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Archive - Aug 2016

August 31st

Discovery That Integrins Can Restrain Themselves (Auto-Inhibitory Mode) May Have “Profound Implications” for Inflammatory Diseases & Lead to New Treatment Approaches

As an arm of the innate immune system, white blood cells called neutrophils form the first line of defense against invading pathogens. Neutrophils spend most of their lives racing through the bloodstream, patrolling for bacteria or other foreign particles. Once they arrive at tissues besieged by infectious agents, neutrophils halt on a dime and then blast through the vessel wall to reach the inflammatory attack site. They do this by activating integrins, a class of adhesion receptors that can switch on in less than a second. Now, a paper published by La Jolla Institute for Allergy and Immunology (LJI) researchers, and collaborators, reveals an entirely unanticipated way in which neutrophil receptors grab onto a capillary wall in preparation to breach it, as well as a cute trick they use to keep cells from sticking to each other or busting through the wrong place. That work, led by LJI immunologist Klaus Ley, M.D., and published in the August 31, 2016 issue of Nature Communications, suggests a novel way that integrins could be targeted to either dampen inflammation, as in the case of autoimmune disease, or to boost immune responses against infection. The new open-access article is titled “Neutrophil Recruitment Limited by High-Affinity Bent β2 Integrin Binding Ligand in cis.” "Once neutrophils sense a site of infection behind a capillary wall, they need to get out of circulation fast. Previously, we knew they initiated that by switching on adhesion molecules to grab onto a vessel in less than a second," says Dr. Ley, a professor and Head of LJI's Division of Inflammation Biology. "In our new study we have discovered an unexpected way that these molecules change their shape to do that." Many researchers thought that integrin receptors protruding from neutrophils became adherent via a "switchblade" mechanism.

Tasmanian Devils Show Rapid Evolution to Develop Resistance to Deadly Transmissible Cancer

Tasmanian devils are evolving in response to a highly lethal and contagious form of cancer, a Washington State University(WSU) researcher has found. Dr. Andrew Storfer, WSU Professor of Biology, and an international team of scientists discovered that two regions in the genomes of Australia's iconic marsupials are changing in response to the rapid spread of devil facial tumor disease (DFTD), a nearly 100 percent fatal and transmissible cancer first detected in 1996. The work, published online on August 30, 2016,in Nature Communications, suggests some Tasmanian devil populations are evolving genetic resistance to DFTD that could help the species avoid extinction. Additionally, the genomic data will support future medical research exploring how animals evolve rapidly in response to cancer and other pathogens. The open-access article is titled “Rapid Evolutionary Response to a Transmissible Cancer in Tasmanian Devils.” "Our study suggests hope for the survival of the Tasmanian devil in the face of this devastating disease," Dr. Storfer said. "Ultimately, it may also help direct future research addressing important questions about the evolution of cancer transmissibility and what causes remission and reoccurrence in cancer and other diseases." Tasmanian devils are the largest carnivorous marsupials in the world and an integral part of Australia's natural heritage. Devils display significant aggression toward one another, which often involves biting on the face. This sometimes transmits DFTD, one of only three known forms of transmissible cancer and by far the deadliest.

August 30th

Increased Blood Flow to Brain Found Key to Evolution of Human Intelligence; Study Shows Blood Flow to Brain Has Increased 600% Over Same Time That Brain Size Has Increased 350%

A University of Adelaide-led project has overturned the theory that the evolution of human intelligence was simply related to the size of the brain. The new work has shown that this evolution is likely more closely linked to the supply of blood to a growing and increasingly demanding brain. An international collaboration between Australia and South Africa showed that the human brain evolved to become not only larger, but more energetically costly and blood-requiring than previously believed. The research team calculated how blood flowing to the brain of human ancestors changed over time, using the size of two holes at the base of the skull that allow arteries to pass to the brain. The findings, published in the Royal Society Journal Open Science, allowed the researchers to track the increase in human intelligence across evolutionary time. "Brain size has increased about 350% over human evolution, but we found that blood flow to the brain increased an amazing 600%," says project leader Professor Emeritus Roger Seymour, from the University of Adelaide. "We believe this is possibly related to the brain's need to satisfy increasingly energetic connections between nerve cells that allowed the evolution of complex thinking and learning. To allow our brain to be so intelligent, it must be constantly fed oxygen and nutrients from the blood. The more metabolically active the brain is, the more blood it requires, so the supply arteries are larger. The holes in fossil skulls are accurate gauges of arterial size." The study was a new collaboration between the Cardiovascular Physiology team in the School of Biological Sciences at the University of Adelaide (Australia) and the Brain Function Research Group and Evolutionary Studies Institute at the University of the Witwatersrand (South Africa).

