From owner-ageing@net.bio.net Fri Dec 03 22:00:00 1993 Path: biosci!daresbury!doc.ic.ac.uk!pipex!howland.reston.ans.net!darwin.sura.net!news-feed-1.peachnet.edu!concert!rutgers!princeton!phoenix.Princeton.EDU!harnad From: harnad@phoenix.Princeton.EDU (Stevan Harnad) Newsgroups: bionet.neuroscience,bionet.cellbiol,bionet.molbio.ageing,bionet.genome.chromosomes Subject: Neural Transplantation: Call for Commentators Keywords: neural grafts, gene therapy, brain damage, functional recovery Message-ID: <1993Dec2.224215.21986@Princeton.EDU> Date: 2 Dec 93 22:42:15 GMT Sender: news@Princeton.EDU (USENET News System) Organization: Princeton University Lines: 222 Xref: biosci bionet.neuroscience:2127 bionet.cellbiol:197 bionet.molbio.ageing:578 bionet.genome.chromosomes:117 Originator: news@nimaster Nntp-Posting-Host: phoenix.princeton.edu BBS Special Issue CONTROVERSIES IN NEUROSCIENCE II: Neural Transplantation Below are the abstracts of 3 forthcoming target articles for a special issue on Neural Transplantation that will appear in Behavioral and Brain Sciences (BBS), an international, interdisciplinary journal that provides Open Peer Commentary on important and controversial current research in the biobehavioral and cognitive sciences. This will be the second in a new series called "Controversies in Neuroscience," undertaken in collaboration with Paul Cordo and the RS Dow Neurological Science Institute. Commentators must be current BBS Associates or nominated by a current BBS Associate. To be considered as a commentator on any of these articles, to suggest other appropriate commentators, or for information about how to become a BBS Associate, please send email to: harnad@clarity.princeton.edu or harnad@pucc.bitnet or write to: BBS, 20 Nassau Street, #240, Princeton NJ 08542 [tel: 609-921-7771] Please specify which article or articles you would like to comment on. (Commentators are allotted 1000 words to comment on one article, 1750 words to comment on two, and a maximum of 2250 words to comment on all three target articles.) To help us put together a balanced list of commentators, please give some indication of the aspects of the topic on which you would bring your areas of expertise to bear if you were selected as a commentator. Within the next week or so, electronic drafts of the full text of each article will be available for inspection by anonymous ftp, archie, gopher or versonica on host princeton.edu directory pub/harnad/BBS according to the instructions that follow after the abstracts. These drafts are for inspection only; please do not prepare a commentary until you are formally invited to do so. 1. NEURAL TRANSPLANTATION AND RECOVERY OF COGNITIVE FUNCTION John D. Sinden, Helen Hodges & Jeffrey A. Gray Filename: bbs.sinden 2. FETAL BRAIN TISSUE GRAFTS AS THERAPY FOR BRAIN DYSFUNCTIONS Donald G. Stein & Marylou M. Glasier Filename: bbs.stein 3. GENE REPLACEMENT THERAPY IN THE CENTRAL NERVOUS SYSTEM Edward A.Neuwelt, Michael A. Pagel, Leslie L. Muldoon & Alfred Geller Filename: bbs.neuwelt --------------------------------------------------------------------- 1. NEURAL TRANSPLANTATION AND RECOVERY OF COGNITIVE FUNCTION John D. Sinden, Helen Hodges & Jeffrey A. Gray Department of Psychology Institute of Psychiatry De Crespigny Park Denmark Hill London SE5 8AF England spjtjds@ucl.ac.uk jgray@ux.psych.lon.ac.uk KEYWORDS: Cholinergic system, cerebral ischaemia, cognitive function, neural grafts. ABSTRACT: Cognitive deficits were produced in rats using different methods of damaging the brain: chronic ingestion of alcohol, causing widespread damage to diffuse cholinergic and aminergic projection systems; lesions (by local injection of the excitotoxins, ibotenate, quisqualate and AMPA) to the nuclei of origin of the forebrain cholinergic projection system (FCPS), which innervates the neocortex and hippocampal formation; transient cerebral ischaemia, producing focal damage, especially in the CA1 pyramidal cells of the dorsal hippocampus; and lesions (by local injection of the neurotoxin, colchicine) to the granule cells of the dentrate gyrus. Following chronic alcohol or lesions of the FCPS, transplants of cholinergically rich fetal brain tissue into the terminal areas (neocortex or hippocampus) restored performance almost to control levels, with a time-course consistent with growth of the transplants and integration with host tissue; transplants of cholinergically poor fetal tissue (hippocampus) were without effect, as were transplants of cholinergically rich tissue into the region containing the nuclei of origin of the FCPS. Grafts of primary cells enriched in glia and cultured neuroblastoma cells into the terminal areas of the FCPS were equally effective, suggesting that there are multiple mechanisms by which neural transplants can restore cognitive function following diffuse cholinergic damage. In contrast, after ischaemia- or neurotoxin-induced damage to CA1 or dentate granule cells respectively, cholinergically rich fetal transplants into the damaged hippocampal formation were ineffective in restoring performance. However, after ischaemic damage, performance was restored by suspension grafts of CA1 cells but not by transplants containing CA3 pyramidal cells or granule cells; and after colchicine damage, performance was restored by solid grafts containing granule but not CA1 pyramidal cells. Furthermore, electrophysiological evidence has demonstrated functional, graft type-specific host-graft fuctional neuronal connectivity. Thus, restoration of cognitive function by neural transplants is possible after damage to either diffuse (cholinergic) or point-to-point (intrahippocampal) forebrain systems, but the transplant must be appropriate to the damage to be repaired. Since the different types of brain damage studies provide partial analogues of human alcoholic dementia, Alzheimer's disease and heart attack, these results are encouraging with regard to the eventual application of neural transplant surgery to the treatment of cognitive deficits in humans. ----------------------------------------------------------------------- 2. FETAL BRAIN TISSUE GRAFTS AS THERAPY FOR BRAIN DYSFUNCTIONS: SOME PRACTICAL AND THEORETICAL ISSUES Donald G. Stein & Marylou M. Glasier Laboratory of Brain Research and CNS Plasticity Institute of Animal Behavior Rutgers University Newark, NJ 07102 stein@draco.rutgers.edu KEYWORDS: Brain damage; functional recovery; grafts; neural grafts; neural transplants ABSTRACT: Grafting embryonic neural tissue into the brains of adult patients is currently being used to treat Parkinson's disease and is being given serious consideration as therapy for a variety of other degenerative and traumatic disorders. This target article evaluates the use of transplants to promote recovery from brain injury and highlights the kinds of questions and problems that must be addressed before this form of therapy is routinely applied. It has been argued that neural transplantation can promote functional recovery through the replacement of damaged nerve cells, the reestablishment of specific nerve pathways lost as a result of injury, the release of specific neurotransmitters, or the production of factors that promote neuronal growth. The latter two mechanisms, which need not rely on anatomical connections to the host brain, are open to examination through nonsurgical, less intrusive therapy. Subjective judgments in