotechnology) HistoNet listserver Scroll down this page to read the description of this email discussion forum for histotechnique (MicroWorld Resources). Visit this site to search the Archives of the HistoNet Listserver . Histology Glossary An on-line glossary of terms used to describe histologically prepared specimens (Eric Shelden). Anatomy Histology Center - Martindale's Health Science Guide A collaborative effort of Jim Martindale and the University of California, Irvine (among others). This is an incredible compilation of links to histology anatomy resources, as well as other biological links and some terrific general science reference material links. WebPath The Internet Pathology Laboratory for Medical Education (University of Utah, College of Medicine) Images of Tissues prepared for Histology LUMEN: Histology Index This site is part of the Loyola University Medical Education Network (LUMEN). Kansas "JayDoc" HistoWeb From the Department of Anatomy Cell Biology, University of Kansas. University of Delaware - Mammalian Histology course Includes images from histologic sections, electron microscopy, diagrams and 3D models. Other Good General Histology Sites with Images: University of Michigan - Histology course University of Western Australia - Histology Human Anatomy University of Illinois - Internet Atlas of Histology University of California at Davis - Human Microscopic Anatomy Integrated Medical Curriculum - Histology (registration required) University of Arkansas - Microanatomy Web Atlas University of Southern California - General Histology, a digital atlas University of Texas at Houston - Histology Review Carousels University of Pennsylvania - Veterinary Histology Indiana University - PERLjam Histology Good sites for Images of specific tissues: "The Whole Brain Atlas" - Harvard University DERMIS - Dermatology On-line Atlas Blood Morphology - University of Washington Safety Repetitive Strain Disorders Some general background information on this problem (Leica Microsystems Nussloch GmbH). The Vermont SIRI MSDS archive If you can't locate the Material Safety Data Sheet that came with a particular product, this is a good place to start. Other MSDS resources include: MSDS Solutions.com and the Cornell University MSDS database . Occupational Safety Health Administration (OSHA, USA): Laboratory Safety , Bloodborne Pathogens , Ionizing Radiation , Ergonomics Links to other resources Microscopy Imaging Resources on the WWW... -- Interesting and Educational K-12 Educational Resources Sites with Microscope Images -- Microscopy General Microscopy Free Microscopy-related Publications Light Microscopy Histology Confocal Microscopy Fluorescence Techniques Electron Microscopy -- Digital Imaging Introduction to Digital Images Hardware (cameras, scanners, printers) Software (commercial, freeware) Digital Imaging Ethics Other Sections... -- Information about the Core -- Educational Informational Materials SWEHSC user's QUICK LINKS page Cellular Imaging Core SWEHSC Center for Toxicology University of Arizona TOP Douglas W. Cromey, M.S. Manager, SWEHSC Cellular Imaging Core Office: AHSC 4212 Voice: 520-626-2824 FAX: 520-626-2097 Email: Cromey@Arizona.edu Funded by NIEHS grant ES06694 1996-2005, The University of Arizona Last update: March 11, 2005 Page Content: Doug Cromey Web Master: Mike Kopplin Internet Atlas of Histology More than 1000 labeled images, with descriptions, practice labs, and quizzes. Created by the UIUC College of Medicine. Internet Atlas of Histology, College of Medicine, University of Illinois at Urbana-Champaign College of Medicine University of Illinois at Urbana-Champaign Internet Atlas of Histology, COM-UIUC Welcome! The COM-UIUC Histology web site contains an extensive set of histological specimens, featuring the excellent COM-UIUC collection of plastic sections prepared by Aulikki Kokko-Cunningham, M.D. The web interface permits you to quickly change magnification to examine areas of interest in great detail. There are over 1000 labeled histological features with accompanying functional descriptions. All of this material can be accessed efficiently using an object index or a search page. If you haven't visited this site before, a good place to start is the "Atlas Demo". Guided tours through many Atlas specimens and self-assessment quizzes are also available. Atlas Demo Brief tutorial introducing the Atlas web interface... Slides List of links to all of the specimens, brief specimen discriptions... Objects List of links to all labeled histological features, brief functional descriptions... Search Search engine for slides, histological features, and associated descriptions... UIUC-COM Histology Home Page Guided tours through the Atlas, self-assessment quizzes... Contributors UC-Davis Human Microscopic Anatomy Thorough atlas with hyperlinked notes and slides, as well as good organ reviews by slides, study set of slides, and sample quizzes. HISTOLOGY HISTOLOGY'S NEW WEBSITE Home | Courses | Calendar | Curriculum About OCS | Academic Programs | Search Links UC Davis Health System | 1999 UC Regents. All rights reserved. Histology Technical Methods An alphabetical protocol index. Histology Lab: PROTOCOL INDEX Histotechnology Technical methods ALPHABETIC INDEX Methods Index Pathology Homepage PROTOCOL INDEX Welcome and Introduction protocols 10% FORMAL SALINE 3-AMINOPROPYLTRIETHOXYSILANE TREATED SLIDES 4% PARAFORMALDEHYDE ACETYL CHOLINESTERASE ACID PHOSPHATASE ACID PICRO MALLORY ADENOSINE TRIPHOSPHATASE (ATPASE) ALCIAN BLUE TECHNIQUE ALKALINE CONGO RED TECHNIQUE ALKALINE PHOSPHATASE (APAAP) TECHNIQUE ALKALINE PHOSPHATASE BIELSCHOWSKY METHOD CARAZZI'S HAEMATOXYLIN CELESTINE BLUE SOLUTION CHROME GELATINISED SLIDES AND COVERSLIPS COMBINED ALCIAN BLUE - P.A.S CRESYL FAST VIOLET TECHNIQUE FOR NISSL CRESYL FAST VIOLET CROSS-PALMGRENS METHOD CYTOCHROME OXIDASE TECHNIQUE DECALCIFICATION E.P.S.R. ELASTIC VAN GIESON (EVG) FEULGEN REACTION FOR DNA FORMALDEHYDE PRECAUTIONS FOUCHET METHOD GALLYAS TECHNIQUE GIEMSA FOR Helicobacter pylori GILLS HAEMATOXYLIN GIMENEZ STAIN GLUTARALDEHYDE GOMORI TRICHROME GORDON AND SWEETS RETICULIN METHOD GRAM STAIN GRIMELIUS HAEMATOXYLIN AND EOSIN TECHNIQUE HAEMATOXYLIN VAN GIESON HAGA-YAMAGCHI METHENAMINE SILVER TECHNIQUE HARRIS'S HAEMATOXYLIN HIGH IRON DIAMINE HIGHMANS CONGO RED INDIRECT PEROXIDASE TECHNIQUE Fixed tissue INDIRECT PEROXIDASE TECHNIQUE JONES METHENAMINE SILVER LACTASE LEUCINE-AMINO PEPTIDASE M.S.B TECHNIQUE MASSON FONTANA MASSON FONTANA MASSONS TRICHOME MAY GRUNWALD - GIEMSA MELANIN BLEACH METHENAMINE SILVER FOR FUNGI METHYL GREEN PYRONIN MILLERS ELASTIC STAIN Mount sections in aqueous mountant Mount sections in DPX MYODENYLATE DEAMINASE NADH DIAPHORASE NON-SPECIFIC ESTERASE OIL RED O PAPANICOLAOU METHOD PERIODIC ACID SCHIFFS ORANGE G PERIODIC ACID, SCHIFFS PERLS TECHNIQUE PEROXIDASE - ANTI - PEROXIDASE TECHNIQUE PHLOXINE TARTRAZINE PHOSPHORYLASE PHOSPHOTUNGSTIC ACID HAEMATOXYLIN POLY-L-LYSINE COATED SLIDES REMOVAL OF FORMALIN PIGMENT RESIN EMBEDDING FOR HIGH RESOLUTION MORPHOLOGY RESIN PROCESSING OF BONE RESIN STAINING METHODS RUBEANIC ACID TECHNIQUE SCHMORL TECHNIQUE SECTIONING RESIN EMBEDDED TISSUE SHIKATA TECHNIQUE SOLOCHROME CYANIN TECHNIQUE SOUTHGATES MUCICARMINE STAIN FOR ACID FAST BACILLI STAINING RESIN SECTIONS OF BONE SUCCINATE DEHYDROGENASE SUCRASE THE AVIDIN BIOTIN (ABC) TECHNIQUE TOLUIDINE BLUE IN SORENSONS pH 6.8 BUFFER TOLUIDINE BLUE TRYPSIN DIGESTION VAN GIESON VON KOSSA WARTHIN - STARRY WEIL'S MYELIN STAIN NOTE: No responsibility is assumed by The University of Nottingham or the Queens Medical Centre NHS Trust for any injury and or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions or ideas contained in the material herein. It is the users responsibilty to ensure that all procedures are carried out according to appropriate Health and Safety requirements. Copyright 1997 University of Nottingham Medical School Division of Histopathology. This page was last built on Tue, May 6, 1997 with Frontier . Thanks for looking in. Comments to James.Lowe@nottingham.ac.uk JayDoc HistoWeb A comprehensive histology atlas from the Kansas University Medical Center. JayDoc HistoWeb This web page uses frames, but your browser doesn't support them. Download the latest version of Netscape to take advantage of frames and the JayDoc Histoweb LUMEN Histology Lesson plans with slides and practicals for the Loyola University Medical Education Network histology course. LUMEN Histology home page Histology Zoomified Histology Cell and Molecular Biology Lessons Part 1: Epithelium and Simple Glands Practical 1A Practical 1B Part 2: Stains, Cells, and Ultrastructure (EM) Practical 2A Practical 2B Part 3: Connective Tissue Proper Practical 3A Practical 3B Part 4: Connective Tissue Cells Practical 4A Practical 4B Part 9: Specialized Connective Tissue - Cartilage and Bone Practical 9A Practical 9B Part 10: Endochondral Ossification Practical 10A Practical 10B Part 13: Skin (Integument) and Tongue Practical 13A Practical 13B Host Defense Lessons Part 11: Bone Marrow and Hemopoiesis Practical 11A Practical 11B Part 12: Lymphoid Tissues and Organs Practical 12A Practical 12B Function of the Human Body Lessons Part 5: Blood and Capillaries Practical 5A Practical 5B Part 6: Neural Tissue Practical 6A Practical 6B Part 7: Muscle Practical 7A Practical 7B Part 8: Cardiovascular System Practical 8A Practical 8B Part 14: Endocrine Glands Practical 14A Practical 14B Part 15: Respiratory Tract Practical 15A Practical 15B Part 16: Urinary Tract - Kidney Practical 16A Practical 16B Part 17: Gastrointestinal Tract Practical 17A Practical 17B Part 18: Gastrointestinal Mucosa and Cells Practical 18A Practical 18B Part 19: Major Digestive Glands - Liver, Salivaries, and Pancreas Practical 19A Practical 19B Part 20: Male Reproductive Tract Practical 20A Practical 20B Part 21: Female Reproductive Tract - Ovary, Oviduct, and Uterus Practical 21A Practical 21B Part 22: Female Reproductive Tract - Cervix, Vagina, Umbilical Cord, Placenta, and Mammary Gland Practical 22A Practical 22B Neural Tissue Histology on the Internet LUMEN SEARCH 1998 Loyola University Chicago Stritch School of Medicine. Allrights reserved. Please send questions or comments to: John A. McNulty, Ph.D. Updated: Jan 23, 2005 Created: Aug 1, 1995 University of Pennsylvania Histology Homepage Slides arranged by tissue or organ types, for non-human mammals and birds. From School of Veterinary Medicine. Histology Homepage View by Tissues(labs 1-11) View by Organ Systems(labs 12-23) Mission statement: This section is a compendium of images from the histology lab sessions. Since they were made from the some of the same kodachromes that were used to make the Color Atlas of Veterinary Histology (Bacha, Wood), many of the images will be the same as seen in the book. It is organized by labs and easy to quickly navigate through, providing a quick and easy reference to the images presented in lab. Credit goes to Dr. Patricia McManus of the University of PA School of Vet. Med. for the slides in the mammalian avian blood and bone marrow sections. Some pages require the use of the quicktime plug-in . Digital Atlas of Histology Brazilian atlas with high resolution microscopic images, designed for bimedical students and professionals. Welcome to the DIGITAL ATLAS OF HISTOLOGY Verso portugus Welcome to the DIGITAL ATLAS OF HISTOLOGY !!!! This ATLAS was elaborated to professionals, scientists, students and for every one who loves Histology. It is being developed by the Laboratory of Microscopy and Image Processing, department of Histology - UERJ, and it is free. The ATLAS is constantly renewed and upgraded , receiving new images and texts. In few months we will release a new image database in Cellular Biology, Embryology and Anatomy, and we will add new tips about books and web pages that present correlated subjects. In order to inform about changes, upgrades and to receive your suggestion, we would like to invite you to fulfill the formulary, before surf the ATLAS. It will not take more than 2 minutes, and the information posted will be used only for our academic purposes. Many thanks. Sincerely, Prof. Luiz Henrique Monteiro Leal FULLFILL OUR ELECTRONIC FORMULARY IF YOU HAVE ALREADY FULFILLED THE FORMULARY, CLICK HERE TO ENTER. National Society for Histotechnology Incorporated in 1974 for the purpose of advancing professional growth, standards, knowledge and performance of histotechnology through continuing and formal education programs. NSH Home NSH Home National Society for Histotechnology 4201 Northview Drive Suite 502 Bowie, MD 20716-2604 phone: 301-262-6221 fax: 301-262-9188 e-mail: histo@nsh.org WELCOME TO NSH The National Society for Histotechnology is a non-profit organization, committed to the advancement of histotechnology, its practitioners and quality standards of practice through leadership, education and advocacy. The NSH web site serves as a valuable resource for activities of the Society.Access the various links--there is a wealth of knowledge at your fingertips! NEWS RELEASES Save Funding for Medical Technology Programs As the Federal government's fiscal year comes to an end, Congress will begin to issue a series of Continuing Resolutions or CRs. In the current proposed CR, funding amounts are being determined based on the lower of two amounts suggested by either the House or Senate in FY'06 appropriations legislation. Title VII allied health professions training programs provide funding for the establishment, maintenance or expansion of medical technology programs. Once again, virtually all federal funding for Title VII allied health professions programs have been eliminated. We need your help in getting funding restored for these essential programs. Please take action today and urge your Senators to work with House appropriators to restore funding for these essential programs. If you have suggestions or questions about the NSH or its activities, please feel free to contact the National Office , the Officers or Directors CALL FOR NOMINATIONS We all know them. colleagues and peers who strive to make a difference in the histology profession. These people are talented, dedicated and their enthusiasm is infectious. They are passionate about NSH and histotechnology. T hrough your nominations, we can continue the tradition of leadership that has helped position NSH as the top organization for the profession of histotechnology. Nominate yourself or someone you know today! University of Delaware Mammalian Histology Course syllabus and class resources, including microscopic images, ultrastructural images, 3-D models, and labelled diagrams. UDHISTOLOGY Mammalian Histology-B408 Department of Biological Sciences University of Delaware Mammalian Histology (B408) is taught in the fall semester annually and is one of the courses required for the Medical Scholars Program with the Jefferson Medical College. Consequently, it is taught at a comprehensive level and concentrates heavily on human tissues and organ systems. A strong component of this course is tissue structure at the ultrastructural level and how it relates to structure-functional relationships at the light microscopic level. A sizeable collection of color light microscopic images as well as black and white electron microscopic images have been archived and can be accessed by links with this home page. These images files have been produced by: Dr. Roger C. Wagner Professor of Biological Sciences University of Delaware 28499@udel.edu Dr. Fred E. Hossler Professor of Anatomy and Cell Biology East Tennessee State University College of Medicine This page was constructed by Anuj Parikh , MSP class of 1998. In addition, labeled illustrations used in lecture have been digitized and may be used for study purposes. Three dimensional models are often useful for understanding the volume structure represented by two dimensional images and several of these are also linked to this page. Click here for COURSE SYLLABUS and LABORATORY GUIDE WAGNER-HOSSLER MICROSCOPIC ANATOMY IMAGES Color Histology Images Color (8-bit) gif files of light microscopic images are archived according to tissue type and organ systems. The majority of these are stained with hematoxylin and eosin but in several cases more specialized stains are employed. Index pages and files can be accessed by clicking on red button above. Compressed Histology Images This is an archive of compressed histology images that can be examined as though the viewer were using a microscope. These high resolution images have been compressed without loss of image resolution, resulting in faster downloading times and excellent quality. Cell and Tissue Ultrastructure Transmission and scanning electron micrographs are archived as 8 bit grey-scale images and are listed according to tissue type and organ system. These are meant to compliment the light microscopic images and reveal structural detail not observable by light microscopy. Labeled Illustrations Digitized images of overheads of labed illustrations used in lectures are listed according to lecture schedule and can be broused for study purposes. Three Dimensional Models Three dimensional models of tissue and cell structures have been constructed and rendered to provide realistic interpretations of volume structures not evident in two dimensional tissue sections. Links to microscopic anatomy pages on the WWW: Histology World This page last updated Today. Laboratory of Histology and Embryology Research focusing on histology, cell biology, microscopy, neurobiology, and stereology. From the University of Oporto, Portugal. Lab Histology and Embryology - ICBAS Free Web Hosting Provider - Web Hosting - E-commerce - High Speed Internet - Free Web Page - Photo Sharing Popular Searches: LAB. HISTOLOGY AND EMBRYOLOGY - DEP. MICROSCOPY Institute of Biomedical Sciences Abel Salazar (ICBAS), Lg. Prof. Abel Slazar no. 2, 4099-003 Porto, Portugal Phone: 351 22 206 22 54 20 Fax: 351 22 206 22 32 E-mail history This Laboratory was oficially founded along with the ICBAS itself, back in 1975. The first Head of the Lab. was Dr. Daniel Furtado da Silva (MD), up to 1983. From this date, the Head has been Prof. Dr. Rogrio Monteiro (MD, PhD), who currently holds the position of Full Professor. Our Laboratory, together with the Cell Biology Lab. and the Cytogenetics Lab., make the "Department of Microscopy". The available facilities and equipment allow studies in the fields of light and transmission electron microscopy, including immunocytochemistry, as well as molecular biology techniques (such as PCR and Northern blot). Hardware and software for performing 3D reconstructions form serial images, image analysis and design-based stereology is also available. Cell culture and karyotype analysis is routinely made in the Department. teaching and technical staff working at the laboratory 1. Rogrio A.F. Monteiro, MD, PhD Chair of the Histology courses for medical and veterinary students. 