Labslink Research News

New Mouse Lymphoma Assay (MLA) Data Processing Workbook

Fri, 27 Apr 2012 02:49:09 PDT

Working with Mouse Lymphoma Assay (MLA) experts, Perceptive Instruments Ltd have developed an Excel spreadsheet, designed to work with the Sorcerer Colony Counter, specifically for soft agar MLA investigations. Sorcerer is the only MLA specific colony counting system on the market. Globally, MLA is the most widely used in vitro mammalian cell gene mutation assay. Mammalian cell cultures can be used to detect genetic mutations induced by chemical substances. Typically, MLA detects mutations at the thymidine kinase locus caused by base pair changes, frame-shifts and deletions. The assay is used routinely by contract research laboratories and research institutes. The MLA workbook can be used to record daily culture maintenance data. Then, by counting both mutant plates and viability plates, the spreadsheet will automatically calculate the mutant frequency, mutant index and relative plating efficiency. Before you begin counting colonies, the spreadsheet can be configured for your experimental set-up. The number of positive/negative controls and test cultures are easily chosen and the spreadsheet is instantly created with the correct number of rows and columns. The MLA workbook seamlessly integrates with the Sorcerer Colony Counter and allows accurate colony counting with instant size distribution information. The Petri-viewer optimally illuminates the soft agar MLA plates then colony count and size data is generated in approximately 0.1 seconds. Sorcerer is fast and accurate and used by many of the leading contract research laboratories across the globe. This new soft agar MLA data processing spreadsheet is included with every Sorcerer purchase. Existing Perceptive Instruments Ltd customers with maintenance contracts or a valid warranty on their Sorcerer system should contact us for a free copy. Perceptive Instruments Ltd, founded in 1990, develops, manufactures and supplies image analysis and data processing solutions for many areas of scientific research and industry. Our products are used primarily in the pharmaceutical & health care industries, as well as environmental monitoring, food and manufacturing industries. www.perceptive.co.uk

Scientists discover key factor in regulating placenta and fetal growth

Mon, 21 Sep 2009 05:59:17 PDT

Scientists funded by the Biotechnology and Biological Sciences Research Council (BBSRC) have shown that a common biological protein molecule called SHP-2 is crucial for encouraging placenta growth. The research is published today in Endocrinology......> full story

Breathing technique can reduce frequency, severity of asthma attacks

Mon, 21 Sep 2009 05:54:38 PDT

As the health care reform debate turns to cutting costs and improving treatment outcomes, two professors at Southern Methodist University in Dallas are expanding a study that shows promise for reducing both the expense and suffering associated with chronic asthma......> full story

New Insights Into Cardiac Aging

Sat, 19 Sep 2009 05:53:36 PDT

Investigators at Burnham Institute for Medical Research (Burnham) have found that the conserved protein d4eBP modulates cardiac aging in Drosophila (fruit flies). The team also found that d4eBP, which binds to the protein dEif4e, protects heart function against aging. This research enhances our understanding of the TOR and FoxO signaling pathways and provides a more specific target for further research into cardiac aging. Since the TOR and FoxO genes are conserved between Drosophila and humans, this work may lead to new, tissue-specific methods to protect the heart. The paper was published in the journal Aging Cell. Much research has shown that altering the expression of specific genes can extend the lifespan of various organisms. Overexpression of dFoxO and reduced expression of dTOR both work to extend Drosophila lifespan. However, researchers needed to investigate the mechanisms behind these pathways, as well as how these signaling pathways influence aging in specific tissues, in this case the heart. “The relationships between these genes are very complex,” said Rolf Bodmer, Ph.D., who directs Burnham’s Development and Aging Program. “We wanted to analyze how two opposing genes function and control their downstream effectors, and we wanted to understand how these aging factors apply to a specific organ.” The Bodmer laboratory, in collaboration with the laboratory of Sean Oldham, Ph.D., an expert in TOR signaling, altered the expression levels of dTOR pathway components in heart tissue and tested the hearts’ stress response. Increased dTOR activation resulted in higher failure rates, while reductions in dTOR activity promoted more youthful hearts. Noting that upregulated dFoxO and downregulated dTOR lead to similar consequences, the laboratory looked for downstream factors that were influenced by both pathways. One possibility was d4eBP, which reduces messenger RNA translation by binding to dEif4e. The team found that increased d4eBP levels produced the same healthier hearts as decreased dTOR activity, while increased dEif4e levels resulted in higher failure rates. The team also showed that when dTOR and its antagonistic effecter d4eBP were co-expressed, the hearts did not differ significantly from when d4eBP was expressed by itself, indicating that there is a straight signaling path from dTOR to d4eBP/dEif4e. These new findings also introduce the interesting biological concept that changes in (TOR-dependent) mRNA translation factors (d4eBP and dEif4e) influence the age-dependent functional performance of the heart. About Burnham Institute for Medical Research
Burnham Institute for Medical Research is dedicated to discovering the fundamental molecular causes of disease and devising the innovative therapies of tomorrow. Burnham, with operations in California and Florida, is one of the fastest-growing research institutes in the country. The institute ranks among the top four institutions nationally for NIH grant funding and among the top 25 organizations worldwide for its research impact. For the past decade (1999-2009), Burnham ranked first worldwide in the fields of biology and biochemistry for the impact of its research publications (defined by citations per publication), according to the Institute for Scientific Information. Burnham utilizes a unique, collaborative approach to medical research and has established major research programs in cancer, neurodegeneration, diabetes, and infectious, inflammatory, and childhood diseases. The Institute is especially known for its world-class capabilities in stem cell research and drug discovery technologies. Burnham is a nonprofit public benefit corporation.

