October 14, 2008, 7:52 PM CT

Researchers continue to find genes for type 1 diabetes

Genetics scientists have identified two novel gene locations that raise the risk of type 1 diabetes. As they continue to reveal pieces of the complicated genetic puzzle for this disease, the scientists expect to improve predictive tests and devise preventive strategies.

"As we add to our knowledge of the biology of type 1 diabetes and better understand details of the disease's genetic risk, we will be able to develop better diagnostic tests that meaningfully predict who will develop diabetes," said study leader Hakon Hakonarson, M.D., Ph.D., director of the Center for Applied Genomics at The Children's Hospital of Philadelphia.

The study appeared online Oct. 7 in Diabetes, the journal of the American Diabetes Association. Hakonarson's co-leader in the study was Constantin Polychronakos, M.D., director of Pediatric Endocrinology at McGill University in Montreal.

Type 1 diabetes, formerly called juvenile diabetes, commonly begins in childhood, when the body's immune system malfunctions and destroys insulin-producing beta cells in the pancreas. Without insulin, blood sugar levels run out of control and can impair blood flow and damage the eyes, nerves and kidneys. It is second only to asthma as the most common chronic disease in American children. Patients are dependent for life on insulin injections or insulin medications......... Posted by: JoAnn      Read more         Source

October 8, 2008, 9:59 PM CT

Human Mind and Future Infrastructure Systems

The National Science Foundation (NSF) Office of Emerging Frontiers in Research and Innovation (EFRI) has announced 12 grants for fiscal year 2008, awarding a total of $23,779,056 over four years to 54 researchers representing 20 institutions.

Interdisciplinary teams will pursue transformative, fundamental research in two areas of great promise: understanding the brain and how its abilities may be used through cognitive optimization and prediction; and developing ways to make complex, interdependent infrastructure systems more resilient and sustainable.

What scientists learn from the brain may open a number of new paths of discovery, in areas such as computing, robotics, medicine and education. Understanding how the brain moves the hand, for example, could illuminate entirely novel ways to help people who are paralyzed or use prosthetic limbs. Understanding how the brain visually recognizes objects will enable advances in artificial vision systems, robotic intelligence and more.

The second area of research will examine complex challenges in our nation's interwoven infrastructures as demands on these interdependent systems are changing. Scientists will investigate how to increase their resiliency and sustainability as, for example, numerous electric vehicles interact with the power grid. In addition to drawing electricity from the grid, electric vehicles may send stored energy to the grid. New research may find a role for these vehicles in stabilizing the electric power grid during a catastrophe and in managing fluctuations in electricity from renewable energy sources......... Posted by: Scott      Read more         Source

October 8, 2008, 9:36 PM CT

Proteins in sperm unlock understanding infertility

Proteins found in sperm are central to understanding male infertility and could be used to determine new diagnostic methods and fertility therapys as per a paper published by the journal Molecular and Cellular Proteomics (MCP). The article demonstrates how proteomics, a relatively new field focusing on the function of proteins in a cell, can be successfully applied to infertility, helping identify which proteins in sperm cells are dysfunctional.

"Up to 50 percent of male-factor infertility cases in the clinic have no known cause, and therefore no direct therapy. In-depth study of the molecular basis of infertility has great potential to inform the development of sensitive diagnostic tools and effective therapies," write co-authors Diana Chu, assistant professor of biology at San Francisco State University and Tammy Wu, post-doctoral fellow at SF State. The study is included in a special Oct. 10 issue of MCP dedicated to the clinical application of proteomics.

"We suggest how the study of proteins is useful in the clinic, to help people move from infertile to fertile and ultimately to help couples have a baby," Chu said. "The ultimate goal is that a doctor could be able to say to a patient, 'this is the protein that is misregulated in your sperm and this is the drug that corrects it or decreases the level of that protein.' Understanding sperm proteins also means that a doctor could be able to inform patients of the likely success rates of different fertility therapies, an important factor given the high cost of fertility therapys"......... Posted by: Scott      Read more         Source

October 7, 2008, 10:50 PM CT

Atomic-resolution views suggest function of enzyme

An atomic-resolution view of an enzyme found only in the eye has given scientists at the University of Washington (UW) clues about how this enzyme, essential to vision, is activated. The enzyme, phosphodiesterase 6 (PDE6), is central to the way light entering the retina is converted into a cascade of signals to the brain.

This particular form of the enzyme comes from the cone photoreceptors of the retina and has not been well-researched, in contrast to its rod form. Rods are involved in night vision and motion sensation; the cones are responsible for color sensitivity, visual acuity, daylight vision, and adjustment to bright light.

The section of the enzyme molecule that most interests the scientists is the so-called GAF A domain. A small messenger molecule, cGMP, binds to the GAF A domain to regulate the enzyme.