2. Eduardo Rocha, PhD Chair of "Comparative Histology and Embryology" course for biologists. 3. Daniel Silva, MD 4. Ricardo Marcos, DVM 5. Maria H. Oliveira, Principal Histotechnician 6. Fernanda C. Malho, Histotechnician 7. Ndia Santos, Histotechnician Supporting teacher (from the aquatic health laboratory) 1. Pedro Rodrigues, MSc, PhD current Chair of the "Imunology and Health" course for aquatic science students. histological services We provide internal and external services upon specific request, being the payment for external directly made to the ICBAS treasure Department: 1. Light microscopy - processing tissue to paraffin blocks, sectioning, staining with HE or with several special stains; 2. Electron microscopy - processing tissue to epoxy blocks, semithin and ultrathin sectioning, contrasting with UALC; 3. Histology collections - we sell some sets a year of high quality slides for study, upon previous request and agreement; 4. Cytology services (animal ctyologies) - processing of cells and fluids and consequent veterinary diagnosis. teaching activities We teach histology and embryology to students of the following graduations of our Institute: Medicine, Veterinary Medicine and Aquatic Sciences. We give several courses within the academic year (4h week per course). "Comparative Histology and Embryology I and II" is given in to Aquatic Sciences studentes, "Human Histology and Embryology" for Medicine students, and "Animal Histology and Embryology I and II" for Veterinary students. Students attend classical, but very interactive, plenary lectures, along with lab sessions for observation and discussion of both slides and projected images. Teaching based on group discussion, presentations, and problem-solving, are implemented together with classical training. We are continuously building a supporting WEBPAGE (in portuguese) giving relevant information and aimed to be a forum. research activities The research lines that are being developed at this time are concerned with: 1. Sequencing and expression of brown trout PPARs (peroxisome proliferator activated receptors). Study of organ and gender nuances. 2. Seasonal, temperature and gender-related influences on the structure of the liver of brown trout and tilapia. 3. Estrogenic effects over some structural and functional aspects of brown trout liver, namely hepatocytic peroxisomes. 4. Quantitative morphology of the Ito cells and Hepatocytes of the rat liver, taking into account lobular heterogeneity. 5. Stereological evaluation of the ageing effects in the rat cerebellum, both on neurons and glial cells. 6. Stereological and immunocytochemical characterization of cow aspirated cumulus-oocyte complexes to be used in vitro. 7. Gill qualitative and quantitative histopathology under waterborne influence, using tilapia as a model organism. researchers with whom there are currently research collaborations 1. Alexandre Lobo da Cunha, PhD (Lab. Cell Biology) 2. Mrio Sousa, MD, PhD (Lab. Cell Biology) 3. Maria Joo Rocha, PhD ( CESPU ) 4. Pedro Rodrigues, PhD (Lab. Aquatic Health) 5. Pedro Monteiro, PhD ( IBMC ) 6. Rui MF Henrique, MD (Institute of Oncology - Porto) research students curretly working at the Laboratory 1. Albina Dolores Resende (PhD Student) 2. Carla Batista Pinto (PhD Student) 3. Figueiredo Fernandes (PhD Student) 4. Ana Calado (PhD Student) 5. Mariza (PhD Student) 6. Maja Jordanova (PhD Student) 7. Joo Carrola (MSc Student) 8. Eva (BSc Thesis) links 1. Home Page 2. Histology Stuff 3. Students' Page 4. Science in Portugal International Society for the History, Philosophy, and Social Studies of Biology (ISHPSSB) The Society sponsors an annual meeting, a listserv, and semiannual newsletters, and offers educational resources and a beginner's guide for research in the history of biology. ISHPSSB Home Officers By-Laws Meetings Program Membership Journal Newsletter Listserv Committees Student Bulletin Board Prizes Operations Handbook Archives Site map Educational Resources Links The International Society for History, Philosophy, and Social Studies of Biology (ISHPSSB) brings together scholars from diverse disciplines, including the life sciences as well as history, philosophy, and social studies of science. ISHPSSB summer meetings are known for innovative, transdisciplinary sessions, and for fostering informal, co-operative exchanges and on-going collaborations. What's New: A message from our president, Gar Allen, concerning a potential Journal affiliation. Recent student announcements Student Rep: Meet the Candidates 2005 Marjorie Grene Prize 2005 MEETING GUELPH, ONTARIO Many thanks to our host David Castle, the University of Guelph and everyone involved for organising a splendid meeting last summer. For more information about the meeting, please visit the Meetings page. This site is maintained by Frdric Bouchard . Historica Botanica Miscellany, reference information and research concerning the history of botany. Web historicabotanica.blogspot.com Historica Botanica BlogThis! Historica Botanica Dedicated to information and material related to the history of botany particularly in the 19th and 20th century English speaking world. If you have contributions of interest to post, please contact me at the email address on the left of this page. Saturday, June 04, 2005 Link to Brief Biographies of Botanists Click HERE for a link to some botanical biographical notes. posted by Dan @ 11:33 AM 0 comments Sunday, April 03, 2005 New Link Added I have just added a link (left side of this page- at the top of the column titled " Some Sites of Interest " ) to Cornell University's Plant Pathology Herbarium Photograph Collection. Their collection has some wonderful historical images, and is well worth viewing. posted by Dan @ 12:01 PM 0 comments Monday, March 14, 2005 Number 13 - Name That Botanist By Childe Hassam, 1892 Here is a little twist on the "Name That Botanist" series I've been offering. This 1892 Childe Hassam painting illustrates the mother of a botanist in her garden on Appledore Island (Isles of Shoals), off the coast of Maine. She was an important American poet, and is the subject of a most interesting webpage concerning her style of dress in a circa 1858 CDV at which time she may have been pregnant with the botanist in question. Our fellow was born in Newton, Massachusetts. His mother was born in Portsmouth, New Hampshire. She is the subject of many webpages . Click here to see a 1919 letter from her son to University of Connecticut botanist George Safford Torrey . The letter mentions the Entomophthora, a favorite group of our subject. He also was expert on the Laboulbeniales. He studied at Harvard under William Gilson Farlow, and after a brief sojourn in plant pathology at the University of Connecticut returned to the Harvard faculty in 1891. This letter was written during his first year of retirement from the active faculty at Harvard, and displays his new title of "Professor-Emeritus and Honorary Curator of the Herbarium and Laboratories of Cryptogamic Botany". He has been called the greatest mycologist of his time ( Mycologia 25:69-89, 1933 ). This seems to be an example of hereditary excellence - by no means a unique case in the botanical world (DeCandolle, Michaux, Hooker, Bessey, Eaton, J.W. Bailey, to name but a few); although the fact that their high achievements were in such different disciplines is unusual. Click here for some additional biographical information and a photograph. posted by Dan @ 7:11 PM 0 comments Sunday, February 20, 2005 COMING SOON! - The Beck Brothers of Schenectady Soon to be posted: A look at the 19th Century scientific Beck brothers of Schenectady, New York John Brodhead Beck Lewis Beck Theodric Romeyn Beck Keep an eye on Historica Botanica! posted by Dan @ 5:52 PM 0 comments Number 12 - Name That Botanist Click on image to enlarge This albumen carte-de-visite is attributed to New York photographer A.W. Jordan. The sitting can probably be dated to the early 1870s, the decade during which he flourished, and near the end of the life (1796-1873) of the subject- illustrious American botanist, Professor of Chemistry, and Assayer of the U.S. Mint. Click HERE for the ID posted by Dan @ 5:06 PM 0 comments Thursday, January 27, 2005 Number 11 - Name That Botanist Click on image to enlarge This English mycologist, cleric, and Fellow of the Royal Society has here been photographed circa 1865. Born on April 1, 1803, he died July 30, 1889. He described the fungi of the Wilkes Expedition, the H.M.S. Challenger, Charles Wright's North Pacific Exploring Expedition, Darwin's Beagle voyage, and many more from South America, the Arctic, Australia, Africa and every corner of the globe. He has left us a large body of published work. If you haven't already solved it, perhaps you can match him up with his photo of some 20 years later, shown on the " CYBER-TRUFFLE'S FUNGAL VALHALLA (PORTRAITS OF MYCOLOGY'S LATE GREATS ) " site, linked to on the left hand column of this page. Or.... Click here for his ID. posted by Dan @ 10:10 AM 0 comments Saturday, January 01, 2005 Happy New Year From George Lincoln Goodale Here is a New Year's greeting from Harvard botanist and Asa Gray protg, George Lincoln Goodale , to Charles Eliot Norton from 1896. He thanks Norton for the paper by Edouard Piette (1827-1906), probably his Les plantes cultives de la priode de transition au Mas dAzil which appeared in lAnthropologie, vii, no. 1 1896. Mas d'Azil is the paleolithic cave site in the Pyrenees excavated by Piette. Goodale is perhaps best known for having been instrumental in bringing the Ware Collection of Blaschka Glass Models of Plants to the Botanical Museum of Harvard. Click on image to enlarge BEST WISHES FOR A HAPPY NEW YEAR FROM HISTORICA BOTANICA! posted by Dan @ 9:33 PM 0 comments Saturday, December 25, 2004 Christmas Greeting From Ruth Ashton Nelson and Memoriam to Aven Nelson The following 1952 Christmas card was found tipped in to a first edition (1909) copy of the New Manual of Botany of the Central Rocky Mountains (Vascular Plants) by John M. Coulter; revised by Aven Nelson. Ruth Ashton Nelson, Aven Nelson's wife, was some 30 years his junior, and also a botanist who specialized in the flora of the Rocky Mountains. Happy Holidays from Historica Botanica! Click on the images to enlarge. posted by Dan @ 9:10 PM 0 comments Some Sites of Interest Cornell University Plant Pathology Herbarium Photograph Collection The Joseph Dalton Hooker Website Farlow Library of Cryptogamic Botany exhibit of Icones Farlowianae Historical index of mycologists Cyber-Truffle's Fungal Valhalla, portraits of mycology's late greats Who's In a Name Plant Explorers.com Flora of North America, Chapter 7: Taxonomic Botany and Floristics Fred Jordan Bookbinder Conservator 19th C. Western North Carolina Botanists by George Ellison Torrey Botanical Society History CHAPTER I. EARLY LIFE OF JOHN TORREY CHAPTER II. FOUNDING OF THE TORREY BOTANICAL CLUB CHAPTER III. FOUNDING OF THE NEW YORK BOTANICAL GARDEN BY THE TORREY BOTANICAL CLUB CHAPTER IV. SPLIT BETWEEN FIELD AND ACADEMIC CHAPTER V. THE AGE OF LABORATORY WORK CHAPTER VI. ENVIRONMENTAL CONCERNS AND THIER IMPACT ON THE TORREY BOTANICAL SOCIETY CHAPTER VII. HARD TIMES FOR NEW YORK VICINITY BOTANY CHAPTER VIII. INCREASING DISSATISFACTION AMONG THE FIELD BOTANISTS CHAPTER IX. GREGORY R. LONG AND THE NEW POLITICS OF FUND RAISING CHAPTER X. A NEW START? CHAPTER XI. WHATEVER HAPPENED TO... CHAPTER XII.CONCLUSIONS CHAPTER XIII. MISSION STATEMENT TORREY TURTLE ROCK PARK and GRAVE TORREY GRAVE Contact Historica Botanica E-mail Edit-Me Archives 06 01 2004 - 06 30 2004 07 01 2004 - 07 31 2004 08 01 2004 - 08 31 2004 09 01 2004 - 09 30 2004 10 01 2004 - 10 31 2004 11 01 2004 - 11 30 2004 12 01 2004 - 12 31 2004 01 01 2005 - 01 31 2005 02 01 2005 - 02 28 2005 03 01 2005 - 03 31 2005 04 01 2005 - 04 30 2005 06 01 2005 - 06 30 2005 Free Counter Internet Web Directory - The internet's fastest growing directory of the best web sites. Fully searchable and updated regularly. The Discovery of the Cell The site is devoted to the history of the cell biology for the last 400 years. discoveryofthecell.net Fabre, Jean-Henri Casimir ( 1823 - 1915 ) The life and work of this entomologist. E-Texts and Gallery. FABRE, Jean Henri : e-museum Jean-Henri FABRE Jean-Henri Fabre, his life, his work Translation: Sue Asscher Chinese | Danish | German | English | French | Hebrew | Italian | Japanese | Korean | Polish | Russian | Spanish | Swedish | Open our site in full screen mode Open our site in normal screen Use our internal research engine Map of the site Contact us Version franaise Versione italiana Map of the site Jean-Henri Casimir Fabre The Life and the Work of Jean-Henri Fabre, E-text... Robert Hooke Site devoted to the life and work of Robert Hooke, one of the leading scientists of 17th century England, and first Curator of Experiments at the Royal Society. Home Page Robert Hooke (18 July 1635 - 3 March 1703) - natural philosopher, inventor, architect.... Robert Hooke is one of the most neglected natural philosophers of all time. The inventor of, amongst other things, the iris diaphragm in cameras, the universal joint used in motor vehicles, the balance wheel in a watch, the originator of the word 'cell' in biology, he was Surveyor of the City of London after the Great Fire of 1666, architect, experimenter, worked in astronomy - yet is known mostly for Hooke's Law. He fell out with Newton, and certainly had a difficult temperament. He deserves more from History than he received in his lifetime. The picture above shows the memorial tablet to Dr Robert Hooke unveiled by the Dean of Westminster in Westminster Abbey on March 3rd 2005, the 302nd anniversary of Hooke's death. More details are here. (Picture courtesy of Dr Robert Woodward.) Contents | Contact Images: Hooke memorial window, St Helen's Bishopsgate (now destroyed); flea, from Micrographia; title page from Micrographia; drawing of cells (the first Biological use of the word) in cork. This edition: March 11th 2005 e-mail: webmaster Robert Hooke Science Centre, 7 - 9 Dean Bradley St, London SW1P 3EP, U.K. Tel: 020 7963 1150; facsimile 020 7963 1148. Hosted by Westminster School, www.westminster.org.uk in honour of Robert Hooke OW. 2000 - 2003 Webmaster roberthooke.org.uk unless otherwise credited. All rights reserved. Hans Spemann Bio And Photo Contains information about Hans Spemann 1935 Nobel Laureate in Medicine Hans Spemann's Contributions to Developmental Biology Hans Spemann Hans Spemann was born on June 27, 1869, in Stuttgart Germany. Spemann's name will always be associated with the work he did on experimental embryology. He made himself a master of micro-surgical technique. In 1924, while working on the relatively large eggs of amphibians he discovered, together with Hilde Mangold, the existence of an area in the embryo, the portions of which, upon transplantation into a different part of a second embryo ,induced the secondary embryonic primordia. The name "organizer centre" or "organizer" was given by him to those parts. For this discovery of the organizer effect in embryonic development, he was awarded the Nobel Prize in 1935. Later Spemann showed that different parts of the organization centre produced different parts of the embryo. The anterior parts of it tend to produce parts of the head, and the posterior parts of it parts of the tail. Further, tail organizers, when they are grafted into the head region of another embryo, may produce heads instead of tails, the reason being that they are influenced by the head organizer in their new environment. Earlier Spemann had transplanted the optic cups of new embryos into the outermost layer of the region of the abdomen and had found that they induced the production , in this new situation, of a lens of the eye. This was interpreted as being evidence of the existence of secondary organizers which operate after the induction exerted by the primary organizer has been completed. By these and other experiments of a similar kind Spemann laid the foundations of the theory of embryonic induction by organizers, which led later to biochemical studies of this process and the ultimate development of the modern science of experimental morphogenesis. He described his researches in his book Embryonic Development and Induction (1938). Spemann died in Freiburg Germany, on September 9, 1941. Experiments This page is for genreal information purposes only. The sources of this information is found in the bibliography. Galton, Francis: Pioneer of Heredity A critical account of the nineteenth century scientist's work on genetics, evolution and biological statistics. Book written by Michael Bulmer, in PDF format. Joseph Dalton Hooker A leading nineteenth century botanist, and close friend of Charles Darwin. The Joseph Dalton Hooker website: Welcome! Welcome! About this site Joseph Dalton Hooker was arguably the most important British botanist of the nineteenth century. A traveller and plant-collector, he was one of Charles Darwins closest friends and eventually became director of Britains Royal Botanic Gardens, Kew. The image on the left shows Joseph Hooker in 1896. It was taken by William J. Hawker (No. 1 Gervis Buildings, Bournemouth) and I am very grateful to Daniel Weinstock M.D. (of Geneva, New York) who sent me a copy. These pages are intended to provide some basic information about Joseph Hooker. They include: more detailed biographical notes , including details of Hookers immediate family . Information about Hookers collectors and correspondents in Australia and New Zealand, A selection of Hookers writings . links to web resources that contain information about Hooker, the history of botany in general and the history of