National Institute For Medical Research Research Articles

Dysregulation of connexins and inactivation of NFATc1 in the cardiovascular system of Nkx2–5 null mutants

1 Present address: National Institute for Medical Research, Mill Hill, London NW7 1AA, UK 2 Present address: Station SCRIBE-Inra. Laboratoire de Physiologie des Poissons, Campus de Beaulieu, 35042 Rennes cedex, France 3 Present address: Novartis Institutes for Biomedical Research, 100 Technology Square, Cambridge, MA, USA In humans, mutations of the gene encoding the transcription factor Nkx2-5 result in the heart in electrical conduction defects and morphological abnormalities. In this organ Nkx2-5 is expressed in both the myocardium and the endocardium. Connexins (Cxs) are gap junction channel proteins that have been shown to be involved in both heart development and cardiac electrical conduction, suggesting a possible correlation between expression of Cxs and Nkx2-5. To evaluate this correlation, the expression of Cxs has been investigated in the cardiovascular system of wild-type and Nkx2-5–/– 9.2 days post-conception (dpc) mouse embryos. The disruption of the Nkx2-5 gene results in the loss of Cx43 in the heart, due in part to the poor development of the ventricular trabecular network, as well as specific downregulation of Cx45 gene expression. In addition, the nuclear translocation of NFATc1 in the endocardial endothelial cells is inhibited in the Nkx2-5–/– embryos. These results indicate for the first time that Nkx2-5 is involved in the transcriptional regulation of the Cx45 gene expression. In the mutant embryos the aorta is collapsed, and the vascular endothelial Cxs, Cx40 and Cx37, are no longer expressed in its posterior region. Poor development of the trabeculae and downregulation of Cx45 may contribute both to failure of the myocardial function and to hemodynamic insufficiency. The latter, in turn, may result in the dysregulation of Cx40 and -37 expressions along the whole length of the aorta. Direct or indirect effects of Nkx2-5 inactivation on the Cx45 gene expression could explain the absence of the endocardial cushions in the heart of Nkx2-5–/– embryos.

Lysophosphatidic Acid Inhibits Adipocyte Differentiation via Lysophosphatidic Acid 1 Receptor-dependent Down-regulation of Peroxisome Proliferator-activated Receptor γ2

Lysophosphatidic acid (LPA) is a bioactive phospholipid acting via specific G protein-coupled receptors that is synthesized at the extracellular face of adipocytes by a secreted lysophospholipase D (autotaxin). Preadipocytes mainly express the LPA(1) receptor subtype, and LPA increases their proliferation. In monocytes and CV1 cells LPA was recently reported to bind and activate peroxisome proliferator-activated receptor gamma (PPARgamma), a transcription factor also known to play a pivotal role in adipogenesis. Here we show that, unlike the PPARgamma agonist rosiglitazone, LPA was unable to increase transcription of PPARgamma-sensitive genes (PEPCK and ALBP) in the mouse preadipose cell line 3T3F442A. In contrast, treatment with LPA decreased PPARgamma2 expression, impaired the response of PPARgamma-sensitive genes to rosiglitazone, reduced triglyceride accumulation, and reduced the expression of adipocyte mRNA markers. The anti-adipogenic activity of LPA was also observed in the human SGBS (Simpson-Golabi-Behmel syndrome) preadipocyte cell line, as well as in primary preadipocytes isolated from wild type mice. Conversely, the anti-adipogenic activity of LPA was not observed in primary preadipocytes from LPA(1) receptor knock-out mice, which, in parallel, exhibited a higher adiposity than wild type mice. In conclusion, LPA does not behave as a potent PPARgamma agonist in adipocytes but, conversely, inhibits PPARgamma expression and adipogenesis via LPA(1) receptor activation. The local production of LPA may exert a tonic inhibitory effect on the development of adipose tissue.