"The domain binds to this small molecule with extremely high sensitivity," said UW biochemist Clemens Heikaus, who along with Sergio E. Martinez, now a research associate at Rutgers, carried out the study. "From our structure, we can infer why it prefers cGMP over other messenger molecules." He added that the domain is quick in recognizing and responding to the messenger molecule to create an instantaneous flow of information to the brain......... Posted by: Mike      Read more         Source

October 6, 2008, 10:28 PM CT

Why current publication practices may distort science

The current system of publishing medical and scientific research provides "a distorted view of the reality of scientific data that are generated in the laboratory and clinic," says a team of scientists in this week's PLoS Medicine

In their Essay, Neal Young (National Institutes of Health, USA), John Ioannidis (Tufts University School of Medicine, USA and University of Ioannina School of Medicine, Greece), and Omar Al-Ubaydli (George Mason University, USA) apply principles from the field of economics to present evidence consistent with a distortion.

There is an "extreme imbalance," they say, between the abundance of supply (the output of basic science laboratories and clinical investigations) and the increasingly limited venues for publication (journals with sufficiently high impact). The result is that only a small proportion of all research results are eventually chosen for publication, and these results are unrepresentative of scientists' repeated samplings of the real world.

The authors argue that there is a moral imperative to reconsider how scientific data are judged and disseminated.

A prior Essay by one of the co-authors, John Ioannidis, which was entitled "Why most published research findings are false" (http://dx.doi.org/10.1371/journal.pmed.0020124) has been the most viewed PLoS Medicine article of all time and was called "an instant cult classic" in a Boston Globe op-ed of July 27 2006 (http://www.boston.com/news/science/articles/2006/07/27/science_and_shams/)......... Posted by: Janet      Read more         Source

October 3, 2008, 5:27 AM CT

Brain pathway responsible for obesity

University of Wisconsin-Madison researchers, for the first time, have found a messaging system in the brain that directly affects food intake and body weight.

Published in the Oct. 3, 2008 issue of Cell, the findings--from a study in mice--point to a entirely new approach to treating and preventing obesity in humans. The discovery also offers hope for new ways to treat related disorders, such as type 2 diabetes and cardiovascular diseases--the most prevalent health problems in the United States and the rest of the developed world.

Led by Dongsheng Cai, an assistant professor of physiology at the UW School of Medicine and Public Health, the scientists looked specifically at the hypothalamus--the brain structure responsible for maintaining a steady state in the body--and for the first time observed that a cell-signaling pathway primarily linked to inflammation also influences the regulation of food intake. Stimulating the pathway led the animals to increase their energy consumption, while suppressing it helped them maintain normal food intake and body weight.

The research stems from recent explorations into the problem called metabolic inflammation, a by-product of too much food or energy consumption. Unlike the classical inflammation typically observed in infections, injuries and diseases such as cancer, the metabolic inflammation seen in obesity-related diseases is much milder, doesn't lead to overt symptoms or cause tissues damage......... Posted by: JoAnn      Read more         Source

October 1, 2008, 8:40 AM CT

Genes influence effectiveness of weight-loss drug

Obese patients with a specific genetic make-up lose more weight when taking the weight loss drug sibutramine and undergoing behavioral treatment in comparison to those without this genetic make-up, reports a new study in Gastroenterology, the official journal of the American Gastroenterological Association (AGA) Institute.

The obesity epidemic continues to be an increasingly global problem: an estimated 1.6 billion adults worldwide are overweight (body mass index [BMI]>25) and 400 million are obese (BMI>30). In addition, the incidences of diabetes and other debilitating diseases attributable to obesity continue to rise.

While there are numerous options for the therapy of obesity, this study examined sibutramine, a medicine approved for the long-term therapy of obesity. The drug creates a feeling of fullness, prevents decline in metabolic rate linked to low calorie diets and causes weight loss, particularly when combined with behavioral treatment. However, weight loss with the drug is highly variable. Therefore, a research team at the Mayo Clinic assessed the influence of specific markers of candidate genes controlling serotonergic and adrenergic mechanisms (α2A-receptor, 5-HTTLPR and GNβ3) on weight loss/body composition in response to sibutramine or placebo......... Posted by: JoAnn      Read more         Source

September 28, 2008, 8:42 PM CT

'Hub' of fear memory formation identified in brain cells

A protein mandatory for the earliest steps in embryonic development also plays a key role in solidifying fear memories in the brains of adult animals, researchers have revealed. An apparent "hub" for changes in the connections between brain cells, beta-catenin could be a potential target for drugs to enhance or interfere with memory formation.

The results are published online this week and appear in the recent issue of Nature Neuroscience

The protein beta-catenin acts like a Velcro strap, fastening cells' internal skeletons to proteins on their external membranes that connect them with other cells. In species ranging from flies to frogs to mice, it also can transmit early signals that separate an embryo into front and back or top and bottom.

