Anti-inflammatory drug can prevent neuron loss in Parkinson’s model

An experimental anti-inflammatory drug can protect vulnerable neurons and reduce motor deficits in a rat model of Parkinson’s disease, researchers at Emory University School of Medicine have shown.The results were published Thursday, July 24 in the Journal of Parkinson’s Disease.The findings demonstrate that the drug, called XPro1595, can reach the brain at sufficient levels and have beneficial effects when administered by subcutaneous injection, like an insulin shot. Previous studies of XPro1595 in animals tested more invasive modes of delivery, such as direct injection into the brain.”This is an important step forward for anti-inflammatory therapies for Parkinson’s disease,” says Malu Tansey, PhD, associate professor of physiology at Emory University School of Medicine. “Our results provide a compelling rationale for moving toward a clinical trial in early Parkinson’s disease patients.”The new research on subcutaneous administration of XPro1595 was funded by the Michael J. Fox Foundation for Parkinson’s Research (MJFF). XPro1595 is licensed by FPRT Bio, and is seeking funding for a clinical trial to test its efficacy in the early stages of Parkinson’s disease.”We are proud to have supported this work and glad to see positive pre-clinical results,” said Marco Baptista, PhD, MJFF associate director of research programs. “A therapy that could slow Parkinson’s progression would be a game changer for the millions living with this disease, and this study is a step in that direction.”In addition, Tansey and Yoland Smith, PhD, from Yerkes National Primate Research Center, were awarded a grant this week from the Parkinson’s Disease Foundation to test XPro1595 in a non-human primate model of Parkinson’s.Evidence has been piling up that inflammation is an important mechanism driving the progression of Parkinson’s disease. XPro1595 targets tumor necrosis factor (TNF), a critical inflammatory signaling molecule, and is specific to the soluble form of TNF. This specificity would avoid compromising immunity to infections, a known side effect of existing anti-TNF drugs used to treat disorders such as rheumatoid arthritis.”Inflammation is probably not the initiating event in Parkinson’s disease, but it is important for the neurodegeneration that follows,” Tansey says. “That’s why we believe that an anti-inflammatory agent, such as one that counteracts soluble TNF, could substantially slow the progression of the disease.”Postdoctoral fellow Christopher Barnum, PhD and colleagues used a model of Parkinson’s disease in rats in which the neurotoxin 6-hydroxydopamine (6-OHDA) is injected into only one side of the brain. This reproduces some aspects of Parkinson’s disease: neurons that produce dopamine in the injected side of the brain die, leading to impaired movement on the opposite side of the body.When XPro1595 is given to the animals 3 days after 6-OHDA injection, just 15 percent of the dopamine-producing neurons were lost five weeks later. …

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Soy-dairy protein blend increases muscle mass, study shows

A new study published online in the Journal of Applied Physiology shows additional benefits of consuming a blend of soy and dairy proteins after resistance exercise for building muscle mass. Researchers from the University of Texas Medical Branch found that using a protein blend of soy, casein and whey post-workout prolongs the delivery of select amino acids to the muscle for an hour longer than using whey alone. It also shows a prolonged increase in amino acid net balance across the leg muscle during early post-exercise recovery, suggesting prolonged muscle building.The study was conducted by researchers from UTMB in collaboration with DuPont Nutrition and Health. “This study sheds new light on how unique combinations of proteins, as opposed to single protein sources, are important for muscle recovery following exercise and help extend amino acid availability, further promoting muscle growth,” said Blake B. Rasmussen, chairman of UTMB’s Department of Nutrition and Metabolism and lead researcher of the study.This new research, using state-of-the-art methodology, builds on an earlier publication reporting that a soy-dairy blend extends muscle protein synthesis when compared to whey alone, as only the blended protein kept synthesis rates elevated three to five hours after exercise. Together, these studies indicate that the use of soy-dairy blends can be an effective strategy for active individuals seeking products to support muscle health.”Because of the increased demand for high-quality protein, this study provides critical insight for the food industry as a whole, and the sports nutrition market in particular,” said Greg Paul, global marketing director for DuPont Nutrition and Health. “With more and more consumers recognizing the importance of protein for their overall health and well-being, the results of this study have particular relevance to a large segment of the population, from the serious sports and fitness enthusiast to the mainstream consumer.”The double-blind, randomized clinical trial included 16 healthy subjects, ages 19 to 30, to assess if consumption of a blend of proteins with different digestion rates would prolong amino acid availability and lead to increases in muscle protein synthesis after exercise. The protein beverages provided to study subjects consisted of a soy-dairy blend (25 percent isolated DuPont Danisco SUPRO soy protein, 50 percent caseinate, 25 percent whey protein isolate) or a single protein source (whey protein isolate). Muscle biopsies were taken at baseline and up to five hours after resistance exercise. The protein sources were ingested one hour after exercise in both groups.The study demonstrates that consuming a soy-dairy blend leads to a steady rise in amino acids, the building blocks of muscle. …

