Protein researchers closing in on the mystery of schizophrenia

Schizophrenia is a severe disease for which there is still no effective medical treatment. In an attempt to understand exactly what happens in the brain of schizophrenic people, researchers from the University of Southern Denmark have analysed proteins in the brains of rats that have been given hallucinogenic drugs. This may pave the way for new and better medicines.Seven per cent of the adult population suffer from schizophrenia, and although scientists have tried for centuries to understand the disease, they still do not know what causes the disease or which physiological changes it causes in the body. Doctors cannot make the diagnosis by looking for specific physiological changes in the patient’s blood or tissue, but have to diagnose from behavioral symptoms.In an attempt to find the physiological signature of schizophrenia, researchers from the University of Southern Denmark have conducted tests on rats, and they now believe that the signature lies in some specific, measurable proteins. Knowing these proteins and comparing their behavior to proteins in the brains of not-schizophrenic people may make it possible to develop more effective drugs.It is extremely difficult to study brain activity in schizophrenic people, which is why researchers often use animal models in their strive to understand the mysteries of the schizophrenic brain. Rat brains resemble human brains in so many ways that studying them makes sense if one wants to learn more about the human brain.Schizophrenic symptoms in ratsThe strong hallucinogenic drug phenocyclidine (PCP), also known as “angel’s dust,” provides a range of symptoms in people which are very similar to schizophrenia.”When we give PCP to rats, the rats become valuable study objects for schizophrenia researchers,” explains Ole Nrregaard Jensen, professor and head of the Department of Biochemistry and Molecular Biology.Along with Pawel Palmowski, Adelina Rogowska-Wrzesinska and others, he is the author of a scientific paper about the discovery, published in the international Journal of Proteome Research.Among the symptoms and reactions that can be observed in both humans and rats are changes in movement and reduced cognitive functions such as impaired memory, attention and learning ability.”Scientists have studied PCP rats for decades, but until now no one really knew what was going on in the rat brains at the molecular level. We now present what we believe to be the largest proteomics data set to date,” says Ole Nrregaard Jensen.PCP is absorbed very quickly by the brain, and it only stays in the brain for a few hours. Therefore, it was important for researchers to examine the rats’ brain cells soon after the rats were injected with the hallucinogenic drug.”We could see changes in the proteins in the brain already after 15 minutes. And after 240 minutes, it was almost over,” says Ole Nrregaard Jensen.The University of Southern Denmark holds some of the world’s most advanced equipment for studying proteins, and Ole Nrregaard Jensen and his colleagues used the university’s so-called mass spectrometres for their protein studies.352 proteins cause brain changes”We found 2604 proteins, and in 352 of them, we saw changes that can be associated with the PCP injections. These 352 proteins will be extremely interesting to study in closer detail to see if they also alter in people with schizophrenia — and if that’s the case, it will of course be interesting to try to develop a drug that can prevent the protein changes that lead to schizophrenia,” says Ole Nrregaard Jensen about the discovery and the work that now lies ahead.The 352 proteins in rat brains responded immediately when the animals were exposed to PCP. …

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Genetic cause of heart valve defects revealed

Heart valve defects are a common cause of death in newborns. Scientists at the University of Bonn and the caesar research center have discovered “Creld1” is a key gene for the development of heart valves in mice. The researchers were able to show that a similar Creld1 gene found in humans functions via the same signaling pathway as in the mouse. This discovery is an important step forward in the molecular understanding of the pathogenesis of heart valve defects. The findings have been published in the journal “Developmental Cell.”Atrioventricular septal defect (AVSD) is a congenital heart defect in which the heart valves and cardiac septum are malformed. Children with Down’s syndrome are particularly affected. Without surgical interventions, mortality in the first months of life is high. “Even in adults, unidentified valve defects occur in about six percent of patients with heart disease,” says Prof. Dr. Michael Hoch, Executive Director of the Life & Medical Sciences (LIMES) Institute of the University of Bonn.For years, there have been indications that changes in the so-called Creld1 gene (Cysteine-Rich with EGF-Like Domains 1) increase the pathogenic risk of AVSD. …

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Tumor suppressor gene linked to stem cells, cancer biologists report

Just as archeologists try to decipher ancient tablets to discern their meaning, UT Southwestern Medical Center cancer biologists are working to decode the purpose of an ancient gene considered one of the most important in cancer research.The p53 gene appears to be involved in signaling other cells instrumental in stopping tumor development. But the p53 gene predates cancer, so scientists are uncertain what its original function is.In trying to unravel the mystery, Dr. John Abrams, Professor of Cell Biology at UT Southwestern, and his team made a crucial new discovery — tying the p53 gene to stem cells. Specifically, his lab found that when cellular damage is present, the gene is hyperactive in stem cells, but not in other cells. The findings suggest p53’s tumor suppression ability may have evolved from its more ancient ability to regulate stem cell growth.”The discovery was that only the stem cells light up. None of the others do. The exciting implication is that we are able to understand the function of p53 in stem cells,” said Dr. Abrams, Chair of the Genetics and Development program in UT Southwestern’s Graduate School of Biomedical Sciences. “We may, in fact, have some important answers for how p53 suppresses tumors.”The findings appear online in the journal eLife, a joint initiative of the Howard Hughes Medical Institute, the Max Planck Society, and the Wellcome Trust.p53 is one of the hardest working and most effective allies in the fight against cancer, said Dr. Abrams. …