During long-term memory formation, structural changes take place in the synapses the connections between neurons in the brain, says Kerry Ressler, MD, PhD, associate professor of psychiatry and behavioral sciences at Emory University School of Medicine. Ressler is a researcher at Emory University's Yerkes National Primate Research Center, where the research was conducted, and a Howard Hughes Medical Institute investigator.

"We thought beta-catenin could be a hub for the changes that take place in the synapses during memory formation," says Ressler. "But because beta-catenin is so important during development, we couldn't take the standard approach of just knocking it out genetically"......... Posted by: Daniel      Read more         Source

September 24, 2008, 6:21 PM CT

Balancing the brain

Neuroresearchers at Children's Hospital Boston have identified the first known "master switch" in brain cells to orchestrate the formation and maintenance of inhibitory synapses, essential for proper brain function. The factor, called Npas4, regulates more than 200 genes that act in various ways to calm down over-excited cells, restoring a balance that is thought to go askew in some neurologic disorders. The findings are reported in the September 24 advance online edition of the journal Nature

Synapses, the connections between brain cells, can be excitatory or inhibitory in nature. At birth, the rapidly developing brain teems with excitatory synapses, which tend to make nerve cells "fire" and stimulate their neighbors. But if the excitation isn't eventually balanced, it can lead to epilepsy, and diseases like autism and schizophrenia have been linked to an imbalance of excitation and inhibition. The creation of inhibitory connections is also necessary to launch critical periods -- windows of rapid learning during early childhood and adolescence, when the brain is very "plastic" and able to rewire itself.

Npas4 is a transcription factor, a switch that activates or represses other genes. The researchers, led by Michael Greenberg, PhD, director of the Neurobiology Program at Children's, demonstrated that the activity of as a number of as 270 genes changes when Npas4 activity is blocked in a cell, and that Npas4 activation is linked to an increased number of inhibitory synapses on the cell's surface......... Posted by: Daniel      Read more         Source

September 22, 2008, 10:22 PM CT

Half of trials supporting FDA applications go unpublished

Over half of all supporting trials for FDA-approved drugs remained unpublished 5 years after approval, says new research published in this week's PLoS Medicine The most important trials determining efficacy, and those with statistically significant results and larger sample sizes, are more likely would be published.

Ida Sim and his colleagues from the University of California San Francisco searched the medical literature to determine the publication status of all 909 clinical trials that supported the 90 new drug approval applications approved by the US Food and Drug Administration (FDA) between 1998 and 2000. Eventhough 76% of the pivotal trials (typically large Phase II or III trials designed to provide evidence on the overall risks and benefits of a drug) had been published in medical journalscommonly within 3 years of FDA approvalonly 43% of all of the submitted trials had been published.

The scientists also found evidence of selective reporting of the results from these trials. For example, Sim and his colleagues report that a pivotal trial in which a new drug works better than an old drug is more likely would be published than a trial in which the new drug does no better. This is a form of publication bias that may lead to an inappropriately favorable record in the medical literature of a drug's true risk-benefit profile relative to other standard therapies, and can lead to preferential prescribing of newer and more-expensive therapys, say the authors......... Posted by: Scott      Read more         Source

September 18, 2008, 10:39 PM CT

Breakthrough in spinal injury treatment

Manipulating embryo-derived stem cells before transplanting them may hold the key to optimizing stem cell technologies for repairing spinal cord injuries in humans. Research published in BioMed Central's open access Journal of Biology, may lead to cell based therapies for victims of paralysis to recover the use of their bodies without the risk of transplant induced pain syndromes.

Dr. Stephen Davies, Associate Professor of Neurosurgery at the University of Colorado Denver School of Medicine, reported that in collaboration with scientists at the University of Rochester, NY his research team has transplanted two types of the major support cells of the brain and spinal cord, cells called astrocytes. These two types of astrocytes, which are both made from the same embryo-derived stem cell-like precursor cell, have remarkably different effects on the spinal repair process.

Using signal molecules known to be involved in the generation of embryonic astrocytes during spinal cord development, the scientists were able to make pure cultures of two different types of astrocytes from the GRP cells.

When Dr. Davies and his team transplanted these two types of astrocytes into the injured spinal cord, they had dramatically different effects. One type of astrocyte called GDAsBMP was remarkably effective at promoting nerve regeneration and recovery of limb motion when transplanted into spinal cord injuries. However, the other type of astrocyte cell generated called GDAsCNTF, not only failed to promote nerve fiber regeneration or functional recovery but also caused neuropathic pain, a severe side effect that was not seen in rats treated with GDAsBMP......... Posted by: Daniel      Read more         Source

September 16, 2008, 10:14 PM CT

Pazopanib shrinks lung cancers before surgery

Pazopanib, a new oral angiogenesis inhibitor, has demonstrated interesting activity in difficult to treat non-small-cell lung cancer, US scientists report.