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East African honeybees safe from invasive pests … for now

Several parasites and pathogens that devastate honeybees in Europe, Asia and the United States are spreading across East Africa, but do not appear to be impacting native honeybee populations at this time, according to an international team of researchers.The invasive pests include including Nosema microsporidia and Varroa mites.”Our East African honeybees appear to be resilient to these invasive pests, which suggests to us that the chemicals used to control pests in Europe, Asia and the United States currently are not necessary in East Africa,” said Elliud Muli, senior lecturer in the Department of Biological Sciences, South Eastern Kenya University, and researcher at the International Centre of Insect Physiology and Ecology, Kenya.The team first discovered Varroa mites in Kenya in 2009. This new study also provides baseline data for future analyses of possible threats to African honeybee populations.”Kenyan beekeepers believe that bee populations have been experiencing declines in recent years, but our results suggest that the common causes for colony losses in the United States and Europe — parasites, pathogens and pesticides — do not seem to be affecting Kenyan bees, at least not yet,” said Christina Grozinger, professor of entomology and director of the Center for Pollinator Research, Penn State. “Some of our preliminary data suggest that the loss of habitat and drought impacting flowering plants, from which the bees get all their food, may be the more important factor driving these declines.”According to Harland Patch, research scientist in entomology, Penn State, not only are flowering plants important for honeybees, but the insects are important for plants as well.”Honeybees are pollinators of untold numbers of plants in every ecosystem on the African continent,” Patch said. “They pollinate many food crops as well as those important for economic development, and their products, like honey and wax, are vital to the livelihood of many families. People say the greatest animal in Africa is the lion or the elephant, but honeybees are more essential, and their decline would have profound impacts across the continent.”In 2010, the researchers conducted a nationwide survey of 24 locations across Kenya to evaluate the numbers and sizes of honeybee colonies, assess the presence or absence of Varroa and Nosema parasites and viruses, identify and measure pesticide contaminants in hives and determine the genetic composition of the colonies.”This is the first comprehensive survey of bee health in East Africa, where we have examined diseases, genetics and the environment to better understand what factors are most important in bee health in this region,” said Grozinger. The results appeared today in PLOS ONE.The researchers found that Varroa mites were present throughout Kenya, except in the remote north. In addition, Varroa numbers increased with elevation, suggesting that environmental factors may play a role in honeybee host-parasite interactions. Most importantly, the team found that while Varroa infestation dramatically reduces honeybee colony survival in the United States and Europe, in Kenya, its presence alone does not appear to impact colony size.The scientists found Nosema at three sites along the coast and one interior site. At all of the sites, they found only a small number of pesticides at low concentrations. Of the seven common honeybee viruses in the United States and Europe, the team only identified three species, but, like Varroa, these species were absent from northern Kenya. …

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Rural versus urban causes of childhood concussion

Researchers at Western University (London, Canada) have found youth living in rural areas are more likely to sustain concussions from injuries involving motorized vehicles such as all-terrain vehicles and dirt bikes, whereas youth living in urban areas suffer concussions mostly as a result of sports. Hockey accounts for 40 per cent of those injuries. The study which reveals where and how children are receiving concussions is published in the Journal of Trauma and Acute Care Surgery.Dr. Doug Fraser, a scientist with the Children’s Health Research Institute at Lawson Health Research Institute and Tanya Charyk Stewart, the Injury Epidemiologist for the Trauma Program at Children’s Hospital, London Health Sciences Centre (LHSC) and their team tracked all the youth under the age of 18 who presented to the LHSC emergency departments with a concussion over a six year period. There were 2,112 paediatric concussions, with a steady increase in number treated each year.”It was important for us to learn about who is getting injured, where they’re getting injured, and why they’re getting injured. Once you answer those questions, then you can implement targeted injury prevention programs,” says Dr. Fraser, an associate professor in the Departments of Paediatrics, Physiology & Pharmacology and Clinical Neurological Sciences at Western’s Schulich School of Medicine & Dentistry.Concussions are a particular concern for children and adolescents because their brains are still developing and they are more susceptible to effects of a head injury. The goal following this research is to create injury prevention programs that target and educate those at high risk of sustaining a concussion.Concussions can often be predictable. Along with properly following the rules of the sport and wearing the protective equipment, Charyk Stewart suggests, “In sports, if you have been hit, then just get off the field immediately and stop play. If you are experiencing any symptoms, be seen by a doctor.”Dr. …

