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

http://feeds.feedburner.com/~r/sciencedaily/top_news/top_science/~4/ZOo6MCSeck8

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.”


Read More: Discovery may help to explain mystery of "missing" genetic risk, susceptibility to common diseases

#Cancer, #Common, #Count, #Discovery, #Disease, #Genetic, #London, #Major, #People, #Professor, #Research, #Standard

Study on flu evolution may change textbooks, history books

http://feeds.feedburner.com/~r/sciencedaily/living_well/~4/eRsV6Kgp_r0

A new study reconstructing the evolutionary tree of flu viruses challenges conventional wisdom and solves some of the mysteries surrounding flu outbreaks of historical significance.The study, published in the journal Nature, provides the most comprehensive analysis to date of the evolutionary relationships of influenza virus across different host species over time. In addition to dissecting how the virus evolves at different rates in different host species, the study challenges several tenets of conventional wisdom, for example the notion that the virus moves largely unidirectionally from wild birds to domestic birds rather than with spillover in the other direction. It also helps resolve the origin of the virus that caused the unprecedentedly severe influenza pandemic of 1918.The new research is likely to change how scientists and health experts look at the history of influenza virus, how it has changed genetically over time and how it has jumped between different host species. The findings may have implications ranging from the assessment of health risks for populations to developing vaccines.”We now have a really clear family tree of theses viruses in all those hosts — including birds, humans, horses, pigs — and once you have that, it changes the picture of how this virus evolved,” said Michael Worobey, a professor of ecology and evolutionary biology at the University of Arizona, who co-led the study with Andrew Rambaut, a professor at the Institute of Evolutionary Biology at the University of Edinburgh. “The approach we developed works much better at resolving the true evolution and history than anything that has previously been used.”Worobey explained that “if you don’t account for the fact that the virus evolves at a different rates in each host species, you can get nonsense — nonsensical results about when and from where pandemic viruses emerged.”"Once you resolve the evolutionary trees for these viruses correctly, everything snaps into place and makes much more sense,” Worobey said, adding that the study originated at his kitchen table.”I had a bunch of those evolutionary trees printed out on paper in front of me and started measuring the lengths of the branches with my daughter’s plastic ruler that happened to be on the table. Just like branches on a real tree, you can see that the branches on the evolutionary tree grow at different rates in humans versus horses versus birds. And I had a glimmer of an idea that this would be important for our public health inferences about where these viruses come from and how they evolve.”"My longtime collaborator Andrew Rambaut implemented in the computer what I had been doing with a plastic ruler. We developed software that allows the clock to tick at different rates in different host species. Once we had that, it produces these very clear and clean results.”The team analyzed a dataset with more than 80,000 gene sequences representing the global diversity of the influenza A virus and analyzed them with their newly developed approach. The influenza A virus is subdivided into 17 so-called HA subtypes — H1 through H17 — and 10 subtypes of NA, N1-N10. …


Read More: Study on flu evolution may change textbooks, history books

#Arizona, #Count, #Ecology, #Evolutionary, #Health, #Major, #Nature, #Rambaut, #Science, #Study, #Worobey

America"s natural gas system is leaking methane and in need of a fix

http://feeds.feedburner.com/~r/sciencedaily/top_news/top_science/~4/SMDScu11ewQ

The first thorough comparison of evidence for natural gas system leaks confirms that organizations including the Environmental Protection Agency (EPA) have underestimated U.S. methane emissions generally, as well as those from the natural gas industry specifically.Natural gas consists predominantly of methane. Even small leaks from the natural gas system are important because methane is a potent greenhouse gas — about 30 times more potent than carbon dioxide. A study, “Methane Leakage from North American Natural Gas Systems,” published in the Feb. 14 issue of the journal Science, synthesizes diverse findings from more than 200 studies ranging in scope from local gas processing plants to total emissions from the United States and Canada.”People who go out and actually measure methane pretty consistently find more emissions than we expect,” said the lead author of the new analysis, Adam Brandt, an assistant professor of energy resources engineering at Stanford University. “Atmospheric tests covering the entire country indicate emissions around 50 percent more than EPA estimates,” said Brandt. “And that’s a moderate estimate.”The standard approach to estimating total methane emissions is to multiply the amount of methane thought to be emitted by a particular kind of source, such as leaks at natural gas processing plants or belching cattle, by the number of that source type in a region or country. The products are then totaled to estimate all emissions. The EPA does not include natural methane sources, like wetlands and geologic seeps.The national natural gas infrastructure has a combination of intentional leaks, often for safety purposes, and unintentional emissions, like faulty valves and cracks in pipelines. In the United States, the emission rates of particular gas industry components — from wells to burner tips — were established by the EPA in the 1990s.Since then, many studies have tested gas industry components to determine whether the EPA’s emission rates are accurate, and a majority of these have found the EPA’s rates too low. …