In a phase II trial, 30 out of 35 patients treated with preoperative pazopanib for a minimum of two weeks saw their tumor size shrink by up to 85%.

"This is a positive result that will be explored further," said Prof. Nasser Altorki from Weil Medical College of Cornell University in New York.

"To my knowledge, no other results on the effect of angiogenesis inhibitors in early stage operable lung cancer have been published.

The results presented here with pazopanib indicate a highly active drug in this setting and further development in lung cancer is underway to fully understand the value of this drug in this disease"......... Posted by: Scott      Read more         Source

September 14, 2008, 10:39 PM CT

Extremely exact images from inside the body

It will be the only magnetic resonance tomograph of the modern 7 tesla generation in the world, in which a metrology institute is also involved. Magnetic resonance tomographs, which use a magnetic field of 7 tesla, have still not been in operation in hospitals and clinics, but have solely served research. For the first time in the world, cardiovascular research carried out on such a device is now also to play an important role. The magnetic resonance tomograph costing approximately seven million Euros and weighing 35 tonnes was delivered to its new location, the Experimental and Clinical Research Center (ECRC) of the Max Delbrück Center (MDC) for Molecular Medicine in Berlin-Buch on 11th September.

In contrast to the 1.5 and 3 tesla devices which have largely been the norm to date, its higher magnetic field will provide sharper images and better insights into the smallest structures of the human body. The aim is to detect the risk or commencement of an illness at a very early stage in heart, brain and cancer research. Above all, heart research by magnetic resonance tomography is viewed as very difficult. As such, a demanding task will be waiting for PTB researchers from January 2009, when the device has been fully installed: as the partner dealing with physics and technical issues in the joint project, they are responsible for making the unique potential of this tomograph useful for applications in clinics. The PTB will, moreover, find the ideal conditions to advance its work on patient safety in high-field tomographs and on the development of new concepts in MRT imaging. The other partners in the project, besides the Max Delbrück Center and the PTB, are Siemens, the constructors of the 7 tesla device, and the Charite hospital. The new ultra-high-field MRT equipment of the ECRC has been completed with a 9.4 tesla small animal MRT of the Bruker company which was supplied three weeks ago......... Posted by: Scott      Read more         Source

September 14, 2008, 10:13 PM CT

Tuberculosis drug shows promise against latent bacteria

A new study has shown that an investigational drug (R207910, currently in clinical trials against multi-drug resistant tuberculosis strains) is quite effective at killing latent bacteria. This revelation suggests that R207910 may lead to improved and shortened therapys for this globally prevalent disease.

Despite numerous therapy advances, tuberculosis (TB) remains a serious disease fueled by co-infection of HIV patients, the rise of drug-resistant strains, and the ability of Mycobacterium tuberculosis to become dormant and linger in the lungs. In fact, one third of the world population is infected, asymptomatically, with latent TB and is at risk of developing active TB disease during their life time.

Anil Koul and his colleagues at Johnson & Johnson tested R207910 on dormant M. tuberculosis in three different laboratory models of latency. R207910 targets a protein (ATP synthase) essential for making cellular energy (ATP) in actively replicating TB. The scientists reasoned that even dormant bacteria, which are essentially physiologically "turned off", still need to produce small quantities of ATP to survive. As such, a block in ATP synthesis might be an Achilles heel for killing dormant bacteria.

This reasoning proved to be correct and R207190 was able to kill dormant bacteria by greater than 95% whereas current drugs like isoniazid had no effect. Surprisingly, they observed that R207910 is slightly more effective in killing dormant bacteria as in comparison to actively replicating ones, a unique spin as all known TB drugs are more effective on replicating bugs. Koul and his colleagues hope to validate these results clinically, and note that ATP synthase should be looked at as a drug target for other persistent bacterial infections......... Posted by: Mark      Read more         Source

September 14, 2008, 10:07 PM CT

Faster, cheaper way of analyzing the human genome

Investigators at the Translational Genomics Research Institute (TGen) today announced a faster and less expensive way for researchers to find which genes might affect human health.

Using bar-codes, not unlike what shoppers find in grocery stores, TGen scientists found a way to index portions of the nearly 3-billion-base human genetic code, making it easier for researchers to zero in on the regions most likely to show variations in genetic traits.

The findings were published recently in the online version of the journal Nature Methods The study will be published in print in the journal's October edition.

Dr. David Craig, associate director of TGen's Neurogenomics Division, said the new method should cost only one-tenth, or less, of the current cost of sequencing genes usually done to analyze Single Nucleotide Polymorphisms (SNPs), and in performing Genome-Wide Association (GWA) studies.

"Our goal is to find the genetic basis of disease,'' said Craig, the study's lead author. "It (the new method) provides us a way to immediately use next-generation sequencing technology for studying hundreds to thousands of individuals.''.