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Success of new bug-fighting approach may vary from field to field

A new technique to fight crop insect pests may affect different insect populations differently, researchers report. They analyzed RNA interference (RNAi), a method that uses genetic material to “silence” specific genes — in this case genes known to give insect pests an advantage. The researchers found that western corn rootworm beetles that are already resistant to crop rotation are in some cases also less vulnerable to RNAi.The study is reported in the journal Pesticide Biochemistry and Physiology.”Our results indicate that the effectiveness of RNAi treatments could potentially vary among field populations depending on their genetic and physiological backgrounds,” the researchers wrote.The western corn rootworm will likely be one of the first crop pests to be targeted with RNAi technology, said Manfredo Seufferheld, a former University of Illinois crop sciences professor who led the study with crop sciences graduate student Chia-Ching Chu, entomology research associate Weilin Sun, Illinois Natural History Survey insect behaviorist Joseph Spencer and U. of I. entomology professor Barry Pittendrigh.Controlling the western corn rootworm costs growers more than $1 billion a year in the U.S. Current methods for keeping the bug in check — crop rotation and genetically modified corn — face challenges from populations of resistant western corn rootworms at various locations across the Corn Belt, Spencer said.Seufferheld and his colleagues recently discovered an important factor that helps rootworms overcome crop rotation, the practice of alternately planting soybeans and corn in the same field year to year. They found that microbes in the guts of rotation-resistant rootworms help those beetles that stray into soybean fields survive on soybean leaves for a few days — just long enough for the females to lay their eggs in soil that will be planted in corn the following year.Rather than studying a laboratory population of insects, in the new analysis the team tested RNAi on rootworm beetles collected from fields in three locations in the Midwest — two in Illinois with established rotation-resistant populations and the third from an area in Missouri with no evidence of rotation resistance.”After generations in the laboratory, insects gradually lose their natural diversity,” Seufferheld said. This makes it easier to control them, and may not accurately reflect actual insect responses in the field, he said. Seufferheld now works for Monsanto and is based in Buenos Aires, where he is in charge of insect resistance management.The team targeted two genes that are regulated differently in rotation-resistant and non-resistant rootworms. The first, DvRs5, codes for an enzyme that helps the rootworms digest plant proteins. …

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Team models photosynthesis, finds room for improvement

Teaching crop plants to concentrate carbon dioxide in their leaves could increase photosynthetic efficiency by 60 percent and yields by as much as 40 percent, researchers report in a new study.The team used a computer model to simulate how adding genes from a type of photosynthetic algae known as cyanobacteria might influence photosynthetic efficiency in plants. Cyanobacteria contain small structures, called carboxysomes, which concentrate carbon dioxide at the site of photosynthesis.”Photosynthesis is the most studied of all plant processes, so we really know this in great detail and can represent it well in silico,” said University of Illinois plant biology professor Stephen Long, who led the study with postdoctoral researcher Justin McGrath. “We’ve modeled the whole system, and added all the components in a cyanobacterial system one at a time to our computer simulation to see if they give us an advantage.”The team found that some of the carboxysome genes hindered, while others greatly enhanced photosynthetic efficiency in crop plants such as soybean, rice and cassava. For example, adding a gene for a bicarbonate transporter, which carries carbon dioxide across the carboxysome membrane, enhances photosynthesis by 6 percent, Long said.”And if we put in about eight components of the carboxysome system, the model says that we could get a 60 percent increase in photosynthesis,” he said.The new findings appear in the journal Plant Physiology.Modeling photosynthesis in crop plants has proven to be an efficient way to determine which kinds of genetic manipulations will be most fruitful, Long said. This prevents a lot of wasted time and money spent trying things in the laboratory that are doomed to fail.The work is very exciting, but will take many years to implement, Long said. “It will take about five years before we have our first test of concept in a model plant. And then, even if everything goes (according) to plan, it might be 15 or 20 years before we see this in any crop,” he said.”The United Nations Food and Agricultural Organization predicts that we’re going to need about 70 percent more primary foodstuffs by the middle of this century,” Long said. “So obviously new innovations like this are needed to try and get there, especially since the approaches of the Green Revolution are now approaching their biological limits.”Story Source:The above story is based on materials provided by University of Illinois at Urbana-Champaign. Note: Materials may be edited for content and length.