selecting which patients will receive grafts and in assessing the outcome of graft therapy make evaluation of the procedure methodologically difficult. In addition, little long-term assessment of transplant efficacy and effect has been done in nonhuman primates. Carefully controlled human studies, with multiple testing paradigms, are also needed to establish the efficacy of transplant therapy. ----------------------------------------------------------------------- 3. GENE REPLACEMENT THERAPY IN THE CENTRAL NERVOUS SYSTEM: VIRAL VECTOR MEDIATED THERAPY OF GLOBAL NEURODEGENERATIVE DISEASE Edward A.Neuwelt, Michael A. Pagel, Leslie L. Muldoon Oregon Health Sciences University, Portland OR 97201 Alred Geller Children's Hospital Boston, MA 02115 KEYWORDS: adenovirus; blood-brain barrier; gene therapy; herpes virus; pHexosaminidase ABSTRACT: This target article describes the current state of global gene replacement in the brain through the use of viral vectors and it assesses possible solutions to some of the many problems inherent in gene therapy for the central nervous system (CNS). Gene replacement therapy is a way to generate normal human proteins in deficient cells, making cures possible for certain genetically inherited enzyme deficiences, metabolic diseases, and cancers. The two major issues to be addressed are the delivery of genetic material to the brain and the expression of recombinant genetic material in CNS target cells. Focal inoculation of recombinant virions or other genetic vectors has limitations when there is global brain disease. A new blood-brain-barrier (BBB) disruption technique, in which hypertonic mannitol transiently shrinks the BBB endothelium, allows the passage of high molecular weight compounds and even viruses. CNS gene therapy will require a viral vector system that allows long-term, nontoxic gene expression in neurons or glial cells. Retroviral vectors have limitations in CNS gene replacement, although they are suitable for expressing recombinant genes in intracerebral grafts, or toxic genes in brain tumors. Mutant neurotropic viruses with reduced neurotoxicity (e.g., defective herpes simplex virus type 1 [HSV-1], the HSV-1 amplicon vector system we have developed, or adenovirus mutants) have potential for direct treatment of neurons. Injecting these vectors into rodent brains can lead to the stable expression of foreign genetic material in postmitotic neuronal cells. We discuss our BBB disruption delivery technique, our defective HSV-1 aplicon vector system, and our feline model for the neuronal lysosomal storage disorder Gm2-gangliosidosis (Sandhoff disease), which may prove to be a useful model system for CNS gene therapy. ---------------------------------------------------------------------- To help you decide whether you would be an appropriate commentator for this article, electronic drafts are retrievable by anonymous ftp from princeton.edu according to the instructions below (the filenames are bbs.sinden bbs.stein and bbs.neuwelt). Please do not prepare a commentary on these drafts. Just let us know, after having inspected them, what relevant expertise you feel you would bring to bear on what aspect of each article. ------------------------------------------------------------- To retrieve a file by ftp from a Unix/Internet site, type either: ftp princeton.edu or ftp 128.112.128.1 When you are asked for your login, type: anonymous Enter password as per instructions (make sure to include the specified @), and then change directories with: cd /pub/harnad/BBS To show the available files, type: ls Next, retrieve the file you want with (for example): get bbs.sinden When you have the file(s) you want, type: quit In case of doubt or difficulty, consult your system manager. A more elaborate version of these instructions for the U.K. is available on request (thanks to Brian Josephson). The files are also retrievable through archie, gopher, veronica, etc. ---------- Where the above procedures are not available (e.g. from Bitnet or other networks), there are two fileservers: ftpmail@decwrl.dec.com and bitftp@pucc.bitnet that will do the transfer for you. To one or the other of them, send the following one line message: help for instructions (which will be similar to the above, but will be in the form of a series of lines in an email message that ftpmail or bitftp will then execute for you). ------------------------------------------------------------- From owner-ageing@net.bio.net Sat Dec 04 22:00:00 1993 Path: biosci!CS.Arizona.EDU!organpipe.uug.arizona.edu!uunet!mnemosyne.cs.du.edu!nyx!jcypser From: jcypser@nyx.cs.du.edu (Jim Cypser) Newsgroups: bionet.molbio.ageing Subject: tumor suppressor genes Message-ID: <1993Dec5.040656.10046@mnemosyne.cs.du.edu> Date: 5 Dec 93 04:06:56 GMT Sender: usenet@mnemosyne.cs.du.edu (netnews admin account) Distribution: na Organization: Nyx, Public Access Unix at U. of Denver Math/CS dept. Lines: 3 X-Disclaimer: Nyx is a public access Unix system run by the University of Denver for the Denver community. The University has neither control over nor responsibility for the opinions of users. Has anyone heard any speculation about the possible roles of tumor suppressor genes in ageing? From owner-ageing@net.bio.net Sun Dec 05 22:00:00 1993 Path: biosci!news.cs.umb.edu!hsdndev!yale!yale.edu!spool.mu.edu!howland.reston.ans.net!europa.eng.gtefsd.com!uunet!mnemosyne.cs.du.edu!nyx!jcypser From: jcypser@nyx.cs.du.edu (Jim Cypser) Newsgroups: bionet.molbio.ageing Subject: tumor suppressor genes Message-ID: <1993Dec5.040656.10046@mnemosyne.cs.du.edu> Date: 5 Dec 93 04:06:56 GMT Sender: usenet@mnemosyne.cs.du.edu (netnews admin account) Distribution: na Organization: Nyx, Public Access Unix at U. of Denver Math/CS dept. Lines: 3 X-Disclaimer: Nyx is a public access Unix system run by the University of Denver for the Denver community. The University has neither control over nor responsibility for the opinions of users. Has anyone heard any speculation about the possible roles of tumor suppressor genes in ageing? From owner-ageing@net.bio.net Mon Dec 06 22:00:00 1993 Path: biosci!JUDY.ENG.UCI.EDU!liang From: liang@JUDY.ENG.UCI.EDU (liang) Newsgroups: bionet.molbio.ageing Subject: CHINESES_BIOTECH_NET_FOUNDED Message-ID: <9312061945.AA20422@judy.eng.uci.edu> Date: 6 Dec 93 19:45:23 GMT Sender: daemon@net.bio.net Distribution: bionet Lines: 12 CBNet (Chinese Biotechnology Network) is a non-profit organization composed of professionals in biological, chemical, medical sciences, engineering and related fields. The CBNet sponsors the Chinese Biotechnology Internet Forum (CBIF) newsletter. To subscribe CBIF, please send an email to Listserv@UCSD.Edu with the message body: Add CB-Net. From owner-ageing@net.bio.net Mon Dec 06 22:00:00 1993 Path: biosci!JUDY.ENG.UCI.EDU!liang From: liang@JUDY.ENG.UCI.EDU (liang) Newsgroups: bionet.molbio.ageing Subject: CHINESES_BIOTECH_NET_FOUNDED Message-ID: <9312060500.AA19321@judy.eng.uci.edu> Date: 6 Dec 93 05:00:21 GMT Sender: daemon@net.bio.net Distribution: bionet Lines: 12 CBNet (Chinese Biotechnology Network) is a non-profit organization composed of professionals in biological, chemical, medical sciences, engineering and related fields. The CBNet sponsors the Chinese Biotechnology Internet Forum (CBIF) newsletter. To subscribe CBIF, please send an email to Listserv@UCSD.Edu with the message body: Add CB-Net. From owner-ageing@net.bio.net