John Pearson, the head of TGen's Bioinformatics Research Unit, said the new method would allow researchers worldwide to more easily tune their sequencing experiments, and conduct their experiments with greater speed......... Posted by: Scott      Read more         Source

September 11, 2008, 9:39 PM CT

Developing Drug to Stop Cancer Recurrence

After years of working toward this goal, researchers at the OU Cancer Institute have found a way to isolate cancer stem cells in tumors so they can target the cells and kill them, keeping cancer from returning.

A research team led by Courtney Houchen, M.D., and Shrikant Anant, Ph.D., discovered that a particular protein only appears in stem cells. Until now, scientists knew of proteins that appeared in both regular cancer cells and stem cells, but none that just identified a stem cell.

The group has already begun work to use the protein as a target for a new compound that once developed would kill the stem cells and kill the cancer. By targeting the stem cells, researchers and physicians also would be able to stop the cancer from returning.

Houchen and Anant are focusing on adult cancer stem cells because of the major role they play in the start of cancer, the growth of cancer, the spread of cancer and the return of cancer.

Current therapies generally do not target stem cells in tumors. This allows stem cells to wait until after chemotherapy or radiation therapys to begin dividing. Scientists believe these stem cells are often responsible for the return of cancer after therapy. The identification of the stem cell marker enables scientists to develop new therapeutics that can target these cells......... Posted by: Janet      Read more         Source

September 11, 2008, 9:21 PM CT

Keeping nerve axons on target

Neurons constituting the optic nerve wire up to the brain in a highly dynamic way. Cell bodies in the developing retina sprout processes, called axons, which extend toward visual centers in the brain, lured by attractive cues and making U-turns when they take the wrong path. How they find targets so accurately is a central question of neuroscience today.

Using the mouse visual system, a team of Salk Institute for Biological Studies researchers led by Dennis O'Leary, Ph.D., identified an unanticipated factor that helps keep retinal axons from going astray. They report in the Sept. 11 issue of Neuron that p75, a protein previously known to regulate whether neurons live or die, leads a double life as an axon guidance protein.

"Historically, we thought that factors that mediate cell survival and those controlling axon guidance were part of two separate processes," says O'Leary, a professor in the Molecular Neurobiology Laboratory, "But in this study we show a direct interaction between these two systems".

Collaborating with Kuo-Fen Lee, Ph.D., professor in the Clayton Foundation Laboratories for Peptide Biology, the O'Leary team observed a defect in mice genetically engineered to lack p75. Through their synaptic connections, retinal axons develop a two-dimensional map of the retina in their targets in the brain. In the mice lacking p75, retinal axons stopped short of their final target and formed a map that was shifted forward to the superior colliculus, a major visual center in the brain......... Posted by: Mike      Read more         Source

September 11, 2008, 8:29 PM CT

Mad cow disease also caused by genetic mutation

New findings about the causes of mad cow disease show that sometimes it may be genetic.

"We now know it's also in the genes of cattle," said Juergen A. Richt, Regents Distinguished Professor of Diagnostic Medicine and Pathobiology at Kansas State University's College of Veterinary Medicine.

Until several years ago, Richt said, it was thought that the cattle prion disease bovine spongiform encephalopathy -- also called BSE or mad cow disease -- was a foodborne disease. But his team's new findings suggest that mad cow disease also is caused by a genetic mutation within a gene called Prion Protein Gene. Prion proteins are proteins expressed abundantly in the brain and immune cells of mammals.

The research shows, for the first time, that a 10-year-old cow from Alabama with an atypical form of bovine spongiform encephalopathy had the same type of prion protein gene mutation as found in human patients with the genetic form of Creutzfeldt-Jakob disease, also called genetic CJD for short. Besides having a genetic origin, other human forms of prion diseases can be sporadic, as in sporadic CJD, as well as foodborne. That is, they are contracted when people eat products contaminated with mad cow disease. This form of Creutzfeldt-Jakob disease is called variant CJD......... Posted by: Mark      Read more         Source

September 10, 2008, 10:11 PM CT

Immaturity of the brain may cause schizophrenia

The underdevelopment of a specific region in the brain may lead to schizophrenia in individuals. As per research published recently in BioMed Central's open access journal Molecular Brain, dentate gyrus, which is located in the hippocampus in the brain and believed to be responsible for working memory and mood regulation, remained immature in an animal model of schizophrenia.