Peter N. Campbell (1921–2005)

Professor Peter Campbell passed away the night of February 7 after some months in the hospital following a car accident. Peter was one of the founders of Federation of European Biochemical Societies (FEBS) and his death is a great loss to his family and the scientific community at large. Peter was born in Kent, England in 1921. He started to study Chemistry at University College London in 1939, and received the PhD degree in Biochemistry in 1949 under Professor Sir Frank Young. From 1949 to 1954 Peter worked at the National Institute for Medical Research at Mill Hill in London under T.S. Work and thereafter moved to the Courtauld Institute of Biochemistry at the Middlesex Hospital Medical School in London. In 1961 he received a Doctor of Science degree from the University of London. In 1967 Peter was appointed to the Chair of Biochemistry at the University of Leeds and in 1976 he became Director of the Courtauld Institute of Biochemistry and Courtauld professor of Biochemistry at the University of London. He was also appointed Emeritus Professor of Biochemistry at the University of London. Peter published numerous scientific articles and was widely recognised for his work on protein synthesis. Moreover, he published several books, including Biochemistry Illustrated, a much acclaimed student text in biochemistry. The fifth edition of this book, which is co-authored together with Anthony Smith and Timothy Peters, is due in May this year. Peter was founding editor of Biochemical Education and Essays in Biochemistry, and edited for many years Biotechnology and Applied Biochemistry for the International Union of Biochemistry and Molecular Biology (IUBMB). Besides his love for research and teaching, Peter dedicated a great deal of his time to serve the scientific community at large. He was instrumental in establishing FEBS together with P.S. Datta and W.J. Whelan and acted as Secretary of the Biochemical Society from 1958 to 1964. He was the British delegate at the first Council meeting of FEBS in London in 1964 and was later elected Chairman of the Summer Schools Committee – afterwards renamed Advanced Courses Committee. One of Peter's outstanding ideas was to start in 1989 the Scientific Apparatus Recycling Scheme (SARS), a programme that since then has supplied numerous pieces of equipment and literature to Central and Eastern Europe and Africa. Peter was a strong believer in the capacity and potential of scientists in these countries and did his utmost to support them both in educational and scientific matters. Peter was very fond of the people and the countries he travelled to and was passionate about his work with SARS. In Horst Feldmann's book Forty Years of FEBS – A Memoir, Peter tells himself in chapter 6, page 146 about the SARS programme and how it developed under his guidance. In 1999 FEBS started the Working Group on Central and Eastern European Countries, and Peter was a dedicated member of this working group providing much expertise and enthusiasm as well as numerous contacts. In many ways Peter was a true FEBS ambassador. Peter's involvement in science went beyond Europe. He was a founder of the African Societies for Biochemistry and Molecular Biology and served as chairman of the IUBMB Committee on Symposia. Later he founded the Education Committee of IUBMB. In 1981 Peter was awarded the FEBS Diplôme d'Honneur for his invaluable contributions to FEBS and the scientific community. This honour is conferred only to those who have given so much of their time to the benefit of others. Peter received the IUBMB Distinguished Service Award in 2000 in recognition of his services to the Union. We shall miss Peter terribly, and extend our condolences to his wife Molly, his children Alistair and Julia as well as to his many friends around the world.

Mirk/dyrk1B Decreases the Nuclear Accumulation of Class II Histone Deacetylases during Skeletal Muscle Differentiation

Mirk/dyrk1B is a member of the dyrk/minibrain family of serine/threonine kinases that mediate the transition from growth to differentiation in lower eukaryotes and mammals. Depletion of endogenous Mirk from C2C12 myoblasts by RNA interference blocks skeletal muscle differentiation (Deng, X., Ewton, D., Pawlikowski, B., Maimone, M., and Friedman, E. (2003) J. Biol. Chem. 278, 41347-41354). We now demonstrate that knockdown of Mirk blocks transcription of the muscle regulatory factor myogenin. Co-expression of Mirk with MEF2C, but not MyoD or Myf5, enhanced activation of the myogenin promoter in a Mirk kinase-dependent manner. Mirk activated MEF2 not through direct phosphorylation of MEF2 but by phosphorylation of its inhibitors, the class II histone deacetylases (HDACs). MEF2 is sequestered by class II HDACs such as HDAC5 and MEF2-interacting transcriptional repressor (MITR). Mirk antagonized the inhibition of MEF2C by MITR, whereas kinase-inactive Mirk was ineffective. Mirk phosphorylates class II HDACs at a conserved site within the nuclear localization region, reducing their nuclear accumulation in a dose-dependent and kinase-dependent manner. Moreover, less mutant MITR phosphomimetic at the Mirk phosphorylation site localized in the nucleus than wild-type MITR. Regulation of class II HDACs occurs by multiple mechanisms. Others have shown that calcium signaling leads to phosphorylation of HDACs at 14-3-3-binding sites, blocking their association with MEF2 within the nucleus. Mirk provides another level of regulation. Mirk is induced within the initial 24 h of myogenic differentiation and enables MEF2 to transcribe the myogenin gene by decreasing the nuclear accumulation of class II HDACs.