Wed Dec 08 22:00:00 1993 Path: biosci!daresbury!doc.ic.ac.uk!warwick!pipex!uunet!olivea!spool.mu.edu!uwm.edu!caen!batcomputer!ghost.dsi.unimi.it!genes!pongor From: pongor@genes.icgeb.trieste.it (Sandor Pongor) Newsgroups: bionet.molbio.ageing Subject: Mail server for protein functional domain homologies - ICGEB Trieste Keywords: mail server, molecular biology, protein domains, sequences Message-ID: <1993Dec9.100651.21676@genes.icgeb.trieste.it> Date: 9 Dec 93 10:06:51 GMT Organization: ICGEB Lines: 148 SS BBB A SS EEEE H H EEEE L PPP S S B B A A S S E H H E L P P S B B A A S E H H E L P P S BB AAAAA S EEE HHHHH EEE L PPP S B B A A S E H H E L P S B B A A S E H H E L P S S B B A A S S E H H E L P SSS BBB A A SSS EEEE H H EEEE LLLL P ---------------------------------- This is the help file of the SBASE Email Server at the International Centre for Genetic Engineering and Biotechnology AREA Science Park, Padriciano 99, 34012 Trieste, Italy. ---------------------------------- The SBASE Email Server is at present experimental. Please send comments to sbase-comment@icgeb.trieste.it. Thanks. The SBASE e-mail server accepts a specially formatted mail message containing a protein query sequence, and, as a response, it sends the list of the most probable domain homologies. A database search is performed against the SBASE library of protein domains using the BLAST algorithm, and the search results, provided with annotations, are returned in a mail message. How to use: Getting HELP: ============ This help file can be gotten by sending an email to sbase@icgeb.trieste.it containing the word HELP alone in the first line of the message body. Making a QUERY: =============== Send e-mail to sbase@icgeb.trieste.it using the below example Note: the parameters before the token BEGIN are optional, (here the defaults are listed), the lines after BEGIN are required. Example: MATRIX PAM120 SCORE PARAMETER 35 ANNOTATIONS YES BEGIN > mysequence LRNGVDINTCNQNGLNGLHLASKEGHVKMVVELLHKEIILETTTKKGNTALHIAALAGQDEVVRELVNYG GLNGLHLASKEGHVKMVVELLHKEIILETTTKKGNTALHIAALAGQDEVVRELVNYG Response time ============= Requests are handled immediately, in serial order. At present, response time is quite short and is restricted by the network load rather than CPU availability. Please note that large output files, such as sometimes occur with very short query sequences, may need a long time to traverse the net. Evaluation of the output: ========================= The output of the server are BLAST search results against the SBASE protein domain library. The output file contains the BLAST search results, organized as follows: 1) List of the best scoring domain entries. As SBASE entries are named by domain names (function, structure, etc.), this list already may give some information on the expected domain composition. 2) List of alignments. For each SBASE entry you will find the complete annotation of the domain, followed by one (or several) alignments with (different parts of) the query. If one domain is found several times in your query, you may find several alignments with the same or related entries at different parts of the query. Please note that it depends on the score parameter whether or not you see all the alignments. Do not use very low cutoff values because that results in prohibitively long output files. (For the time being, we have set the default cutoff to 35 and the minimum cutoff to 30). 3) Run statistics. This is usually not essential for the evaluation of the results; you can get a complete description of these and other blast parameters by sending a HELP message to blast.ncbi.nlm.nih.gov Important: Failure to see a homology with a known domain may be due to several reasons: i) The domain type is not (yet) included in the SBASE domain library; ii) The threshold score parameter was set too high for the domain to be detected; iii) A different scoring matrix may be necessary in order to detect the alignment with the domain type in question. In the present experimental version of the SBASE server we support only the matrices used by BLAST; "customized matrices" will be added later to the final version. Papers to reference in reporting results: ========================================= Pongor, S., Skerl, V., Cserzo, M. and Hatsagi, Z., Simon, G. and Bevilacqua, V. (1992): The SBASE domain library release 2.0& A collection of annotated protein sequence segments, Nucleic Acids. Res , 21, 311-315 Altschul, Stephen F., Warren Gish, Webb Miller, Eugene W. Myers, and David J. Lipman (1990) Basic local alignment search tool J. Mol. Biol. 215:403-410. Software availability ===================== The Sbase database is available by anonymous ftp at ftp.icgeb.trieste.it:/pub/sbase2 The blast software is available by anonymous ftp at ncbi.nlm.nih.gov:/pub/ Protection of your sequence data ================================ The query sequences are not stored in any form. Further info: ============= Server functions: Zsolt Hatsagi Tel: +39-40-3757342 Valeria Bevilacqua, systems manager (valeria@icgeb.trieste.it) Tel.: +39-40-3757330 General info: Sandor Pongor Tel: +39-40-3757300 FAX: +39-40-226-555 Mail: International Centre for Genetic Engineering and Biotechnology AREA Science Park, Padriciano 99 34012 Trieste, Italy From owner-ageing@net.bio.net Thu Dec 09 22:00:00 1993 Path: biosci!MBCMAIL.AB.UMD.EDU!collins From: collins@MBCMAIL.AB.UMD.EDU (John Collins) Newsgroups: bionet.molbio.ageing Subject: protein sequencing lab Message-ID: <9312101415.A03088@mbcmail.ab.umd.edu> Date: 10 Dec 93 19:15:13 GMT Sender: daemon@net.bio.net Distribution: bionet Lines: 43 ---------------------------------- Forwarded ---------------------------------- From: John Collins Date: 12/10/93 2:18PM To: John Collins Subject: protein sequencing lab ------------------------------------------------------------------------------- Dear Colleague: I would like to call to your attention the availability of the PROTEIN SEQUENCING LAB, a core facility of the University of Maryland. We offer: PROTEIN/PEPTIDE SEQUENCING AMINO ACID ANALYSIS PEPTIDE MAPPING AND PURIFICATION BY HPLC IDENTIFICATION OF MODIFIED AMINO ACIDS DATABASE HOMOLOGY SEARCHES SECONDARY STRUCTURE PREDICTIONS HYDROPATHY PROFILES CONFIDENTIALITY EXPERIENCED, HELPFUL STAFF PERSONAL ATTENTION CONSULTATIONS PROPOSAL WRITING ASSISTANCE COLLABORATIONS FAST, QUALITY SERVICE COMPETITIVE PRICES Our mailing address is: Dr. John H. Collins Protein Sequencing Lab Dept. of Biological Chemistry Univ. Maryland School of Medicine 108 N. Greene St. Baltimore, MD 21201 For further information contact me, the lab director, John H. Collins, Ph.D., Professor of Medical Biotechnology and Biological Chemistry. tel: (410) 706-8102 fax: (410) 706-7364 e-mail: collins@mbcmail.ab.umd.edu From owner-ageing@net.bio.net Fri Dec 10 22:00:00 1993 Path: biosci!bcm!cs.utexas.edu!howland.reston.ans.net!wupost!cheswicks!fredgate From: Kevin.Lakamp@f12.n8012.z86.toadnet.org (Kevin Lakamp) Newsgroups: bionet.molbio.ageing Subject: Rewarding work Message-ID: <755523453.AA01973@cheswicks.toadnet.org> Date: 10 Dec 93 05:26:02 GMT Lines: 6 X-FTN-To: Maria Dawson Working with the elderly is indeed rewarding. But, like the field of education, many "social" type positions do not carry the monetary rewards. And, the positions that do carry the monetary rewards often times are filled by people motivated by profit. I am currently looking for work as a nursing