People with Alcohol Dependency May Lack Key Enzyme (Histone Methyltransferase PRDM2) That Affects Gene Expression & Reduces Impulse Control; Discovery May Drive New Treatments of Alcoholism

A research group under the leadership of Linköping University (Sweden) Professor Markus Heilig has identified an enzyme whose production is turned off in nerve cells of the frontal lobe when alcohol dependence develops. The deficiency in this enzyme leads to continued use of alcohol despite adverse consequences. The discovery was published online on August 30, 2016 in Molecular Psychiatry, and could mean completely new possibilities for treating alcoholism. The open-access article is titled “Dependence-Induced Increase of Alcohol Self-Administration and Compulsive Drinking Mediated by the Histone Methyltransferase PRDM2.” “We've worked hard for this. The enzyme, PRDM2, has previously been studied in cancer research, but we didn't know that it has a function in the brain," says Dr. Heilig, Professor of Psychiatry and Head of the Center for Social and Affective Neuroscience (CSAN) at Linköping University. Dr. Heilig and his research group are linking together research into alcoholism and other addictive illnesses with advanced brain research. It has long been suspected that people with alcohol dependence have impaired function in the frontal lobes of the brain, but the underlying biological mechanisms have not been known. The research team behind the paper, which includes researchers from both Linköping University and the University of Miami, is the first to identify this molecular mechanism. If frontal function is impaired, it is difficult for human beings to control their impulses.

Dogs Can Distinguish Vocabulary Words & Intonation of Human Speech Using Same Regions of Brain As Humans

Dogs have the ability to distinguish vocabulary words and the intonation of human speech through brain regions similar to those that humans use, a new study reported by Attila Andics, Ph.D., and Eötvös Loránd, Ph.D, University in Budapest, Hungary, and colleagues. The article, to be published in the September 2, 2016 issue of Science, is titled "Neural Mechanisms for Lexical Processing in Dogs." The authors note that vocabulary learning "does not appear to be a uniquely human capacity that follows from the emergence of language, but rather a more ancient function that can be exploited to link arbitrary sound sequences to meanings." Words are the basic building blocks of human languages, but they are hardly ever found in nonhuman vocal communications. Intonation is another way that information is conveyed through speech, where, for example, praises tend to be conveyed with higher and more varying pitch. Humans understand speech through both vocabulary and intonation. Here, in this new work, Dr. Andics and colleagues explored whether dogs also depend on both mechanisms. Dogs were exposed to recordings of their trainers' voices as the trainers spoke to them using multiple combinations of vocabulary and intonation, in both praising and neutral ways. For example, trainers spoke praise words with a praising intonation, praise words with a neutral intonation, neutral words with a praising intonation, and neutral words with neutral intonation. Researchers used fMRI to analyze the dogs' brain activity as the animals listened to each combination. Their results reveal that, regardless of intonation, dogs process vocabulary, recognizing each word as distinct, and further, that they do so in a way similar to humans, using the left hemisphere of the brain.

Integrated Genetic-Epigenetic Study of Schizophrenia Is Published; Evidence Found for Co-Localization of Genetic Associations and Differential DNA Methylation

An international study led by the University of Exeter Medical School has made advances in understanding the ways in which genetic risk factors alter gene function in schizophrenia. The study, published online on August 30, 2016 in Genome Biology and funded by the Medical Research Council (MRC), combined genetic sequence information with measures of gene regulation in schizophrenia patients and matched controls. The article is titled “An Integrated Genetic-Epigenetic Analysis of Schizophrenia: Evidence for Co-Localization of Genetic Associations and Differential DNA Methylation.” Schizophrenia is an inherited, neuropsychiatric disorder characterized by episodes of psychosis and altered brain function. Despite previous research successfully identifying genetic variants associated with schizophrenia, scientists remain uncertain about which genes cause the condition and how their function is regulated. The new study, which used blood samples from 1,714 individuals, is the largest of its kind. It has helped to clarify which specific genes are actually affected by the genetic variants associated with schizophrenia, and provides a blueprint for researchers to undertake similar analyses for other complex diseases. The r esearch team included collaborators from King's College London, University College London and the University of Aberdeen, as well as colleagues in Finland, China, Germany, and the Netherlands. The team focused on both the underlying genetic sequence and DNA methylation, an epigenetic mark that regulates both gene expression and function. By profiling genetic and regulatory variation in the same samples, the group found that many of the genetic variants previously found to be associated with schizophrenia have potential effects on gene regulation.

August 29th

Exosomes May Contribute to Alzheimer’s; Reduction in Number May Slow Disease Progression and Protect Cognition

Vesicles, fluid-filled sacs that brain cells make to trap amyloid, a hallmark of Alzheimer's, appear to also contribute to the disease, scientists report. Reducing the production of these vesicles, called exosomes, could help reduce the amount of amyloid and lipid that accumulates, slow disease progression, and help protect cognition, scientists at the Medical College of Georgia (MCG) at Augusta University reported in the August 17, 2016 issue of The Journal of Neuroscience. The article is titled “Neutral Sphingomyelinase-2 Deficiency Ameliorates Alzheimer's Disease Pathology and Improves Cognition in the 5XFAD Mouse.” When confronted with amyloid, astrocytes (plentiful brain cells that support neurons) start making exosomes, to capture and neutralize it, said Dr. Erhard Bieberich, a neuroscientist in the MCG Department of Neuroscience and Regenerative Medicine and the study's corresponding author. "If you swarm astrocytes with amyloid, you trigger an aggressive response," he said. Happy astrocytes, on the other hand, don't make exosomes. Not unlike a landfill, the real problems begin when the biological sacs get piled too high. In such volume and close proximity to neurons, exosomes begin to interfere with communication and nutrition, neurons stop functioning well and eventually begin to die, a scenario that fits with disease progression, Dr. Bieberich said. MCG scientists followed the process in an animal model with several genetic mutations found in types of Alzheimer's that tend to run in families and produce brain plaques early in life. One mouse group also was genetically programmed to make a nonfunctional form of the enzyme neutral sphingomyelinase-2.