Rosa Susan Penelope Beddington. 23 March 1956 – 18 May 2001

A summary of the life of the developmental biologist Rosa Susan Penelope Beddington reads: born in Hurstbourne Tarrant, Hampshire, 23 March 1956; Research Fellow, Lister Institute for Preventive Medicine, Oxford, 1983–88; research scientist, ICRF, Oxford, 1988–91; Senior Research Fellow, Centre for Genome Research, Edinburgh, 1991–93; Head, Division of Mammalian Development, MRC National Institute for Medical Research, 1993–2001; married Rev. Robin Denniston 1987; died in Great Tew, Oxfordshire, 18 May 2001.

Mash1 specifies neurons and oligodendrocytes in the postnatal brain

Progenitors in the telencephalic subventricular zone (SVZ) remain mitotically active throughout life, and produce different cell types at embryonic, postnatal and adult stages. Here we show that Mash1, an important proneural gene in the embryonic telencephalon, is broadly expressed in the postnatal SVZ, in progenitors for both neuronal and oligodendrocyte lineages. Moreover, Mash1 is required at birth for the generation of a large fraction of neuronal and oligodendrocyte precursors from the olfactory bulb. Clonal analysis in culture and transplantation experiments in postnatal brain demonstrate that this phenotype reflects a cell-autonomous function of Mash1 in specification of these two lineages. The conservation of Mash1 function in the postnatal SVZ suggests that the same transcription mechanisms operate throughout life to specify cell fates in this structure, and that the profound changes in the cell types produced reflect changes in the signalling environment of the SVZ.

Incidence of gastrointestinal cancers in France

Monitoring cancer incidence and time trends is essential for cancer research and health care planning. The aim of the study was to compare the incidence of gastrointestinal cancers in twelve administrative area in France to estimate the national cancer incidence during 2000 compared with the preceding 20 years. Incidence data was provided by cancer registries and mortality data by the French national medical research institute (INSERM). The two data sets were modeled separately over the period 1988-1997 using age-cohort models. The incidence/mortality ratio obtained from these models was applied to the mortality rates of an age-cohort model of the entire population. The estimated number of new cases of gastrointestinal cancer was 61,465 in 2000. Colorectal cancer was the leading localization with 36,257 cases. The incidence of gastrointestinal cancers was slightly higher in northern than in southern area. Incidence of esophageal cancer was three times that of liver cancer. Variations in incidence were less marked for other localizations. The incidence of gastric and esophageal cancer in the male population decreased between 1980 and 2000, on average by slightly more than 2% per year. Incidence of other cancers increased. The number of new cases of colorectal cancer increased by 50%. The rise in the incidence of liver cancer was particularly striking, with an increase from 2000 incident cases in 1980 to nearly 6000 in 2000. For most localizations, incidence of gastrointestinal cancers displays few geographical differences in France, but there has been a striking change in incidence trends over the past 20 years.

In vitro maturation of fresh and frozen-thawed mouse round spermatids.

Both initiation and maintenance of spermatogenesis are hormonally regulated by follicle stimulating hormone (rFSH) and testosterone. Co-culture systems also have important roles in the maintenance of spermatogenic cells. In this study, the effects of FSH and testosterone, co-culture system with Vero cells and co-culture supplemented with the hormones for maturation of frozen-thawed spermatids were determined. Testicular cells were suspended from the testis of National Medical Research Institute (NMRI) male mice and divided into two parts. The first aliquot of suspension was allocated for using as fresh and the rest was quickly cryopreserved. The frozen specimens were thawed and washed using Dulbecco modified Eagle's minimum essential medium (DMEM) medium. The fresh specimens were cultured in four groups: control (cultured on DMEM with 10% FBS), hormone (cultured on a medium supplemented with rFSH and testosterone), co-culture (cultured on Vero cells) and co-culture + hormone (cultured on Vero cells combined with rFSH and testosterone). The frozen-thawed specimens were cultured accordingly. The number of spermatids was recorded daily and the survival rates of each group were evaluated using Trypan blue test. The results showed that the number of the elongating spermatids was increased during the first day of the culture of fresh hormone, co-culture and co-culture + hormone groups. Viability rates of all kinds of the spermatid reduced during the 96 h of culturing. Our findings showed that the addition of hormone could support cell viability better than the co-culture. They also confirmed that the fresh round spermatid cells can progress into elongating and elongated spermatid only within the first 2 days of the culture in hormone, co-culture and co-culture + hormone groups. In the frozen-thawed specimens no extra significant increase in the number of cells was observed.