natural history more generally A guide to some of the archival sources concerning Hooker, including NEW online catalogue of Kews Hooker papers . A guide to published sources about Hooker. You can search this site. There is also some information about Jim Endersby , who runs this site and technical details about it. This site went live in May 2001, since when it has received over 40,000 visitors. It was redesigned in October 2002 and is being updated as and when I have time. Last updated 27 11 04 info@jdhooker.org.uk [Welcome] [ Biography ] [ Writings ] [ Collectors ] [ Links ] [ Archives ] [ Sources ] [ Search ] [ Site info ] Evolution of Evolution Essay on the interaction of human history, including women's history, and the development of evolution theory. Evolution of Evolution Evolution of Evolution Politics and Theories of Chance and Determinism By Heidi Hileman Queen Elizabeth - Charles Darwin Queen Elizabeth I of England ascended to the throne in 1558. The last women of sole political power had been a Greek Egyptian Pharaoh named Cleopatra in the mid-1st century B.C. She reemerged in the 16th century as Elizabeth I. Her century is marked by the break away of Protestant churches from the authority of the Pope, whose Catholic authority had been instituted by the sword of the French King, Charlemagne, in the 8th century. Elizabeth was raised during intense religious strife between the Catholics and Protestants. She began her reign with rejections of marriage alliances with Spain, France and English nobles to rule as the Virgin Queen. As Queen she managed to pass a unification act that created a single Church of England that excluded papal authority. Elizabeth, however, seemed to be more enchanted with the arts encouraging the works of Shakespeare. Elizabeth has to be one of the luckiest Queens who ever lived. While being a caring monarch, she had inherited a destitute country torn by religious civil war and her country desperately needed time to heal. The Spanish were not happy with England's exploration of the America's. The Spanish lead by Columbus had arrived first in America and eventually Spain had had enough when a revolt broke out against Spanish controlled ports in the Netherlands, aided by the English who had refused to align themselves with Spain. King Phillip II of Spain dispatched a fleet of ships, the Armada, in June of 1588 to blockade the northern harbors. The English fought back against the blockade; though the English had only a destitute navy, they did have home ground advantage, so there were give and takes on both sides. The deciding blow came, however, with a terrible storm in August that broke Spanish moral and sent only 67 ships out of 130 back home to Spain. How different life might be if the Spanish had won or even if a long seize had prevented the English from settling North America before the Spanish. Would we now be speaking Spanish in North American instead of English. I doubt the United States as we know it with its constitutional democracy would have been created by the Spanish for they had a strong faith in divine order. It was their belief in Catholicism that had driven the Moors out and reestablished Spain as a world power, creating a Spain who had become extremely wealthy through dominance on the seas. The Spanish had lost more than sunken ships that could have easily been rebuilt with their wealth, but it was a loss of faith in the power of providence to protect the defense of their faith. Least the Protestants claim in was an act of God on their behalf, Queen Elizabeth reign had been spared and her reign was one of the worldliness and individuality, a journey that had begun with the signing of the Magna Charta in 1215. The Puritans felt the forces that had protected Elizabeth were evil and after Elizabeth's death sought to rid England of artistic corruption. Moderate protestants eventually gained control and some of the Puritans fled to New England and eventually innocent women were hanged for being witches. In the states Thomas Jefferson sided with the libertarians and wrote the Declaration of Independence with a stated a belief in "life, liberty and the pursuit of happiness." But perhaps it would be wise not to assume it was a libertarian wind either. Life and order are also virtues which necessitates a written constitutional to maintain civil liberties. Perhaps it was just an unexpected hurricane, a random anomaly that happens in nature from time to time. It certainly was the way Darwin saw the evolution of life in the 1860's when he published case studies to prove species mutated. It is important at this point, however, to emphasize that Darwin's first chapter in his book The Origin of Species is on domestication. But in the absence of domestication, life becomes an accident. A roll of the dice from which fitness would determine the outcome. How picky have his critics been over his choice of the word fitness. Certainly goodness should have been stated rather than fitness. But what is fitness? It could be goodness. Jesus, however, died despite his innocence with the advancement of the Roman military might; even though Rome too eventually crumbled, but for them it was corruption from within. What of England, are they the most fair of all people because God had destroyed their enemies with a mighty storm? Or are we, as evolutionary theory states, a connected human race, connected through our ancestry with the chimpanzees. Even more troubling for many, is in the absence of human domestication does not God have a role in determining the destiny of man. But what is God. There are so many definitions of God or Goddess today that the very act of defining it can leave people arguing about a person's rights of worship which puts God in the realms of choice and individuality. Darwin theories today are used in medicine to understand and care for the natural evolutionary development of the body from birth to death, and to stop unwanted mutations such as deadly bacteria, viruses, and cancer that prematurely destroys the body. When we are sick and visit a physician, we are generally not in the mood for a moral examination before the doctor will treat our illnesses. Many illnesses are a product of chance and those that are our fault, the lectures can wait until we are on the mend. Darwin is used in biology in the development and care of new crops, livestock and personal pets. It makes one wonder if the Kansas School Board of Education decision to make the teaching of evolutionary theory voluntary, believes in educating farmers. Perhaps they want to return to the Garden of Eden by allowing natural selection to have its way without care for domestication. Darwin is also used in reconstruction of history. This is generally where the problems begin with creationists and their interpretations of the Bible. Genesis has a creation myth that has a seven day time limit on it. One interpretation is that each day is a thousand years. Another interpretation is the earth was created in a shorter time frame than would allow natural selection to have happened, therefore the earth must have been created by divine order. Radio-isotope dating shows that multi-cellular organisms to have existed for over 700 millions years which does allow natural selection to have been at work. It was actually Thomas Henry Huxley in 1863 in Evidence as to Man's Place in Nature who suggested that man evolved from Apes. Current genetic testing has shown that our closest relative is the chimpanzees. This is another supposed contradiction of the Bible because Genesis says Adam was created from the dust of the earth, which creationists interpret as Adam being created separate from the animals in a single act of creation. This scripture could just as easily say be interpreted as Adam evolved from dust to single cell to ape to man. Even among secular Americans there is a feeling that Darwin undermined the power of religion to motivate the soul. The facts are Darwin's book was written after the American constitution which had already separated state from church, while the Church of England, which is still supported by England today, buried Darwin in Westminster Abbey in 1882. Pythagoras - Hypatia The formal scientific debate over evolution began in the 4th century BC. Alexander the Great was the Greek conquerer who extended the Greek empire through out the middle east. Conquering, however, might not be the right word. The Persian army literally allowed Alexander to defeat their king in single combat, then they willingly picked up their swords to follow him into Egypt. Egypt's New Kingdom dynasty had previously collapsed and easily feel into his hands. So why did the Persians so willing follow a foreigner? Intellectuals are fond of pointing out that Aristotle, a scholar trained by Plato of Athens, was Alexander's tutor. After Alexander's rise to power, Aristotle became a great teacher in Athens with a school he called the Lyceum whose purpose was to classify nature. Aristotle was an innovative scientist, having begun the classification of species that has been improved upon to this day. A natural question with such classification is: Where did the different species come from? Aristotle said perfect patterns were set in the beginning by an unchanging heaven and as such cats would always be cats, dogs would always be dogs, and men would always be superior to women, as kings were to the common man. Aristotle had a very different view of the heavens, not at all like the tradition stories handed down by Athens. The pantheon of gods ruled by Zeus and Hera were seen as the planets, a word which in ancient Greek meant vagabonds, because they wondered aimless through the night sky without any apparent rhyme or reason. Or so it would seem if Earth was the center of the universe. The planetary patterns are very predictable when seen as revolving around the sun. Two centuries before, Pythagoras of Samos (Grecian) founded the Pythagorean school in Italy in the 6th century BC which came to speculated the planets revolved around the sun, as the sun revolved around a fiery center of the cosmos. Pythagoreans first revealed the formula for the right triangle that set off a revolution in trigonometry, navigation and the evolution of change. Pythagoreans viewed the plurality of number as the cause of all natural phenomena. While space and time consisted of points or instants, space and time also had a property called continuity of change which eventually led to introduction of the time-space continuum by the German scientist Hermann Minkowski in 1908. Zeno of Elea was a student of Parmenides and both belonged to the Eleatic school which believed in the unity and permanence of being. Together they traveled to Athens for a visit where Zeno used a dialectic style to present his paradoxes. The most famous of which are Dichotomy, Achilles and Arrow. Dichotomy argues that before a moving object can travel a given distance it must first travel half the distance; before half, a fourth; before fourth, an eight; and so on through an infinite number of distances. It is impossible to cover an infinite number of divisions in a finite time, therefore the beginning of motion is impossible. If Achilles races against a slow tortoise who has been given a head start, Achilles can never pass the tortoise because no matter how fast Achilles runs the tortoise will always be a bit ahead of him; therefore change in position is impossible. The Arrow argues that an object in flight always occupies a space equal to itself, but that which occupies a space equal to itself is not in motion; therefore motion is an illusion. Today the resolution comes in the adding all the fractions 1 2+1 4+1 8+1 16+... together to get the limit of the infinite sum which converges to 1 so motion is possible. As the years rolled by, Aristotle could see no changes in the heavens. The planets continued to be unruly, as the sun remained constant as the giver of light, as cats continued to be cats; dogs, dogs; men, men and women, women. And so based upon observation, Aristotle proclaimed the heavens and all patterns set in the beginning by the heavens as timeless. The Greeks not only saw Earth as the center, but Greece as the center of the Earth, which in turn would make them center of the cosmos. Apollo's temple at Delphi had a rounded stone, Apollo's priests proclaimed as the very navel of the Earth. Only humans experienced time and as such were capable of falling from grace destroying that which was set in the beginning, but such changes were never for the better. Ironically enough, the word heaven began in honor of the women Hatshepsut, a Pharaoh of Egypt, the first great women of power in recorded history in the 14th century B.C., who like the Pharaohs before and after, were seen as descendants of the Gods. It was rumored, however, that her nephew Thutmose III, heir to the throne, impatient of having to wait his turn; had her killed. The Greeks picked up the martyred Pharaoh and made her Hera, Goddess of Heaven. The early stories of perfection, The Garden of Eden from which man fell, originally came from the Tigris Euphrates river valley. Perhaps such a lush valley was always being overrun by invaders and each time was a loss of Eden. Abraham of Ur originated in this fertile valley before he moved to what was soon to be called Israel. The early Greek myths, however, are more like the Egyptian myths about bringing order out of chaos. Aristotle was adopting a middle east view point when he choose to believe in perfection. Though I personally wonder, if the Greek saints embellished the first chapters of Genesis to make it sound like their Greek Aristotle. So in the end they were the same. There was nothing new in Aristotle's view of universe to have fascinated the middle eastern Persians who already had such myths, even if they had heard of Aristotle. There is another possible answer for the Persian fascination with the Greeks. For the previous four hundred years, the Greeks had been hosting the Olympic games in the name of Zeus, their father God. Perhaps the Persians were more interested in playing games than in fighting wars. But if the beginnings of interracial games was so powerful why was Alexander a king, instead of democratic leader? While Athens was the birthplace of democracy, it was also the home of Aristotle, Alexander the Great's teacher. Plato was Aristotle's teacher. Plato was upset when his teacher Socrates, who had adoptive Zeno's dialectic style of telling paradoxes, was sentenced to death by an Athenian democratic jury. According to Plato, Socrates, in the market place of Athens, had taught the importance of listening to one's inner voice to find one's inner truth. This upset the priests of Athena's temple who feared Socrates would become more powerful and take away their followers. The priests incited the people to put Socrates to death for insulting their city and its temple. After Socrates death, Plato took it upon himself to chastise Athens for their cruel behavior and insist upon freedom of speech. Plato, however, did not trust democracies and taught that a righteous king who cared for his citizens was the best of all possible governments. Plato taught Aristotle. Aristotle taught Alexander the child who would become King of an extensive Greek empire. Alexander's new capital was Alexandria in Egypt. It was in Alexandria, the geometer Euclid in the beginning of the 3rd century BC, combined the knowledge of Egyptian building with Greek theory, to become the father of scientific reasoning and theoretical geometry. Euclid, however, remained silent on the nature of the solar system. Alexandria flourished as an intellectual capital until it fell victim to the Christians. At the turn of the 5th century, a women mathematician and inventor named Hypatia lectured in the Museum founded by Euclid. She claimed to be a neo-Platonist, a pagan and a follower of Pythagorean works. She was dragged by a mob of Christian monks into their church where she was killed as they scraped her flesh from her bones and her flesh burnt. Orestes, a former student of Hypatia and at the time of her death, the Roman Prefect of Alexandria; demanded an investigation. The investigation never took place. Orestes resigned and left Alexandria. Interest in science diminished until the plague ravished Europe in the 14th century. Nicolaus Copernicus - Present The Christian God was in his heavens and all was right with the world in Europe when the plague struck in 1348, killing an estimated one-third of its population in its initial attack; reoccuring every 17 to 25 years usually in urban centers for the next four centuries. For the devoutly religious, the plague was attributed to the will of God as punishment for sin and the response was to appeal for divine intervention by means of religious processions, offerings and self-denial. Heretics, witches, Jews and others of questionable character were frequently persecuted during an outbreak of the plague. Scientific theory interested in physical causes reemerged from the dark ages to explain the biological causes of the plague. By about 1500, the theory of contagion was introduced and case studies where isolation practices were followed seemed to confirm theories of the person-to-person spread of the disease. It wasn't until the 1890's, that the ecological trio of rodent host, flea vector, and Y. pestis was understood, thanks to the discovery of "germs" by Louis Pasteur in France in the previous decade. Science was insisting upon the truth of our physical existence even though such truths may challenge our emotional security. In the 16th century Nicolaus Copernicus in his youth, observed an eclipse by the moon of the star Aldebaran in 1497 and wondered about Aristotle's changeless universe. Copernicus had seen an irregular change in the heavens which lead him to muse on the retrograde paths of the planets. In the sunset of his life, in 1543, he published his book The Revolutions of the Heavenly Spheres expanding upon the Pythagorean heliocentric model. Copernicus theorized that the earth rotates daily on its axis and revolves yearly around the sun in a circular orbit as do the other planets. Science was again fascinated by heliocentric geocentric argument and many scientists set out to prove or disprove it. In 1582, Pope Gregory