home administrator, but it's tough since I make more money driving a truck than many of the administrators I know. Go figure. From owner-ageing@net.bio.net Sun Dec 12 22:00:00 1993 Path: biosci!daresbury!not-for-mail From: gmalet@surfer.win.net (Gary Malet) Newsgroups: bionet.molbio.ageing Subject: Internet health messaging Date: 13 Dec 1993 02:16:48 -0000 Lines: 43 Sender: daemon@mserv1.dl.ac.uk Distribution: bionet Message-ID: <2egjag$2c4@mserv1.dl.ac.uk> Reply-To: gmalet@surfer.win.net (Gary Malet) Original-To: ageing@dl.AC.UK You have been identified as a provider of an important health resource on Internet. I am contacting you for the "Healthtel Project" which is dedicated to expanding Internet messaging regarding health issues, clinical research, and medical practice. We offer a shareware windows hypertext database called Healthmatrix that catalogues the extensive health resources available on Internet. The Healthmatrix program is available by anonymous ftp from: OAK.Oakland.Edu pub/msdos/windows3/hmatrix.zip WIN3: Internet Health Science Resources List Your resource is listed in Healthmatrix! Please review the entry for your health resource and send any corrections to Lee Hancock- LE07144@UKANVM.BITNET. We would appreciate a text description of your resource to add to our next version of the program. Healthtel also offers a freeware windows based email program called Healthtel Mail and News. Forward us your street address and we will send diskettes of our Healthtel software and brochure. This can be handed out to colleagues and interested parties to promote the use of your resource. Healthmatrix provides an in depth description of our services. ***************************************************************************** Dr. Gary Malet |7 W 5th Street | "communication, Family Physician |Stockton, Ca. 95206 | search, Healthtel, Inc.-windows based |VOICE 209-466-6878 | delivery, medical telecommunications |FAX 209-466-7201 | networking" gmalet@doc.healthtel.com |Compuserve 72630.1535| ***************************************************************************** From owner-ageing@net.bio.net Mon Dec 13 22:00:00 1993 Path: biosci!EIS.CALSTATE.EDU!dbeadle From: dbeadle@EIS.CALSTATE.EDU (Dan Beadle) Newsgroups: bionet.molbio.ageing Subject: unsubscribe Date: 14 Dec 1993 14:06:25 -0800 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 4 Sender: daemon@net.bio.net Distribution: bionet Message-ID: NNTP-Posting-Host: net.bio.net unsubscribe Dan Beadle From owner-ageing@net.bio.net Tue Dec 14 22:00:00 1993 Path: biosci!bcm!cs.utexas.edu!uunet!munnari.oz.au!uniwa!newsman!Jim.Cummins From: cummins@possum.murdoch.edu.au (Jim Cummins) Newsgroups: bionet.molbio.ageing Subject: Longevity in C. elegans Date: 15 Dec 1993 05:17:10 GMT Organization: Murdoch University, Western Australia Lines: 12 Sender: -Not-Authenticated-[6523] Message-ID: <2em6kmINNkl4@newsman.csu.murdoch.edu.au> NNTP-Posting-Host: vetmac3.csu.murdoch.edu.au X-Posted-From: InterNews 1.0@newsman.csu.murdoch.edu.au. Xdisclaimer: No attempt was made to authenticate the sender's name. A recent paper in Nature (Kenyon C, Chang J, Gensch E, Rudner A, Tabtiang, R: "A C. elegans mutant that lives twice as long as wild type". Nature 366: 461-646: 1993) demonstrated that a single mutation in a gene involved in development (daf-2) results in a 2.3 fold increase in healthy, fertile lifespan. Anyone have any ideas on how this might function? Jim Cummins School of Veterinary Studies Murdoch University Western Australia 6150 Tel +61-9-360 2668 Fax +61-9-310 4144 For every complex problem there's a simple solution. And it's wrong! From owner-ageing@net.bio.net Wed Dec 15 22:00:00 1993 Path: biosci!bcm!cs.utexas.edu!uunet!olivea!charnel!rat!decwrl!morrow.stanford.edu!msob-a-fp-dynamic.stanford.edu!user From: altman@camis.stanford.edu (Russ B. Altman) Newsgroups: bionet.molbio.ageing Subject: NMR Symposium (Jardetzky) Followup-To: bionet.molbio.ageing Date: 16 Dec 1993 18:32:23 GMT Organization: Stanford University Medical Center Lines: 56 Distribution: world Message-ID: NNTP-Posting-Host: msob-a-fp-dynamic.stanford.edu INTERNATIONAL SYMPOSIUM ON BIOLOGICAL NMR in Honor of Professor Oleg Jardetzky on his 65th Birthday Fairchild Auditorium, Stanford University March 24-26, 1994 Organizers: Dr. John L. Markley, Dr. Stanley J. Opella, and Dr. Russ B. Altman Preliminary List of Speakers: K. Akasaka (Kobe), R. B. Altman (Stanford), C. H. Arrowsmith (Toronto), E. D. Becker (NIDDK, NIH), S. Chan (CalTech), J. S. Cohen (Georgetown U.), M. Cohn (Pennsylvania), P. Cozzone (Marseille), C. M. Dobson (Oxford), O. Jardetzky, (Stanford), T. S. Jardetzky (Harvard), J.-F. Lefevre (Strasbourg), M. Levitt (Stanford), W. N. Lipscomb (Harvard), L. Litt (UC San Francisco), J. L. Markley (Wisconsin), H. M. McConnell (Stanford), S. J. Opella (Pennsylvania), L. Pauling (Linus Pauling Inst.), G. C. K. Roberts (Leicester), J. K. M. Roberts (UC Riverside), R. G. Shulman (Yale), D. Wemmer (UC Berkeley) To register, please fill out the following information and send by Email to holbrook@camis.stanford.edu or print out, fill out, and fax to 415/723-2253 Robin Holbrook, Stanford Magnetic Resonance Laboratory, Stanford University, Stanford, CA 94305-5055 - Phone: 415/723-6270 Registration : $ 80 (incl. coffee breaks, lunch 3/24 & 3/25 & Banquet Friday Nite) Student Registration: $ 30 (Banquet not included) Banquet only: $ 35 Additional Guest/Spouse for Banquet: $ 35 ___________________________(name) Total Enclosed (or mailed separately) $________ (Check or money order -U.S.$- payable to Stanford University) I would like to attend: ___________________________________________________ Name ___________________________________________________ Department ___________________________________________________ Institution/Company ___________________________________________________ Address ___________________________________________________ City/State/Zip/Country ___________________________________________________ Telephone Fax Send information on local hotel accomodations (indicate one) ____Yes, please ____No, thank you A limited amount of space will be available, on a first-come, first-served basis, to display scientific posters (maximum size of poster: 4' x 4'). Submit a poster title to Robin Holbrook to reserve a poster board. From owner-ageing@net.bio.net Thu Dec 16 22:00:00 1993 Newsgroups: bionet.molbio.ageing Path: biosci!daresbury!zeta.bmc.uu.se!corax.udac.uu.se!sunic!EU.net!uknet!pipex!howland.reston.ans.net!agate!boulder!cnsnews!elegans.Colorado.EDU!gehle From: gehle@ibg.colorado.edu (GEHLE VAUGHN M) Subject: Re: Longevity in C. elegans Message-ID: Sender: usenet@cnsnews.Colorado.EDU (Net News Administrator) Nntp-Posting-Host: elegans.colorado.edu Organization: IBG, University of Colorado, Boulder References: <2em6kmINNkl4@newsman.csu.murdoch.edu.au> Date: Fri, 17 Dec 1993 11:16:20 GMT Lines: 58 In article <2em6kmINNkl4@newsman.csu.murdoch.edu.au>, Jim Cummins wrote: >A recent paper in Nature (Kenyon C, Chang J, Gensch E, Rudner A, >Tabtiang, R: "A C. elegans mutant that lives twice as long as wild >type". Nature 366: 461-646: 1993) demonstrated that a single mutation >in a gene involved in development (daf-2) results in a 2.3 fold >increase in healthy, fertile lifespan. Anyone have any ideas on how >this might function? > >Jim Cummins >School of Veterinary Studies >Murdoch University >Western