Scientists Pinpoint Protein Link To Fat Storage

Fri, 18 Sep 2009 06:02:08 PDT

A protein found present in all cells in the body could help scientists better understand how we store fat. Researchers at the University of Edinburgh have found that the protein invadolysin, which is essential for healthy cell division, is present in lipid droplets – the parts of cells used to store fat......> full story

Building A Complete Metabolic Model

Fri, 18 Sep 2009 05:50:32 PDT

Investigators at Burnham Institute for Medical Research (Burnham), University of California, San Diego (UC San Diego), The Scripps Research Institute (TSRI), Genomics Institute of the Novartis Research Foundation (GNF) and other institutions have constructed a complete model, including three dimensional protein structures, of the central metabolic network of the bacterium Thermotoga maritima (T. maritima). This is the first time scientists have developed such a comprehensive model of a metabolic network overlaid with an atomic resolution of network proteins......> full story

NIH Funds Grantees Focusing On Epigenomics Of Human Health And Disease

Thu, 17 Sep 2009 05:53:21 PDT

The National Institutes of Health announced today that it will fund 22 grants on genome-wide studies of how epigenetic changes — chemical modifications to genes that result from diet, aging, stress, or environmental exposures — define and contribute to specific human diseases and biological processes. The awards will build on the important work undertaken as part of the NIH Roadmap for Medical Research's Epigenomics Program. Approximately $62 million will be awarded over the next five years to study the epigenome in a number of diseases and conditions, including tumor development, hardening of the arteries, autism, glaucoma, asthma, aging, and abnormal growth and development. "Epigenomics represents the next phase in our understanding of genetic regulation of health and disease," says NIH Director Francis Collins, M.D., Ph.D. "These awards will address the extent to which diet and environmental exposures produce long lasting effects through changes in DNA regulation." The initiative was launched through the NIH Director's Office and, as part of the Roadmap, is expected to profoundly alter the way we understand, diagnose, and treat disease. "This is the largest effort to date to apply epigenetics on a genome-wide scale to specific diseases," said James F. Battey, M.D., Ph.D., director of the National Institute on Deafness and Other Communication Disorders, one of the lead NIH institutes for this Roadmap program. The Roadmap Epigenomics Program was designed to characterize epigenetic modifications and to correlate the presence or absence of specific modifications with disease status. DNA methylation is a fundamental epigenetic modification that regulates gene expression and chromosome stability. This and other epigenetic modifications control gene activity by changing the three-dimensional structure of chromosomes. (See scientific illustration of epigenetic mechanisms at http://nihroadmap.nih.gov/epigenomics/epigeneticmechanisms.asp.) The awards announced today are funded by 11 NIH institutes and the NIH Office of the Director and are part of the NIH Roadmap for Medical Research's Epigenomics Program that began in 2007. The NIH contributors include the National Cancer Institute, the National Eye Institute, the National Heart, Lung, and Blood Institute, the National Institute on Aging, the National Institute of Allergy and Infectious Diseases, the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute on Drug Abuse, the National Institute of Environmental Health Sciences, the National Institute of Mental Health, and the Office of Behavioral and Social Sciences Research and the Office of Strategic Coordination in the NIH Office of the Director. "The new grantees being announced will join a larger collaborative research effort that is working together to understand epigenetics and how it affects human health and disease," said Nora D. Volkow, M.D., director of the National Institute on Drug Abuse. This health and disease-focused component of the NIH Roadmap Epigenomics Program builds on the previous four interrelated initiatives, but is the first to tackle questions related to diseases. The other four initiatives include the establishment of four epigenome mapping centers, the funding of an epigenomics data analysis and coordination center, the development of innovative technology in epigenetics, and the discovery of novel epigenetic changes. "These studies will help increase our understanding of how factors such as environmental exposures, alcohol, drug abuse and stress can modify the effect of epigenetics on diseases," said Linda S. Birnbaum, Ph.D., director of the National Institute of Environmental Health Sciences. The following awards are being made by NIH:

David A. Bennett, Rush University Medical Center, Chicago, Exploring the role of the Brain Epigenome: Cognitive Decline and Life Experiences.
Paul D. Coleman, Sun Health Research Institute, Sun City, Ariz., DNA Methylation in Alzheimer’s Disease and Normally Aged Brain.
Jessica J. Connelly, University of Virginia, Charlottesville, Epigenomics of Atherosclerosis.
Francine Hughes Einstein, Yeshiva University, New York City, Genome-wide DNA Methylation Profiles Associated with Abnormal Intrauterine Growth.
Margaret Daniele Fallin, Johns Hopkins University, Baltimore, Environment, the Perinatal Epigenome, and Risk for Autism and Related Disorders.
Gary Hugh Gibbons, Morehouse School of Medicine, Atlanta, Vascular Epigenome Dynamics in African-American Hypertensives.
Tim H.M. Huang, Ohio State University, Columbus, Ohio, Epigenomics of Bisphenol A Exposure and Disease Risk.
Terumi Kohwi-Shigematsu, Lawrence Berkeley National Laboratory, Berkeley, Calif., Determinants for Genome-Wide Epigenomics in Metastatic Breast Cancer.
Yongmei Liu, Wake Forest University Health Sciences, Winston-Salem, N.C., Epigenome-Wide Association Study of DNA Methylation and Atherosclerosis.
Stephen J. Meltzer, Johns Hopkins University, Baltimore, The Temporal Epigenomic Program of Barrett’s Neoplastic Progression.
Shannath L. Merbs, Johns Hopkins University, Baltimore, Pangenomic Analysis of DNA Methylation Marks in Glaucoma and Macular Degeneration.
Jonathan Mill, King’s College, London, A Multi-faceted Approach to Epigenomic Profiling in Alzheimer's Disorder. Roel A. Ophoff, University of California, Los Angeles, Epigenetic and Disease: The Role of DNA Methylation in Schizophrenia Susceptibility.
Art Petronis, Centre for Addiction and Mental Health, Toronto, DNA Methylome Analysis in Bipolar Disorder.
Gerd P. Pfeifer, City of Hope, Beckman Research Institute, Duarte, Calif., Aging and the Unstable Epigenome.
Evan D. Rosen, Beth Israel Deaconess Medical Center, Boston, Epigenomics of Human Insulin Resistance.
David A. Schwartz, National Jewish Health, Denver, Asthma: An Epidemic Caused by Epigenetics.
Kathleen E. Sullivan, Children's Hospital of Philadelphia, Pa., Epigenomics of Systemic Lupus Erythematosus (SLE).
Katalin Susztak, Yeshiva University, New York City, Epigenetics Landscape of Chronic Kidney Disease.
Benjamin Tycko, Richard Mayeux, Columbia University, New York City, Epigenomics of Alzheimer's Disease.
Kyoko Yokomori, University of California, Irvine, Epigenomic Analysis of Facioscapulohumeral Muscular Dystrophy.
Richard A. Young, Whitehead Institute for Biomedical Research, Cambridge, Mass., Epigenomic Mapping in Human Tumor Cells.

The Epigenomics Program is part of the National Institutes of Health's (NIH) Roadmap for Medical Research funded through the NIH Common Fund and is managed by the National Institute of Environmental Health Sciences, the National Institute on Drug Abuse, the National Institute on Deafness and Other Communication Disorders, the National Institute of Diabetes and Digestive and Kidney Diseases, and the Office of Strategic Coordination. The Roadmap is a series of initiatives designed to pursue major opportunities and gaps in biomedical research that no single NIH institute could tackle alone, but which the agency as a whole can address to make the biggest impact possible on the progress of medical research. Additional information about the NIH Roadmap can be found at www.nihroadmap.nih.gov. The National Institutes of Health (NIH) — The Nation's Medical Research Agency — includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov. "Epigenomics represents the next phase in our understanding of genetic regulation of health and disease," says NIH Director Francis Collins, M.D., Ph.D. "These awards will address the extent to which diet and environmental exposures produce long lasting effects through changes in DNA regulation." The initiative was launched through the NIH Director's Office and, as part of the Roadmap, is expected to profoundly alter the way we understand, diagnose, and treat disease. "This is the largest effort to date to apply epigenetics on a genome-wide scale to specific diseases," said James F. Battey, M.D., Ph.D., director of the National Institute on Deafness and Other Communication Disorders, one of the lead NIH institutes for this Roadmap program. The Roadmap Epigenomics Program was designed to characterize epigenetic modifications and to correlate the presence or absence of specific modifications with disease status. DNA methylation is a fundamental epigenetic modification that regulates gene expression and chromosome stability. This and other epigenetic modifications control gene activity by changing the three-dimensional structure of chromosomes. (See scientific illustration of epigenetic mechanisms at http://nihroadmap.nih.gov/epigenomics/epigeneticmechanisms.asp.) The awards announced today are funded by 11 NIH institutes and the NIH Office of the Director and are part of the NIH Roadmap for Medical Research's Epigenomics Program that began in 2007. The NIH contributors include the National Cancer Institute, the National Eye Institute, the National Heart, Lung, and Blood Institute, the National Institute on Aging, the National Institute of Allergy and Infectious Diseases, the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute on Drug Abuse, the National Institute of Environmental Health Sciences, the National Institute of Mental Health, and the Office of Behavioral and Social Sciences Research and the Office of Strategic Coordination in the NIH Office of the Director. "The new grantees being announced will join a larger collaborative research effort that is working together to understand epigenetics and how it affects human health and disease," said Nora D. Volkow, M.D., director of the National Institute on Drug Abuse. This health and disease-focused component of the NIH Roadmap Epigenomics Program builds on the previous four interrelated initiatives, but is the first to tackle questions related to diseases. The other four initiatives include the establishment of four epigenome mapping centers, the funding of an epigenomics data analysis and coordination center, the development of innovative technology in epigenetics, and the discovery of novel epigenetic changes. "These studies will help increase our understanding of how factors such as environmental exposures, alcohol, drug abuse and stress can modify the effect of epigenetics on diseases," said Linda S. Birnbaum, Ph.D., director of the National Institute of Environmental Health Sciences. The following awards are being made by NIH:

David A. Bennett, Rush University Medical Center, Chicago, Exploring the role of the Brain Epigenome: Cognitive Decline and Life Experiences.
Paul D. Coleman, Sun Health Research Institute, Sun City, Ariz., DNA Methylation in Alzheimer’s Disease and Normally Aged Brain.
Jessica J. Connelly, University of Virginia, Charlottesville, Epigenomics of Atherosclerosis.
Francine Hughes Einstein, Yeshiva University, New York City, Genome-wide DNA Methylation Profiles Associated with Abnormal Intrauterine Growth.
Margaret Daniele Fallin, Johns Hopkins University, Baltimore, Environment, the Perinatal Epigenome, and Risk for Autism and Related Disorders.
Gary Hugh Gibbons, Morehouse School of Medicine, Atlanta, Vascular Epigenome Dynamics in African-American Hypertensives.
Tim H.M. Huang, Ohio State University, Columbus, Ohio, Epigenomics of Bisphenol A Exposure and Disease Risk.
Terumi Kohwi-Shigematsu, Lawrence Berkeley National Laboratory, Berkeley, Calif., Determinants for Genome-Wide Epigenomics in Metastatic Breast Cancer.
Yongmei Liu, Wake Forest University Health Sciences, Winston-Salem, N.C., Epigenome-Wide Association Study of DNA Methylation and Atherosclerosis.
Stephen J. Meltzer, Johns Hopkins University, Baltimore, The Temporal Epigenomic Program of Barrett’s Neoplastic Progression.
Shannath L. Merbs, Johns Hopkins University, Baltimore, Pangenomic Analysis of DNA Methylation Marks in Glaucoma and Macular Degeneration.
Jonathan Mill, King’s College, London, A Multi-faceted Approach to Epigenomic Profiling in Alzheimer's Disorder. Roel A. Ophoff, University of California, Los Angeles, Epigenetic and Disease: The Role of DNA Methylation in Schizophrenia Susceptibility.
Art Petronis, Centre for Addiction and Mental Health, Toronto, DNA Methylome Analysis in Bipolar Disorder.
Gerd P. Pfeifer, City of Hope, Beckman Research Institute, Duarte, Calif., Aging and the Unstable Epigenome.
Evan D. Rosen, Beth Israel Deaconess Medical Center, Boston, Epigenomics of Human Insulin Resistance.
David A. Schwartz, National Jewish Health, Denver, Asthma: An Epidemic Caused by Epigenetics.
Kathleen E. Sullivan, Children's Hospital of Philadelphia, Pa., Epigenomics of Systemic Lupus Erythematosus (SLE).
Katalin Susztak, Yeshiva University, New York City, Epigenetics Landscape of Chronic Kidney Disease.
Benjamin Tycko, Richard Mayeux, Columbia University, New York City, Epigenomics of Alzheimer's Disease.
Kyoko Yokomori, University of California, Irvine, Epigenomic Analysis of Facioscapulohumeral Muscular Dystrophy.
Richard A. Young, Whitehead Institute for Biomedical Research, Cambridge, Mass., Epigenomic Mapping in Human Tumor Cells.

Inhibitors Of Important Tuberculosis Survival Mechanism Identified

Thu, 17 Sep 2009 05:44:01 PDT

Attempts to eradicate tuberculosis (TB) are stymied by the fact that the disease-causing bacteria have a sophisticated mechanism for surviving dormant in infected cells. Now, a team of scientists including researchers from the U.S. Department of Energy’s (DOE) Brookhaven National Laboratory, Stony Brook University (SBU), Weill Cornell Medical College, and The Rockefeller University has identified compounds that inhibit that mechanism......> full story

Sending science down the phone: New technology will map research across the world

Wed, 16 Sep 2009 06:16:33 PDT

New mobile phone software will help epidemiologists and ecologists working in the field to analyse their data remotely and map findings across the world, without having to return to the lab, according to research published in PLoS One today. The authors of the study, from Imperial College London, say the software will also enable members of the public to act as 'citizen scientists' and help collect data for community projects......> full story

UNC study: Color-coded chart improves parents’ understanding of body mass index (BMI)

Wed, 16 Sep 2009 06:14:33 PDT

A new study shows that parents are more likely to understand a body mass index (BMI) chart if it’s color-coded, like a traffic light, than the standard charts currently in use......> full story