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Ancient sea creatures filtered food like modern whales

Ancient, giant marine animals used bizarre facial appendages to filter food from the ocean, according to new fossils discovered in northern Greenland. The new study, led by the University of Bristol and published today in Nature, describes how the strange species, called Tamisiocaris, used these huge, specialized appendages to filter plankton, similar to the way modern blue whales feed today.The animals lived 520 million years ago during the Early Cambrian, a period known as the ‘Cambrian Explosion’ in which all the major animal groups and complex ecosystems suddenly appeared. Tamisiocaris belongs to a group of animals called anomalocarids, a type of early arthropod that included the largest and some of the most iconic animals of the Cambrian period. They swam using flaps down either side of the body and had large appendages in front of their mouths that they most likely used to capture larger prey, such as trilobites.However, the newly discovered fossils show that those predators also evolved into suspension feeders, their grasping appendages morphing into a filtering apparatus that could be swept like a net through the water, trapping small crustaceans and other organisms as small as half a millimetre in size.The evolutionary trend that led from large, apex predators to gentle, suspension-feeding giants during the highly productive Cambrian period is one that has also taken place several other times throughout Earth’s history, according to lead author Dr Jakob Vinther, a lecturer in macroevolution at the University of Bristol.Dr Vinther said: “These primitive arthropods were, ecologically speaking, the sharks and whales of the Cambrian era. In both sharks and whales, some species evolved into suspension feeders and became gigantic, slow-moving animals that in turn fed on the smallest animals in the water.”In order to fully understand how the Tamisiocaris might have fed, the researchers created a 3D computer animation of the feeding appendage to explore the range of movements it could have made.”Tamisiocaris would have been a sweep net feeder, collecting particles in the fine mesh formed when it curled its appendage up against its mouth,” said Dr Martin Stein of the University of Copenhagen, who created the computer animation. “This is a rare instance when you can actually say something concrete about the feeding ecology of these types of ancient creatures with some confidence.”The discovery also helps highlight just how productive the Cambrian period was, showing how vastly different species of anomalocaridids evolved at that time, and provides further insight into the ecosystems that existed hundreds of millions of years ago.”The fact that large, free-swimming suspension feeders roamed the oceans tells us a lot about the ecosystem,” Dr Vinther said. “Feeding on the smallest particles by filtering them out of the water while actively swimming around requires a lot of energy — and therefore lots of food.”Tamisiocaris is one of many recent discoveries of remarkably diverse anomalocarids found in rocks aged 520 to 480 million years old. “We once thought that anomalocarids were a weird, failed experiment,” said co-author Dr Nicholas Longrich at the University of Bath. “Now we’re finding that they pulled off a major evolutionary explosion, doing everything from acting as top predators to feeding on tiny plankton.”The Tamisiocaris fossils were discovered during a series of recent expeditions led by co-author David Harper, a professor at Durham University. “The expeditions have unearthed a real treasure trove of new fossils in one of the remotest parts of the planet, and there are many new fossil animals still waiting to be described,” he said. …

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New theory on cause of endometriosis

Changes to two previously unstudied genes are the centerpiece of a new theory regarding the cause and development of endometriosis, a chronic and painful disease affecting 1 in 10 women.The discovery by Northwestern Medicine scientists suggests epigenetic modification, a process that enhances or disrupts how DNA is read, is an integral component of the disease and its progression. Matthew Dyson, research assistant professor of obstetrics and gynecology at Northwestern University Feinberg School of Medicine and and Serdar Bulun, MD, chair of obstetrics and gynecology at Feinberg and Northwestern Memorial Hospital, also identified a novel role for a family of key gene regulators in the uterus.”Until now, the scientific community was looking for a genetic mutation to explain endometriosis,” said Bulun, a member of the Center for Genetic Medicine and the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. “This is the first conclusive demonstration that the disease develops as a result of alterations in the epigenetic landscape and not from classical genetic mutations.”The findings were recently published in PLoS Genetics.Women develop endometriosis when cells from the lining of the uterus, usually shed during menstruation, grow in other areas of the body. The persistent survival of these cells results in chronic pelvic pain and infertility. Although the cause of the disease has remained unknown on a cellular level, there have been several different models established to explain its development.Endometriosis only occurs in menstruating primates, suggesting that the unique evolution behind uterine development and menstruation are linked to the disease. Scientists consider retrograde menstruation — cells moving up the fallopian tubes and into the pelvis — as one probable cause. Previous models, however, have been unable to explain why only 10 percent of women develop the disease when most experience retrograde menstruation at some point. Nor do they explain instances of endometriosis that arise independent of menstruation.Bulun and Dyson propose that an epigenetic switch permits the expression of the genetic receptor GATA6 rather than GATA2, resulting in progesterone resistance and disease development.”We believe an overwhelming number of these altered cells reach the lining of the abdominal cavity, survive and grow,” Bulun said. “These findings could someday lead to the first noninvasive test for endometriosis.”Clinicians could then prevent the disease by placing teenagers predisposed to this epigenetic change on a birth control pill regimen, preventing the possibility of retrograde menstruation in the first place, Bulun said.Dyson will also look to use the epigenetic fingerprint resulting from the presence of GATA6 rather than GATA2 as a potential diagnostic tool, since these epigenetic differences are readily detectable.”These findings have the potential to shift how we view and treat the disease moving forward,” Bulun said.Story Source:The above story is based on materials provided by Northwestern University. …