XIII introduced our current calendar which accounts for leap year every four years, including the three we skip on the beginning of each century on three out of four centuries. After Gregory's leadership ended in 1585, Copernicus ideas were meet with opposition by religious leader who felt it was their duty to console their followers with the faith that the Earth and its human inhabitants were at the center of the universe. The philosopher Giordano Bruno, influenced by 15th century humanism, neo-Platonism and Copernican theories expounded the primacy of the intellect, the naturalness of religion and the infinity of the universe, was condemned for heresy in Rome by the Inquisition under the leadership of Pope Clement VIII. He refused to recant and was burned at the stake on Feb. 17, 1600. Undaunted, Johannes Kepler, the imperial mathematician in Prague, in the 1609 published Celestial Mechanics. Using a detailed mathematical analysis, based on a life-time of astronomical observations by Tycho Brahe, Kepler proved that Mars revolved around the sun and extended his proof to theorize that all the planets revolved around the sun. Kepler realized that an ellipse (an elongated circle) gave 5% greater accuracy with observed observations than a circular orbit. He also suggested that the attraction between sun and planets diminished inversely with the distance of the planet from the sun. In Italy, in 1632, Galileo Galilei published Dialogue Concerning the Two Chief World Systems using conceptual arguments based on many of his own experiments, that contrary to Aristotle, heaven and earth are composed of the same kinds of matter. To reconcile the earth's motion based on Kepler's proof with man's experience in everyday life, Galileo set forth the concept of the relativity of motion (Einstein), the idea of inertia, the law of uniform acceleration and its application to falling bodies (Newton), calling for a unified science of physics and astronomy. Galileo was tried by the Inquisition closely guided by Pope Urban VIII, whose verdict along with Catholic church authorities was encouraged by academic followers of Aristotle, for heresy. Galileo would have been burnt alive as a heretic, but choose to rescind his beliefs and died under house arrest. Pope John Paul II, in 1992, acknowledged it was a mistake to have tried Galileo. Enter Isaac Newton, the father of determinism, where nature plays out on a regular time table like a clock with his Laws of Motion and Gravity. But is nature the consistent clock or is it human's approximations that gives us rhythmic time. Newton thought he was born on December 25, 1642, but England was into all things Protestants so they didn't adopted Gregorian calendar until 1752. Readjusting for leap year, Newton was born on January 4, 1643. Calendars have always been such a strange issue. There are 365.2422 sidereal days in a year, a year measures the time it takes the sun to return to its original position in the heavens after one revolution around the sun and a sidereal day an even division of the year; contrasted with 365 solar days in a year, a solar day measuring the time it takes the earth to complete one rotation. Time is discontinuous when different velocities are compared, so keeping the vernal (spring) equinox on the same day of the calendar has been a challenge. Trusting in the Zodiac to measure the seasons was often more reliable. We currently only have to add a day on leap year every four years, minus three leap years in four centuries to keep count. We skipped leap year on the years 1700, 1800, 1900, but we will be keeping leap year in the year 2000. Even the myths that surround Newton's origins and discoveries, such as the apple that fell in his garden that lead to his discovery of gravity, which Newton himself encouraged perhaps to hide the fact that Robert Hooke had previously provided a conceptual link between central attraction and a force falling off inversely with the square of the distance, are distorted. The story is told that Edmund Halley, a friend of Hooke, asked Newton what type of curve does a planet describe in its orbit around the sun, assuming an inverse square law of attraction. Newton successfully showed Halley that one could derive an ellipse. Halley was so impressed he agreed to finance Newton's now famous Naturalis Principia Mathematicia in 1687. The way one derives an ellipse with an inverse square law is to draw two parabolas (half an ellipse) and connect them, but placement of the tip of the parabola depends on observed data. The algebraic equation of an ellipse, that doesn't require patching two parabolas together, requires two foci and we only have one sun. With Newton's patchwork we can derive with varying degrees of accuracy the orbits of the planets. Einstein improved on calculation of the orbits of planets such as Mercury that are closer to the sun, while Einstein's and Newton's method are equally reliable for planets farther away such as Pluto. Edmund Halley published his important study of cometary orbits, Synopsis Astronomiae Cometicae, in 1705. In it he analyzed available observations of comets in accordance with Newtonian mechanics and predicted that comets made elongated elliptical orbits around the sun. In particular he forecast that a comet he observed in 1682 would return in 1758. The comet, which now bears his name, did return after Halley's death and further convinced skeptics of the power of Newtonian mechanics, but the comet follows a strange elongated ellipse the defies simple rules of gravity attraction. In the 20th century when Richardson was measuring the coast of England, he decided that there must be more than two dimensions to all the curves along the coastline. Chaos theory agrees. A smooth ball or box would be an exact three dimensions. Mountains and valleys in a planet's surface create more than three dimensions, but less than four. The suns, planets, asteroids belts, etc with 3+ (fractal) dimensions and various densities fold space so that a comet could ride on the manifolds like a ship on an ocean current. NASA is currently mapping a host of manifolds that exist naturally in our solar system. They are hoping that spaceships can ride these space currents to save fuel. Enter Einstein's Special Theory of Relativity in 1905 that suggests an inverse relationship between speed and time. In order to explain why light did not degrade, Einstein suggested that at the speed of light the time between the ticks of the clock was infinite so time ceased to exist. As velocity slowed the clock started ticking, with the slower the velocity the faster the ticks. Edwin Hubble observations in 1929 showed the universe was expanding and the time dependence of the Hubble coefficient implied an early period of rapid expansion named the Big Bang. This could reconfirmed Einstein's theory since as the earth slowed we gained extra days on leap year. However, relativity has maintains a neighbor to neighbor connection on the large scale that does not account for the sudden appearance of an extra day. Discontinuous time is obvious when comparing solar days with sidereal years. If we focus on seconds that maintain consistency with sidereal days, then solar days would become inconsistent so that by the end of the first year midnight would be come 6 AM, the end of the second year midnight would be noon, the third 6 PM and finally back to midnight again. We choose instead to focus on days and let the years be inconsistent. There are both continuous to themselves, but the inability to maintain two focuses at once confirms the Heisenberg principle of uncertainly extended to include varying velocities. Werner Heisenberg was a German atomic physicist who in 1927 introduced the Heisenberg uncertainty principle that stated position and velocity cannot be precisely determined at the same time. Previous Bohr, in 1913, theorized discrete atomic spectral emission lines were caused by a quantum jump where electrons jump from one permitted energy level to another of lower energy emitting a quantum of energy equal to the difference in energy between the higher and lower energy levels. When electrons jump from a lower to a higher energy level they absorb a quantum of energy. Heisenberg uncertainty principle allowed the use of probability theory in quantum theory to determine the outcome of the spectral lines. In the 1940s, George Gamow and his collaborators suggested the center of the universe may have been as hot and dense as the interior of a star and nuclear reactions would have occurred. Eventually this lead to the suggestion of cold, dark, densely packed subatomic matter that as it increased in density became hot enough to explode. Perhaps in the explosion there might be primordial cold matter made by the collapse of irregularities in the very early stages of the universe. Primordial cold matter would glow white hot emitting radiation in the form of X rays and gamma rays. The Hubble telescope has successfully detected this radiation at the center of galaxies. So where do we go from here. Will the Big Bang become the Big Crunch? See Cosmic Spirals 1999 Heidi Hileman References Cosmic Spirals Net Advance of Evolution Lefalophodon An informal and incomplete guide to the history of evolutionary biology from about 1800 to about 1950. Its main emphases are on the late 19th century and on paleontology. Lefalophodon: An Informal History of Evolutionary Biology Web Site Lefalophodon An Informal History of Evolutionary Biology Web Site This is an informal and incomplete guide to the history of evolutionary biology from about 1800 to about 1950. It is maintained by John Alroy . Its main emphases are on the late 19th century and on paleontology. However, I hope to see the coverage become more comprehensive in the near future. If you have any comments or suggestions or wish to contribute to the site, I strongly encourage you to do so; please write me . The only limits on contributions are that they must follow the site's format and carry your byline. Contributors to date include Mark Largent. New features on the site include a facelift of the bibliography page , and reviews of A Passion for Birds (M. Barrow) and Zarafa (M. Allin). The site's other main features currently are: Biographies of major (and not so major) figures Photo gallery : pages that have photos and little else. A timeline of major events between 1800 and 1950 An annotated bibliography of history of biology books A page of Darwin quotes A page detailing major 19th century scientific expeditions Institutional pages, including: The American Museum of Natural History The University of Chicago Harvard University The Smithsonian Institution Stazione Zoologica at Naples I am planning to create "famous historical episodes" pages (e.g., for the voyage of the Beagle, the Cope-Marsh war, the case of the midwife toad, etc.). Please read this important note if you are seeking to obtain permission to copy images. So, what does "Lefalophodon" mean ? This web site has no formal connection to the University of California, which takes no responsibility for the site or any of the information found on it. Lefalophodon Home - Timeline - Bibliography - Related Sites - Comments Suggestions The History of Evolution Not just the historical aspects of evolution, but also the evolution of all species. The History of Evolution The History of Evolution The basic idea underlying the Principia Cybernetica Project is that evolution leads to the spontaneous emergence of systems of higher and higher complexity or "intelligence": from elementary particles, via atoms, molecules, living cells, multicellular organism s, plants, and animals to human beings, culture and society. This gives us a view of the history of evolution as a kind of progression towards higher complexity (albeit essentially unpredictable, with many side-tracks and dead-ends). Such an encompassing view may allow us to answer the basic questions : "Who are we? Where do we come from? Where are we going to?" (The last question requires an extrapolation of this development towards the future .) Although the growth of complexity during evolution is not universal (many systems evolve towards higher simplicity), it appears as the most striking factor from a long-term perspective. Most of the time this complexity increase, and evolution in general, occurs rather slowly or continuously, but during certain periods evolution accelerates spectacularly. This results in changes which from a long term perspective may be viewed as momentous events, separating discrete types of organization. Each time a higher level of control or organization has developed we say that a Metasystem Transition (MST) has taken place. The MST concept makes it possible to reconstruct the sequence of evolutionary events from the beginnning of time to the present as a partially ordered series of metasystem transitions. These transitions can be roughly classified in four categories or "tracks": Prebiotic : the developments taking place before the origin of the life, i.e. the emergence of physico-chemical complexity: the Big Bang, space and time, energy and particles, atoms and the different elements, molecules up to organic polymers, simple dissipative structures. Biological : the origin of life and the further development of the specifically biological aspects of it: DNA, reproduction, autopoiesis, prokaryotes vs. eukaryotes, multicellularity, sexual reproduction, the species. Cognitive : the origin of mind, i.e. the basic cybernetic, cognitive organization, going from simple reflexes to complex nervous systems, learning, and thought. Social : the development of social systems and culture: communication, cooperation, moral systems, memes Although most of the transitions taken place sequentially within each main track, and these track emerge roughly in the order they are presented here, there is also essential interaction between the categories. For example, communication and cooperation between organisms (social track) takes place before rational thought (cognitive track) emerges, and is in a mutual positive feedback relation with that cognitive transition. Similarly, sexual reproduction (biological) appears in parallel with the emergence of reflexes (cognitive) and influences the appearance of social cooperation via its formation of family groupings. For a chronology of some of these transitions, see the Cosmological and Evolutionary Geological Timelines. Copyright 1994 Principia Cybernetica - Referencing this page Author F. Heylighen , C. Joslyn , V. Turchin , Date Nov 16, 1994 (modified) Aug 1993 (created) Home Metasystem Transition Theory Up Prev. Next Down Physical Evolution [empty] Biological Evolution Cognitive Evolution (stages) Social Evolution Discussion CHANGE MY MIND , Comment by Trevor Mott References request , Comment by Tristan Doelnitz I have a question... , Comment by anonymous Potentially turning the tables... , Comment by Darrell Gudmundson Add comment... The Huxley File The works of Thomas Henry Huxley (1825-1895): physiologist, anatomist, anthropologist, agnostic, educator, and Darwin's bulldog. THE HUXLEY FILE THE HUXLEY FILE Created by Charles Blinderman, Professor of English and Adjunct Professor of Biology, and David Joyce, Professor of Mathematics and Computer Science, Clark University T. H. Huxley, President of the Royal Society Portrait by John Collier, 1883 Preview This, THE HUXLEY FILE, is addressed to an audience ranging from those who never heard of Thomas Henry Huxley to those who are familiar with him and may even have read some of his work. For specific guidance on the various subjects he wrote about fields ranging from the design of marine invertebrate structure to the design of a good human society the cybernaut may refer to any of the 21 guides concluding this preview. Selections in THE HUXLEY FILE that appear only in obscure Victorian magazines or hidden archives will be of interest to those who do know him and may even have studied and published on him. Born on May 4, 1825, and expired on June 29, 1895, THH, it is hoped this project will prove, deserves resurrection into the fame he once enjoyed. THE HUXLEY FILE is a memorial to his achievements in many fields, its ambition to bring forth THH so that we can advance our understanding of Victorian culture, of the contrasting features of superstition and of science, and of our own time; and take pleasure in reading one of the finest writers of any time any where. If THH is known at all, it is as "Darwins bulldog." This self-imposed nickname recognizes the collegiate defenseand enthusiastic offensehe undertook in support of the theory of evolution. In November of 1859, after reading the newly-published Origin of Species, he warned Charles Darwin that there would be mischief from anti-evolutionists, and that he himself, T. H. Huxley, was sharpening up his claws preparing to annihilate these creationist critics. He devoted himself for most of his career defending Darwinism and related notorious subversive subjects "Darwinism" was defined in the Victorian period and is defined today not only as Darwin's theory of natural selection, but as a comprehensive network that includes a philosophical view of the ethical as well as practical significance of scientific investigation; as a type of materialism; as agnosticism; as an assault on the historical validity of scripture; and as a model for the design of a political and economic community. To all of these, THH contributed, so significantly that though we are not aware of it, much of what educated free people think today of deity, or religion, of science, of their values, and of their own origin and future traces back to Huxley as originator, as he was the inventor of the word "agnostic" itself. Huxley's career testifies to the richness of scientific investigation, the establishment of young rebels as a powerful party, and the pervasive intrusions of secularism during the Victorian period. He advises us on science as a proper discipline for the school curriculum, on vivisection, on compassion, competition, and capitalism, the U. S. Civil War, nature, chalk, protoplasm, dinosaurs, the pantheon and the pyramids. On the inequality of the races and genders, Thomas Huxley was not so keen or humane a radical as John Stuart Mill and Harriet Taylor, but did