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Team sport compensates for estrogen loss

When women enter menopause, their estrogen levels taper. This increases their risk of cardiovascular disease. New research from University of Copenhagen shows that interval-based team sport can make up for this estrogen loss as it improves their conditions, reduces blood pressure and thereby protects the cardiovascular system.While aging and an array of physical transformations go hand in hand for all, menopause has a significant influence on physical changes in women.Estrogen, the primary female sex hormone, is an important guardian of the female vascular system. Thus, as estrogen levels fall during menopause, the risks of increased blood pressure and development of cardiovascular disease increases.A new study by the University of Copenhagen’s Centre for Team Sport and Health documents and addresses the issue.Changes to the cardiovascular system occur soon after menopause”Results demonstrate that blood pressure among post-menopausal women is 10% higher immediately after menopause than in similarly-aged, pre-menopausal women. They also had higher levels of an early marker for arteriosclerosis,” explains postdoc Michael Nyberg.The new aspect of this study is that researchers have investigated the effects of estrogen in women of the same age, both before and after menopause. Previous studies didn’t look at similarly aged pre- and post-menopausal women. Instead, they investigated women with 15-20 year gaps in age. Therefore, they were unable to determine whether changes were due to age or estrogen loss.Results of the recent study have now been published in the journal, The American Journal of Physiology.Floorball prevents cardiovascular disease among womenIn a bid to prevent increased risk of cardiovascular disease, the study examined the effect of 12-week floorball training among post-menopausal women. The results were clear.”Following just 12 weeks of twice weekly practices, the women’s conditions had improved and their blood pressure was reduced by 4 mmHg, which correlates with a 40% lower risk of stroke,” explains Professor and Centre Director Jens Bangsbo.Continuing, Bangsbo asserts that, “Furthermore, there was a positive development in relation to levels of substances vital to blood vessel function, including a 20% decrease in markers associated with arteriosclerosis.””The results demonstrate that team sports that include interval exercise are a fantastic opportunity for hormone treatment, in relation to estrogen, because one can avoid an array of undesirable side-effects,” according to postdoc, Michael Nyberg.Team sport — fun as well as healthy”Another advantage of a team sport like floorball is that participants have fun. That’s important, because when a person is engaged in a team sport, they aren’t preoccupied with the otherwise intense exercise in which they are engaged. …

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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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Eucalypt in Ethiopian highlands: Increasing productivity of important tree

Researchers at the UPM are collaborating in a eucalypts breeding program in the Ethiopian highlands which will increase this species productivity.This program is developed by the research group of Forest Physiology and Genetics and the cooperative group of Support to Forestry Development of the Universidad Politcnica de Madrid (UPM). Also, it is supported by several national and international institutions that will contribute to satisfy the demand of woody biomass and other financial needs of Ethiopian farmers.For years, these two research groups have been collaborating with Forestry Research Center and the St. Mary’s College and supported by Ence and the Council of Alcorcn. Also, they are working on providing the Ethiopian highlands with tools and knowledge for better forestry management. This could constitute a valuable tool to achieve sustainability when using and supplying natural resources. The main project consists of a eucalypt breeding program that will result in improvements in many areas.The great demand for forest products to use for agriculture by the population of the Ethiopian highlands has resulted in the deforestation of a region with the lowest human development rate in the world. The eucalypt is the species with the highest demand among Ethiopian farmers and has an important environmental and socioeconomic key role in the highlands area. The consumption of eucalypt is been boosted because of its compatibility with the grazing system and its high yields even in marginal agricultural soils of abandoned lands. However, farmers are lacking of start materials and the current techniques make production difficult.Within the improvement program, the researchers established an experimental test with eucalypt plants from Ethiopia and Spain in order to compare their potential productivity in local conditions. The Spanish plant, that had a certain rate of improvement, showed a growth and survival rate between 27% and 35%, a rate higher than the Ethiopian plants. …

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Finding could explain age-related decline in motor function