Australia 6150 Tel +61-9-360 2668 Fax +61-9-310 4144 >For every complex problem there's a simple solution. And it's wrong! In article <2em6kmINNkl4@newsman.csu.murdoch.edu.au>, Jim Cummins wrote: >A recent paper in Nature (Kenyon C, Chang J, Gensch E, Rudner A, >Tabtiang, R: "A C. elegans mutant that lives twice as long as wild >type". Nature 366: 461-646: 1993) demonstrated that a single mutation >in a gene involved in development (daf-2) results in a 2.3 fold >increase in healthy, fertile lifespan. Anyone have any ideas on how >this might function? I haven't yet read Cynthia's paper, so I don't know how much of a description she gives of dauer larvae. Here is a brief and incomplete description: C elegans has an alternate developmental larval stage called the dauer. Dauers are very long-lived (70 days or more compared to the normal adult lifespan of about 15 days), and do not eat, nor reproduce. It is a method of surviving adverse environmental conditions. Usually dauer formation is induced by a lack of food, or overcrowding. Once food is again encountered, the dauer continues its arrested development to become an adult. It is not known how the dauer is able to survive for so long, but one interesting point is that dauer larvae have very high levels of SOD and catalase. Daf mutants are defective in one of the genes in the pathway to dauer formation so that regardless of environmental conditions, larvae enter the dauer pathway. Some of the daf mutants are long-lived as adults (like daf-2), others are not. What is likely happening is that some of the dauer mutants turn on parts of the dauer genetic program that never get shut down, even after the dauer continues on to adulthood, so that the long-lived daf mutants probably are continuing to use as adults the metabolic programs that allow long life in the dauer stage. One of those programs is probably increased resistance to oxygen radical damage provided by the elevated SOD and catalase levels. I work in Tom Johnson's lab and we are working on another long-lived mutant strain of C elegans, age-1 mutants, that also have high levels of SOD and catalase, only the levels are normal through most of the adult lifespan and only increase in "old age". My suspicion is that the daf-2 mutant has elevated SOD and catalase throughout its entire adult lifespan, but we have not yet tested this, and I don't know if Cynthia Kenyon has either. Vaughn M. Gehle, Ph. D. Institute for Behavioral Genetics University of Colorado gehle@ibg.colorado.edu From owner-ageing@net.bio.net Thu Dec 16 22:00:00 1993 Path: biosci!rutgers!mbcl!malyankar From: malyankar@mbcl.rutgers.edu Newsgroups: bionet.molbio.ageing Subject: Gene expression & aging Message-ID: <3142.2d10c953@mbcl.rutgers.edu> Date: 17 Dec 93 00:47:15 GMT Lines: 11 This is just a comment on an earlier post about longevity in C.elegans As far as I remember, Pereira-Smith in Baylor had described some complementation groups for immortalization in mammalian cells. Maybe, this is one of the genes that belong to one of the groups? Another topic is the immortalization of mouse fibroblasts. I am currently working on the post-transcriptional control of a gene expressed in mouse 3T3 cells but not in primary mouse embryo fibroblasts. Does anyone out there in netland have a gene that behaves in the same way? Transcriptional/Translational control mechanisms in ageing cells are IMHO sorely neglected. Someone tell me I'm wrong! --Uriel. From owner-ageing@net.bio.net Sun Dec 19 22:00:00 1993 Path: biosci!bloom-beacon.mit.edu!usc!sdd.hp.com!sgiblab!munnari.oz.au!uniwa!newsman!Jim.Cummins From: cummins@possum.murdoch.edu.au (Jim Cummins) Newsgroups: bionet.molbio.ageing Subject: Re: Longevity in C. elegans Date: 20 Dec 1993 01:36:09 GMT Organization: Murdoch University, Western Australia Lines: 23 Sender: -Not-Authenticated-[6523] Message-ID: <2f2vi9INN4e7@newsman.csu.murdoch.edu.au> References: <2em6kmINNkl4@newsman.csu.murdoch.edu.au> NNTP-Posting-Host: vetmac3.csu.murdoch.edu.au X-Posted-From: InterNews 1.0@newsman.csu.murdoch.edu.au. Xdisclaimer: No attempt was made to authenticate the sender's name. Gee, thanks Vaughn for that info. Since posting the original message I came across a paper by Pamela Larsen of MIT (PNAS 90: 8905-8909, 1993) demonstrating age-related elevated levels of SOD and catalase in C elegans. This is thus consistent with the idea that aging is related to oxidative damage. I'm interested in this question from the point of view of mitochondrial DNA alterations and control of oxidative stress in male infertility: many "unexplained" cases of spermatogenenic failure look like premature testicular aging. As male infertility is characterised by defective oxidative phosphorylation and sperm dysfunction caused by free radical-induced lipid peroxidation, the mtDNA story looks like being an interesting one linking age and reproductive function. Maybe reproductive decline with age is genetically pre-programmed? I've got a review coming out shortly: be happy to attach a copy to anyone interested: e mail me directly. Jim Cummins School of Veterinary Studies Murdoch University Western Australia 6150 Tel +61-9-360 2668 Fax +61-9-310 4144 For every complex problem there's a simple solution. And it's wrong! From owner-ageing@net.bio.net Sun Dec 19 22:00:00 1993 Path: biosci!daresbury!not-for-mail From: Sydney Shall Newsgroups: bionet.molbio.ageing Subject: Mortalizing genes Date: 20 Dec 1993 14:46:01 -0000 Lines: 47 Sender: daemon@mserv1.dl.ac.uk Distribution: bionet Message-ID: <2f4dr9$crl@mserv1.dl.ac.uk> Original-To: ageing@dl.ac.uk Malyankar commented on the recent report of a mutation in C. elegans which results in the extension of the lifespan. he then wonders what the connection is to the complementation work of Olivia Pereira-Smith in Houston, and reported several years ago. The genes identified by Pereira-Smith in her complementation studies have not yet been isolated, as far as I know. It is unlikely in my view that these genes would correspond with the gene mutated in C. elegans in this recent report, because the complementation work used the phenotypes of immortal growth and of mortalization, that means a limited reproductive lifespan. There are probably genes to be isolated which regulate separately the phenotype of mortalization and the lifespan either of cells or of organisms. Sydney SHALL ************************************************************************** ************************************************************************** Sydney SHALL, Laboratory of Cell and Molecular Biology, Biology Building, University of Sussex, Brighton, East Sussex BN1 9QG, ENGLAND. Telephone: +44.273.67.83.03 FAX: +44.273.67.84.33 E-Mail: Janet: S.Shall@uk.ac.sussex Elsewhere: S.Shall@sussex.ac.uk EARN/BITNET: S.Shall%sussex@ukacrl ******************************************************************************* ******************************************************************************* From owner-ageing@net.bio.net Sun Dec 19 22:00:00 1993 Path: biosci!daresbury!not-for-mail From: Sydney Shall Newsgroups: bionet.molbio.ageing Subject: Ageing in C. elegans Date: 20 Dec 1993 14:46:30 -0000 Lines: 42 Sender: daemon@mserv1.dl.ac.uk Distribution: bionet Message-ID: <2f4ds6$csi@mserv1.dl.ac.uk> Original-To: AGEING@dl.ac.uk Vuaghn Gehle has offered a possible explanation for the long-lived C. elegans mutant that Cynthia Kenyon et