Genes May Explain Why Children Who Live Without Dads Have Earlier Sex

Wed, 16 Sep 2009 06:11:32 PDT

Using data from the National Longitudinal Survey of Youth, researchers used a novel and complex study design to better understand the association between fathers' absence and children's sexuality. Contrary to previous research, this study shows that the association can be best explained by genetic influences......> full story

ISU researchers study insecticide-free method for control of soybean aphids

Wed, 16 Sep 2009 06:02:34 PDT

Two Iowa State University researchers are examining a new method of controlling soybean aphids without the use of chemical pesticides. Bryony Bonning, professor of entomology, and Allen Miller, professor of plant pathology and director of the Center for Plant Responses to Environmental Stresses, are looking at a way to genetically modify soybeans to prevent damage from aphids. If the research is successful, soybeans will carry in-plant protection from aphids, similar to the way genetically modified corn now keeps the European Corn Borer from destroying corn yields, but using a different molecular tool. Modified corn technology has been in use for about 12 years. The study is being funded by a Grow Iowa Values Fund Grant. The goal of the grant program is to support development of technologies with commercial potential and to support the growth of companies using those technologies. The researchers are working with Pioneer Hi-Bred, a DuPont business, as their corporate partner. Previous research at Iowa State University indicated that if major soybean aphid outbreaks were left untreated, the loss in yield could exceed $250 million in Iowa. The annual cost to prevent the yield loss with insecticides can reach $64 million for Iowa soybean growers. Soybean aphid outbreaks have become an annual phenomenon in Iowa, according to Miller. The current research focuses on introducing a gene into soybeans that is harmless to mammals, but creates a toxin that is lethal to aphids that feed on soybean plants. In order to be effective, the toxin needs to be taken intact into the body cavity of the aphid, not broken down by the digestive system in the bug. Miller and Bonning identified a plant virus coat protein eaten by soybean aphids that doesn't break down and goes into the aphid body cavity intact. They know the virus coat protein remains intact because the aphids often spread the virus from plant to plant while they are feeding. Coat proteins make up the outer shell of a virus particle. The researchers devised a method to use virus coat proteins to their advantage. The researchers have fused their toxin to the virus' protein coat. Since the protein coat is only part of the virus to be used, there is no risk of an infectious virus. Also, the coat protein is from a virus that normally doesn't infect soybeans. When the hybrid toxin coat protein is eaten by the aphid, the fatal toxin should get into the aphid body cavity intact. "What we thought was, if this (virus) protein has this ability to be taken up into the aphid (intact), let's take advantage of that specialization and fuse that to other proteins that are toxic," said Miller. In addition to possibly curbing the aphid problem and the yield loss it causes, there are other benefits to the farmers and the ecosystems. "The (potential) economic impact overall is huge," said Bonning. "There will be less insecticide use, and also less fossil fuel used to apply the insecticides." Also, spraying soybeans with insecticides doesn't just control the aphids, according to Bonning. "When you spray, you also control beneficial insects," said Bonning. "Lady beetles are affected, for example, and they are a natural enemy of the aphids. So when the aphids come back to a field after spraying, there won't be any lady beetles to naturally control the aphid populations." Miller adds that if growers spray for aphids and don't eliminate them all, the aphids simply disperse to other fields, making the problem worse. "There are many reasons not to spray, but you can't tell the growers to stop spraying until you give them an alternative for soybean aphid management," said Bonning.

UT Scientists Discover Link between Protein and Lung Disease

Wed, 16 Sep 2009 05:55:14 PDT

In a development that could lead to a novel approach to the treatment of a devastating lung disease, biochemists at The University of Texas Health Science Center at Houston report they are the first to link the osteopontin (OPN) protein to chronic obstructive pulmonary disease (COPD). Findings appear online and will be in the January 2010 print issue of The FASEB Journal, the journal of The Federation of American Societies for Experimental Biology.....> full story

Scientists Identify Gene For Short-circuiting Excess Mucus In Lung Disease, Common Colds

Tue, 15 Sep 2009 06:25:25 PDT

Scientists have identified the main genetic switch that causes excessive mucus in the lungs, a discovery that one day could ease suffering for people with chronic lung diseases like asthma and cystic fibrosis, or just those fighting the common cold......> full story

Inner Workings of Molecular Thermostat Point to Pathways to Fight Diabetes, Obesity, According to Penn Study