Scientists from the School of Medicine at The University of Texas Health Science Center at San Antonio have found a clue as to why muscles weaken with age. In a study published today in The Journal of Neuroscience, they report the first evidence that “set points” in the nervous system are not inalterably determined during development but instead can be reset with age. They observed a change in set point that resulted in significantly diminished motor function in aging fruit flies.”The body has a set point for temperature (98.6 degrees), a set point for salt level in the blood, and other homeostatic (steady-state) set points that are important for maintaining stable functions throughout life,” said study senior author Ben Eaton, Ph.D., assistant professor of physiology at the Health Science Center. “Evidence also points to the existence of set points in the nervous system, but it has never been observed that they change, until now.”Dr. Eaton and lead author Rebekah Mahoney, a graduate student, recorded changes in the neuromuscular junction synapses of aging fruit flies. These synapses are spaces where neurons exchange electrical signals to enable motor functions such as walking and smiling. “We observed a change in the synapse, indicating that the homeostatic mechanism had adjusted to maintain a new set point in the older animal,” Mahoney said.The change was nearly 200 percent, and the researchers predicted that it would leave muscles more vulnerable to exhaustion.Aside from impairing movement in aging animals, a new functional set point in neuromuscular junctions could put the synapse at risk for developing neurodegeneration — the hallmark of disorders such as Alzheimer’s and Parkinson’s diseases, Mahoney said.”Observing a change in the set point in synapses alters our paradigms about how we think age affects the function of the nervous system,” she said.It appears that a similar change could lead to effects on learning and memory in old age. An understanding of this phenomenon would be invaluable and could lead to development of novel therapies for those issues, as well.Story Source:The above story is based on materials provided by University of Texas Health Science Center at San Antonio. Note: Materials may be edited for content and length.

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Physical cues help mature cells revert into embryonic-like stem cells

Oct. 21, 2013 — Bioengineers at the University of California, Berkeley, have shown that physical cues can replace certain chemicals when nudging mature cells back to a pluripotent stage, capable of becoming any cell type in the body.The researchers grew fibroblasts cells taken from human skin and mouse ears on surfaces with parallel grooves measuring 10 micrometers wide and 3 micrometers high. After two weeks of culture in a special cocktail used to reprogram mature cells, the researchers found a four-fold increase in the number of cells that reverted back to an embryonic-like state compared with cells grown on a flat surface. Growing cells in scaffolds of nanofibers aligned in parallel had similar effects.The study, published online Sunday, Oct. 20, in the journal Nature Materials, could significantly enhance the process of reprogramming adult cells into embryonic-like stem cells that can differentiate, or develop, into any type of tissue that makes up our bodies.The 2012 Nobel Prize in Physiology or Medicine was awarded to scientists who discovered that it was possible to reprogram cells using biochemical compounds and proteins that regulate gene expression. These induced pluripotent stem cells have since become a research mainstay in regenerative medicine, disease modeling and drug screening.”Our study demonstrates for the first time that the physical features of biomaterials can replace some of these biochemical factors and regulate the memory of a cell’s identity,” said study principal investigator Song Li, UC Berkeley professor of bioengineering. “We show that biophysical signals can be converted into intracellular chemical signals that coax cells to change.”The current process for reprogramming cells relies on a formula that uses a virus to introduce gene-altering proteins into mature cells. Certain chemical compounds, including valproic acid, that can dramatically affect global DNA structure and expression are also used to boost the efficiency of the reprogramming process.”The concern with current methods is the low efficiency at which cells actually reprogram and the unpredictable long-term effects of certain imposed genetic or chemical manipulations,” said study lead author Timothy Downing, who did this research as a graduate student in the UC Berkeley-UC San Francisco Joint Graduate Program in Bioengineering. “For instance, valproic acid is a potent chemical that drastically alters the cell’s epigenetic state and can cause unintended changes inside the cell. Given this, many people have been looking at different ways to improve various aspects of the reprogramming process.”Previous studies have shown that physical and mechanical forces can influence cell fate, but the effect on epigenetic state and cell reprogramming had not been clear.The new study found that culturing cells on micro-grooved biomaterials improved the quality and consistency of the reprogramming process, and was just as effective as valproic acid.”Cells elongate, for example, as they migrate throughout the body,” said Downing, who is now a research scientist in Li’s lab. …

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Life without insulin is possible, study suggests

Sep. 3, 2013 — Several millions of people around the world suffer from insulin deficiencies. Insulin is a hormone, secreted by the beta cells in the pancreas, which plays a major role in the regulation of energy substrates such as glucose. This insufficiency, primarily caused by diabetes (types 1 and 2), has lethal consequences if it is not treated. As of now, only daily insulin injections allow patients to survive.Several millions of people around the world suffer from insulin deficiencies. Insulin is a hormone, secreted by the beta cells in the pancreas, which plays a major role in the regulation of energy substrates such as glucose. This insufficiency, primarily caused by diabetes (types 1 and 2), has lethal consequences if it is not treated. As of now, only daily insulin injections allow patients to survive. This approach, however, brings on serious side effects. Thanks to their research which was published in the journal Cell Metabolism, the University of Geneva (UNIGE) scientists identified the underlying mechanisms, proving that life without insulin is possible, and paving the way for new diabetes treatments.While life without insulin was inconceivable, a group of researchers, led by Roberto Coppari, professor in the Department of Cell Physiology and Metabolism at UNIGE, has just demonstrated that insulin is not vital for survival. …