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Big step for next-generation fuel cells and electrolyzers

A big step in the development of next-generation fuel cells and water-alkali electrolyzers has been achieved with the discovery of a new class of bimetallic nanocatalysts that are an order of magnitude higher in activity than the target set by the U.S. Department of Energy (DOE) for 2017. The new catalysts, hollow polyhedral nanoframes of platinum and nickel, feature a three-dimensional catalytic surface activity that makes them significantly more efficient and far less expensive than the best platinum catalysts used in today’s fuel cells and alkaline electrolyzers.This research was a collaborative effort between DOE’s Lawrence Berkeley National Laboratory (Berkeley Lab) and Argonne National Laboratory (ANL).”We report the synthesis of a highly active and durable class of electrocatalysts by exploiting the structural evolution of platinum/nickel bimetallic nanocrystals,” says Peidong Yang, a chemist with Berkeley Lab’s Materials Sciences Division, who led the discovery of these new catalysts. “Our catalysts feature a unique hollow nanoframe structure with three-dimensional platinum-rich surfaces accessible for catalytic reactions. By greatly reducing the amount of platinum needed for oxygen reduction and hydrogen evolution reactions, our new class of nanocatalysts should lead to the design of next-generation catalysts with greatly reduced cost but significantly enhanced activities.”Yang, who also holds appointments with the University of California (UC) Berkeley and the Kavli Energy NanoSciences Institute at Berkeley, is one of the corresponding authors of a paper in Science that describes this research. The paper is titled “Highly Crystalline Multimetallic Nanoframes with Three-Dimensional Electrocatalytic Surfaces.” The other corresponding author is Vojislav Stamenkovic, a chemist with ANL’s Materials Science Division, who led the testing of this new class of electrocatalysts.Fuel cells and electrolyzers can help meet the ever-increasing demands for electrical power while substantially reducing the emission of carbon and other atmospheric pollutants. These technologies are based on either the oxygen reduction reaction (fuel cells), or the hydrogen evolution reaction (electrolyzers). Currently, the best electrocatalyst for both reactions consists of platinum nanoparticles dispersed on carbon. Though quite effective, the high cost and limited availability of platinum makes large-scale use of this approach a major challenge for both stationary and portable electrochemical applications.”Intense research efforts have been focused on developing high-performance electrocatalysts with minimal precious metal content and cost,” Yang says. “In an earlier study, the ANL scientists showed that forming a nano-segregated platinum skin over a bulk single-crystal platinum/nickel alloy enhances catalytic activity but the materials cannot be easily integrated into electrochemical devices. …

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Abdominal fat accumulation prevented by unsaturated fat

New research from Uppsala University shows that saturated fat builds more fat and less muscle than polyunsaturated fat. This is the first study on humans to show that the fat composition of food not only influences cholesterol levels in the blood and the risk of cardiovascular disease but also determines where the fat will be stored in the body. The findings have recently been published in the American journal Diabetes.The study involved 39 young adult men and women of normal weight, who ate 750 extra calories per day for seven weeks. The goal was for them to gain three per cent of their starting weight. The project received considerable attention when it started in 2011, partly because the extra calories were ingested in the form of muffins with high fat content, baked in the lab by Fredrik Rosqvist, a doctoral candidate and first author of the study.One half of the subjects were random to eat surplus calories from polyunsaturated fat (sunflower oil), while the other half got their surplus calories from saturated fat (palm oil). Both diets contained the same amount of sugar, carbohydrates, fat, and protein; the only difference between muffins was the type of fat.The increase in body fat and the distribution of fat in the body was measured using a magnetic resonance imaging (MRI scans) before and after the weight gain, as was the muscle mass in the body. Gene activity was measured in the abdominal visceral fat before and after the weight gain with the help of a gene chip that studies several thousand genes at a time.Despite comparable weight gains between the two diet groups, the surplus consumption of saturated fat caused a markedly greater increase in the amount of fat in the liver and abdomen (especially the fat surrounding the internal organs, visceral fat) in comparison with the surplus consumption of polyunsaturated fat. Moreover the total amount of body fat was greater in the saturated fat group, while, on the other hand, the increase in muscle mass was three times less for those who ate saturated fat compared with those who ate polyunsaturated fat. Thus, gaining weight on excess calories from polyunsaturated fat caused more gain in muscle mass, and less body fat than overeating a similar amount of saturated fat. Since most of us are in positive energy balance, and consequently gain weight slowly but gradually over time, the present results are highly relevant for most Western populations.”Liver fat and visceral fat seems to contribute to a number of disturbances in metabolism. …