Workshop—predicting the structure of biological molecules

This April, in Cambridge (UK), principal investigators from the Mathematical Biology Group of the Medical Research Council's National Institute of Medical Research organized a workshop in structural bioinformatics at the Centre for Mathematical Sciences. Bioinformatics researchers of several nationalities from labs around the country presented and discussed their computational work in biomolecular structure prediction and analysis, and in protein evolution. The meeting was intensive and lively and gave attendees an overview of the healthy state of protein bioinformatics in the UK.

Early studies on recombination and DNA repair in Ustilago maydis

This historical review covers the period 1960 to mid-1980s. The first experiments were carried out at the John Innes Institute, Bayfordbury, Hertford, with a one year interlude in the Department of Genetics, University of Washington, Seattle. In 1965, I moved to the National Institute for Medical Research, Mill Hill, London, and became head of a new Genetics Division. The research on Ustilago was divided broadly into (1) experimental genetic studies, and (2) DNA enzymology, largely under the direction of the late Geoffrey Banks. The approaches involved isolating and characterizing mutants defective in repair and recombination (the first in any eukaryotic organism), with the longer term aim of identifying the function of genes through studies of enzymes and proteins which interact with DNA. An enzyme capable of recognizing mismatched bases in DNA was identified. A novel method exploited the inducible nitrate reductase gene, and revealed relationships between recombination, mutation, repair, transcription and cell survival. Several different studies provide strong evidence for the presence of an inducible repair pathway, dependent on recombination. Much more recently, the revolution in molecular genetics has been in exploited in several laboratories working with Ustilago maydis, and these have produced some completely new insights into recombination and repair.

Walter Laing Macdonald Perry KT OBE, Baron Perry of Walton. 21 June 1921 – 17 July 2003

Lord Perry of Walton died suddenly on 17 July 2003, at the age of 82 years. Walter Laing Macdonald Perry was a native of Dundee, educated at Morgan Academy Dundee, Ayr Academy, Dundee High School and St Andrews University (MB ChB, MD and DSc), winning the Rutherford Silver Medal for his MD thesis and the Sykes Gold Medal for his DSc thesis. After Casaulty Officer and House Surgeon posts in 1943-44, he served as a Medical Officer in the Colonial Medical Service in Nigeria in 1944-46, then briefly as a Medical Officer in the RAF, 1946-47, before embarking on a scientific career on the staff of the Medical Research COuncil at the National Institute for Medical Research from 1947 to 1958, serving as Director of the Department of Biological Standards from 1952 to 1958. Professionally, he achieved MRCP (ED) in 1963 and was elected FRCPE in 1967, FRCP in 1978, FRSE in 1960 and FRS in 1985. In 1958 he came to Edinburgh as Professor of Pharmacology, holding the Chair from 1958 to 1968. During this time he also served as Dean of the Faculty of Medicine (1965-67) and Vice-Principal of the University (1967-68) before leaving to become the inaugural Vice-Chancellor of the Open University in 1968, a post he held until 1980. During this period at the Open University he developed a second distinguish career as a university administrator and a promotor and facilitator of open and distance learning, in which fields he later performed extensive work on behalf of the United Nations. A third career, in politics and public life, began with his ennoblement to a life peerage in 1979, taking the title of Walton in the County of Buckinghamshire, the initial base of the Open University. Latterly Walter sat as a Liberal Democrat, having twice been Social Democratic Party deputy leader in the Lords in the 1980s. He took an active role in the Lords' Select Committee on Science and Technology and held interests in and spoke on many areas of public policy, including fisheries policy. Recognition of his distinguished careers came with a succession of honours; OBE in 1957, Knight Bachelor in 1974 and Baron in 1979; 10 honorary degrees from UK, North American, College London; the Wellcome Gold Medal in 1993 and Inaugural Royal Medal of the Royal Society of Edinburgh in 2000. He was Chairman, President or member of numerous commercial, educational, public interest and scientific bodies. Lord Perry's publications included sole or part authorship of approximately 90 books, research papers and abstracts. Shining through of Walter Perry's careers are strengths of commitment and sheer hard work, rigorous analysis of scientific, educational and organizational problems, experimentation and pursuit of clear objectives. Against scepticism, elitism and ill-informed criticism he drove through the establishment of the Open University. It is today respected internationally, is by some orders of magnitude our largest university in terms of student enrollment and is demonstrably successful outcome from an experiment initiated 40 years ago. It represents a fine monument to Walter Perry.