al have recently described. I wonder if there is supporting data indicating the damaging effects of oxygen radicals in those cases where SOD or another enzyme is thought to be defective. I have in mind increased protein damage and particularly increased DNA damage. I wonder how much of an increase in oxygen radicals cells (or organisms) can meet without displaying (a) signs of increased damage and (b) lethality. Sydney SHALL ************************************************************************** ************************************************************************** Sydney SHALL, Laboratory of Cell and Molecular Biology, Biology Building, University of Sussex, Brighton, East Sussex BN1 9QG, ENGLAND. Telephone: +44.273.67.83.03 FAX: +44.273.67.84.33 E-Mail: Janet: S.Shall@uk.ac.sussex Elsewhere: S.Shall@sussex.ac.uk EARN/BITNET: S.Shall%sussex@ukacrl ******************************************************************************* ******************************************************************************* From owner-ageing@net.bio.net Sun Dec 19 22:00:00 1993 Newsgroups: bionet.molbio.ageing Path: biosci!bcm!cs.utexas.edu!howland.reston.ans.net!paladin.american.edu!gatech!news-feed-1.peachnet.edu!umn.edu!news From: "Jonathan Hibbs" Subject: Re: Longevity in C. elegans To: cummins@possum.murdoch.edu.au Message-ID: <21477.hibbs002@maroon.tc.umn.edu> X-Minuet-Version: Minuet1.0_Beta_11 Sender: news@news2.cis.umn.edu (Usenet News Administration) Nntp-Posting-Host: dialup-2-159.gw.umn.edu X-Popmail-Charset: English Reply-To: Organization: University of Minnesota, Twin Cities Date: Mon, 20 Dec 1993 22:48:56 GMT Lines: 15 I'd appreciate a clarification of the C. elegans work. In the various papers where nematode lifespan has been lengthened by genetic manipulation, do the existing cells simply live longer or do they undergo additional divisions? My understanding of the C. elegans model is that every cell's fate is accounted for, and a preordained number of divisions occur, leading me to infer that no additional cell divisions occur in the longevity mutants, but I have not seen this addressed explicitly. If more divisions do occur, I wonder whether telomerase expression is affected by the longevity mutations, and whether telomerase activity has been documented in C. elegans at all. Thanks for the previous thought-provoking posts on this issue. Jonathan Hibbs, Division of Infectious Diseases, Univ. of Minnesota Hospitals, Box 250, Minneapolis MN 55455; email hibbs002@maroon.tc.umn.edu From owner-ageing@net.bio.net Mon Dec 20 22:00:00 1993 Path: biosci!daresbury!doc.ic.ac.uk!agate!spool.mu.edu!uwm.edu!msuinfo!harbinger.cc.monash.edu.au!uniwa!newsman!Jim.Cummins From: cummins@possum.murdoch.edu.au (Jim Cummins) Newsgroups: bionet.molbio.ageing Subject: Re: Ageing in C. elegans - SOD Date: 21 Dec 1993 02:22:35 GMT Organization: Murdoch University, Western Australia Lines: 11 Sender: -Not-Authenticated-[6523] Message-ID: <2f5mlbINN777@newsman.csu.murdoch.edu.au> References: <2f4ds6$csi@mserv1.dl.ac.uk> NNTP-Posting-Host: vetmac3.csu.murdoch.edu.au X-Posted-From: InterNews 1.0@newsman.csu.murdoch.edu.au. Xdisclaimer: No attempt was made to authenticate the sender's name. Amyotrophic lateral sclerosis (Lou Gehrig's disease) is linked to defects in the SOD1 gene, encoding for cytosol SOD. See Rosen RD et asl. Nature 362: 59-62, 1993. There's also a review on the general topic of oxidants and antioxidants by Ames et al in PNAS 90: 7915-7922, 1993. Jim Cummins School of Veterinary Studies Murdoch University Western Australia 6150 Tel +61-9-360 2668 Fax +61-9-310 4144 For every complex problem there's a simple solution. And it's wrong! From owner-ageing@net.bio.net Mon Dec 20 22:00:00 1993 Newsgroups: bionet.molbio.ageing Path: biosci!daresbury!doc.ic.ac.uk!warwick!uknet!pipex!uunet!boulder!cnsnews!elegans.Colorado.EDU!gehle From: gehle@ibg.colorado.edu (GEHLE VAUGHN M) Subject: Re: Longevity in C. elegans Message-ID: Sender: usenet@cnsnews.Colorado.EDU (Net News Administrator) Nntp-Posting-Host: elegans.colorado.edu Organization: IBG, University of Colorado, Boulder References: <21477.hibbs002@maroon.tc.umn.edu> Date: Tue, 21 Dec 1993 14:30:18 GMT Lines: 27 In article <21477.hibbs002@maroon.tc.umn.edu>, Jonathan Hibbs wrote: >I'd appreciate a clarification of the C. elegans work. In the various >papers where nematode lifespan has been lengthened by genetic manipulation, >do the existing cells simply live longer or do they undergo additional >divisions? My understanding of the C. elegans model is that every cell's >fate is accounted for, and a preordained number of divisions occur, >leading me to infer that no additional cell divisions occur in the >longevity mutants, but I have not seen this addressed explicitly. If more >divisions do occur, I wonder whether telomerase expression is affected by >the longevity mutations, and whether telomerase activity has been >documented in C. elegans at all. In adult C elegans, only the germ cells divide; all other cells are terminally differentiated. That is probably why preventing oxygen radical damage seems to be so important in slowing C elegans aging and also why I think that C elegans makes a nice model for the aging brain. So, sorry, but no, the telomerase theory doesn't apply with the worm. Vaughn Gehle, Ph.D. Institute for Behavioral Genetics University of Colorado gehle@ibg.colorado.edu From owner-ageing@net.bio.net Tue Dec 21 22:00:00 1993 Path: biosci!daresbury!not-for-mail From: Sydney Shall Newsgroups: bionet.molbio.ageing Subject: C. Elegans ageing and cell division Date: 22 Dec 1993 11:17:12 -0000 Lines: 65 Sender: daemon@mserv1.dl.ac.uk Distribution: bionet Message-ID: <2f9abo$ruq@mserv1.dl.ac.uk> Original-To: AGEING@dl.ac.uk Vaughn Gehle has explained that C. Elegans has no cell division in the adult form (except in the germ cells); and he comments that this makes it a good model for the ageing of the mammalian brain. I would add also for mammalian muscle tissue. However, I would still qualify this with the observation that in both tissues there are supporting cells, such as glia and astrocytes which do divide, and which may contribute to the decrease in functional ability of the ageing brain. But, essentially I think that his point is very strong. It really does give pause for thought for the telomerase hypothesis. It also raises the question of what do we say about the rest of the mammalian body, in which there is active cell turnover. My response is that we should view ageing in mammals as two partly separate problems; ageing of post-mitotic tissues like brain and muscle, on the one hand, and ageing of all the other tissues in which there is cell reolication and tissue turnover. Fot the non-dividing, post-mitotic tissues like the neurones and muscle there are good models in C. elegans and Drosophila melanogaster. For the tissues that can regenerate, that is in which the cells continuously are dividing, the best current model may be the growth of normal, mortal cell strains in vitro; by which I mean the study of the so-called Hayflick limit. Finally, I should like to ask the C. elegans people the specific question; in the long-lived C. elegans mutants have you looked to see whether there is (unexpectedly) any cell division? It seems to me very important to establish experimentally that in C. elegans one is *ALWAYS* looking at post-mitotic cells. A sub-question