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Zebrafish discovery may shed light on human kidney function

Researchers say the discovery of how sodium ions pass through the gill of a zebrafish may be a clue to understanding a key function in the human kidney. The findings from a collaboration between Mayo Clinic and the Tokyo Institute of Technology appear in the online issue of the American Journal of Physiology-Regulatory, Integrative and Comparative Physiology.The researchers discovered a protein responsible for gas exchanges in the fish gill structure. Specifically they studied and characterized the Na+/H+ (sodium/hydrogen) exchanger named NHE3, responsible for controlling sodium and hydrogen ions across the gill. The researchers also directly demonstrated that NHE3 can function as a Na+/NH4+ (sodium/ammonium) exchanger.”This is significant because the fish tends to mimic the process in humans,” says Michael Romero, Ph.D., a Mayo Clinic physiologist who works in nephrology. “This is the true beauty of comparative physiology– a lot of the organs function by very similar processes, down to ionic transfer.”In this case the protein allows the sodium ions to be absorbed from the forming urine while at the same time discarding waste from normally functioning cells, thus keeping the body in balance and serving as an energy saving system. The researchers say the same NHE3 protein performs a similar function in the intestine, pancreas, liver, lungs and reproductive system.The gill is used in the fish as a transport system: sodium ions are nutrients and ammonium carries away waste. It’s a key process allowing zebrafish to extract sodium ions from fresh water. In humans, NHE3 is involved in the acid-waste control system in the kidney, but there hasn’t been a good analysis of that process in humans. Part of this acid-control process in the human kidney is “ammoniagenesis” which requires the initial part of the kidney tubule (proximal tubule) to export ammonia/ammonium. Physiologically, it has been assumed that NHE3 can perform a Na+/NH4+ exchange, but this has never been experimentally demonstrated.Ammoniagenesis and increased renal sodium bicarbonate absorption are partly under the control of the renin-angiotensin-aldosterone system (RAAS), which means that this work enhances understanding of human hypertension. …

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Discovery may help to explain mystery of ‘missing’ genetic risk, susceptibility to common diseases

A new study could help to answer an important riddle in our understanding of genetics: why research to look for the genetic causes of common diseases has failed to explain more than a fraction of the heritable risk of developing them.Susceptibility to common diseases is believed to arise through a combination of many common genetic variants that individually slightly increase the risk of disease, plus a smaller number of rare mutations that often carry far greater risk.However, even when their effects are added together, the genetic variants so far linked to common diseases account for only a relatively small proportion of the risk we know is conveyed by genetics through studies of family history.But the major new study, published in the journal PLOS Genetics, shows for the first time in cancer that some common genetic variants could actually be indicators of the presence of much more influential rare mutations that have yet to be found.Scientists at The Institute of Cancer Research, London, led an international consortium made up of more than 25 leading academic institutions on the study, which was funded by the European Union.The research, involving 20,440 men with prostate cancer and 21,469 without the disease, identified a cluster of four common genetic variants on chromosome 17 that appeared to give rise to a small increase in prostate cancer risk, using the standard statistical techniques for this type of study.But the study found an alternative explanation for the risk signal — a small proportion of the men with these common variants were in fact carriers of a rare mutation in the nearby HOXB13 gene, which is known to be linked to prostate cancer. Under this ‘synthetic association’, the number of people carrying a cancer risk variant was much lower than had been assumed, but those people who did inherit a variant had a much higher risk of prostate cancer than had been realised.The discovery shows that the prevailing genetic theory — that common cancers are predominantly caused by the combined action of many common genetic variants, each with only a very small effect — could potentially underestimate the impact of rare, as yet undiscovered mutations.The results are important because they show that there is a need for renewed effort by geneticists to find the causal variants, whether common or rare, behind the many common cancer-associated variants identified in recent years.Identifying any underlying rare mutations with a big effect on disease risk could improve the genetic screening and clinical management of individuals at greater risk of developing cancer, as well as other diseases.Study co-leader Dr Zsofia Kote-Jarai, Senior Staff Scientist at The Institute of Cancer Research (ICR), said: “As far as we are aware, this is the first known example of a ‘synthetic association’ in cancer genetics. It was exciting to find evidence for this theory, which predicts that common genetic variants that appear to increase risk of disease by only a modest amount may indeed sometimes be detected purely due to their correlation with a rarer variant which confers a greater risk.”Our study does not imply how widespread this phenomenon may be, but it holds some important lessons for geneticists in cancer, and other common diseases. It demonstrates the importance of identifying the causal genetic changes behind the many common variants that have already been shown to influence risk of disease.”Our study also demonstrates that standard methods to identify potential causal variants when fine-mapping genetic associations with disease may be inadequate to assess the contribution of rare variants. Large sequencing studies may be necessary to answer these questions unequivocally.”Study co-leader Professor Ros Eeles, Professor of Oncogenetics at The Institute of Cancer Research and Honorary Clinical Consultant at The Royal Marsden NHS Foundation Trust, said: “One important unanswered question in cancer genetics — and in genetics of common disease more generally — is why the genetic mutations we’ve discovered so far each seem to have such a small effect, when studies of families have shown that our genetic make-up has a very large influence on our risk of cancer.”Our study is an important step forward in our understanding of where we might find this ‘missing’ genetic risk in cancer. At least in part, it might lie in rarer mutations which current research tools have struggled to find, because individually each does not affect a large number of people.”