help to diminish stereotypes about skin color and stature being signals of intellectual and emotional value. Huxley's achievements are pertinent today in helping us understand our own culture, for example, on these issues of immediate concern, especially in the U. S. Here's a list of problems of today that interest or afflict people throughout the worldproblems which THH helps us understand and perhaps solve: the role of the government in advancing the academic program of the population, in supporting museums, in supervising health; the contest between religious fundamentalism and secularism, e.g., the use of the Bible in public education, the validity of scripture as a historical, scientific, and ethical guide; the assertion of the reality of demons and witches, and of other irrationalities; the credibility of materialistic language in mapping reality; the attack on science as being not an analysis of reality but an expression of the scientist's racial, gender, class and other prejudices; the movement to abolish the canons and traditions of a liberal education; the promotion of cultural illiteracy; the movement to replace a search for facts in historical survey with a search for that which will satisfy idiosyncratic, racial, gender, class and other credenda; the necessity of vivisection; the trustworthiness of natural selection as an explanation of evolution; the scenario of evolution, particularly of human evolution; the inherited or acquired features that distinguish among the races and between the genders; the relevance of race as a classifying system for the human species; the importance of knowing about cultures other than the western; and the danger to the species of global over-population. Those merely interested in Huxley and scholars engaged in research on him, on Darwinism, on Victorian culture, on the history of science, and on topics such as those noted will find that THE HUXLEY FILE, in which reside over 1000 items, justifies its title. The 1000 figure covers 680 pieces of published and unpublished text by THH; more than 150 pictures by and on him, with an uncounted number of pictures in text by and for him; and 120 commentaries on him. Cybernauts will find here the entirety of the nine-volume Collected Essays; 40 selections from the five-volume Scientific Memoirs; and also a large number of Huxley essays that were never collected, from The Westminster Review, Youth's Companion, etc.; among these, the most important hidden pieces are the three essays he wrote for a club, The Metaphysical Society, on whether a frog has a soul, whether immortality is reasonable, whether Jesus was actually resurrected; several pieces that exist only in draft form, such as his teenage journal "Thoughts and Doings," "AgnosticismA Fragment" and "The Natural History of Christianity"; letters published in The Times, Nature, etc.; most of the letters appear in Leonard Huxley, ed., The Life and Letters of Thomas Huxley and Julian Huxley, ed., Thomas Henry Huxley's Diary of the Voyage of H.M.S. Rattlesnake which is the best provider of THH's diary items; some of the letters come from collections in libraries around the world. a cornucopia of illustrations ranging from his doodles and sketches of natives to cartoons and portraits of him, illustrations not attached to any text, and a number illustrating texts such as Man's Place in Nature and Oceanic Hydrozoa. 120 commentaries on him, some praising his work, others attacking it, such as Powheads, Porwiggles and Protoplasm. It's perhaps a bit late to say this, but this introduction and all the guides may be skipped, the cybernaut travelling directly to these selections. The audience of THE HUXLEY FILE, then, is educated people of whatever culture (THH was translated into Chinese and Japanese, as well as into European languages Hungarian, Russian, Italian, German, French, Spanish, and Italian), especially high school and college teachers who can select and present for their students sections from THE HUXLEY FILE to enrich, liberalize, and vitalize courses in at least these fields: (1) education, (2) biology, (3) anthropology, (4) philosophy, (5) religion, (6) social studies, and (7) style. Though these categories are designed to help understand Huxley's contributions, it's important to note that he was not a strict disciplinariana river of text, essay or letter, could and often did flow with relevant material on all of these and other tributaries as well. Huxley's popularization adventures resulted in what he called "fugitive pieces," many of them written when he was assailed by insomnia, and most of them constituting Collected Essays ; but since he was a professional biologist, an ample supply of his Scientific Memoirs is offered, though most of those pieces would not be understood or appreciated by most of us lay people. PREVIEW TABLE of CONTENTS BIBLIOGRAPHIES 1. THH Publications 2. Victorian Commentary 3. 20th Century Commentary INDICES 1. Letter Index 2. Illustration Index TIMELINE FAMILY TREE Gratitude and Permissions C. Blinderman D. Joyce Clark University 1998 THE HUXLEY FILE GUIDES 1. THH: His Mark 2. Voyage of the Rattlesnake 3. A Sort of Firm 4. Darwin's Bulldog 5. Hidden Bond: Evolution 6. Frankensteinosaurus 7. Bobbing Angels: Human Evolution 8. Matter of Life: Protoplasm 9. Medusa 10. Liberal Education 11. Scientific Education 12. Unity in Diversity 13. Agnosticism 14. New Reformation 15. Verbal Delusions: The Bible 16. Miltonic Hypothesis: Genesis 17. Extremely Wonderful Events: Resurrection and Demons 18. Emancipation: Gender and Race 19. Aryans et al.: Ethnology 20. The Good of Mankind 21. Jungle Versus Garden Biochemistry History Short biographies of Biochemists Marshall Nirenberg, who cracked the genetic code, and Sir Frederick Gowland Hopkins, discoverer of vitamins Some Material on the History of Biochemistry. Some Material on the History of Biochemistry by Nigel J.T. Thomas Ph.D. Biography and Major Scientific Achievement of Sir Frederick Gowland Hopkins. Pioneer of the discipline of Biochemistry, and discoverer of vitamins and essential amino acids. Biography and Major Scientific Achievement of Marshall W. Nirenberg. The man who cracked the genetic code. To Home Page: Imagination, Mental Imagery, Consciousness, Cognition: Science, Philosophy History. The World of Richard Dawkins Biographical and research resource about the evolutionary biologist, including a schedule of events, list of publications, and other resources in evolution. The World of Richard Dawkins (photo of Dawkins by Lisa Lloyd) Upcoming Events... Lecture - Guest Lecture "Is Evolution Predictable?' Location: London, UK Date time: Tuesday, 22nd November 2005, at 5:30pm More Headlines... Note: This is the "Home page", but I suggest bookmarking the Headlines page instead. Richard Dawkins was educated at Oxford University and has taught zoology at the universities of California and Oxford. He is the Charles Simonyi Professor of the Public Understanding of Science at Oxford University. His books about evolution and science include The Selfish Gene , The Extended Phenotype , The Blind Watchmaker , River Out of Eden , Climbing Mount Improbable , and most recently, Unweaving the Rainbow unofficial website created by John Catalano New York, USA Est. Aug 1996 Editorial philosophy of this site Site Awards Designations ( View Award Icons ) one of Yahoo! picks of the week an OMNIVISION Winner Great Books 5-Star Site DETOX Award Planet Science Site of the Day in The Paleo Ring Science Site of the day This Paleo Ring site is owned by John Catalano . [ Next Site | Previous Site | Next 5 | Problems? ] Want to apply for membership? Random - Previous - Next - List - Join This Science Books site is owned by John Catalano . [ Previous 5 Sites | Previous | Next | Next 5 Sites | | Random Site | List Sites | Join the ring ] John Catalano Site headlines site map search what's new? newsletter Dawkins calendar books writings media quotes videos software biography bibliography more pages Features Behe's box C is for Creation the Gould Files book of month the green room Links best useful "new?" central science news bookstores biology evolution evo creation memetics artificial life other science philosophy art, music, + Evolution: Selected Papers and Commentary Full-text versions of key papers in evolutionary biology from the nineteenth century onwards, with particular emphasis on the work of William Bateson and Darwin's close research associate, George Romanes. Evolution: The Origin and Subsequent Elaboration of the 'Chromosomal' Hypothesis of Hybrid Sterility Evolution SELECTED PAPERS AND COMMENTARY To really understand evolution we must first understand the historical development of ideas on evolution. But to really understand its history, we must first understand evolution. OVERVIEW Introduction: Species Barriers Origin of Species (Darwin 1859), Revisited Two Levels of Information in DNA Haldane's Rule Non-Genic ("Chromosomal") Speciation Allen, Romanes and Gould SELECTED PAPERS on the Four Black Boxes: 1. Variation 2. Heredity 3. Phenotypic ("Natural") Selection Isolation Hybrid Sterility (Darwin 1862) Variation (Hooker 1862) Pangenesis (Darwin 1868) Inutility of Characters (Gulick 1872) Natural and Artificial Selection (Belt 1874) Inutility of Characters. Paradox of Sex. Random Drift (Delboeuf 1877) 4. Reproductive ("Physiological") Selection Isolation An Unnoticed Factor in Evolution (Catchpool 1884) Physiological Selection (Romanes 1886) Physiological Selection (Romanes 1887) 4. "Physiological" Selection Isolation, the "Chromosomal" basis Hybridism and the Germ-Cell (Guyer 1900, 1902) Cytological Basis for the Mendelian Laws (Cannon 1902) Chromosomes of the Germ Cells (Montgomery 1901) Chromosomes in Heredity (Sutton 1903) Two Levels of Genetic Information (Bateson Saunders 1902) Heredity and Variation in Modern Lights (Bateson 1909) A Phenomenon of Arrangement (Bateson 1914) Chromosomes, Polyploidy and Why Sex Evolved (Winge 1917) Speciation in Retroviruses (1995) Origin of Species (1996) Thinking about Stem-Loops (1998) Acknowledgements Other Web Sites New Book on Evolution Introduction: Species Barriers The idea of barriers against members of other species was evident in the nineteenth century in the context of infectious disease ( Click here ). These barriers are both external (e.g. hygiene), and internal (e.g. the immune response). Internally, our bodies ("self") can detect and destroy members of other species ("not-self"; i.e. viruses, bacteria, protozoa). Another, no less subtle form of self not-self discrimination, involves our detection of a mate ("near-self") who will be our "physiological complement" such that the union will produce healthy offspring ("hybrids"). An incestuous relationship with a close relative ("too near-self") will probably result in less healthy offspring. On the other hand, extreme out-breeding, such as with an ape (not-self), is prohibited by species barriers. There is more to this than just the inability to copulate (the gamete transfer barrier). There are both external components (e.g. mate choice), and internal components. Even if the male sperm could meet and fuse with the female ovum, the resulting cell ("zygote") might be unable to grow into an adult organism (developmental barrier resulting in "hybrid inviability"). Even if these transfer and developmental barriers were overcome, in the gonad (testes, ovary) the two sets of parental chromosomes might be unable to pair for gamete-production (gonadal barrier resulting in "hybrid sterility"). Our modern understanding of these barriers began with Charles Darwin's The Origin of Species (1859). The debate on the primary mechanism of "speciation" continues to this day. The issues involved are complex. What are the relative importances of the three barriers (transfer, developmental, gonadal) in keeping species separate ("reproductively isolated")? Do the barriers appear sequentially, and if so, which appears first? Are there fewer barriers between closely allied species, than between distantly related species, or does one barrier just replace another barrier? Are the barriers we find between closely related species indicative of the first barriers to appear? Does a barrier arise suddenly in an all-or-none fashion, or does it arise slowly, so that reproductive isolation is initially only partial? If one barrier is replaced, does it disappear completely? Is there a group of species, members of which, for some reason related to their biology, have not progressed beyond the first barrier? What is the molecular basis of each barrier? Four years after the death of Darwin in 1882 a major conceptual advance was made by Darwin's close research associate, George John Romanes. Whereas the work of Gregor Mendel (1865) may have been unrecognized until 1900 because of the relative obscureness of its originator and his location, George Romanes was at centre stage. George Romanes and, his wife and biographer, Ethel Romanes. Photographs of these portraits were kindly provided by their grandson Giles Romanes (also the grandson of Almroth Wright). The portrait on the left is signed by T.H. Huxley's son-in-law, John Collier (1850-1934), who, at Romanes' suggestion, was commissioned by the Linnean Society to provide the famous 1881 portrait of Darwin. Yet Romanes' contributions to evolutionary theory are only just gaining recognition. Perhaps for the reason given at the top of this page, Biohistorians have not found it easy to tell the story. John Lesch observed in 1975 that: "The development of evolutionary theory in the two decades from Darwin's death to the turn of the century remains very largely terra incognita for the historian." William Provine concluded in 1986 that: "Evolutionary biology in the period 1859-1925 is extraordinary complex". These web pages makes available some of the primary documentation in the area, so that you can try to sort out the issues for yourself. It is obviously biased towards my own particular evolutionary views, but I provide links to other sites, giving alternative perspectives. D. R. Forsdyke The Origin of Species, Revisited: A Victorian who Anticipated Modern Developments in Darwin's Theory By Donald R. Forsdyke Queen's Quarterly (1999) 106, 112-133 (With copyright permission from the Editor, Boris Castel.) In his later years Charles Darwin's closest professional relationship was with George John Romanes, to whom he entrusted the burden of his life's work. Four years after Darwin's death, Romanes published a theory of the origin of species by means of "physiological selection". This resolved the major problems in Darwin's theory, but replaced them with a "peculiarity" of the reproductive system which would allow selective fertility between "physiological complements". To most of his contemporaries, and those who came afterwards, this did not convey much. However, bioinformatic analysis of DNA sequence data emerging from genome projects now allows an interpretation. Surprisingly, the words of a "pore flahr gel" can help us understand work which Alfred Wallace, with the unknowing aid of a Kingston lady, had condemned to a century of obscurity. 1848 was a good year for the Reverend George Romanes, professor of classics at Queen's College, Kingston, Ontario. He inherited a "considerable fortune" and his third, and most illustrious son, George John Romanes, was born. The Presbyterian minister had been in Canada for 14 years, and "relieved of any necessity to continue the duties of his chair", he returned to Europe (1850), eventually settling in London. The children, two surviving boys and two girls, grew up as free spirits. The publication of Charles Darwin's The Origin of Species by Means of Natural Selection, when George John was eleven, went unnoticed. Some last-minute private tutoring facilitated George John's entrance to Cambridge University, where he bloomed. His initial interest in theology, gave way to a life-long interest in biology while maintaining his spiritual concerns. The biography relates that he "finally abandoned the idea of a profession" (medicine or the church), and "resolved to devote himself to scientific research."1,2 In 1874 Romanes published some of his views on evolution in the scientific journal, Nature3. Darwin sent him "a friendly little note" and invited him to visit. "From that time began an unbroken friendship, marked on one side by absolute worship, reverence, and affection, on the other by an almost fatherly kindness and a wonderful interest in the younger man's work and in his career. ... Mr. Darwin met him, as he often used to tell, with outstretched hands, a bright smile, and a 'How glad I am that you are so young!'" Darwin had postulated that organisms with variations conferring some advantage in the "struggle for existence" would more likely survive and produce offspring. This process of "natural selection" also discriminated against organisms with disadvantageous variations. The codiscoverer of evolution by means of natural selection, Alfred Russel Wallace, held rigidly to the theory as originally formulated, while Darwin was more flexible. Wallace was also a leading advocate of the credibility of supernatural phenomena, arguing that natural selection was insufficient to account for the evolution of the human brain (1869)4, and publishing The Scientific Aspect of the Supernatural (1866)5, and Miracles and Modern Spiritualism (1874)6. In 1876 Romanes and his elder brother James were deceived by a "medium" who claimed to be able to communicate with spirits. Romanes wrote two letters to the sceptical Darwin expressing an inclination (short-lived) to believe in the phenomena he had observed. James, who was 14 when the family left Canada, had a friend in Kingston with an interest in spiritualism and he sent her drafts of the letters. Romanes later (1880) expressed doubt publicly concerning "the ascertained facts of clairvoyance and mesmerism" which had been proclaimed in a letter in Nature7. This brought a first contact with Wallace8. There were two meetings at which Romanes made no mention of his earlier credulity. Meanwhile, Romanes had formed a close working relationship with the elderly Darwin. Well aware of inconsistencies in the theory of the origin of species by natural selection, Darwin had made their resolution his life's main