would be whether the number of cells in the adults of long-lived mutants are different to the wild-type; the question is whether the mutant gene has an execution point in the larval stages. Sydney ************************************************************************** ************************************************************************** Sydney SHALL, Laboratory of Cell and Molecular Biology, Biology Building, University of Sussex, Brighton, East Sussex BN1 9QG, ENGLAND. Telephone: +44.273.67.83.03 FAX: +44.273.67.84.33 E-Mail: Janet: S.Shall@uk.ac.sussex Elsewhere: S.Shall@sussex.ac.uk EARN/BITNET: S.Shall%sussex@ukacrl ******************************************************************************* ******************************************************************************* From owner-ageing@net.bio.net Tue Dec 21 22:00:00 1993 Newsgroups: bionet.molbio.ageing Path: biosci!daresbury!doc.ic.ac.uk!uknet!EU.net!howland.reston.ans.net!spool.mu.edu!bloom-beacon.mit.edu!uhog.mit.edu!nntp.club.cc.cmu.edu!cantaloupe.srv.cs.cmu.edu!tsf From: tsf@CS.CMU.EDU (Timothy Freeman) Subject: Re: C. Elegans ageing and cell division In-Reply-To: Sydney Shall's message of 22 Dec 1993 11:17:12 -0000 Message-ID: Originator: tsf@U.ERGO.CS.CMU.EDU Sender: news@cs.cmu.edu (Usenet News System) Nntp-Posting-Host: u.ergo.cs.cmu.edu Organization: Carnegie Mellon University References: <2f9abo$ruq@mserv1.dl.ac.uk> Distribution: bionet Date: Wed, 22 Dec 1993 18:49:14 GMT Lines: 12 In article <2f9abo$ruq@mserv1.dl.ac.uk> Sydney Shall writes: Vaughn Gehle has explained that C. Elegans has no cell division in the adult form (except in the germ cells); and he comments that this makes it a good model for the ageing of the mammalian brain. I would add also for mammalian muscle tissue. Don't muscle cells divide when people do body building to get bigger muscles? -- Tim Freeman Do you call yourself free? I want to hear your ruling idea, and not that you have escaped from a yoke. -- Thus Spoke Zarathustra, Nietzsche From owner-ageing@net.bio.net Wed Dec 22 22:00:00 1993 Path: biosci!daresbury!doc.ic.ac.uk!uknet!pipex!uunet!news.moneng.mei.com!uwm.edu!msuinfo!harbinger.cc.monash.edu.au!uniwa!newsman!Jim.Cummins From: cummins@possum.murdoch.edu.au (Jim Cummins) Newsgroups: bionet.molbio.ageing Subject: Re: C. Elegans ageing and cell division Date: 23 Dec 1993 02:42:40 GMT Organization: Murdoch University, Western Australia Lines: 18 Sender: -Not-Authenticated-[2792] Message-ID: <2fb0j0INNdej@newsman.csu.murdoch.edu.au> References: <2f9abo$ruq@mserv1.dl.ac.uk> NNTP-Posting-Host: vetmac3.csu.murdoch.edu.au X-Posted-From: InterNews 1.0@newsman.csu.murdoch.edu.au. Xdisclaimer: No attempt was made to authenticate the sender's name. In article tsf@CS.CMU.EDU (Timothy Freeman) writes: > > Don't muscle cells divide when people do body building to get bigger muscles? Muscle grows by hypertophy, not hyperplasia. Mitosis has been observed in rare circumstances in the vicinity of injured intestine and stomach. Regeration of injured skeletal muscle is thought to take place by recruitment of nuclei from adjacent living fibers, bu t this is not part of normal growth and development. This makes muscle a prime target for age-related damage through mitochondrial dysfunction (deletion/mutation accumulation) and free radicals. Jim Cummins School of Veterinary Studies Murdoch University Western Australia 6150 Tel +61-9-360 2668 Fax +61-9-310 4144 For every complex problem there's a simple solution. And it's wrong! From owner-ageing@net.bio.net Wed Dec 22 22:00:00 1993 Path: biosci!daresbury!doc.ic.ac.uk!agate!howland.reston.ans.net!europa.eng.gtefsd.com!uunet!nwnexus!wwwtech From: wwwtech@halcyon.com (Wilson WindowWare) Newsgroups: bionet.molbio.ageing Subject: Re: C. Elegans ageing and cell division Date: 22 Dec 1993 18:58:23 -0800 Organization: Northwest Nexus Inc. Lines: 42 Sender: news@nwfocus.wa.com Distribution: bionet Message-ID: <2fb1gf$dcu@nwfocus.wa.com> References: <2f9abo$ruq@mserv1.dl.ac.uk> NNTP-Posting-Host: nwfocus.wa.com Regarding ageing in C. Elegans discussion: 1. I am unfamiliar with recent work in lifespan extended mutants of C. elegans. Were these worms grown on E. coli, and were nutritional factors adequately controlled? 2. I did work on axenic cultures of worms with no attempt to work on lifespan mutants. My control worms lived some 30 days, maximum, and there was a short (<3day) length of time between high survival (95%) and zero survival. Do the mutants do better than this? If so, they might truly be resisting free radicals, etc. Otherwise, the mutation might involve an increased ability of the worms to resist attack by the very bacteria they feed on. The crux issue is the question of what is the natural maximum lifespan of C. elegans cells. Once this is somehow established, then can it be influenced through genetic selection? 3. Part of this work involved a grant application that NIH liked a lot, but was buried in a program project that sank under the weight of the other grant requests. The gist of the grant involved a combination gentic/biochemical/nutritional/ultrastructural approach to aging in C. elegans. Old worms show ultrastructural alterations in the form of disrupted cell structure and the accumulation of ageing pigments. Because you can scan a cross section of a worm at high resolution, and you can quantify ageing markers as well as tell exactly their cellular origins, you should be able to correlate ageing changes with structure. Ultrastructural phenotype selection should be an effective way to get mutants because the worms were easily prepared for the scope and the cells were so easy to pinpoint. 3a. The biochemical part was important. We had a bulk axenic culture method that allowed for the growth of decent masses of worms. I hoped that the intracellular pigments, and other, markers could be used as tags useful in corellating structure and chemistry. So, I guess I'm wondering whether any of these leads have been followed up in the 16 years since I did that work? -- ||| Jim Stiles | Internet: wwwtech@halcyon.com||| | Wilson WindowWare | Compuserve: 76702,1072 | | 2701 California Ave SW, | MCI: WWW | ||| Suite 212, Seattle WA 98116 USA | AOL: wwwwtech ||| From owner-ageing@net.bio.net Wed Dec 22 22:00:00 1993 Path: biosci!daresbury!doc.ic.ac.uk!agate!library.ucla.edu!network.ucsd.edu!sdcc12!sdcc3!dclopton From: dclopton@sdcc3.ucsd.edu (David Clopton) Newsgroups: bionet.molbio.ageing Subject: Re: C. Elegans ageing and cell division Message-ID: <58648@sdcc12.ucsd.edu> Date: 23 Dec 93 10:07:00 GMT References: <2f9abo$ruq@mserv1.dl.ac.uk> Sender: news@sdcc12.ucsd.edu Distribution: bionet Lines: 16 Nntp-Posting-Host: sdcc3.ucsd.edu In tsf@CS.CMU.EDU (Timothy Freeman) writes: >Don't muscle cells divide when people do body building to get bigger muscles? For the overwhelming majority of people, no, muscle cells do not divide. I have been told by some physiologists that there MAY be some evidence that under VERY heavy-duty body-building that there may be some division of muscle cells, but that this is still far from proven. All that happens is that the individual muscle fibers get larger in body builders. They still have the same number they started with.... David Clopton dclopton@uscd.edu "All standard disclaimers apply" From owner-ageing@net.bio.net Wed Dec 22 22:00:00 1993 Path: biosci!lhc!darwin.sura.net!howland.reston.ans.net!pipex!uknet!daresbury!not-for-mail From: Sydney Shall Newsgroups: bionet.molbio.ageing Subject: Nuscle development Date: 23 Dec 1993 12:36:34 -0000 Lines: 38 Sender: daemon@mserv1.dl.ac.uk Distribution: bionet Message-ID: <2fc3ci$64l@mserv1.dl.ac.uk> Original-To: AGEING@dl.ac.uk Timothy Freeman asks whether muscles divide when one exercises. The answer is no they do not. When you exercise the mass of the muscles that you have is increased, but not the number of cells. The only time that I know of in the adult at which you might get cell division is during muscle regeneration after injury; and in this case it is almost certainly not the muscle cells which are dividing, but another set of accessory cells which will give rise to muscle cells. ************************************************************************** ************************************************************************** Sydney SHALL, Laboratory of Cell and Molecular Biology, Biology Building, University of Sussex, Brighton, East Sussex BN1 9QG, ENGLAND. Telephone: +44.273.67.83.03 FAX: +44.273.67.84.33 E-Mail: Janet: S.Shall@uk.ac.sussex Elsewhere: S.Shall@sussex.ac.uk EARN/BITNET: S.Shall%sussex@ukacrl ******************************************************************************* ******************************************************************************* From owner-ageing@net.bio.net Sat Dec 25 22:00:00 1993 Newsgroups: bionet.molbio.ageing Path: biosci!news.cs.umb.edu!hsdndev!howland.reston.ans.net!nctuccca.edu.tw!cccanews!news!nchud5.nchu.edu.tw!dec8.ncku.edu.tw!mail.ncku.edu.tw!tienyi From: tienyi@mail.ncku.edu.tw () Subject: Werner's syndrome, Open for study Message-ID: <1993Dec26.151612.27631@dec8.ncku.edu.tw> Sender: usenet@dec8.ncku.edu.tw (USENET Manager) Organization: National Cheng Kung University, Tainan, Taiwan X-Newsreader: TIN [version 1.1 PL8] Date: Sun, 26 Dec 1993 15:16:12 GMT Lines: 21 Hi, I happened to see a patient with Werner's syndrome (progeria of adult), ie, a disease characterized by premature ageing. I would like to do some studies. Any suggestions for this rare precious model of ageing? -- 00 TIEN-YI TZUNG 00000000 NATIONAL CHENG KUNG UNI HOSPITAL 00000000 00 E-mail : tienyi@mail.ncku.edu.tw 0000000000000000000 ________________________________________ 00 00000000000000 000 000 0000000000 000 000000 00000000 000 000 000 0000 000 000 000 000 000 000 0000 000 0000000000 000 000 000 000 000 0000 000 000 000 000 00000 000 0000 000 0000000 000 000 000 000 ________________________________________________ 000 _______ From owner-ageing@net.bio.net Wed Dec 29 22:00:00 1993 Path: biosci!daresbury!doc.ic.ac.uk!warwick!pipex!uunet!munnari.oz.au!uniwa!newsman!Jim.Cummins From: cummins@possum.murdoch.edu.au (Jim Cummins) Newsgroups: bionet.molbio.ageing Subject: Re: Werner's syndrome, Open for study Date: 29 Dec 1993 01:11:17 GMT Organization: Murdoch University, Western Australia Lines: 27 Sender: -Not-Authenticated-[2792] Message-ID: <2fqlflINN42n@newsman.csu.murdoch.edu.au> References: <1993Dec26.151612.27631@dec8.ncku.edu.tw> NNTP-Posting-Host: vetmac3.csu.murdoch.edu.au X-Posted-From: InterNews 1.0@newsman.csu.murdoch.edu.au. Xdisclaimer: No attempt was made to authenticate the sender's name. Check out Thweatt R, Goldstein S (1993): Werner syndrome and biological aging - a molecular genetic hypothesis. Bioessays 15:421-42 "Cultured fibroblasts derived from subjects with WS are found to undergo premature replicative senescence and thus provide a cellular model system to study the disorder. Recently, several overexpressed gene sequences isolated from a WS fibroblast cDNA library have been shown to possess the capacity to inhibit DNA synthesis and disrupt many normal biochemical processes. Because a similar constellation of genes is overexpressed in WS and senescent normal fibroblasts, these data suggest the existence of a common molecular genetic pathway for replicative senescence in both types of cell. We propose that the primary defect in WS is a mutation in a gene for a trans-acting repressor protein that reduces its binding affinity for shared regulatory regions of several genes, including those that encode inhibitors of DNA synthesis (IDS). The mutant WS repressor triggers a sequence of premature expression of IDS and other genes, with resulting inhibition of DNA synthesis and early cellular senescence, events which occur much later in normal cells." (from Medline) Jim Cummins School of Veterinary Studies Murdoch University Western Australia 6150 Tel +61-9-360 2668 Fax +61-9-310 4144 For every complex problem there's a simple solution. And it's wrong! From owner-ageing@net.bio.net Wed Dec 29 22:00:00 1993 Path: biosci!daresbury!doc.ic.ac.uk!uknet!pipex!uunet!psgrain!library.ucla.edu!europa.eng.gtefsd.com!darwin.sura.net!udel!pacs.sunbelt.net!lynx.unm.edu!Mr-Hyde.aoc.nrao.edu!bgreschk Newsgroups: alt.drugs,sci.bio,bionet.molbio.ageing,misc.legal Subject: Need help finding a drug. Message-ID: <1993Dec30.192438.7089@Mr-Hyde.aoc.nrao.edu> From: bgreschk@Mr-Hyde.aoc.nrao.edu (Bob Greschke) Date: Thu, 30 Dec 93 19:24:38 GMT Organization: Yea, right! I can't even find my car keys most of the time. Lines: 44 Xref: biosci alt.drugs:26741 sci.bio:6050 bionet.molbio.ageing:605 misc.legal:27150 Hello. My dad is in his late 70's and has a bad heart. He spent most of '92 and most of the first part of '93 in the hospital. Since his heart doesn't pump very well he had a lot of trouble with with fluids building up. About mid '93 the doctors found that he responded very well to a drug called Manoplax. In fact he's almost back to running circles around me when I go to visit! As luck would have it the doctors came across this drug just in time for the FDA to pull it off the market because it was found to kill laboratory rats when cases of it were dropped on them (or something like that :-). I don't know the specifics of the ban, but he's had no side effects. We've tried to get the drug from friends in Canada and Mexico, but they either haven't heard of it there, or they no longer have it. My brother living in the Philippines even tried to find it over there, but couldn't. My dad has enough pills left to last into February. 1. Is it possible to get some special FDA approval so he can get the drug? I mean if taking 1000 pills a day is going to cause him to get cancer (or whatever it causes) 30 or so years down the road it's not much of a concern. 2. Can we get this drug from somewhere in Europe? The pills he has were produced in a factory in Illinois, but I believe the drug was developed by Boots Pharmaceutical in Nottingham, England. If someone in jolly ol' England could find a mail or e-mail address for them that might be a big help. 3. Does anyone out there have any of these pills left over? Just thought I'd ask :-). Sorry about posting to the diverse group of groups, but I couldn't find a group at our site that really fit the bill. Is there one? If there is please feel free to post this there. The post to misc.legal begs the question: is importing something like this legal? -- not that I REALLY care :-). I just don't want anyone else to get into any trouble. Any help would be appreciated. -- Bob Greschke | sail.ing, 1.n. the fine art of getting wet and Socorro, New Mexico USA | becoming ill while slowly going -------------------------+ nowhere at great expense. Internet: bgreschk@aoc.nrao.edu - A Sailor's Dictionary