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Cortical convolutions controlled in sections: Non-coding DNA sequence affects brain’s characteristic folding, study shows

Researchers have tied a particular gene to the development of cortical convolutions — the prominent but enigmatic folds covering the surface of the human brain. Their discovery should shed some light on these characteristic contours, which have been the subject of wild speculation for ages, and perhaps also provide a better understanding of how such brain ridges form, how they evolved from our pre-human ancestors and, ultimately, how they influence brain function.The exact role of cortical convolutions remains unknown, but theories have abounded. (Some, for example, have suggested that the folds act as the body’s cooling system and others have even proposed that Albert Einstein’s genius could have been traced to a single cortical fold on his brain.)Now, leveraging advances that permit a closer look at how these folds develop, research published in the 14 February issue of Science shows that a mutation affecting GPR56 causes cortical convolutions around the brain’s Sylvian fissure — a particularly deep indentation — to develop thinner and more convoluted than usual. The finding, which suggests that genes may assert control over the brain’s physical folding on a section-by-section basis, provides insight into the mysterious cortical development process.”There is already a list of genetic mutations that cause abnormal neocortical folding, which can be used for prenatal testing,” explained Byoung-il Bae from the Division of Genetics and Genomics at Boston Children’s Hospital and Harvard Medical School in Boston, Massachusetts, one of the lead authors of the Science report. “We intend to add this mutation to some of the panels.”Bae and colleagues from around the world investigated the genomes of five individuals with abnormalities on Broca’s area, or the language center of the brain. These study participants were from three different families — one Turkish and two Irish-American — and they suffered from refractory seizures as well as intellectual and language difficulties.The researchers found that all five patients harbored a mutation on a particular regulatory element that influences the GPR56 gene. Such regulatory DNA doesn’t code for any proteins itself but promotes the expression of genes elsewhere on the genome. Geneticists have long-suspected that such non-coding regions of the genome could play important roles in evolution. To observe the specific effects of the GPR56 “promoter” DNA sequence, Bae and his team used genetically modified mice.They discovered that low expression of GPR56 (gauged by low levels of mRNA) decreases the production of neuroprogenitor cells — those that will eventually give rise to neurons — around Broca’s area and the Sylvian fissure. By contrast, overexpression of the gene boosts the production of such progenitor cells in that region. …

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Prostate cancer advance could improve treatment options

Findings published today in the British Journal of Cancer, and funded by the Association for International Cancer Research (AICR), show how a genetic mutation in untreated patients is linked to aggressive cancer later in life. It was previously thought that the mutation only occurred in response to therapy.The research highlights why relapses could occur in some men following hormone therapy. And it could help identify those patients that will develop fatal prostate cancer much earlier for life-extending therapy.Prostate cancer is the most common cancer in men in the UK, with more than 40,000 new cases diagnosed every year. Treatment options for patients diagnosed with early stage prostate cancer vary from “watchful waiting” to hormone-withdrawal therapy, radiotherapy or surgery.Additional tests for indicators of aggressive cancer are necessary to help categorise patients so that those with a low-risk of the disease spreading can avoid unnecessary treatment, and those diagnosed with a high-risk can be targeted for more aggressive first line therapy.Hormone-withdrawal therapy often results in a dramatic remission, however the disease invariably relapses with a resistant form of the cancer. A third of these are due to an increase in copy number of a particular gene called the ‘androgen receptor’. The gene is on the X-Chromosome and so there is normally only one copy of this gene present in men. Prostate cancer thrives on male hormones, and one way that they develop to grow better is to increase the number of copies of the androgen receptor gene. This also enables the cancer to resist therapy.Lead researchers Dr Jeremy Clark and Prof Colin Cooper from UEA’s school of Biological Sciences carried out the research at the Institute of Cancer Research, London, and at UEA.Dr Clark said: “By the age of 60, the majority of men will have signs of prostate cancer. However, only a small proportion of men will die of the disease. The question is — which of these cancers are dangerous and which are not? …

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New pathway for fear discovered deep within brain