Read More: America"s natural gas system is leaking methane and in need of a fix

#Agency, #Alzheimer, #Brandt, #California, #Count, #Department, #Energy, #Epa, #People, #Pregnancy, #Science

Children living close to fast food outlets more likely to be overweight

http://feeds.feedburner.com/~r/sciencedaily/top_news/top_health/~4/ZgpXSEmnZIg

Children living in areas surrounded by fast food outlets are more likely to be overweight or obese according to new research from the University of East Anglia (UEA) and the Centre for Diet and Activity Research (CEDAR).New research published today looked at weight data from more than a million children and compared it with the availability of unhealthy food from outlets including fish and chip shops, burger bars, pizza places, and sweet shops.They found that older children in particular are more likely to be overweight when living in close proximity to a high density of unhealthy eating outlets.It is hoped that the findings will help shape planning policy to help tackle childhood obesity.Prof Andy Jones, from UEA’s Norwich Medical School, led the research. He said: “We found that the more unhealthy food outlets there are in a neighborhood, the greater the number of overweight and obese children. The results were more pronounced in secondary school children who have more spending power to choose their own food.”But the association was reversed in areas with more healthy food options available.”This is important because there is an epidemic of obesity among children in the UK and other industrialized countries. It can lead to childhood diabetes, low self-esteem, and orthopedic and cardiovascular problems. It is also a big problem because around 70 per cent of obese children and teenagers also go on to have weight problems in later life.”Study co-author Andreea Cetateanu, from UEA’s school of Environmental Sciences, said: “We know that fast food is more common in deprived areas of the UK and that over-weight children are more likely to come from socio-economically deprived populations. But associations between children’s weight and the availability of junk food have not been shown before at a national scale.”If we can use these findings to influence planning decisions and help create a more healthy food environment, we may be able to help reverse this trend for future generations.”Public health policies to reduce obesity in children should incorporate strategies to prevent high concentrations of fast food and other unhealthy food outlets. But there is no quick fix — and any interventions for tackling childhood obesity and creating environments that are more supportive for both physical activity and better dietary choices must be part of the bigger picture looking at the whole obesity system.”The research team used data from the National Child Measurement Programme which records the height and weight of one million children at the majority of state schools in England annually.They took into account factors such as people living in rural locations having to travel further to buy food, and other variables such as the proportion of children living in low income households and measurements of green space which have both been associated with exercise in children.Story Source:The above story is based on materials provided by University of East Anglia. Note: Materials may be edited for content and length.


Read More: Children living close to fast food outlets more likely to be overweight

#Alzheimer, #Count, #Medical, #National, #Pregnancy, #Programme, #Science, #Study, #Uea, #University