focus. At the time of his friendship with Romanes, Darwin was much concerned with "Pangenesis" as a possible explanation for the inconsistencies9. Pangenesis suggested that the testes and ovaries (gonads) were merely collecting centers for hereditary (and perhaps acquired) information dispersed about the adult body as independent units which he called "generative elements" or "gemmules". In an 1875 letter he wrote to Romanes: "I hope with all my heart that you are getting on pretty well with your experiments; I have been led to think a good deal on the subject, and I am convinced of its high importance, though it will take years of hammering before physiologists will admit that the sexual organs only collect the generative elements."1, 10 A later letter (1876) began: "As you are interested in Pangenesis, and will some day, I hope, convert an 'airy nothing' into a substantial theory..."10. Darwin's correspondence suggests a sharing, not only of the experimental, but also the theoretical burden of his life's work. Romanes's experiments to prove the gemmule hypothesis came to nothing, but served to focus his attention on the gonads. Following Darwin's death (1882), Romanes devoted much time trying to find errors in August Weismann's alternative (but correct) proposal that the germ line (contained in the gonad) was quite distinct from the rest of the body ("soma"). Romanes's book, An Examination of Weismannism eventually appeared in 1893, but by this time Weismann's ideas were becoming widely accepted11. Key features of Weismann's proposal, and the Darwinian alternative, appear in Figure 1. Here we see that the germ line is part of an unending cycle, and so is potentially immortal. The soma (that's you and me) lasts for one generation and is then discarded. Figure 1. The eternal cycling of the germ line. Following the gonad-specific process known as "meiosis", the male gonad (testis) produces male gametes (spermatozoa), and the female gonad (ovary) produces female gametes (ova). [1 = ovum. 2 = polar body. 3 = zona pellucida] These unite (fertilization) to produce a unicellular "zygote", which then multiplies and differentiates to produce an adult organism. Tissues of the organism are either the "soma" (e. g. liver, brain, kidney), or the "germ-line" (contained in the gonad). Weismann proposed (correctly) that the soma (mortal) merely provides a supporting role for the germ-line (potentially immortal). Darwin proposed (incorrectly) that throughout life the germ-line would collect "gemmules" of information from the soma. The germ line cycle can be interrupted, so that an organism is "reproductively isolated", either because the gametes cannot meet ("transfer barrier"), or because the zygote does not develop to produce a healthy adult ("viability barrier"), or because meiosis fails in the gonad ("sterility barrier"). Romanes died in 1894 at age 46, and is remembered today mainly as Darwin's protege, and for the annual Romanes Lecture series which he endowed at Oxford. However, Darwin's mantle had been safely entrusted. Four years after Darwin's death Romanes published an extraordinary paper in the Journal of the Linnean Society, entitled "Physiological Selection: An Additional Suggestion on the Origin of Species"12. In a formidable display of deductive reasoning, paralleled only by that of Darwin himself, Romanes resolved the three major problems in Darwin's theory -- "inutility of characters", "blending inheritance", and "hybrid sterility". We are concerned here mainly with the latter. Darwin's theory was based on observations of plant and animal species "under domestication". Darwin thought it appropriate to extrapolate these observations to natural species. Yet he was aware (and the biologist Thomas Huxley constantly reminded him) that, if crosses between members of closely related natural species were possible, the "hybrid" offspring were invariably sterile. If we consider the horse and the ass as members of separate natural species, when a cross is made between them the resulting mule, although otherwise healthy, has maldeveloped testes or ovaries, and cannot reproduce. Conversely, the offspring of crosses between members of "species" created by man (the breeder and horticulturist), are invariably fertile. If one defines a species as a group of organisms which do not breed (produce fertile offspring) with members of other species (e.g. cats do not breed with dogs), then "species" arising under domestication (e.g. poodle and bulldog) are not true species even though they may differ greatly from each other anatomically; they are "varieties", or "races". Hence Darwin confronted a serious problem. Returning again to Figure 1, we see that failure to produce offspring may have three fundamental causes. The germ-line cycle may be interrupted because: (i) The sperm and ovum (gametes) are unable to reach each other or will not fuse to form the zygote. (ii) the zygote cannot develop into an adult organism, so that the "soma" is not present to support the survival of the germ-line in the gonad. (iii) The formation of gametes in the gonad is impaired. These are sometimes referred to as the transfer barrier, the viability barrier, and the sterility barrier, respectively. Romanes focussed primarily on the sterility barrier, often the only barrier separating members of closely related species (i. e. species likely to have arisen recently from a common originating species). He suggested that, like cells of all other organs and tissues, germ line cells might undergo random variations. Variations, for example, in height or eye colour were familiar to everyone. No one knew what caused variations, but no one doubted their existence. Romanes emphasized one possible class of variation affecting germ line cells, which would make an organism less fertile with other members of the species but not influence somatic characters. Normally the loss of fertility would be highly disadvantageous because the organism would leave no offspring. However, he further argued that if two organisms underwent the same type of variation, they would still be fertile between themselves. They would be "physiological complements". Hence, at any time-point a species would consist of the parental group (comprising the majority of species members), and numerous small variant groups. Members of each variant group would be less fertile with members of the parental group and of the other variant groups. Members of each group, to varying degrees, would be "reproductively isolated" from members of the other groups, but remain quite fertile with each other. Hybrid sterility would be an extreme manifestation of the phenomenon. Romanes demonstrated that irrespective of any selective factors in the environment (no "survival of the fittest" required), members of the reproductively variant groups would tend also to be somatically variant, just as members of the parental group would tend to be somatically variant (e.g. changes in height or muscular strength). In the absence of environmental selection, however, somatic variations of members of the large parental group would not be sustained, because these members were crossing freely with each other, a process which tended to blend and neutralize variations. For example, although humans vary in height, tall people cross with small people and the average height tends to remain constant. On the other hand, variations within a small variant group would not be subjected to this "swamping" effect due to blending with members of the parental group (i.e. there would be less non-variants to dilute the variation). Because of this reproductive isolation, the variation would be sustained. If, by chance, the variation happened to confer some advantage to members of the variant group, relative to members of the parental group, that would be a bonus. The selective advantage conferred would allow the commencement of classical Darwinian natural selection. The major difference between the old Darwinian formulation (natural selection), and the new Romanesian formulation (physiological selection) was that in the first case, natural selection preceded reproductive isolation, where in the second case reproductive isolation preceded natural selection (Figure 2). Reproductive isolation, in any shape or form, would suffice, but the most usual form of isolation would result from physiological selection. Of course in a large population it would be very unlikely that a male and a female whose gonads had undergone the same rare variation would encounter each other. Thus the variation would probably not be perpetuated. Indeed, as Romanes pointed out, successful speciation was rare. Figure 2. Distinction between the Darwinian and Romanesian Theories of evolution. Wallace criticized the physiological selection theory publicly (1886)13 and Romanes responded publicly (1887)14. At this time Wallace, famous as much for his books on spiritualism as for his work on evolution, visited North America on a lecture tour. In his 1905 biography he relates that he visited Queen's University, where: "After the lecture [on "Darwinism"] some friends of Principal Grant came in, and ... a lady who was interested in spiritualism ... asked me if I knew that Romanes was a spiritualist, and had tried to convert Darwin. I told her that I knew he was interested in ... spiritualism, but that I thought it most improbable that he had said anything to Darwin. "But," she said, "Professor Romanes's brother is a great friend of mine, and he gave me the drafts of the letters they jointly wrote to Darwin. Would you like to see them?" I said I certainly should, and she promised to bring them the next morning. ... She said I might take notes on the contents as they were given to her without any restriction."8 The name of the lady is not disclosed, but we know that Wallace had made the acquaintance in Washington of the family of the Reverend J. A. Allen, whom he later visited at his home in Kingston. Wallace also took tea at Sir Richard Cartwright's "fine country house in a spacious park a few miles in the country". Wallace was everything that Romanes was not. Wallace was relatively poor, a socialist (he published Land Nationalization in 188215), an anti-vaccinationist (he published Vaccination a Delusion in 189816), an advocate of spiritualism, and, with the death of Darwin, the preeminent authority on evolution. At the close of the nineteenth century there was a sense of complacency both in the biological and the physical sciences. It seemed that the major issues had been resolved, and now it was just a question of sorting out the details17,18. In this environment authorities carried much weight. In a book entitled Darwinism (1889), Wallace modified views previously expressed in correspondence with Darwin (1868)10, 19. The correspondence contained a nineteen-point "proof" concerning the role of natural selection in hybrid sterility, which began: "Let there be a species which has varied [note: past tense] into two forms each adapted to certain existing conditions better than the parent form, which they soon supplant [Wallace's italics]"10. Darwin replied: "I demur to probability and almost to possibility of ... [point 1] as you start with two forms which are not mutually sterile, and which yet have supplanted the parent-form". Two decades later in his 1889 book Wallace admitted: "The preceding argument ... [now decreased to eleven points] depends entirely upon the assumption that some amount of infertility characterizes the distinct varieties which are in process of differentiation into species; and it may be objected that of such infertility there is no proof"19. Under Wallace's scheme, the event which concerned Romanes -- the initiation of the speciation process -- already had happened. Wallace dealt with events subsequent to the process of reproductive isolation (i.e. maintenance rather than initiation; Figure 3). The idea that the infertility he noted might relate to what Romanes proposed did not occur to Wallace. In a separate section of his book he described physiological selection as "another form of infertility," which he then proceeded to attack19. Romanes responded publicly once more in 1890, this time not only with scientific arguments, but also noting that one should not rely on the judgement of a person of "incapacity and absurdity" whose past views were highly questionable, namely, on spiritualism, socialism and vaccination20. Wallace wrote Romanes some sour private letters, which were later published8. These letters protested the "appeal to popular scientific prejudice," revealed Wallace's knowledge of Romanes's earlier flirtation with spiritualism as gleaned from the Kingston letters, and threatened to make "known the fact of the existence of these letters and their general tenor." This would show that Romanes's private judgements did not accord with his public posture of scepticism with respect to spiritualism. In short, Romanes was a hypocrite. A century later, of course, there are many reasons to conclude that Romanes's mature judgements with respect to spiritualism, socialism and vaccination were correct. Perhaps his judgement on physiological selection was also correct. With Romanes's untimely death in 1894, the physiological selection theory lost its most powerful advocate. The most able of his English contemporaries, William Bateson (1861-1926), was deeply involved in detailed study of variations, work given great impetus by the discovery in 1900 of a 35-year-old paper by Gregor Mendel21. This forgotten paper provided a foundation for the new science of genetics. In a 1904 address Bateson extolled the virtues of the "practical man" who will "stoop to examine Nature" in "the seed bed and the poultry yard". Bateson seemed not to think highly of those (unnamed) with a philosophical bent of mind, who were interested in hybrid sterility achieved by some imaginary form of selection: "For the concrete in evolution we are offered the abstract. Our philosophers debate with great fluency whether between imaginary races sterility grew up by an imaginary Selection ... and for many whose minds are attracted by the abstract problem of inter-racial sterility there are few who can name for certain ten cases in which it has already been observed"22. Bateson sent a copy of his data-laden book, Materials for the Study of Variation23, to Huxley, who replied (1894):, "How glad I am to see ... that we are getting back from the region of speculation into that of fact again. There have been threatenings of late that the field of battle of Evolution was being transferred to Nephelococcygia [meaning nonsense].24" In private correspondence in 1888, Huxley had expressed the view that "even people like Romanes" did not really understand Darwin's theory, which was why Romanes had got it "so hopelessly wrong"24. Thus, Romanes did not have the support of some of the most influential people of the time, -- Wallace, Huxley, and Bateson. While Romanes pursued his evolutionary studies, Conan Doyle was creating the great detective Sherlock Holmes, who advised: "When you have eliminated the impossible, then whatever remains, however improbable, must be the truth".25 In Holmesian style Romanes had eliminated the "impossible", but "what remained" seemed so "improbable" that few could be convinced that physiological selection "must be the truth". Romanes could not go into specifics as to the cause of the reproductive selection he was postulating, beyond what he termed a "physiological peculiarity" of the reproductive system, the most obvious manifestation of which was the phenomenon of hybrid sterility. Nor could he elaborate upon occasional remarks that speciation (selective fertility) required the "suitable mating of 'physiological complements'." To some, there may not have appeared much difference between this view and the notion of divine creation. Indeed, the outspoken purpose of people such as the botanist Alexis Jordan, whose observations Romanes used to buttress his case, was to disprove Darwin in favour of divine creation26. It may not have added to his scientific credibility that Romanes was the son of a Presbyterian minister, that his major ally was the Reverend John Gulick,27 and that Romanes, known among his friends as "the philosopher" had written books with such titles as A Candid Examination of Theism (1878)28, Mind and Motion (1886)29, and Thoughts on Religion (1895)30. In 1879 he had declined an invitation from Huxley, well known for his agnostic views, to join the Association of Liberal Thinkers24. In 1886 Romanes had regarded his studies as merely paving the way for future investigations: "My suggested explanation of the origin of species opens up another and more ultimate problem, namely, granted that species have originated in the way supposed, what have been the causes of the particular kind of variation in the reproductive system which the theory requires?"12 To give his Victorian audience a concrete example of one form of physiological selection, Romanes had mentioned a change in the time of flowering of a plant, which would restrict the plant to fertilization only by other members of the species which had undergone the same change in flowering time: "Suppose the variation in the reproductive system is such that the season of flowering or of pairing becomes either advanced or retarded. ...some individuals living on the same geographical area as the rest of their species, have varied in their reproductive system, so that they can only propagate with each other. They are thus perfectly fertile inter se, while absolutely sterile with all the other members of their species. This particular variation being communicated by inheritance to their progeny, there would soon arise on the same area, ... two varieties of the same species, each perfectly fertile within its own limits, while absolutely sterile with one another. That is to say, there has arisen between these two varieties a barrier of intercrossing which is quite as effectual as a thousand miles of ocean; the only difference is that the barrier, instead of being geographical, is physiological".12 Today we would regard such cases as resulting from primary variations in specific genes which affect the time of flowering. However, Romanes sensed that something more than specific genes was