A new allele of the mouse hairless gene interferes with Hox/LacZ transgene regulation in hair follicle primordia

A new autosomal recessive mouse mutation, causing loss of hair in homozygous mice 2–3 weeks after birth, arose spontaneously in a colony at the National Institute for Medical Research (NIMR), Mill Hill, London in early 1998. Complementation analysis confirmed that this mutation was an allele of the hairless gene ( hr). The gene symbol hr rhbm (hairless-rhino-bald Mill Hill) was assigned to reflect the source of the colony. Here we show the molecular defect in these mutants, which is a substantial deletion at the 3′-end of the hairless gene. Morphological and immunological analysis of the new hairless mutation was performed at early postnatal stages. In an effort to address the molecular and cellular mechanisms of the hairless phenotype, we analysed developmental stages before the establishment of alopecia. Using a HoxLacZ reporter line of transgenic mice, epidermal placode formation was followed in embryos. Homozygous mutant embryos ( hr rhbmh /hr rhbmh ), containing the LacZ reporter under the control of a Hoxb4 gene enhancer, display sharp loss of LacZ staining in epidermal cells invaginating to form the embryonic hair follicle placode. In the light of targeted mutagenesis data involving a Hox gene in the hair development [Genes Dev. 12 (1) (1998) 11], we discuss the potential implication of the hr rhbmh locus in cascades of Hox gene regulation during embryogenesis.

Essays in biochemistry. Proteases in biology and medicine N. M. Hooper (ed.), Portland Press Ltd, 201 pp, £19.00, ISBN 1‐85578‐147‐6 (paperback) (2002)

Cell Biochemistry and FunctionVolume 21, Issue 3 p. 298-298 Book Review Essays in biochemistry. Proteases in biology and medicine N. M. Hooper (ed.), Portland Press Ltd, 201 pp, £19.00, ISBN 1-85578-147-6 (paperback) (2002) D. F. Carmignac, Corresponding Author D. F. Carmignac Division of Molecular Endocrinology, National Institute for Medical Research, The Ridgeway Mill Hill, London NW7 1AADivision of Molecular Endocrinology, National Institute for Medical Research, The Ridgeway Mill Hill, London NW7 1AA.Search for more papers by this author D. F. Carmignac, Corresponding Author D. F. Carmignac Division of Molecular Endocrinology, National Institute for Medical Research, The Ridgeway Mill Hill, London NW7 1AADivision of Molecular Endocrinology, National Institute for Medical Research, The Ridgeway Mill Hill, London NW7 1AA.Search for more papers by this author First published: 01 August 2003 https://doi.org/10.1002/cbf.1060Citations: 2AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article.Citing Literature Volume21, Issue3September 2003Pages 298-298 RelatedInformation

Charles A. Janeway, Jr. (1943-2003)

Charles A. Janeway, Jr. (1943-2003)

Charles A. Janeway, Jr. (1943-2003)

Charles A. Janeway, Jr. (1943-2003)

Peter Medawar—Discoverer of Immunologic Tolerance

Peter Medawar—Discoverer of Immunologic Tolerance

EDUCATION: Science for the People

Taking their cue from a series of popular radio broadcasts in the 1950s, the jargon-free Mill Hill Essays offer straight talk about timely questions in medicine and biology. Published annually for the last 7 years by Britain's National Institute for Medical Research (NIMR), the essays aim to explain to a general audience subjects as diverse as the controversy over xenotransplantation and the origin of the 1918-19 “Spanish” flu. In the latest set, Tom Kirkwood, an authority on aging at Newcastle University, U.K., describes how genes for longevity mesh with our understanding of the evolution of senescence, and NIMR scientist Robin Lovell-Badge explores the promise and pitfalls of stem cells.