Tue, 15 Sep 2009 06:15:54 PDT

Best known as the oxygen-carrying component of hemoglobin, the protein that makes blood red, heme also plays a role in chemical detoxification and energy metabolism within the cell. Heme levels are tightly maintained, and with good reason: Too little heme prevents cell growth and division; excessive amounts of heme are toxic. Researchers at the University of Pennsylvania School of Medicine have discovered a molecular circuit involving heme that helps maintain proper metabolism in the body, providing new insights into metabolic disorders such as obesity and diabetes. The work builds on 2007 findings from the same team, led by Mitchell Lazar, MD, PhD, Director of Penn’s Institute for Diabetes, Obesity, and Metabolism, showing that a protein called Rev-erbα coordinates the daily cycles of heme. The new research, published online in Genes & Development, makes it clear that Rev-erbα, by controlling the production of heme, also plays a key role in maintaining the body’s correct metabolism. This happens through a molecular pathway that allows the cell to monitor and adjust internal heme levels, creating more when heme levels fall, and slowing it down when levels rise. The circuit is a negative feedback loop, with Rev-erbα as its central component, explains Lazar. “Rev-erbα is a thermostat for heme." When heme levels are high, Rev-erbα is activated, reducing heme, which leads the cell back towards a normal state. On the other hand, when heme levels are low, Rev-erbα activity is low, and this permits the cell to make more heme, again leading back toward a normal state. Maintaining this stasis allows energy metabolism to occur but avoids harm to the cell due to excessive levels of heme. Understanding the control of heme levels is likely to be relevant to several diseases. For example, obesity is a condition where fat tissue builds up due to low energy expenditure relative to energy intake. Proteins such as Rev-erbα that help maintain a cell’s proper metabolism and energy balance point to their role in such metabolic disorders as obesity and diabetes and suggest ways to intervene. Rev-erbα is a transcription factor, a protein that binds to DNA in front of, or within, genes to alter their expression. Rev-erbα acts as repressor of gene expression, that is, gene expression goes down when it binds to DNA. Lazar has been studying the protein for nearly 20 years, yet he never really knew how it worked. What he did know was that, as a member of a family of nuclear receptor proteins, Rev-erbα could bind DNA and likely had an intracellular binding partner. Typical nuclear receptor proteins are like sensors, registering a specific molecular event and responding accordingly, generally by altering gene expression patterns. So, Lazar asked, "What is the purpose of having a system that responds to changes in cellular heme levels?" He hypothesized that the sensor could act to regulate heme itself. Working with cultured human and mouse cells his team, led by first author, graduate student Nan Wu, monitored heme levels as Rev-erbα abundance changed. What they found confirmed the protein's role in heme regulation: when overexpressed, heme levels dropped; when suppressed, heme levels rose. "That was consistent with the hypothesis," says Lazar. "The question was, how does heme do this?" To figure that out, the team looked for Rev-erbα binding sites within the sequences of genes known to control heme biosynthesis and found one in PGC-1α, a transcription factor that stimulates the production of heme. Since Rev-erb activity is controlled by heme itself, the net effect is that, as heme levels rise, PGC-1α gets repressed, and heme synthesis drops off. The team also demonstrated the physiological consequence of disrupting this pathway. "We reasoned, if heme levels get too low, cells won’t like it," Lazar says, "and they don’t: They stop growing, and they reduce their oxygen consumption in a manner consistent with the role of heme being used to make ATP," a form of cellular energy. Lazar states that, "Up until now, no one knew there even was a mechanism for keeping heme levels in this narrow range. We’ve shown that it exists and have defined molecular players that make it work." In so doing, he and his team have linked heme biosynthesis with both energy metabolism and the body's internal clock. Rev-erbα is a negative regulator of genes involved in energy metabolism. It also, along with PGC-1α and heme, rises and falls over a 24-hour period and even regulates some of the cogs within the clock itself. Now the question is, can this pathway be exploited in the clinic. Lazar's team showed that downregulating heme stifled cell division and metabolism, while upregulating heme enhanced them. It therefore is possible, Lazar says, that by pharmacologically "tickling" Rev-erbα or its other cellular partners to believe the cell has more or less heme than it actually does, researchers may be able to either boost or suppress metabolism accordingly, opening the door to potential therapies for cancer and obesity. The research was supported by the National Institute of Diabetes and Digestive and Kidney Diseases. Lei Yin, Elyisha A. Hanniman, and Shree Joshi, all from Penn, are co-authors.

###

PENN Medicine is a $3.6 billion enterprise dedicated to the related missions of medical education, biomedical research, and excellence in patient care. PENN Medicine consists of the University of Pennsylvania School of Medicine (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System.

Penn's School of Medicine is currently ranked #3 in the nation in U.S.News & World Report's survey of top research-oriented medical schools; and, according to the National Institutes of Health, received over $366 million in NIH grants (excluding contracts) in the 2008 fiscal year. Supporting 1,700 fulltime faculty and 700 students, the School of Medicine is recognized worldwide for its superior education and training of the next generation of physician-scientists and leaders of academic medicine.

The University of Pennsylvania Health System (UPHS) includes its flagship hospital, the Hospital of the University of Pennsylvania, rated one of the nation’s top ten “Honor Roll” hospitals by U.S.News & World Report; Pennsylvania Hospital, the nation's first hospital; and Penn Presbyterian Medical Center, named one of the nation’s “100 Top Hospitals” for cardiovascular care by Thomson Reuters. In addition UPHS includes a primary-care provider network; a faculty practice plan; home care, hospice, and nursing home; three multispecialty satellite facilities; as well as the Penn Medicine at Rittenhouse campus, which offers comprehensive inpatient rehabilitation facilities and outpatient services in multiple specialties.