Fear is primal. In the wild, it serves as a protective mechanism, allowing animals to avoid predators or other perceived threats. For humans, fear is much more complex. A normal amount keeps us safe from danger. But in extreme cases, like post-traumatic stress disorder (PTSD), too much fear can prevent people from living healthy, productive lives. Researchers are actively working to understand how the brain translates fear into action. Today, scientists at Cold Spring Harbor Laboratory (CSHL) announce the discovery of a new neural circuit in the brain that directly links the site of fear memory with an area of the brainstem that controls behavior.How does the brain convert an emotion into a behavioral response? For years, researchers have known that fear memories are learned and stored in a small structure in the brain known as the amygdala. Any disturbing event activates neurons in the lateral and then central portions of the amygdala. The signals are then communicated internally, passing from one group of neurons to the next. …

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Surprising new clue to the roots of hunger, neurons that drive appetite

While the function of eating is to nourish the body, this is not what actually compels us to seek out food. Instead, it is hunger, with its stomach-growling sensations and gnawing pangs that propels us to the refrigerator – or the deli or the vending machine. Although hunger is essential for survival, abnormal hunger can lead to obesity and eating disorders, widespread problems now reaching near-epidemic proportions around the world.Over the past 20 years, Beth Israel Deaconess Medical Center (BIDMC) neuroendocrinologist Bradford Lowell, MD, PhD, has been untangling the complicated jumble of neurocircuits in the brain that underlie hunger, working to create a wiring diagram to explain the origins of this intense motivational state. Key among his findings has been the discovery that Agouti-peptide (AgRP) expressing neurons – a group of nerve cells in the brain’s hypothalamus – are activated by caloric deficiency, and when either naturally or artificially stimulated in animal models, will cause mice to eat voraciously after conducting a relentless search for food.Now, in a new study published on-line this week in the journal Nature, Lowell’s lab has made the surprising discovery that the hunger-inducing neurons that activate these AgRP neurons are located in the paraventricular nucleus — a brain region long thought to cause satiety, or feelings of fullness. This unexpected finding not only provides a critical addition to the overall wiring diagram, but adds an important extension to our understanding of what drives appetite.“Our goal is to understand how the brain controls hunger,” explains Lowell, an investigator in BIDMC’s Division of Endocrinology, Diabetes and Metabolism and Professor of Medicine at Harvard Medical School. “Abnormal hunger can lead to obesity and eating disorders, but in order to understand what might be wrong – and how to treat it – you first need to know how it works. Otherwise, it’s like trying to fix a car without knowing how the engine operates.”Hunger is notoriously complicated and questions abound: Why do the fed and fasted states of your body increase or decrease hunger? And how do the brain’s reward pathways come into play – why, as we seek out food, especially after an otherwise complete meal, do we prefer ice cream to lettuce?“Psychologists have explained how cues from the environment and from the body interact, demonstrating that food and stimuli linked with food [such as a McDonald’s sign] are rewarding and therefore promote hunger,” explains Lowell. “It’s clear that fasting increases the gain on how rewarding we find food to be, while a full stomach decreases this reward. But while this model has been extremely important in understanding the general features of the ‘hunger system,’ it’s told us nothing about what’s inside the ‘black box’ – the brain’s neural circuits that actually control hunger.”To deal with this particularly complex brain region – a dense and daunting tangle of circuits resembling a wildly colorful Jackson Pollack painting – the Lowell team is taking a step-by-step approach to find out how the messages indicating whether the body is in a state of feeding or fasting enter this system. …

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Europe’s oldest footprints uncovered on English coast

The earliest human footprints outside of Africa have been uncovered, on the English coast, by a team of scientists led by Queen Mary University of London, the British Museum and the Natural History Museum.Up to five people left the series of footprints in mud on the bank of an ancient river estuary over 800,000 years ago at Happisburgh in northeast Norfolk.Dr Simon Lewis from Queen Mary’s School of Geography has been helping to piece together the geological puzzle surrounding the discovery — made in May 2013 — which is evidence of the first known humans in northern Europe.Dr Lewis’s research into the geology of the site has provided vital information on the sediments in which the prints were found. “My role is to work out the sequence of deposits at the site and how they were laid down. This means I can provide a geological context for the archaeological evidence of human occupation at the site.”The importance of the Happisburgh footprints is highlighted by the rarity of footprints surviving elsewhere. Only those at Laetoli in Tanzania at about 3.5 million years and at Ileret and Koobi Fora in Kenya at about 1.5 million years are older.A lecturer in physical geography, and co-director of the Happisburgh project (http://www.ahobproject.org/), Dr Lewis added that the chance of encountering footprints such as this was extremely rare; they survived environmental change and the passage of time.Timing was also crucial as “their location was revealed just at a moment when researchers were there to see it” during a geophysical survey. “Just two weeks later the tide would have eroded the footprints away.””At first we weren’t sure what we were seeing,” explains Dr Nick Ashton of the British Museum “but as we removed any remaining beach sand and sponged off the seawater, it was clear that the hollows resembled prints, and that we needed to record the surface as quickly as possible.”Over the next two weeks researchers used photogrammetry, a technique that can stitch together digital photographs to create a permanent record and 3D images of the surface. It was the analysis of these images that confirmed that the elongated hollows were indeed ancient human footprints.In some cases the heel, arch and even toes could be identified, equating to modern shoes of up to UK size 8. While it is not possible to tell what the makers of these footprints were doing at the time, analysis has suggested that the prints were made from a mix of adults and children.Their discovery offers researchers an insight into the migration of pre-historic people hundreds of thousands of years ago when Britain was linked by land to continental Europe.At this time, deer, bison, mammoth, hippo and rhino grazed the river valley at Happisburgh. The land provided a rich array of resources for the early humans with edible plant tubers, seaweed and shellfish nearby, while the grazing herds would have provided meat through hunting or scavenging.During the past 10 years the sediments at Happisburgh have revealed a series of sites with stone tools and fossil bones; this discovery is from the same deposits.The findings are published in the science journal PLOS ONE.The work at Happisburgh forms part of a new major exhibition at the Natural History Museum Britain: One Million Years of the Human Story opening on February 13.Story Source:The above story is based on materials provided by Queen Mary University of London. Note: Materials may be edited for content and length.