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Potential cause of autism discovered

Aug. 28, 2013 — Problems with a key group of enzymes called topoisomerases can have profound effects on the genetic machinery behind brain development and potentially lead to autism spectrum disorder (ASD), according to research announced today in the journal Nature. Scientists at the University of North Carolina School of Medicine have described a finding that represents a significant advance in the hunt for environmental factors behind autism and lends new insights into the disorder’s genetic causes.”Our study shows the magnitude of what can happen if topoisomerases are impaired,” said senior study author Mark Zylka, PhD, associate professor in the Neuroscience Center and the Department of Cell Biology and Physiology at UNC. “Inhibiting these enzymes has the potential to profoundly affect neurodevelopment — perhaps even more so than having a mutation in any one of the genes that have been linked to autism.”The study could have important implications for ASD detection and prevention.”This could point to an environmental component to autism,” said Zylka. “A temporary exposure to a topoisomerase inhibitor in utero has the potential to have a long-lasting effect on the brain, by affecting critical periods of brain development. “This study could also explain why some people with mutations in topoisomerases develop autism and other neurodevelopmental disorders.Topiosomerases are enzymes found in all human cells. Their main function is to untangle DNA when it becomes overwound, a common occurrence that can interfere with key biological processes.Most of the known topoisomerase-inhibiting chemicals are used as chemotherapy drugs. Zylka said his team is searching for other compounds that have similar effects in nerve cells. “If there are additional compounds like this in the environment, then it becomes important to identify them,” said Zylka. “That’s really motivating us to move quickly to identify other drugs or environmental compounds that have similar effects — so that pregnant women can avoid being exposed to these compounds.”Zylka and his colleagues stumbled upon the discovery quite by accident while studying topotecan, a topoisomerase-inhibiting drug that is used in chemotherapy. …

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Researchers develop software tool for cancer genomics

Aug. 26, 2013 — Researchers at the Medical College of Wisconsin (MCW) have developed a new bioinformatics software tool designed to more easily identify genetic mutations responsible for cancers. The tool, called DrGaP, is the subject of a new paper published in the American Journal of Human Genetics.Xing Hua, Ph.D., postdoctoral fellow in biostatistics at the National Cancer Institute, and a former visiting scholar at MCW, is the first author of the paper. Yan Lu, Ph.D., assistant professor of physiology, is corresponding author; and Pengyuan Liu, Ph.D., associate professor of physiology at MCW, is the co-corresponding author.Cancers are caused by the accumulation of genomic alterations, or mutations. Genomic sequencing identifies two specific types of mutations: driver mutations, which are responsible for cancer, and passenger mutations, which are irrelevant to tumor development. A major challenge in cancer genome sequencing is discriminating between the two types of mutations.The authors incorporated statistical methods and bioinformatics tools into the computational tool DrGaP, which stands for “Driver Genes and Pathways.””DrGaP is immediately applicable to cancer genome sequencing studies and will lead a more complete identification of altered driver genes and driver signaling pathways in cancer,” said Dr. Liu. “Biological knowledge of the mutation process is fully integrated into the models, and provides several significant improvements and increased power over current methods.”The researchers note that DrGaP not only recaptured a large majority of driver genes previously reported in other studies, but also identified much longer list of additional candidate genes whose mutations may be linked to cancer. This data demonstrates the extreme complexity of tumor cells and has important implications in targeted cancer therapy.

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Hitting the gym may help men avoid diet-induced erectile dysfunction

Aug. 20, 2013 — Obesity continues to plague the U.S. and now extends to much of the rest of the world. One probable reason for this growing health problem is more people worldwide eating the so-called Western diet, which contains high levels of saturated fat, omega-6 polyunsaturated fatty acids (the type of fat found in vegetable oil), and added sugar. Researchers have long known that this pattern of consumption, as well as the weight gain it often causes, contributes to a wide range of other health problems including erectile dysfunction and heart disease. Other than changing eating patterns, researchers haven’t discovered an effective way to avoid these problems.Searching for a solution, Christopher Wingard and his colleagues at East Carolina University used rats put on a “junk food” diet to test the effects of aerobic exercise. They found that exercise effectively improved both erectile dysfunction and the function of vessels that supply blood to the heart.The article is entitled “Exercise Prevents Western-Diet Associated Erectile Dysfunction and Coronary Artery Endothelial Dysfunction: Response to Acute Apocynin and Sepiapterin Treatment.” It appears in the online edition of the American Journal of Physiology: Regulatory, Integrative, and Comparative Physiology, published by the American Physiological Society.MethodologyFor 12 weeks, the researchers fed a group of rats chow that reflected the Western diet, high in sugar and with nearly half its calories from fat. Another group of rats ate a healthy standard rat chow instead. Half of the animals in each group exercised five days a week, running intervals on a treadmill.At the end of the 12 weeks, anesthetized animals’ erectile function was assessed by electrically stimulating the cavernosal nerve, which causes an increase in penile blood flow and produces an erection. The researchers also examined the rats’ coronary arteries to see how they too responded to agents that would relax them and maintain blood flow to the heart, an indicator of heart health.ResultsThe findings showed that rats who ate the Western diet but stayed sedentary developed erectile dysfunction and poorly relaxing coronary arteries. …