Many stroke patients on "clot-busting" tPA may not need long stays in ICU

http://feeds.feedburner.com/~r/sciencedaily/top_news/top_health/~4/N52F5cqPevU

A Johns Hopkins study of patients with ischemic stroke suggests that many of those who receive prompt hospital treatment with “clot-busting” tissue plasminogen activator (tPA) therapy can avoid lengthy, restrictive monitoring in an intensive care unit (ICU).The study challenges the long-standing protocol that calls for intensive monitoring, mostly done in ICUs, for the first 24 hours after tPA infusion to catch bleeding in the brain, a side effect seen in 6 percent of patients treated with the medication.Results show that a relatively simple measure of stroke severity can accurately single out which patients need ICU monitoring and which can be managed outside of a critical care setting in the hospital.”What we saw in this preliminary study was that, after the initial hour-long infusion of tPA, if an intensive care need had not developed, the chance of needing ICU monitoring — including a symptomatic ‘bleed’ — was extremely low for a large majority of patients, namely those with milder strokes,” says Victor Urrutia, M.D., medical director of the Comprehensive Stroke Center at The Johns Hopkins Hospital and head of the research team.Ischemic stroke, caused by a clot in a blood vessel that cuts off blood flow to the brain, is the most common form of stroke and the second leading cause of death for those over 60. In the United States, an estimated 795,000 people suffer a stroke each year. So far, tPA is the only FDA-approved treatment for acute stroke.In a report on the study published online in the journal PLOS ONE, the Johns Hopkins team analyzed data from 153 stroke patients admitted to the emergency departments of The Johns Hopkins Hospital and Johns Hopkins Bayview Medical Center between 2010 and 2013. After taking into account differences in age, sex, race, hypertension, diabetes, atrial fibrillation, kidney function, blood clotting status, use of statin drugs and other health factors, the team says that what emerged as the best predictor of the need for intensive care was a patient’s score on the National Institutes of Health (NIH) Stroke Scale, a trusted measure of stroke severity. The scale is a proven tool administered at the bedside involving 15 measures and observations, including level of consciousness, language ability, eye movements, vision strength, coordination and sensory loss. Scores range from zero to 42, with mild strokes typically registering 10 or lower. The average score for the Johns Hopkins patient group was 9.8.”What we learned is that the majority of our patients with mild strokes required no critical care, and that we are using scarce, specialized resources for intensive monitoring rather than for intensive care,” says Urrutia, an assistant professor of neurology.”If our upcoming, prospective study verifies what we’ve found about those who don’t need to be in the ICU, our patients will benefit, and we will also reduce costs of care.”Urrutia emphasized that critical care is clearly needed for tPa-linked bleeding, stroke-related brain swelling and critical abnormalities in blood pressure or blood sugar.But, he says, “For patients with an NIH Stroke Scale score of less than 10 without a need for transfer to the ICU after the first hour, the risk of a problem occurring later that needed ICU attention was only about 1 percent.”In the follow-up study, which is scheduled to begin this spring, consenting patients with a low stroke scale score and no other apparent need for intensive care will enter a stroke unit with a less rigorous monitoring schedule and increased family visiting time.Patients in the non-ICU setting will be less physically restricted and subjected to fewer sleep interruptions, lowering the risk of ICU-associated delirium and psychological distress. “We expect benefits to extend to the hospital as well, freeing up the ICU staff and beds for sicker patients,” says Urrutia.The financial benefits of the change in protocol could be significant, Urrutia adds. “Present monitoring for patients with tPA is very costly,” he says.


Read More: Many stroke patients on "clot-busting" tPA may not need long stays in ICU

#Agriculture, #Alternative-Medicine, #Care, #Count, #Health, #Hopkins, #Ischemic, #King, #Medical, #Pregnancy, #Strokescale, #Tpa

The physics of curly hair

http://feeds.feedburner.com/~r/sciencedaily/top_news/top_science/~4/TCBlysm5Shs

The heroes and villains in animated films tend to be on opposite ends of the moral spectrum. But they’re often similar in their hair, which is usually extremely rigid or — if it moves at all — is straight and swings to and fro. It’s rare to see an animated character with bouncy, curly hair, since computer animators don’t have a simple mathematical means for describing it.However, change may be coming soon to a theater near you: In a paper appearing in the Feb. 13 issue of Physical Review Letters, researchers at MIT and the Universit Pierre et Marie Curie in Paris provide the first detailed model for the 3-D shape of a strand of curly hair.This work could have applications in the computer animation film industry, but it also could be used by engineers to predict the curve that long steel pipes, tubing, and cable develop after being coiled around a spool for transport. In the field, these materials often act like a stubborn garden hose whose intrinsic curves make it behave in unpredictable ways. In engineering terminology, these items — and hair — are all examples of a slender, flexible rod.Co-authors on the paper are Pedro Reis, an assistant professor in MIT’s Department of Civil and Environmental Engineering and Department of Mechanical Engineering; Basile Audoly and Arnaud Lazarus, of the Universit Pierre et Marie Curie; and former MIT graduate student James Miller, who is now a research associate at Schlumberger-Doll Research. Miller worked on this project as part of his doctoral thesis research and is lead author of the paper.”Our work doesn’t deal with the collisions of all the hairs on a head, which is a very important effect for animators to control a hairstyle,” Reis says. “But it characterizes all the different degrees of curliness of a hair and describes mathematically how the properties of the curl change along the arc length of a hair.”When Reis set out to investigate the natural curvature in flexible rods, he wasn’t thinking of hair. But as he studied several small flexible, curved segments of tubing suspended from a structure in his lab, he realized they weren’t so different from strands of curly hair hanging on a head. That’s when he contacted Audoly, who had previously developed a theory to explain the 2-D shape of human hair.Using lab experimentation, computer simulation, and theory — “the perfect triangle of science,” Reis says — the team identified the main parameters for curly hair and simplified them into two dimensionless parameters for curvature (relating to the ratio of curvature and length) and weight (relating to the ratio of weight and stiffness). …