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Sneezing sponges suggest existence of sensory organ: Discovery challenges assumptions about ‘primitive’ organism

When Danielle Ludeman decided to leave her hometown of Vancouver to study evolutionary biology at the University of Alberta, she knew she was in for a challenge that would help her discover things about science and, in turn, herself.What she didn’t count on were the hours, days and months she’d spend watching sponges in mid-sneeze.It sounds like a strange way to pass time, but sneezing sponges have become a major part of Ludeman’s studies at the U of A, including a new paper that points to the sneeze as evidence of a sensory organ in one of the most basic multicellular organisms on Earth.”The sneeze can tell us a lot about how the sponge works and how it’s responding to the environment,” said Ludeman, a master’s student in the Faculty of Science. “This paper really gets at the question of how sensory systems evolved. The sponge doesn’t have a nervous system, so how can it respond to the environment with a sneeze the way another animal that does have a nervous system can?”Ludeman started the work as part of an undergraduate research honours project, working under the supervision of Sally Leys, Canada Research Chair in Evolutionary Developmental Biology. It was Leys and a former graduate student who first discovered that sponges do in fact sneeze.The sponge is a filter feeder that relies totally on water flow through its body for food, oxygen and waste removal. Sneezing, a 30- to 45-minute process that sees the entire body of the sponge expand and contract, allows it to respond to physical stimuli such as sediment in the water.Time-lapse sneezesFor their study, Ludeman and Leys used a variety of drugs to elicit sneezes in freshwater sponges and observed the process using fluorescent dye — all recorded using time-lapse video. Their efforts focused on the sponge’s osculum, which controls water exiting the organism, including water expelled during a sneeze.Through a series of lab experiments, the pair discovered that ciliated cells lining the osculum play a role in triggering sneezes. In other animals, cilia function like antennae, helping cells respond to stimuli in a co-ordinated manner. In the sponge, their localized presence in the osculum and their sensory function suggest the osculum is in fact a sensory organ.”For a sponge to have a sensory organ is totally new. This does not appear in a textbook; this doesn’t appear in someone’s concept of what sponges are permitted to have,” said Leys.Leys said the discovery raises new questions about how sensory systems may have evolved in the sponge and other animals, including ones with nervous systems. It’s possible this sensory system is unique to the sponge, she said, evolving over the last 600 million years. …

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Integration brings quantum computer a step closer

An international research group of scientists and engineers led by the University of Bristol, UK, has made an important advance towards a quantum computer by shrinking down key components and integrating them onto a silicon microchip.Scientists and engineers from an international collaboration led by Dr Mark Thompson from the University of Bristol have, for the first time, generated and manipulated single particles of light (photons) on a silicon chip — a major step forward in the race to build a quantum computer.Quantum computers and quantum technologies in general are widely anticipated as the next major technology advancement, and are poised to replace conventional information and computing devices in applications ranging from ultra-secure communications and high-precision sensing to immensely powerful computers. Quantum computers themselves will likely lead to breakthroughs in the design of new materials and in the discovery of new medical drugs.Whilst still in their infancy, quantum technologies are making rapid process, and a revolutionary new approach pioneered by the University of Bristol is exploiting state-of-the-art engineering processes and principles to make leaps and bounds in a field previously dominated by scientists.Featuring on the front cover of Nature Photonics, this latest advancement is one of the important pieces in the jigsaw needed in order to realise a quantum computer. While previous attempts have required external light sources to generate the photons, this new chip integrates components that can generate photons inside the chip.”We were surprised by how well the integrated sources performed together,” admits Joshua Silverstone, lead author of the paper. “They produced high-quality identical photons in a reproducible way, confirming that we could one day manufacture a silicon chip with hundreds of similar sources on it, all working together. This could eventually lead to an optical quantum computer capable of performing enormously complex calculations.”Group leader Mark Thompson explained: “Single-photon detectors, sources and circuits have all been developed separately in silicon but putting them all together and integrating them on a chip is a huge challenge. Our device is the most functionally complex photonic quantum circuit to date, and was fabricated by Toshiba using exactly the same manufacturing techniques used to make conventional electronic devices. We can generate and manipulate quantum entanglement all within a single mm-sized micro-chip.”The group, which, includes researchers from Toshiba Corporation (Japan), Stanford University (US), University of Glasgow (UK) and TU Delft (The Netherlands), now plans to integrate the remaining necessary components onto a chip, and show that large-scale quantum devices using photons are possible.”Our group has been making steady progress towards a functioning quantum computer over the last five years,” said Thompson. “We hope to have within the next couple of years, photon-based devices complex enough to rival modern computing hardware for highly-specialised tasks.”However, these are just the first steps. To realise useful quantum machines will required a new breed of engineering — quantum engineers, individuals capable of understanding the fundamentals of quantum mechanics and applying this knowledge to real world problems.Bristol’s newly established Centre for Doctoral Training in Quantum Engineering will train a new generation of engineers, scientists and entrepreneurs to harness the power of quantum mechanics and lead the quantum technology revolution. This innovative centre bridges the gaps between physics, engineering, mathematics and computer science, working closely with chemists and biologists while interacting strongly with industry.Story Source:The above story is based on materials provided by University of Bristol. …