involved in the general case of formation of new species by physiological selection.12 The Romanes-Gulick correspondence indicates that although acknowledging its relevance, John Gulick (1832-1923) had not really appreciated the importance of hybrid sterility31. Thus, his son and biographer, the biochemist Addison Gulick noted in 1932: "[John] Gulick's writings of 1887 and thereafter give an elaborate discussion of different aspects of sterility, though never quite placing mutual sterility in relief, the way Romanes did, as likely to be the fuse that ignites the whole powder train".27, 31 Romanes and Gulick had been separately climbing towards the peak of a high mountain, for much of the time their heads being lost in the clouds. Every-so-often the clouds would have cleared and they would have been privileged to views, lonely views, which they could partially communicate to each other, but not to their contemporaries on the slopes below. In 1890 Romanes wrote to Gulick: "It appears to be desirable that, as you and I are the only two human beings who recognize the full importance of "segregation" [reproductive isolation] in all its forms, we should submit to each other our views before publication, in order that we may speak as far as possible with a common voice".31 Meanwhile, Bateson was much occupied with overcoming the opposition to Mendel, and seemed to have forgotten Romanes's work. However, late in Bateson's career the overwhelming importance of the phenomenon of hybrid sterility dawned on him, and he began to consider its possible causes. In 1913 Bateson dismissed sterility associated with certain anther variants in plants as being due to a "simple recessive character," implying that sterility due to defects in one or a few defined characters was unlikely to be of general significance for the evolution of species.32 Microscopical studies of the gonads of sterile hybrids supported this view. Normally, the set of chromosomes carrying genes contributed by the mother pair, on a one-to-one basis, with the complementary set of chromosomes carrying the genes contributed by the father. Close identity is essential for this pairing, which is required so that subsequent cell division and multiplication can proceed, resulting in the formation of gametes (sperms and ova). In hybrid sterility the pairing is defective and a degenerate gonad results. Thus the question of the origin of species becomes a question of the origin of hybrid sterility, which, in turn, leads to the question of the nature of the chromosomal incompatibilities which prevent pairing, or conversely, the nature of the chromosomal compatibilities which permit pairing. Reminiscent of Romanes's position, Bateson interpreted hybrid sterility as reflecting complementary chromosomal "factors": "Though we cannot strictly define species, they yet have properties which varieties have not, and ... the distinction is not merely a matter of degree. The first step is to discover the nature of the [chromosomal] factors which by their complementary action inhibit the critical divisions and so cause the sterility of the hybrid".32 Romanes and Bateson used the word "complementary" in converse contexts. Romanes's "physiological complements" were organisms with reproductive systems which were compatible, so that offspring would be produced. Bateson's "complementary factors" were components of the reproductive systems which were incompatible, thus preventing the production of offspring. As we shall see, these were but two sides of the same coin. That hybrid sterility was strictly the result of a failure of the pairing of complementary chromosomes was brought home forcefully by experiments showing that hybrid sterility could be "cured" in certain organisms by artificially doubling the number of chromosomes. This was because each chromosome now had a partner with which it could pair (i.e. chromosomes from the mother could pair with each other, and chromosomes from the father could pair with each other). If the sterility had been due to a defect in particular genes, this "cure" would be unlikely33. Romanes's ally, John Gulick, remained uninfluential despite a major monograph in 190534. He generated a complex classification of types of sterility, which, combined with his cumbrous prose, no doubt confused more than it clarified. But Addison Gulick continued the crusade. In his 1932 biography of his father he wrote: "The problem of physiological isolation has received ... little attention during the last two decades, but the modern picture of the mechanism of reproduction and the physico-chemical processes that it involves would have a very large influence on any consideration of the subject today. The immediate cause of infertility between species would be sought at the present time in either chromosomal incompatibilities or maladjustments of a serological nature .... From several viewpoints the old proposition of Romanes seems today exceedingly plausible, that a rather trivial mutation or group of mutations might set up a barrier of sterility within a species, and cause the two portions to diverge thereafter into well- marked new species".31 Unfortunately, Addison Gulick's campaign came too late. By 1932 the high ground of evolution research had been seized by individuals who approached evolutionary questions from a different perspective. Nevertheless, he attempted to open the argument again in 1938: "With the progress of years we find a striking reinforcement of the scientific cogency of the theory which Romanes and J. T. Gulick championed; namely that a physiological barrier between two otherwise hardly distinguishable stocks may occur frequently, and must have the effect of initiating a train of divergent evolution".35 Addison Gulick's efforts were to no avail. Those responsible for what subsequently became known as "the modern evolutionary synthesis" seem to have been unaware of the physiological selection theory. They spent much time juggling "selection coefficients" and the extent and timing of geographical migrations in order to provide a mathematical underpinning for evolution by natural selection. Their attempts to reconcile Darwin's ideas with Mendelian genetics were described in The Origins of Theoretical Population Genetics by historian William Provine (1971), who concluded: "Thus, with the gap between theoretical models and available observational data so large, population genetics began and continues with a theoretical structure containing obvious internal inconsistencies".36 Romanes himself had doubts concerning "numerical computation involving the doctrine of chances", remarking: "In reference to biological problems of the kind now before us, I do not myself attach much importance to a merely mathematical analysis. The conditions which such problems involve are so varied and complex, that it is impossible to be sure about the validity of the data upon which a mathematical analysis is founded".37 This foreshadowed later attacks on the "arid calculations of the mathematical population geneticists", which Provine relates.36 The arch-population geneticist John Maynard Smith in his book Evolutionary Genetics warned in 1989 that: "To paraphrase Mr. Truman, if you can't stand algebra, keep out of evolutionary biology"!38 In a letter to Darwin a century earlier, Romanes noted: "The mathematicians must be a singularly happy race, seeing that they alone of men are competent to think about the facts of the cosmos. ... Mathematics are ... the sciences of number and measurement, and as such, one is at a loss to perceive why they should be so essentially necessary to enable a man to think fairly and well upon other subjects. But it is, as you once said, that when a man is to be killed by the sword mathematical, he must not have the satisfaction of even knowing how he is killed".1 In human societies priestly groups always have tended to seize the high ground. Those who occupy such ground in modern times not only find it easier to continue their dominance, but come to act as "gate-keepers", -- peer-reviewers who decide what the rest will be allowed to read and whose research will be funded. This has its dangers. In 1976 Richard Dawkin's The Selfish Gene, which magnificently synthesized the work of William Hamilton and George Williams, added a fresh perspective to Darwinian ideas.39-41 However, the new viewpoint was largely biological, and many inconsistencies remained. Then in the 1990s came the genome project and a deluge of DNA sequence data from biochemical laboratories. The first results of the bioinformatic analysis of these data have suddenly given the story fresh impetus. It appears that the chromosomal incompatibility which allows species to originate either arises from "macromutations" which affect chromosome segments31, 33, or is the cumulative result of numerous "micromutations," as proposed by the present author in 199642. In either case, Romanes was right as he did not specify the nature of the "peculiarity of the reproductive system" which would lead to reproductive isolation. The strength of the micromutation proposal is that it allows fine degrees of compatibility, so that a rare reproductive variant would be more likely to find a partially matching physiological complement. The proposal arose from the perception that DNA, the molecule in chromosomes which transmits hereditary information, has two levels of information. There is nothing strange about this. A radio operator has to decide what message to transmit, and on what wavelength to transmit it. Thus the radio signal contains primary information (the message) and secondary information (the wavelength). The message is basically the same whatever wavelength is employed. The role of the secondary information is to allow discrimination between messages; it allows the receiver to tune out unwanted messages. Shaw's 1913 play Pygmalion provides another helpful metaphor43. If asked to recite a nursery rhyme, the "toff" Freddy Eynsford Hill, of some social standing, would have said: "Mary had a little lamb, its fleece was white as snow...". However, the flower seller, Eliza Doolittle, would have said: "Miree ader li-awl laimb, sfloyce wors woyt ers snaa ...". Both sentences convey the primary information that Mary possessed an immature, white, sheep. In class-conscious England at the beginning of the 20th century, however, the sentences would also have communicated the secondary information that Eliza was of "lower class" cockney origin, whereas Freddy was of "middle class" origin. We may regard Eliza's dropped Hs as micromutations. The secondary information, because of such micromutations, constitutes a "reproductive barrier". Cockneys tend to marry cockneys and perpetuate cockney secondary information. The middle class tend to marry into the middle class and perpetuate middle class secondary information. Thus, Eliza appeared to be reproductively isolated from Freddy largely because of her language. Although, perhaps with some difficulty, both could understand each other's primary information, the secondary information (Eliza's dropped Hs) seemed to constitute a barrier. Shaw tells us that Professor Higgins performed the appropriate experiment. He demonstrated that if the linguistic barrier were removed, then the reproductive barrier would also be removed. Eliza and Freddy lived happily-ever-after. We can say that they then possessed "linguistic complements", by which we mean that they approached linguistic identity. Alternatively, we can say that until Professor Higgins had performed his magic, their reciprocal differences, or "complementary factors" (Eliza's dropped Hs, and Freddy's included Hs) kept them reproductively isolated. It is important to note that Eliza's cockney accent was a global characteristic of her speech. Each sentence she spoke was influenced by it. While each sentence provided a discrete piece of "primary" information, which was localized in that sentence, the "secondary" information (her accent) was diffused across all sentences. We should also note that once the marriage knot had been tied (i.e. the barrier to reproduction formally removed), a good chance existed that, even if her accent subsequently regressed (diverged from Freddy's, so that linguistic complementarity was lost), the marriage (reproduction) would continue. Thus the initial secondary information (a reproductive barrier) needed only to be removed temporarily until a more substantial (legal) way of removing the barrier had been substituted. This latter point proves of considerable importance when we move back to the problem of gaining evidence for two levels of information in DNA. Whatever the initial isolation process which led to the divergence between ancestral lines leading to, say, the modern elephant and mouse, it is clear that there is now a more substantial barrier to reproduction between the two (a gamete transfer barrier). It would probably be fruitless to examine these species for molecular clues as to the way the initial divergence took place (Figure 3). In virus species, however, signs of the initial isolation process might still exist. This, indeed, seems to be the case with viruses with the potential to coexist in the same host cell42. Figure 3. A hypothetical evolutionary tree to show that the initial evolutionary events required for divergence from prototypic ancestral forms (circled regions), are distinct from evolutionary events required for the maintenance and further development of a species. The first critical evidence emerged from studies of insect viruses by biochemist Gerard Wyatt in 1952, and there is now supporting data from analyses of retroviruses and herpes viruses44-46. We also know that DNA has at least two levels of information. The primary information occurs in localized "sentences", which are the genes encoding the various characteristics of an organism. The secondary information is the molecular basis of Romanes' "physiological peculiarity" of the reproductive system, and must match between two individuals ("physiological complements") in order that they may reproduce. A divergence in this secondary information, through accumulation of micromutations, appears likely to initiate the speciation process42,47. We should note that Bateson's careful use of the general term "factors" (not "genes") allowed him to encompass any form of information (primary or secondary) which was contained in the chromosomes48. At the conclusion of the 1932 biography of his father, Addison Gulick wrote: "We may anticipate that the evolutionary problems which were outlined by Romanes and Gulick will again be reinstated in more perfect form than is today attainable. Until that time arrives it will remain impossible to estimate the relative importance of the several forces that cause the progressive transformation of species living under the conditions that nature provides".31 It has been a long wait. 35 years passed before the work of Gregor Mendel21 was recognized in 1900. A century has passed since the posthumous publication in 1897 of Romanes' masterpiece, the third volume of his Darwin, and after Darwin, entitled Isolation and Physiological Selection37. Noting the leisurely pace of nineteenth century, compared with twentieth century, science, it can be seen that Romanes was not merely years ahead of his contemporaries, he was light years ahead. However, there are signs of change. Harvard evolutionist Stephen Jay Gould in a 1980 paper "Is a new and general theory of evolution emerging?" notes a new readiness to entertain "chromosomal alterations as isolating mechanisms", and points out49 that: "Some of the new models ... regard reproductive isolation as potentially primary and non-adaptive rather than secondary and adaptive ... . In ... chromosomal speciation, reproductive isolation comes first and cannot be considered an adaptation at all. It is a ... [random] event that establishes a species by the technical definition of reproductive isolation. To be sure, the later success of this species in competition may depend on its subsequent acquisition of adaptations; but the origin itself may be non-adaptive. We can, in fact, reverse the conventional view and argue that speciation, by forming new entities ... [randomly], provides raw material for selection"., Of course, Romanes and Gulick would have warmly agreed with this12,13, 50,51. Notes [For space reasons the notes had to be abbreviated in the paper published in Queen's Quarterly.] 1 E. Romanes, The Life and Letters of George John Romanes (London: Longmans, Green Co., 1896). 2 C. Darwin, The Origin of Species by Natural Selection or the Preservation of Favoured Races in the Struggle for Life (London: John Murray, 1859). 3 G. J. Romanes, "Disuse as a reducing cause in species", Nature, 10 (1874) 164. Romanes became a close friend of Norman Lockyer, the founding editor of Nature, and had him as a summer guest in Scotland in the early 1880s. DRF Aug 2003 4 A. R. Wallace, Review of Principles of Geology by C. Lyell, Quarterly Review 126 (1869) 187-205. 5 A. R. Wallace, The Scientific Aspect of the Supernatural(London: F. Farrah, 1866). 6 A. R. Wallace, On Miracles and Modern Spiritualism (London: James Burns, 1874) 7 G. J. Romanes, ""A Speculation Regarding the Senses"", Nature 21 (1880) 348. 8 A. R. Wallace, My Life (London: Chapman Hall, 1905), Chapter 36. 9 C. Darwin, The Variation of Animals and Plants under Domestication. Volume II, 2nd Edition (London: John Murray, 1875), Chapter 27. How did Darwin come upon the idea of pangenesis? For more on this (Click Here) . 10 F. Darwin and A. C. Seward, More Letters of Charles Darwin (London: John Murray. 1903). [Haeckel had referred to pangenesis as an "airy nothing." In similar vein, Shakespeare in Midsummer Night's Dream wrote: "And as imagination bodies forth, The forms of things unknown, the poet's pen Turns them into shapes, and gives to airy nothing A local habitation and a name."] 11 G. J. Romanes, An Examination of Weismannism (Chicago: Open Court Pub. Co., 1893). It seems that Weismann eventually came round to adopting something like Romanes' physiological selection in his theory of "germinal selection." Thus he wrote (1896): "The variations presented to personal [natural] selection must have themselves been produced by the principle of survival of the fit! And this is effected ... through such profound processes of selection in the interior of the germ plasm as I have endeavoured to sketch ... under the title of germinal selection." 