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Beating blindness with vegetable oil

Aug. 15, 2013 — Scientists working at the Research Center on Aging at the Health and Social Services Centre — University Institute of Geriatrics of Sherbrooke (CSSS-IUGS) have been studying strategies for protecting retinal pigment epithelium (RPE) cells. Dysfunction of the RPE is found in retinopathy and age-related macular degeneration, which is the leading cause of blindness of elderly people in developed countries.Share This:Findings published today in the Canadian Journal of Physiology and Pharmacology suggest that incubating retinal cells with vegetable oils induces biochemical and biophysical changes in the cell membrane, which may have a beneficial effect in preventing or slowing the development of retinopathy.”Membrane fluidity, which refers to the viscosity of the lipid bi-layer of a cell membrane, is a marker of the cell function,” explained Prof. A. Khalil, professor at the Université de Sherbrooke and principal investigator of the study. “A decrease of membrane fluidity can affect the rotation and diffusion of proteins and other bio-molecules within the membrane, thereby affecting the functions of these molecules. Whereas, an increase in membrane fluidity makes for a more flexible membrane and facilitates the transmission of light through the eye.”The researchers discovered that vegetable oil fatty acids incorporate in retina cells and increase the plasma membrane fluidity. They concluded that a diet low in trans-unsaturated fats and rich in omega-3 fatty acids and olive oil may reduce the risk of retinopathy. In addition, the research suggests that replacing the neutral oil used in eye drops with oil that possesses valuable biological properties for the eye could also contribute to the prevention of retina diseases.Share this story on Facebook, Twitter, and Google:Other social bookmarking and sharing tools:|Story Source: The above story is based on materials provided by Canadian Science Publishing (NRC Research Press). Note: Materials may be edited for content and length. …

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A genetic answer to the Alzheimer’s riddle?

Aug. 14, 2013 — What if we could pinpoint a hereditary cause for Alzheimer’s, and intervene to reduce the risk of the disease? We may be closer to that goal, thanks to a team at the University of Kentucky. Researchers affiliated with the UK Sanders-Brown Center on Aging have completed new work in Alzheimer’s genetics; the research is detailed in a paper published today in the Journal of Neuroscience.Share This:Emerging evidence indicates that, much like in the case of high cholesterol, some Alzheimer’s disease risk is inherited while the remainder is environmental. Family and twin studies suggest that about 70 percent of total Alzheimer’s risk is hereditary.Recently published studies identified several variations in DNA sequence that each modify Alzheimer’s risk. In their work, the UK researchers investigated how one of these sequence variations may act. They found that a “protective” genetic variation near a gene called CD33 correlated strongly with how the CD33 mRNA was assembled in the human brain. The authors found that a form of CD33 that lacked a critical functional domain correlates with reduced risk of Alzheimers disease. CD33 is thought to inhibit clearance of amyloid beta, a hallmark of Alzheimers disease.The results obtained by the UK scientists indicate that inhibiting CD33 may reduce Alzheimer’s risk. A drug tested for acute myeloid leukemia targets CD33, suggesting the potential for treatments based on CD33 to mitigate the risk for Alzheimer’s disease. …

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Great-grandmother’s cigarette habit could be the cause of child’s asthma