Athletes with Smaller ACLs May Be More Susceptible to Injury

Tue, 15 Sep 2009 05:59:32 PDT

A study comparing images of the knees in people who did and didn’t have previous injuries to the anterior cruciate ligament suggests that people who tore their ACLs are more likely to have a smaller ligament than do similarly sized people who have never injured a knee......> full story

Conflict between Plant and Animal Hormones in the Insect Gut?

Tue, 15 Sep 2009 05:51:14 PDT

Cis-OPDA (12-oxophytodienoic acid) is a highly reactive plant hormone which simultaneously serves as a precursor molecule of the metabolic "master switch" jasmonic acid. Both signal herbivory in leaves and shoots of plants and activate the plants' defense reaction against caterpillars. Cis-OPDA, when reaching the hemolymph of the caterpillar, has a negative effect on the animal, leading to premature pupation and, apparently, an impaired immune system......> full story

Prolonged Stress Sparks ER To Release Calcium Stores And Induce Cell Death In Aging-Related Diseases

Tue, 15 Sep 2009 05:42:05 PDT

Li et al. explain how prolonged stress sparks the endoplasmic reticulum (ER) to release its calcium stores, inducing cells to undergo apoptosis in several aging-related diseases.The study will appear in the September 21, 2009 issue of the Journal of Cell Biology (online September 14). Stressful conditions cause misfolded proteins to accumulate in the ER......> full story

Instanyl sets new standard in management of breakthrough cancer pain

Sat, 12 Sep 2009 06:17:07 PDT

Lisbon, Portugal 11 September, 2009 – New data presented today further demonstrate the efficacy of Instanyl in management of breakthrough cancer pain. The data which were presented at the 6th congress of the European Federation of Chapters of the International Association for the Study of Pain (EFIC) are from a multinational, crossover trial comparing Instanyl with oral transmucosal fentanyl citrate (OTFC) for the treatment of breakthrough pain in patients with cancer. The study concludes that pain relief was significantly greater for Instanyl compared to OTFC at all time points......> full story

Scientists Discover Mechanism to Make Existing Antibiotics More Effective at Lower Doses

Sat, 12 Sep 2009 05:59:44 PDT

A new study published in the September 11, 2009 issue of Science by researchers at the NYU School of Medicine reveals a conceptually novel mechanism that plays an important role in making human pathogens like Staphylococcus aureus and Bacillus anthracis resistant to numerous antibiotics. The study led by Evgeny A. Nudler, PhD, The Julie Wilson Anderson Professor of Biochemistry at NYU Langone Medical Center, provides evidence that Nitric Oxide, or NO, is able to alleviate the oxidative stress in bacteria caused by many antibiotics and also helps to neutralize many antibacterial compounds......> full story

Mayo Clinic Identifies 2 Genes as Potential Therapeutic Targets for Multiple Sclerosis

Sat, 12 Sep 2009 05:41:42 PDT

A Mayo Clinic study has found that two genes in mice were associated with good central nervous system repair in multiple sclerosis (MS). These findings give researchers new hope for developing more effective therapies for patients with MS and for predicting MS patients' outcomes. This study will be presented at the Congress of the European Committee for Treatment and Research in Multiple Sclerosis in Dusseldorf, Germany, on Sept. 11, 2009......> full story

Scientists Use MicroRNAs to Track Evolutionary History for First Time

Fri, 11 Sep 2009 06:07:44 PDT

The large group of segmented worms known as annelids, which includes earthworms, leeches and bristle worms, evolved millions of years ago and can be found in every corner of the world. Although annelids are one of the most abundant animal groups on the planet, scientists have struggled to understand how the different species of this biologically diverse group relate to each other in terms of their evolutionary history......> full story

Pandemic Flu Can Infect Cells Deep in the Lungs, Says New Research

Fri, 11 Sep 2009 06:01:18 PDT

Pandemic swine flu can infect cells deeper in the lungs than seasonal flu can, according to a new study published today in Nature Biotechnology. The researchers, from Imperial College London, say this may explain why people infected with the pandemic strain of swine-origin H1N1 influenza are more likely to suffer more severe symptoms than those infected with the seasonal strain of H1N1. They also suggest that scientists should monitor the current pandemic H1N1 influenza virus for changes in the way it infects cells that could make infections more serious.......> full story

Beans' Defenses Mean Bacteria Get Evolutionary Helping Hand

Fri, 11 Sep 2009 05:51:20 PDT

Bean plants' natural defences against bacterial infections could be unwittingly driving the evolution of more highly pathogenic bacteria, according to new research published today (10 September) in Current Biology......> full story

Genome Of Irish Potato Famine Pathogen Decoded

Thu, 10 Sep 2009 06:03:59 PDT

A large international research team has decoded the genome of the notorious organism that triggered the Irish potato famine in the mid-19th century and now threatens this season's tomato and potato crops across much of the US......> full story

Sharing The Results Of Research Critical To Advancement Of Biological Sciences

Thu, 10 Sep 2009 05:55:24 PDT

Sharing the fruits of research in the biomedical sciences is critical for the advance of knowledge, yet with the advent of large-scale data gathering following the completion of the genome projects this is becoming harder to facilitate and more difficult to monitor, as reported in Nature today......> full story