Professor Tsuyoshi Miyakawa of Fujita Health University, National Institute for Physiological Sciences (NIPS), and Kyoto University led a research team in Japan, with support from the CREST program of Japan Science and Technology Agency (JST). First, the team investigated behaviors by conducting a systematic and well-defined behavioral test battery with alpha-CaMKII mutant mice, an animal model of schizophrenia. These mice showed abnormal behaviors similar to those of schizophrenic patients. Next, the team found the dentate gyrus neurons in hippocampus of the brain of these mice were not matured morphologically and physiologically. By a gene expression analysis, changes of gene expression correlation to the maturation of dentate gyrus neurons were also found in the brains of schizophrenic patients. Taken together, the immaturity of the dentate gyrus may be an underlying cause for schizophrenia......... Posted by: Daniel      Read more         Source

September 10, 2008, 10:05 PM CT

Killing bacteria isn't enough to restore immune function

A bacterial molecule that initially signals to animals that they have been invaded must be wiped out by a special enzyme before an infected animal can regain full health, scientists at UT Southwestern Medical Center have found.

Using a genetically engineered mouse model, the team observed that simply eradicating the infection-causing bug isn't enough to restore an animal's immune function. Lipopolysaccharide, or LPS, the dominant bacterial "signal" molecule that heralds the invasion, must also be inactivated. The findings are to appear online Sept. 11 in Cell Host & Microbe.

"We think this is the first evidence that killing the causative agent of a bacterial infection isn't enough for an animal to recover fully," said Dr. Robert Munford, professor of internal medicine and microbiology, and senior author of the study. "You've got to get rid of this molecule that the host is responding to or else its immune system remains suppressed."

By sensing and responding to LPS, animals mobilize their defenses to attack and kill the bacteria. This immune response also causes inflammation in the host. For a few days after the infection begins, however, an animal's ability to sense the bacteria is turned down, presumably to prevent further inflammation. In the current study, the scientists observed that mice didn't recover from this "tolerant" period unless the LPS was inactivated by acyloxyacyl hydrolase, an enzyme discovered in 1983 by Dr. Munford and Dr. Catherine Hall, now an assistant professor of internal medicine at UT Southwestern......... Posted by: Scott      Read more         Source

September 10, 2008, 8:43 PM CT

Gap junction protein vital to successful pregnancy

Scientists studying a critical stage of pregnancy implantation of the embryo in the uterus have found a protein that is vital to the growth of new blood vessels that sustain the embryo. Without this protein, which is produced in higher quantities in the presence of estrogen, the embryo is unlikely to survive.

This is the first study to detail the mechanism by which the steroid hormone estrogen spurs cell differentiation and blood-vessel growth in the uterus during pregnancy, the scientists report.

The findings, from scientists at the University of Illinois, Emory University, Baylor College of Medicine and New York University, appear in the journal Development

Connexin 43 (Cx43) belongs to a family of proteins that form junctions between cells that regulate the flow of ions and small signaling molecules from cell to cell. At the time of embryo implantation, this gap junction protein is essential to the rapid growth of new blood vessels needed to support the development of the embryo and allow it to implant in the uterine wall, the scientists discovered.

The scientists chose to study Cx43 after analyzing genes that are activated in the presence of estrogen in uterine cells. They observed that Cx43 was prominent among the genes whose expression was increased in cells after exposure to estrogen......... Posted by: Emily      Read more         Source

September 10, 2008, 7:28 PM CT

Individuals vary their immune response

Is it always good to respond maximally when pathogens or disease strike, or should individuals vary their immune response to balance immediate and future costs? This is the question evolutionary physiologists Oliver Love, Katrina Salvante, James Dale, and Tony Williams asked when they examined how a simple immune response varied at different life stages across the life-span of individual zebra finches (Taeniopygia guttata), as per a research findings reported in the recent issue of the American Naturalist

When transitioning from nest-bound juveniles to adults, female immune responses matured slowly whereas males showed dramatic variation potentially due to the costs of molting into their colorful sexually dimorphic plumage. Adult males showed little variation in immune response despite changes in resource quality. Likewise, when females laid eggs under high-quality resource conditions, immune responses were also consistent with those during non-breeding and similar to male responses. However, when laying on reduced resources females reduced their immune response and their reproductive output consistent with a facultative (resource-driven) effect of reproductive effort on immunity. Moreover, even under high-resource conditions during the chick-rearing stage mothers showed reduced immune responses in comparison to fathers suggesting a residual energetic cost of egg-laying. Perhaps most importantly, immune responses of juveniles of both sexes did not predict their subsequent adult responses. Immune responses of adult females were only predictable when the quality of the environment remained constant; as soon as conditions deteriorated, individual females mandatory flexibility in both the immune and reproductive systems. However, the degree of flexibility came at a cost as only individuals with high immune responses as non-breeders had the capacity to reduce responses when times became tough. These results underlie the fact that immunity is a highly plastic trait that can be modulated in a sex- and context-dependent manner. Given the need for individual flexibility in the immune system, this suggests that an immune response at one stage may provide limited information about immune response at future stages......... Posted by: Janet      Read more         Source

September 3, 2008, 6:38 PM CT

NTP finalizes report on Bisphenol A

Current human exposure to bisphenol A (BPA), a chemical used in a number of polycarbonate plastics and epoxy resins, is of "some concern" for effects on development of the prostate gland and brain and for behavioral effects in fetuses, infants and children, as per a final report released recently by the National Toxicology Program (NTP).