Aug. 5, 2013 — With some 300 million people around the world living with asthma, a study by Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center (LA BioMed) researchers that was released ahead-of- print found for the first time that maternal smoking can cause the third generation of offspring to suffer from the chronic lung disease.The study, published online by the American Journal of Physiology — Lung Cellular and Molecular Physiology, reported that maternal nicotine exposure during pregnancy is linked to asthma in the third generation in disease models. This is known as a “transgenerational” linkage because the third generation was never directly exposed to nicotine or smoking. Previous research had found nicotine exposure was linked to asthma in the second generation, or was a “multigenerational” cause of asthma.”Even though there are multiple causes for childhood asthma, research linking this serious chronic condition to maternal nicotine exposure during pregnancy for up to three generations should give mothers-to-be even more reasons to reconsider smoking,” said Virender K. Rehan, MD, an LA BioMed lead researcher and the corresponding author of the study. “Eliminating the use of tobacco during pregnancy could help halt the rise in childhood asthma and ensure healthier children for generations to come.”Worldwide, approximately 250 million women smoke daily, and the number of people living with asthma is expected to grow by about a third by 2025, reaching approximately 400 million. Twelve percent of women in the U.S. continue to smoke during pregnancy, resulting in the birth of at least 400,000 smoke-exposed infants per year in the U.S. alone.In previous studies, the researchers have concluded that the cause of the second generation’s asthma was epigenetic modification (an environmental factor causing a genetic change). Nicotine was affecting both the lung cells and the sex cells in ways that caused the lungs that developed from those cells to develop abnormally, causing asthma. …

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Potential role of ‘love hormone’ oxytocin in brain function revealed

Aug. 4, 2013 — In a loud, crowded restaurant, having the ability to focus on the people and conversation at your own table is critical. Nerve cells in the brain face similar challenges in separating wanted messages from background chatter. A key element in this process appears to be oxytocin, typically known as the “love hormone” for its role in promoting social and parental bonding.In a study appearing online August 4 in Nature, NYU Langone Medical Center researchers decipher how oxytocin, acting as a neurohormone in the brain, not only reduces background noise, but more importantly, increases the strength of desired signals. These findings may be relevant to autism, which affects one in 88 children in the United States.”Oxytocin has a remarkable effect on the passage of information through the brain,” says Richard W. Tsien, DPhil, the Druckenmiller Professor of Neuroscience and director of the Neuroscience Institute at NYU Langone Medical Center. “It not only quiets background activity, but also increases the accuracy of stimulated impulse firing. Our experiments show how the activity of brain circuits can be sharpened, and hint at how this re-tuning of brain circuits might go awry in conditions like autism.”Children and adults with autism-spectrum disorder (ASD) struggle with recognizing the emotions of others and are easily distracted by extraneous features of their environment. Previous studies have shown that children with autism have lower levels of oxytocin, and mutations in the oxytocin receptor gene predispose people to autism. Recent brain recordings from people with ASD show impairments in the transmission of even simple sensory signals.The current study built upon 30-year old results from researchers in Geneva, who showed that oxytocin acted in the hippocampus, a region of the brain involved in memory and cognition. …

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As climate, disease links become clearer, study highlights need to forecast future shifts

Aug. 1, 2013 — Climate change is affecting the spread of infectious diseases worldwide, according to an international team of leading disease ecologists, with serious impacts to human health and biodiversity conservation. Writing in the journal Science, they propose that modeling the way disease systems respond to climate variables could help public health officials and environmental managers predict and mitigate the spread of lethal diseases.The issue of climate change and disease has provoked intense debate over the past decade, particularly in the case of diseases that affect humans, according to the University of Georgia’s Sonia Altizer, who is the study’s lead author.”For a lot of human diseases, responses to climate change depend on the wealth of nations, healthcare infrastructure and the ability to take mitigating measures against disease,” said Altizer, an associate professor in the UGA Odum School of Ecology. “The climate signal, in many cases, is hard to tease apart from other factors like vector control and vaccine and drug availability.”Climate warming already is causing changes in diseases affecting wildlife and agricultural ecosystems, she said. “In many cases, we’re seeing an increase in disease and parasitism. But the impact of climate change on these disease relationships depends on the physiology of the organisms involved, the location on the globe and the structure of ecological communities.”At the organism level, climate change can alter the physiology of both hosts and parasites. Some of the clearest examples are found in the Arctic, where temperatures are rising rapidly, resulting in faster developing parasites. A lungworm that affects muskoxen, for instance, can now be transmitted over a longer period each summer, making it a serious problem for the populations it infects.”The Arctic is like a ‘canary in the global coal mine,'” said co-author Susan Kutz of the University of Calgary and Canadian Cooperative Wildlife Health Centre.”Climate warming in the Arctic is occurring more rapidly than elsewhere, threatening the health and sustainability of Arctic plants and animals, which are adapted to a harsh and highly seasonal environment and are vulnerable to invasions by ‘southern’ species — both animals and parasites.”A changing climate also is affecting entire plant and animal communities. This is particularly evident in tropical marine environments such as the world’s coral reef ecosystems. In places like the Caribbean, warmer water temperatures have stressed corals and facilitated infections by pathogenic fungi and bacteria. …

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