12 G. J. Romanes, "Physiological Selection: An Additional Suggestion on the Origin of Species", J. Linn. Soc.(Zool.) 19 (1886) 337-411. Reproductive isolation due to differences in the time of flowering (plants), or pairing (animals) he regarded as "extrinsic". The most important form of reproductive isolation with respect to the origin of species was considered due to a "peculiarity" of the reproductive system, which he regarded as "intrinsic". ( For full text - Click Here ) 13 A. R. Wallace, "Romanes versus Darwin", Fortnightly Review 46 (1886) 300-316. 14 G. J. Romanes, "Physiological Selection", Nineteenth Century 21 (1887) 59-80. For full text - Click Here ) 15 A. R. Wallace, Land Nationalization its Necessity and its Aims (London: Trubner Co., 1882). 16 A. R. Wallace, Vaccination a Delusion (London: Swan, Sonnenshein Co., 1898). 17 L. Badash, "The complacency of nineteenth century science", Isis 63 (1972) 48-58. 18 A. M. Silverstein, A History of Immunology (San Diego: Academic Press, 1989), pp. 142-145. 19 A. R. Wallace, Darwinism (London: Macmillan Co., 1889), Chapter 7. 20 G. J. Romanes, "Wallace on Physiological Selection", The Monist 1 (1890) 1-20. 21 G. Mendel, "Versuche uber Pflanzen Hybriden", Verh. naturf. Ver. in Brunn 4 (1865) 3-47. 22 W. Bateson, Presidential Address to the Zoological Society; British Association 1904, in William Bateson, F.R.S. Naturalist. His Essays and Addresses, ed. B. Bateson (Cambridge: Cambridge University Press, 1928), pp. 233-259. 23 W. Bateson, Materials for the Study of Variation (London: Macmillan Co., 1894). 24 T. H. Huxley, Letters, in Life and Letters of Thomas Henry Huxley, ed. L. Huxley (London: Macmillan and Co., 1900). 25 A. Conan Doyle, "The Sign of Four", Lippincott's Monthly Magazine, (Philadelphia) 266 (1890) pp. 172. 26 A. Jordan, "Remarques sur le fait d'existence en societe a l'etat sauvage des especes vegetale affine", Congres de l'Association Francaise pour l'Avancement des Sciences, 1873. 27 J. T. Gulick, "Divergent evolution through cumulative selection", J. Linn. Soc. (Zool.) 20 (1887) 189-274. 28 G. J. Romanes, A Candid Examination of Theism (London: Truebner Co., 1878) 29 G. J. Romanes, Mind and Motion; and Monism (London: Longmans, Green Co., 1886). 30 G. J. Romanes, Thoughts on Religion (Chicago: Open Court Pub. Co., 1895). 31 A. Gulick, John Thomas Gulick: Evolutionist and Missionary (Chicago: University of Chicago Press, 1932). 32 W. Bateson, Problems of Genetics (New Haven: Yale University Press, 1913), pp. 238- 242. 33 T. Dobzhansky, Genetics and the Origin of Species (New York: Columbia University Press, 1937), Chapters 7, 9. 34 J. T. Gulick. Evolution: Racial and Habitudinal (Washington: Carnegie Institute publication number 25, 1905). 35 A. Gulick, "What are genes? 1. The Genetic and Evolutionary Picture", Quart. Rev. Biol. 13 (1938) 1-18. 36 W. B. Provine, The Origins of Theoretical Population Genetics (Chicago: University of Chicago Press, 1971). 37 G. J. Romanes, Darwin, and After Darwin. Isolation and Physiological Selection (London: Longmans, Green, Co., 1897). 38 J. Maynard Smith, Evolutionary Genetics (Oxford: Oxford University Press, 1989). 39 R. Dawkins, The Selfish Gene (New York: Oxford University Press, 1976). 40 W. D. Hamilton, "The Genetic Evolution of Social Behaviour", Journal of Theoretical Biology 17 (1964) 1-54. For more on WDH (Click Here) 41 G. C. Williams, Adaptation and Natural Selection (Princeton: Princeton University Press, 1966). 42 D. R. Forsdyke, "Different biological species 'broadcast' their DNAs at different (G+C)% "wavelengths"", Journal of Theoretical Biology 178 (1996) 405-417. (For full text - Click Here) "Micromutations" were also suggested by Richard Goldschmidt in his Material Basis of Evolution (1940). DRF Aug 2003 43. G. B. Shaw, Bernard Shaw. Complete Plays with Prefaces. Volume I. (New York: Dodd, Mead Co., 1963). A character in another Shaw play "The Doctor's Dilemma" is inspired by Sir Almroth Wright, who shares with George J. Romanes the honour of being grandfather to Giles J. Romanes. 44 G. R. Wyatt, "The nucleic acids of some insect viruses", Journal of General Physiology 36 (1952) 201- 289. 45 E. C. Bronson and J. N. Anderson, "Nucleotide composition as a driving force in the evolution of retroviruses", Journal of Molecular Evolution 38 (1994) 506-532. 46 G. A. Schachtel, P. Bucher, E. S. Mocarski, B. E. Blaisdell, and S. Karlin, "Evidence for selective evolution in codon usage in conserved amino acid segments of human alphaherpesvirus proteins", Journal of Molecular Evolution 33 (1991) 483-494. 47 More scientific background is provided by references in my 1996 paper (note 42). See also D. R. Forsdyke, "An alternative way of thinking about stem-loops in DNA", Journal of Theoretical Biology 192 (1998) 489-504. (For full text - Click Here) The latter paper provides evidence that pairing of chromosomes should be influenced by small fluctuations in the species-dependent component of the base composition of DNA [(C+G)%]. 48 H. A. Orr, "Dobzhansky, Bateson, and the genetics of speciation", Genetics 144 (1996) 1331-1335. I further analyze Bateson's contribution in Journal of Theoretical Biology (1999) 201, 47-61. "Two levels of information in DNA. Relationship of Romanes' "intrinsic" variability of the reproductive system, and Bateson's "residue," to the species-dependent component of the base composition, (C+G)%". [ For full text - Click Here) ] 49 S. J. Gould, 1980. "Is a new and general theory of evolution emerging?" Paleobiology 6 (1980) 119-130. Lest this quotation be deemed prescient, we should note recantation by SJG in 2002 (The Structure of Evolutionary Theory. p. 1003). Here he stated: "I do not, in fact and retrospect ... regard this 1980 paper as among the ... most cogent ... that I have ever written. ... I then read the literature on speciation as beginning to favor sympatric [same country] alternatives to allopatric [different country] orthodoxies ... and predicted that views on this subject would change substantially, ... . I now believe that I was wrong in this prediction." DRF April 2002 There are uncanny similarities between Romanes and Gould. Both were center stage, both were well versed in biohistory, both wrote for popular and scientific audiences, both were attacked by the establishments of their days, and both contracted cancer in their forties. Modern chemotherapies may have given Gould another 20 years, whereas Romanes died at 46. DRF Aug 2003 50 There is a somewhat surrealistic personal twist to this story: My bioinformatic work (note 42) led to a relatively simple view of the origin of species, which made me wonder if one of the perspicacious Victorians close to Darwin might have anticipated me. After following several false trails in my search for a Victorian (e.g. note 36), I came across Romanes in the fall of 1997 and learned of his Canadian origin. Now, it so happens that, with my family, I had moved in 1982 to a grey stone house which forms part of a small block in William Street, Kingston. Shortly after the move we found that in the 1840s the block had housed Queen's College (see Queen's: The First Hundred and Fifty Years (Newburgh: Hedgehog Productions Inc., 1990), pp. 28-29). My 1997 enquiries led to the discovery that Professor George Romanes and his family occupied part of the block from 1846 to 1850 (see M. Angus, "Queen's College on William Street", Historic Kingston 34 (1986) 86-98 and photo of a painting below dated 1914). Since George John Romanes was born in 1848, it seems likely that he was born, and had passed his first two years, but a few yards from where these words are being typed! 51 I thank Geoffrey S. Smith (Department of History, Queen's University), and Charlotte and Ruth Forsdyke for most helpful editorial comments. The painting of 207 William Street by Jane Redpath Drummond (1916) was exhibited at the Agnes Etherington Arts Centre, and the above photograph (courtesy of Dorothy Farr) is displayed with the permission of Mr. Douglas Petty (owner of the original painting). Struggle to Define and Show Relationships between the Four Black Boxes: 1. Variation 2. Heredity 3. Phenotypic ("Natural") Selection Isolation, 4. Reproductive ("Physiological") Selection Isolation Hybrid Sterility (Darwin 1862) Variation (Hooker 1862) Pangenesis (Darwin 1868) Inutility of Characters (Gulick 1872) Natural and Artificial Selection (Belt 1874) Inutility of Characters. Paradox of Sex. Random Drift (Delboeuf 1877) Struggle to Establish "Physiological" Selection Isolation as the most Important Form of Reproductive Selection Isolation An Unnoticed Factor in Evolution (Catchpool 1884) Romanes (1886) Romanes (1887) Struggle to Establish the "Chromosomal" (not "Genic") basis of Physiological Selection Isolation Hybridism and the Germ-Cell (Guyer 1900, 1902) Cytological Basis for the Mendelian Laws (Cannon 1902) Chromosomes of the Germ Cells (Montgomery 1901) Chromosomes in Heredity (Sutton 1903) Two Levels of Genetic Information (Bateson Saunders 1902) Heredity and Variation in Modern Lights (Bateson 1909) A Phenomenon of Arrangement (Bateson 1914) Chromosomes, Polyploidy and Why Sex Evolved (Winge 1917) Speciation in Retroviruses (1995) Origin of Species (1996) Thinking about Stem-Loops (1998) Two Levels of Information in DNA (1999) Haldane's Rule (2000) Non-Genic (Chromosomal) Speciation(2003) Allen, Romanes and Gould (2004) Chromosomal Speciation: A Reply (2004) Some Evolutionary Terms Used in these Pages These definitions may be controversial, but it is to be recalled that progress in science (e.g. physics at the turn of the 19th century) sometimes requires that conventional definitions be challenged. Evolutionary event. Evolution results from the accumulation of many evolutionary "events", each involving some or all of four processes: variation, heredity (inheritance), phenotypic selection, reproductive isolation. An evolutionary event begins with variation and is followed by the process of heredity continuing through the generations. Selection may follow variation. Variation (like does not produce like). There is variation in a biological species and the resulting variant members of the species are candidates for differential selection. Variation is a process which produces the variant features of variant organisms. These variant features are themselves often referred to as variations. Thus the word "variation" must be understood in context either as the process, or as the result of that process. Heredity (like produces like). There is inheritance of a newly acquired variation by at least some of the offspring of variant members, and inheritance of that variation, in turn, by some of their offspring, and some of the subsequent offspring. If a variation is not inherited (overtly or cryptically) then it may be the result of some environmental influence and is not strictly related to the evolutionary event under consideration. Selection. The words "selection" and "isolation" have led to confusion. The words have the same meaning, although one may be preferred in a particular context. Selection is something which can be done when there is more than one of something. If there is only one of something, it is already selected (or isolated). In much of the literature, "selection" when used alone often means phenotypic selection; "isolation" when used alone often means reproductive selection. Phenotypic selection There is positive selection of members of the species with advantageous variations, and negative selection of members of the species with disadvantageous variations. This isolation on the basis of phenotypic adaptations (positive or negative) is the type of selection with which Darwin was primarily concerned. In this respect he and others spoke of "survival of the fittest" and the "struggle for existence". He used the term "natural selection", to distinguish this form of phenotypic selection from the artificial selection carried out by the domestic breeder. However, reproductive isolation selection can also be natural or artificial. Reproductive isolation. Variation, heredity and phenotypic selection can operate so that advantageous phenotypic characteristics would tend to increase in a population, and disadvantageous phenotypic characteristics would tend to decrease in a population. They provide for the adaptation of species, and operate primarily at the level of the individual member of the species (individual selection). However, for the origin of species (i. e. a divergence between two population groups), a fourth process, "reproductive isolation", is needed. To originate species, groups have to be selected. Speciation (species selection) is a form of group selection. A group is a set of units. For our purposes, if there is only one unit in a set it is an individual, and does not constitute a group. A group whose members reproduce only asexually is, by definition, already reproductively isolated from other groups. Species . The most secure definition of a biological species is a group of organisms which is reproductively isolated from other groups of organisms. Members of the group are infertile (sterile) with all other organisms, except those organisms which belong to the group. Degrees of infertility are characteristic of organisms at the species interface (i.e. potential incipient species). Hybrid. The offspring of crosses between members of two anatomically distinct lines (varieties, races) are often referred to as "hybrids". Since the definition of species is based primarily on reproductive performance, rather than anatomical difference, this can lead to confusion. For our purposes any offspring is the hybrid of its parents if the parents are different genomically. If the offspring is more fit than the parents (in terms of being able to perpetuate a line) there is hybrid vigour ("positive heterosis"). If the offspring is less fit, this "negative heterosis" can be manifest as hybrid inviability (developmental barrier) or hybrid sterility (gonadal barrier). For humans, the only possible offspring not a "hybrid" would be the extremely improbable case of a female who inherited absolutely identical sequences from both parents. In the case of a human male, even if the autosomes were absolutely identical, the sex chromosomes would differ; so, under our definition, all males are hybrids. Genome.This term might be interpreted, by the uninitiated, as "gene home". We talk of "the human genome" or "the genome of the bacterium Escherichia coli". We usually mean the most obvious form of genetic material, which in these organisms is DNA. It is true that most of the E. coli genome consists of genes, but in "higher" organisms there is much DNA which is not so obviously "genic". Our genomes are not just "gene homes". Note also that a piece of the genome which we recognize as a "gene" may be serving functions other than those conventionally considered "genic". This is considered more in the Bioinformatics Genomics section of these pages. Further Acknowledgements .The photographs of Romanes and Gulick are from Romanes' Darwin, and After Darwin (Longmans). Photographs of the portraits of George and Ethel Romanes were made available by Giles J. Romanes. The photographs of Charles Darwin and Thomas Huxley are from the History of Medicine Division of the National Library of Medicine, USA ( Click here ). The photographs and drawing of Bateson are from the Report of the Royal Horticultural Conference on Genetics, 1906, as reproduced by H. F. Roberts in Plant Hybridization Before Mendel (Princeton University Press, 1929), and Beatrice Bateson's two books Letters from the Steppe (Methuen, London, 1928), and William Bateson F.R.S. (Cambridge University Press, 1928; original in the National Portrait Gallery, London). In the Delboeuf paper, the beautiful photograph of a South American butterfly (Heliconidae) is from Dr. William T. Hark's Butterfly Web Page ( Click here ), and the orangatan is from the Web Page of the Orangatan Foundation International, Los Angeles. Other acknowledgements are given in individual pages. The pictures of gametes and early divisions of the zygote in the legend to Figure 1 are from the prolife webpage of Simbahayan Sa Maynila, who, in turn, acknowledges Dr. Anna E. Ross of Christian Brothers' University. Translators needed! Some potentially very important works on evolutionary biology by 19th century authors are not available in English translations. Thus, if you enjoy the presentation and would like to help, please consider using your language skills to open up an important literature to the English-speaking world. Donald Forsdyke Other Web Sites on Evolution with a Historical Perspective Darwin correspondence : calender and summary of each letter Darwin's other works online : A complete collection of everything he wrote (in preparation) Darwiniana by Asa Gray, 1876 : full-text of book on-line Encyclopedia of Life Sciences [See Biographies of Mendel, Romanes, Bateson, Muller, Haldane and Chargaff] Electronic Scholarly Fascimile Project on Classical Genetics Electronic Scholarly Fascimile of " Mendel's Principles of Heredity. A Defence". By W. Bateson Fisher, Ronald A, - Papers: University of Adelaide Galton, Francis ["Biometrician"] Gould, Stephen Jay [Advocate of hierarchical levels] Grant Allen [born Kingston 1848] Hooker, Joseph Dalton [Proposer of "Creation by Variation"] Huxley, Thomas Henry [Darwin's "bulldog"] Korthof's Reviews of Books on Evolution Mallet's History of Species Concepts MendelWeb Mivart, St. George on "The Genesis of Species" 1871 Panspermia [An unlikely hypothesis, but a lucid discussion of the issues.] Patterson's Darwiniana links Wallace, Alfred Russel ["Codiscoverer" of Evolution] New Book on Evolution Return to Home Page This page was first posted circa 1998 and last edited on 01 July, 2005 by D. R. Forsdyke WWW page access counter Since 30th March 1999 UCMP Evolution Wing Enter Evolution: Theory and History Excellent evolution resource provided by the University of California. Also contains an interesting account of Darwin's evolutionary antecendants. Traces evolutionary thought as it has developed over tim