The report provides the NTP's current opinion on BPA's potential to cause harm to human reproduction or development. The conclusions are based primarily on a broad body of research involving numerous laboratory animal studies. The report is part of a lengthy review of the scientific literature on BPA and takes into consideration public and peer review comments received on an earlier draft report. The final report is available at http://cerhr.niehs.nih.gov/chemicals/bisphenol/bisphenol.pdf.

"There remains considerable uncertainty whether the changes seen in the animal studies are directly applicable to humans, and whether they would result in clear adverse health effects," said NTP Associate Director John Bucher, Ph.D. "But we have concluded that the possibility that BPA may affect human development cannot be dismissed."

About the impact that these findings may have on consumers, CERHR Director Michael Shelby, Ph.D., said, "Unfortunately, it is very difficult to offer advice on how the public should respond to this information. More research is clearly needed to understand exactly how these findings relate to human health and development, but at this point we can't dismiss the possibility that the effects we're seeing in animals may occur in humans. If parents are concerned, they can make the personal choice to reduce exposures of their infants and children to BPA"......... Posted by: Janet      Read more         Source

September 2, 2008, 8:08 PM CT

Age-related memory loss tied to slip in filtering information quickly

Researchers have identified a way in which the brain's ability to process information diminishes with age, and shown that this break down contributes to the decreased ability to form memories that is linked to normal aging.

The finding, published in the current online early edition of Proceedings of the National Academy of Sciences, fuels the researchers' efforts, they say, to explore strategies for enhancing brain function in the healthy aging population, through mental training exercises and pharmaceutical therapys.

This research, which was conducted by University of California, San Francisco and University of California, Berkeley scientists, builds on the team's seminal 2005 discovery ("Nature Neuroscience," October 2005) that the brain's capacity to ignore irrelevant information diminishes with age.

The capacity to ignore irrelevant information -- such as most of the faces in a crowded room when one is looking for a long-lost friend and to enhance pertinent information -- such as the face of a new acquaintance met during the search for the old friend is key to memory formation. This process is known as top-down modulation.

In the 2005 study, the team recorded brain activity in younger and elderly adults given a visual memory test in which they were shown sequences of images (sets of two faces and two scenes), told to remember a specific category, and then asked to identify an image from that category nine seconds later. The scientists, using functional magnetic resonance imaging (fMRI), determined that the neurons of the older participants (ages 60 to 72) responded excessively to the images they should have ignored, in comparison to the younger adults (ages 19 to 33). This attention to the distracting information directly correlated with how well the participants did on the memory test......... Posted by: Daniel      Read more         Source

August 31, 2008, 9:03 PM CT

Radiation Risks Among Heart Doctors

Patients are not the only ones at risk during cardiac procedures. Doctors performing heart surgery also face health risks, namely to their eyes.

The IAEA is helping to raise awareness of threats, through training in radiation protection correlation to medical uses of X-ray imaging systems.

The issue of radiation protection for medical personnel is especially acute in the case of lengthy angioplasty and other cardiac interventions performed under X-ray fluoroscopic guidance. The procedure can cause extensive radiation exposure to heart specialists that could lead to cataracts, alongside other longer term health risks. Fluoroscopy provides X-ray images of a patient that physicians can view on a display screen or monitor in real time.

The IAEA is helping the medical community to address this problem through a major international initiative aimed at training heart specialists and other medical professionals in radiation protection. This September in Latin America, the IAEA is organizing a study to test the eyes of interventional heart specialists participating in a regional medical conference. The Cardiology Conference is organized by the Latin American Society of Interventional Heart specialists (SOLACI) in Bogota, Colombia.

The study is being led by a team of experts, including Prof. Eliseo Vano, Radiology Department of the Complutense University of Madrid; Prof. Norman Kleiman, Columbia University, New York; local ophthalmologists from Bogota; and Mr. Raul Ramirez of the IAEA Department of Technical Cooperation. The initiative is part of an International Action Plan on the radiological protection of patients spearheaded by the IAEA......... Posted by: Janet      Read more         Source

August 31, 2008, 8:47 PM CT

Magnesium Sulfate Reduces Risk of Cerebral Palsy

Results of a 10-year study reported in the August 28 issue of the New England Journal (NEJM) observed that magnesium sulfate administered to women delivering before 32 weeks of gestation reduced the risk of cerebral palsy by 50 percent. The Beneficial Effects of Antenatal Magnesium Sulfate (BEAM) trial was conducted in 18 centers in the U.S., including Northwestern Memorial, and is the first prenatal intervention ever found to reduce the instance of cerebral palsy correlation to premature birth.