Gene variant heightens risk of severe liver disease in cystic fibrosis

Wed, 09 Sep 2009 06:21:51 PDT

Researchers at the University of North Carolina at Chapel Hill have discovered a genetic risk factor for severe liver disease in people with cystic fibrosis. Those who carry a particular variant of the SERPINA1 gene (also known as alpha-1-antitrypsin or alpha-1-antiprotease) are five times more likely to develop cirrhosis and other liver complications than patients who carry the normal version of the gene......> full story

Better Immune Defense Against Anthrax

Wed, 09 Sep 2009 05:40:31 PDT

Scientists discover a gene in anthrax-causing bacteria may help defend against this form of bio-warfare. Spread of the deadly disease anthrax by spores of the bacterium Bacillus anthracis is a known terrorism risk and protection includes finding ways to treat the disease, according to an academic paper reviewed by Faculty of 1000.......> full story

'Achilles' Heel' In Y Chromosome Linked To Sex Disorders

Tue, 08 Sep 2009 06:15:26 PDT

The unique mechanism behind the evolutionary survival of the human Y chromosome may also be responsible for a range of sex disorders, from failed sperm production to sex reversal to Turner Syndrome.......> full story

Scientists Pinpoint Critical Molecule To Celiac Disease, Possibly Other Autoimmune Disorders

Tue, 08 Sep 2009 06:07:27 PDT

It was nine years ago that University of Maryland School of Medicine researchers discovered that a mysterious human protein called zonulin played a critical role in celiac disease and other autoimmune disorders, such as multiple sclerosis and diabetes. Now, scientists have solved the mystery of zonulin's identity, putting a face to the name, in a sense. Scientists led by Alessio Fasano, M.D., have identified zonulin as a molecule in the human body called haptoglobin 2 precursor.......> full story

Small Molecule Inhibits Pathology Associated With Myotonic Dystrophy Type 1

Tue, 08 Sep 2009 05:48:24 PDT

Researchers at the University of Illinois have designed a small molecule that blocks an aberrant pathway associated with myotonic dystrophy type 1, the most common form of muscular dystrophy......> full story

Designing Probiotics That Ambush Gut Pathogens

Tue, 08 Sep 2009 05:45:44 PDT

Researchers in Australia are developing diversionary tactics to fool disease-causing bacteria in the gut. Many bacteria, including those responsible for major gut infections, such as cholera, produce toxins that damage human tissues when they bind to complex sugar receptors displayed on the surface of cells in the host's intestine......> full story

New developments in reproductive medicine

Mon, 07 Sep 2009 06:20:56 PDT

Three out of ten women who undergo polar body diagnosis go on to have a child. The extensive technique of polar body analysis (PBA) is described by researchers in reproductive medicine at Lübeck in an article in the current edition of Deutsches Ärtzeblatt International, in which they present three successful cases and one failure.....> full story

Building Better Bone Replacements With Bacteria

Mon, 07 Sep 2009 06:08:04 PDT

Bacteria that manufacture hydroxyapatite (HA) could be used to make stronger, more durable bone implants. Professor Lynne Macaskie from the University of Birmingham this week (7-10 September) presented work to the Society for General Microbiology's meeting at Heriot-Watt University, Edinburgh......> full story

Molecular 'GPS' Helps Researchers Probe Processes Important In Aging And Disease

Sat, 05 Sep 2009 06:07:33 PDT

With all the hype about beneficial antioxidants in everything from face cream to cereal bars, you'd think their targets—oxygen radicals—must be up to no good. It's true, the buildup of oxygen radicals and other reactive oxygen species (ROS) in cells contributes to aging and possibly to diseases such as cancer and......> full story

Cancer numbers worry doctor

Sat, 05 Sep 2009 05:49:12 PDT

IN six months Rockhampton doctor Stephen Murray has cut 542 skin cancers from 284 people. He knew it was the skin cancer capital of the world, but these latest statistics even shocked him......> full story

Mice Can Eat 'Junk' And Not Get Fat: Researchers Find Gene That Protects High-fat-diet Mice From Obesity

Fri, 04 Sep 2009 06:10:46 PDT

University of Michigan researchers have identified a gene that acts as a master switch to control obesity in mice. When the switch is turned off, even high-fat-diet mice remain thin......> full story

Canadian Research Breakthrough Holds Promise for Development of Effective Cancer Therapies

Fri, 04 Sep 2009 05:56:58 PDT

Researchers Dr. Marc Therrien at the Institute for Research in Immunology and Cancer (IRIC) of the Université de Montréal, and Dr. Frank Sicheri, at the Samuel Lunenfeld Research Institute of Mount Sinai Hospital in Toronto, have discovered a new target that may be instrumental in the development of new, more effective cancer therapies......> full story

Study Results Promise Faster Recovery From Life-Threatening Blood Cell Shortages

Thu, 03 Sep 2009 06:21:45 PDT

A key compound resupplies bone marrow with fast-acting stem cells that can more quickly rekindle blood cell production, according to a study published online today in the journal Blood. While the study was in mice, in the study authors say it has the potential to increase survival among patients with life-threatening blood cell shortages......> full story