Mutations in Non-Coding Gene (snoRNA) Cause Severely Debilitating Disease of Brain Blood Vessels

The cause of a disease that targets blood vessels in the brain - leading to multiple debilitating symptoms and, often, to early death - has been tracked to a single mutated gene, opening up the immediate possibility of improved patient care through genetic testing, and of future treatments. The research, conducted over 12 years, was led by the teams of Professor Yanick Crow and Dr. Ray O'Keefe from The University of Manchester's Division of Evolution and Genomic Sciences, and included contributions from over 60 academics and scientists from around the world. It was published online today (August 29, 2016) in the journal Nature Genetics. The article is title “'Mutations in SNORD118 Cause the Cerebral Microangiopathy Leukoencephalopathy with Calcifications and Cysts.” This discovery involved the identification of mutations in SNORD118 - a small nucleolar RNA (snoRNA) gene - to cause leukoencephalopathy with calcification and cysts (LCC). LCC is characterized by progressive white matter degeneration in the brain. The disease can present in patients at any stage of life. Dr. Emma Jenkinson, Research Associate at The University of Manchester's Division of Evolution and Genomic Sciences, was lead laboratory researcher on this project. She said that the 12-year study unlocked greater understanding of the development of genetic disorders caused by mutations in non-coding regions of the genome. "The identification of SNORD118 as the instigator of a progressive and frequently fatal brain disease is a very significant step forward in understanding the role of non-coding RNAs in the development of certain diseases.

Telemedicine Could Improve Eye Exam Access for People with Diabetes

Electronic eye exams could become popular in the U.S. among patients who see them as an easy way to visit the eye doctor. After a nationwide telemedicine diabetic screening program in England and Wales, for example, diabetic retinopathy is no longer the leading cause of blindness there. Similar e-health programs could grow stateside, where diabetic retinopathy remains the main driver of new-onset blindness. But it hasn't been known if patients would participate. Researchers at the University of Michigan's (U-M’s) Kellogg Eye Center conducted a study of older adults to find out. If services are convenient, patients will use them, the investigation found. "Telemedicine has been shown to be a safe method to provide monitoring for diabetic eye care. If physicians plan to change the way that people get care, we must create a service that is appealing and tailored to the patients," says senior study author Maria Woodward, M.D., Assistant Professor of Ophthalmology at the Kellogg Eye Center, Early detection and treatment are key to preventing blindness from diabetic retinopathy, but fewer than 65 percent of U.S. adults with diabetes undergo screening. In underserved populations, rates can drop as low as 10 or 20 percent. Shifting screening to a telemedicine program could ease the burden on patients who face high costs of care, lack of access to care or have difficulty with transportation or getting time away from work, researchers say. Finding ways to address screening will become more important in coming decades, as the number of people with diabetes is projected to more than double to 366 million worldwide by 2030. Telemedicine allows primary care doctors to play a critical role in preventing eye damage. Retinal photographs are taken of both eyes at the doctor's office using a no-dilation retina camera.

Zika Infection May Affect Adult Brain Cells, Suggesting Risk May Not Be Limited to Pregnant Women

Concerns over the Zika virus have focused on pregnant women due to mounting evidence that it causes brain abnormalities in developing fetuses. However, new research in mice from scientists at The Rockefeller University and the La Jolla Institute for Allergy and Immunology suggests that certain adult brain cells may be vulnerable to infection as well. Among these are populations of cells that serve to replace lost or damaged neurons throughout adulthood, and are also thought to be critical to learning and memory. “This is the first study looking at the effect of Zika infection on the adult brain,” says Joseph Gleeson, Ph.D., Adjunct Professor at Rockefeller, Head of the Laboratory of Pediatric Brain Disease, and Howard Hughes Medical Institute investigator. “Based on our findings, getting infected with Zika as an adult may not be as innocuous as people think.” Although more research is needed to determine if this damage has long-term biological implications or the potential to affect behavior, the findings suggest the possibility that the Zika virus, which has become widespread in Central and South America over the past eight months, may be more harmful than previously believed. The new findings were published online in Cell Stem Cell on August 18, 2016. The open-access article is titled “Zika Virus Infects Neural Progenitors in the Adult Mouse Brain and Alters Proliferation.” “Zika can clearly enter the brain of adults and can wreak havoc,” says Sujan Shresta, Ph.D., a professor at the La Jolla Institute of Allergy and Immunology. “But it’s a complex disease—it’s catastrophic for early brain development, yet the majority of adults who are infected with Zika rarely show detectable symptoms.