Influenza and the work of the World Health Organization

Before World War I, influenza was not considered a particularly serious problem. The great pandemic of 1918–1919 changed all that, and the possibility that such a catastrophe could occur again has conditioned all subsequent developments. In epidemiological terms, the hallmark of an influenza is the excess mortality that it causes combined with an enormous burden of ill-health that saps the energy of individuals, families and communities throughout the whole world. In order to engage in influenza prevention and control, the global influenza surveillance network was set up by World Health Organization (WHO) in 1948 as a worldwide alert system for the identification of new influenza viruses, gathering information from 110 participating laboratories in 82 countries and four WHO Collaborating Centers for Influenza reference and research: Centers for Disease Control and Prevention, Atlanta (USA), National Institute for Medical Research, London (UK), WHO Collaborating Centre for Influenza Reference and Research, Melbourne (Australia) and the National Institute for Infectious Diseases, Tokyo (Japan). This network helps WHO to monitor influenza activity all over the world and provides the organization with the viral isolates and information it requires to decide which new virus strains will be used to produce influenza vaccines during the following season. Each year, information about the isolates over the previous 12 months is analyzed and used to determine the composition of the influenza vaccine to be administered during the coming influenza season both for the northern and southern hemisphere. If necessary, the recommendations for the southern hemisphere differ from the ones formulated for the northern hemisphere vaccine. The information supplied by this network enables the organization to regularly update its World Wide Web (WWW) site (FluNet), which reports on the situation of diseases. This network will also enable the WHO to detect a new influenza pandemic as early as possible.

The importance of global influenza surveillance for the assessment of the impact of influenza

Morbidity and mortality associated with influenza have been recognized for years.However, the true burden of disease has been difficult to determine. Precise quantificationof morbidity and mortality therefore underlines the need for vigilant surveillance, and agreater need for virological confirmation of cases that do not exhibit typical clinicalmanifestations of influenza. Delayed identification of a new virus variant that may causeanother pandemic may be even more devastating than the 1918 pandemic.1. The global surveillance networkFor more than 50 years, the main objectives of the WHO global influenzasurveillance have remained the same. These objectives are to measure the impact ofthe disease by collection and analysis of epidemiological information on morbidity andmortality, and to anticipate future epidemics, and pandemics, by the collection andanalysis of influenza viruses [1]. Influenza activity is currently monitored both globallythrough the four WHO Collaborating Centres for Reference and Research forInfluenza, Centers for Disease Control and Prevention (CDC), Atlanta, USA; WHOCollaborating Centre for Reference and Research for Influenza, National Institute forMedical Research (NIMR), London, United Kingdom; WHO Collaborating Centre forReference and Research for Influenza, Melbourne, Australia; and the WHO Collabo-rating Centre for Reference and Research for Influenza, National Institute of InfectiousDiseases, Tokyo, Japan; and nationally through a network of 110 National Influenza

TB vaccine awaited

An estimated one-third of the world's population is infected with TB, and a vaccine that is effective in adults is urgently needed. Recently, the planned human trials for two potential vaccine have provoked controversy. Ian Orme, who screens TB vaccines for the US National Institutes of Health, has voiced concerns that the vaccine candidates are not ready for human testing. He is concerned that one of the vaccines – a DNA vaccine – could be dangerous if used in people with latent TB. However, Douglas Lowrie of the National Institute for Medical Research in London, the creator of the DNA vaccine, says that the vaccine has caused heavy TB infections to go into reverse in animal tests. Unrelated findings recently published in the Journal of Immunology might aid in the development of another vaccine. Researchers have identified a lipoprotein from MTB that interferes with antigen presentation to T cells. AV http://news.bmn.com/news/story?day=010727&story=1http://www.eurekalert.org/pub_releases/2001-07/cwru-rfh071301.php