Read More: The physics of curly hair

#Alzheimer, #Count, #King, #Miller, #Mit, #Pierre, #Universit, #Work

Macro-portrait of future bird and wetland scenarios under climate change

http://feeds.feedburner.com/~r/sciencedaily/earth_climate/ecology/~4/ybES9RgHP2o

Using a mountain of satellite photographic data and decades of waterfowl counts, a Texas Tech University biologist said she and others have found a correlation with the amount of waterfowl and the amount of wetlands available across the plains from Canada to Texas.More wetlands meaning more waterfowl may sound like a no-brainer, but researchers were able to land at conclusion using macrosystems ecology said Nancy McIntyre, a professor of biological sciences and curator of birds at the Natural Science Research Laboratory.The research appeared in a special edition of the peer-reviewed journal, Frontiers in Ecology and the Environment, dedicated to macrosystems ecology.”The novelty of what we’re doing is in taking the weather data from the past to be able to say certain types of precipitation conditions led to X amount of available wetlands, which was associated with Y number of birds,” McIntyre said. “If future climate scenarios say we should get fewer but more extreme precipitation events, then we can estimate how many wetlands and birds will be around in the future, so long as no more wetlands are converted into farm use or turned into neighborhoods. That’s work in progress. It sounds straightforward, but it has never been done because of the complexity and the massive amount of data used here.”Macrosystems ecology is a new and emerging science using large amounts of information that are analyzed by faster and smarter computers to not only create greater understanding of how habitats interact, but also make better predictions about how these systems may react in the face of global climate change, she said.”A change in the number of wetlands available can cascade in to the variety and numbers of birds, as well as amphibians, dragonflies and a number of other animals,” McIntyre said. “In the United States, we’ve lost about 50 percent of the nation’s original wetlands in the past 200 years. The losses are particularly bad in the Great Plains, where about 98 percent of the wetlands have disappeared since 1986. With climate change on the horizon, we’re trying to understand how these wetlands and the animals that use them interact.”The research was part of a $1.6 million grant from the National Science Foundation. McIntyre and others looked at freshwater wetlands across the Great Plains from the prairie potholes carved by glacial activity in the north, through the Rainwater Basin of Nebraska down to the playa lakes of the South Plains.”They call it the duck factory of the world,” McIntyre said. “Most of the ducks breed up there and overwinter down here. But there are about 300 species of regularly occurring, breeding land birds in the Great Plains, many of which use these wetlands.”Researchers studied photos from satellites that passed over the same area of land every 16 days, she said. …


Read More: Macro-portrait of future bird and wetland scenarios under climate change

#Alternative-Medicine, #Canada, #Count, #Health, #King, #Natural, #Pregnancy, #Professor, #Texastech, #University