Magnesium sulfate is traditionally used in obstetrics to stop premature labor and prevent seizures in women with hypertension. The BEAM trial studied the link between magnesium sulfate and cerebral palsy by identifying 2,240 women who were likely to give birth more than two months premature. Half of the women intravenously received magnesium sulfate while the other half received a placebo. Children born to the women in the study were examined at two-years-old, and results observed that the children in the magnesium group were 50 percent less likely to develop cerebral palsy in comparison to children in the placebo group.

"This is a substantial breakthrough in maternal fetal medicine that could positively impact the health of thousands of babies," said Alan Peaceman, MD, chair of the Division of Maternal Fetal Medicine at Northwestern Memorial Hospital, professor of Obstetrics and Gynecology at the Northwestern University Feinberg School of Medicine, and an investigator in the study. "After 10 years of studying the effects of magnesium sulfate, it has proven to be a successful method of reducing the outcome of cerebral palsy in premature births"......... Posted by: JoAnn      Read more         Source

August 31, 2008, 8:37 PM CT

Door to new cancer, aging treatments

Scientists at The Wistar Institute have deciphered the structure of the active region of telomerase, an enzyme that plays a major role in the development of nearly all human cancers. The landmark achievement opens the door to the creation of new, broadly effective cancer drugs, as well as anti-aging therapies.

Scientists have attempted for more than a decade to find drugs that shut down telomerasewidely considered the No. 1 target for the development of new cancer therapysbut have been hampered in large part by a lack of knowledge of the enzyme's structure.

The findings, published online August 31 in Nature, should help scientists in their efforts to design effective telomerase inhibitors, says Emmanuel Skordalakes, Ph.D., assistant professor in Wistar's Gene Expression and Regulation Program, who led the study.

"Telomerase is an ideal target for chemotherapy because it is active in almost all human tumors, but inactive in most normal cells," Skordalakes says. "That means a drug that deactivates telomerase would likely work against all cancers, with few side effects".

The study elucidates the active region of telomerase and provides the first full-length view of the telomerase molecule's critical protein component. It reveals surprising details, at the atomic level, of the enzyme's configuration and how it works to replicate the ends of chromosomesa process critical to both tumor development and the aging process......... Posted by: Scott      Read more         Source

August 31, 2008, 8:34 PM CT

The association with stress and depression

The brain is the key organ in the response to stress. It reacts in a complex, orchestrated manner that is correlation to the activation and inhibition of neural structures involved in sensory, motor, autonomic, cognitive and emotional processes. It is the brain which finally determines what in the world is threatening and might be stressful for us, and which regulates the stress responses that can be either adaptive or maladaptive. Chronic stress can affect the brain and lead into depression: Environmental stressors (e.g. job and family situation, neighborhood) and particularly stressful life events such as trauma or abuse are amongst the most potent factors to induce depression. Since the development of novel approaches to antidepressant therapy is based upon an improved neurobiological understanding of this condition, new information about the cellular changes that take place in the brain is required.

Depression: a growing public health burden

Depression is a chronic, recurring, multifactorial, and life-threatening disorder, which represents a collection of psychological, neuroendocrine, physiological and behavioural symptoms. Chronicity and frequency of these symptoms constitute the clinical condition. Depressive disorders affect up to 20% of people at some time in their life. In primary care, an estimated 20��% of patients suffer from depression, but often are not diagnosed correctly (Wittchen, 2000)......... Posted by: JoAnn      Read more         Source

August 31, 2008, 8:31 PM CT

New genes for inflammatory bowel disease in children

Scientists have discovered two new genes that increase the risk of developing inflammatory bowel disease (IBD) in childhood.

While further study is needed to identify the specific disease-causing mutations in these new genes, the scientists say the genes are especially strong candidates to be added to the list of genes already known to affect IBD. "As we continue to find genes that interact with each other and with environmental influences in this complex, chronic disease, we are building the foundation for personalized therapys tailored to a patient's genetic profile," said co-first author Robert N. Baldassano, M.D., director of the Center for Pediatric Inflammatory Bowel Disease at The Children's Hospital of Philadelphia.

"We will resequence the gene regions we have identified to pinpoint the causative mutations in these genes," added study leader Hakon Hakonarson, M.D., Ph.D., director of the Center for Applied Genomics at Children's Hospital. "We strongly suspect one gene will provide a compelling target for drug development, given what's known about its biology".

Both authors direct research programs at Children's Hospital and are also faculty members of the University of Pennsylvania School of Medicine. Their study, performed in collaboration with scientists from the Medical College of Wisconsin, The University of Utah, Cincinnati Children's Hospital and two research hospitals in Italy, appears in advance online publication Aug. 31 in Nature Genetics........ Posted by: Scott      Read more         Source