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Up close and 3-dimensional: HIV caught in the act inside the gut

HIV infection has many unhealthy consequences on the body, but in particular it messes up the gut. The human intestine has the highest concentration of HIV target cells, the majority of which are destroyed within days of infection, and before CD4 T cell counts drop measurably in the blood. A study published on January 30th in PLOS Pathogens reports the first three-dimensional ultra-structural study of HIV infection in vivo. Not only does it reveal details on how the virus quickly infects immune cells in the gut, using them as virus-producing factories, but it also highlights where the virus “hides out” deep within the intestinal tissue.Pamela Bjorkman, from the Howard Hughes Medical Institute and the California Institute of Technology, USA, and colleagues used electron tomography for a high-resolution study of HIV virus in the guts of “humanized” mice, whose immune system is made up to a large degree of human cells. They infected these “BLT mice” (so-called because they have human bone marrow, thymus, and liver cells) with HIV virus and developed methods that allowed them to safely examine and visualize the three-dimensional architecture of infected parts of the gut.They saw HIV-infected human immune cells, caught virus particles in the act of budding from such cells, and also found groups of free immature and mature viruses. For one infected host cell (turned HIV factory) the researchers counted 63 virus particles it had likely released. The actual number is almost certainly much higher, because the method can only visualize virus particles surrounding the host cell within a relatively small part of the tissue. Nevertheless, they discovered that groups of viruses that were farther from the host cell were more mature than those closer to it, which suggested that the host cell releases new virus in a series of “semi-synchronized” waves.Among the samples, the researchers found some where viruses released from one infected cell seemed directly to attach to a neighboring host cell, presumably infecting it. In addition to such “virological synapses,” they also observed free virus particles that appear to have covered some distance between their “mother” cell and the cell that would become their target to infect.These images provide the first 3D ultrastructural details on HIV infection and virus production in a setting that closely resembles the gut of human patients. Some results confirm earlier findings from in vitro experiments — cells grown and infected in a petri dish — but others are seen for the first time and advance the understanding of how HIV infection spreads in real life.”To me, an important finding is that the majority of the viral transmission events within tissue involved free virus rather than virological synapses,” says Bjorkman. …

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Bacteria-eating viruses ‘magic bullets in the war on superbugs’

Oct. 16, 2013 — A specialist team of scientists from the University of Leicester has isolated viruses that eat bacteria — called phages — to specifically target the highly infectious hospital superbug Clostridium difficile (C. diff).Now an exciting new collaboration between the University of Leicester, the University of Glasgow and AmpliPhi Biosciences Corporation could lead to the use of bacteriophages for treating the superbug Clostridium difficile infections.Dr Martha Clokie, from the University of Leicester’s Department of Infection, Immunity and Inflammation has been investigating an alternative approach to antibiotics, which utilizes naturally occurring viruses called bacteriophages, meaning ‘eaters of bacteria’.The work has predominantly been funded by the Medical Research Council (MRC).Dr Clokie said: “Ever since the discovery of the first antibiotic, penicillin, antibiotics have been heralded as the ‘silver bullets’ of medicine. They have saved countless lives and impacted on the well-being of humanity.”But less than a century following their discovery, the future impact of antibiotics is dwindling at a pace that no one anticipated, with more and more bacteria out-smarting and ‘out-evolving’ these miracle drugs. This has re-energised the search for new treatments.”One alternative to antibiotics is bacteriophages, known as phages, which unlike antibiotics, are specific in what they kill and will generally only infect one particular species, or even strain, of bacteria — referred to as the ‘host’. Following attachment to their hosts, they inject their DNA into the bacterium, which then replicates many times over, ultimately causing the bacterial cell to burst open. The phages released from the dead bacterium can then infect other host cells.”Dr. Clokie and her team have achieved the remarkable feat of isolating and characterising the largest known set of distinct C. diff phages that infect clinically relevant strains of C. diff. …

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