Crocodilians can climb trees and bask in the tree crowns

http://feeds.feedburner.com/~r/sciencedaily/top_news/top_science/~4/qU1wGbBFGSs

When most people envision crocodiles and alligators, they think of them waddling on the ground or wading in water — not climbing trees. However, a University of Tennessee, Knoxville, study has found that the reptiles can climb trees as far as the crowns.Vladimir Dinets, a research assistant professor in the Department of Psychology, is the first to thoroughly study the tree-climbing and -basking behavior. The research is published in the journal Herpetology.Dinets and his colleagues observed crocodilian species on three continents — Australia, Africa and North America — and examined previous studies and anecdotal observations. They found that four species climbed trees — usually above water — but how far they ventured upward and outward varied by their sizes. The smaller crocodilians were able to climb higher and further than the larger ones. Some species were observed climbing as far as four meters high in a tree and five meters down a branch.”Climbing a steep hill or steep branch is mechanically similar, assuming the branch is wide enough to walk on,” the authors wrote. “Still, the ability to climb vertically is a measure of crocodiles’ spectacular agility on land.”The crocodilians seen climbing trees, whether at night or during the day, were skittish of being approached, jumping or falling into the water when an approaching observer was as far as 10 meters away. This response led the researchers to believe that the tree climbing and basking are driven by two conditions: thermoregulation and surveillance of habitat.”The most frequent observations of tree-basking were in areas where there were few places to bask on the ground, implying that the individuals needed alternatives for regulating their body temperature,” the authors wrote. “Likewise, their wary nature suggests that climbing leads to improved site surveillance of potential threats and prey.”The data suggests that at least some crocodilian species are able to climb trees despite lacking any obvious morphological adaptations to do so.”These results should be taken into account by paleontologists who look at changes in fossils to shed light on behavior,” said Dinets. “This is especially true for those studying extinct crocodiles or other Archosaurian taxa.”Dinets collaborated with Adam Britton from Charles Darwin University in Australia and Matthew Shirley from the University of Florida.Research by Dinets published in 2013 found another surprising crocodilian characteristic — the use of lures such as sticks to hunt prey. …


Read More: Crocodilians can climb trees and bask in the tree crowns

#Africa, #Alternative-Medicine, #Climbing, #Count, #Department, #Dinets, #Journal, #Species, #Tennessee, #Tree, #Water

Dental care in school breaks down social inequalities

http://feeds.feedburner.com/~r/sciencedaily/living_well/~4/8QhltVzLR4o

A new survey conducted by the University of Copenhagen and the World Health Organization (WHO) is highlighting the role of schools in work to promote health and prevent disease.”Children in Scandinavia generally have healthy teeth and gums, largely on account of dental care in schools for all children, the arrival of fluoride toothpaste on the market, a healthy lifestyle and high living standards. But the situation in the poorest countries of the world is very different to that in Scandinavia. However, it is positive to note that the WHO’s Health Promoting Schools Initiative are gaining ground at global level, and that they are gradually wiping out the social inequities in dental health,” says Poul Erik Petersen, Professor at Department of Odontology at the University of Copenhagen, and a Global Health Specialist.From Myanmar to Madagascar”We have collected data based on questions about health and dental care from 61 countries that run health programs in schools. Our findings reveal that those schools that have set up healthy school environments — and which offer all children education in dental health and disease prevention — are generally well-placed to set children on a path to a healthy lifestyle throughout their lives, with regard to issues such as diet, physical exercise, tobacco, alcohol and HIV control.”Around 60 per cent of the countries that took part in the study run formalized teaching in how to brush teeth, but not all countries have access to clean water and the necessary sanitary conditions. This constitutes a major challenge for the health and school authorities in Asia, Latin America and Africa in particular.”Countries in these regions are battling problems involving the sale of sugary drinks and sweets in the school playgrounds. Selling sweets is often a source of extra income for school teachers, who are poorly paid,” explains Poul Erik Petersen.He continues: “This naturally has an adverse effect on the children’s teeth. Many children suffer from toothache and general discomfort and these children may not get the full benefit of their education.”The biggest challenges to improved dental health in low-income countries are a lack of financial resources and trained staff. Schools in the poorest countries therefore devote little or no time to dental care, and they similarly make only very limited use of fluoride in their preventative work. Moreover, the healthy schools in low-income countries find it harder to share their experience and results.Social inequality is a serious problemSocial inequality in dental health and care is a serious problem all over the world:”However, inequality is greater in developing countries where people are battling with limited resources, an increasing number of children with toothache, children suffering from HIV/AIDS and infectious diseases — combined with a lack of preventive measures and trained healthcare staff,” says Poul Erik Petersen, before adding:”Even in a rich country like Denmark, we see social inequalities to dental care, despite the fact that dental health here is much improved among both children and adults. The socially and financially disadvantaged groups of the population show a high incidence of tooth and mouth complaints compared with the more affluent groups.”The Danish model for municipal dental care was principally built up in the 1970s and 1980s. …


Read More: Dental care in school breaks down social inequalities

#Agriculture, #Alzheimer, #Cancer, #Children, #Count, #Danish, #Health, #Major, #Organization, #University