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Archive - Apr 2012

April 21st

History Is Key Factor in Plant Disease Virulance

The virulence of plant-borne diseases depends not just on the particular strain of a pathogen, but on where the pathogen has been before landing in its host, according to new research results. Scientists from the University of California System and the U.S. Department of Agriculture's Agricultural Research Service (USDA ARS) published the results on April 18, 2012 in PLoS ONE. The study demonstrates that the pattern of gene regulation--how a cell determines which genes it will encode into its structure and how it will encode them--rather than gene make-up alone affects how aggressively a microbe will behave in a plant host. The pattern of gene regulation is formed by past environments, or by an original host plant from which the pathogen is transmitted. "If confirmed, this finding could add a key new dimension to how we look at microbes because their history is going to matter--and their history may be hard to reconstruct," said Dr. Matteo Garbelotto, an environmental scientist at the University of California, Berkeley, and co-author of the paper. Epigenetic factors--for example, gene regulation mechanisms controlled by diet or exposure to extreme environments--are well known to affect the susceptibility of humans to some diseases. The new study is the first to show a similar process for plant pathogens. "Sudden oak death, for example, is one of many pathogens that seemingly came out of nowhere to ravage the forests of California," said Sam Scheiner, a director of the National Science Foundation's (NSF) Ecology and Evolution of Infectious Diseases (EEID) program, which funded the research. "This study shows that such sudden emergence can happen through rapid evolution, and may provide clues for predicting future epidemics." The EEID program is a joint effort of NSF and the National Institutes of Health.

Single Neuron Studies Show Multiple Alzheimer Disease Steps Progress in Parallel

Studying a mouse model of Alzheimer's disease, neuroscientists at the Technische Universitaet Muenchen (TUM) have observed correlations between increases in both soluble and plaque-forming beta-amyloid – a protein implicated in the disease process – and dysfunctional developments on several levels: individual cortical neurons, neuronal circuits, sensory cognition, and behavior. Their results, published April 10, 2012 in Nature Communications, show that these changes progress in parallel and that, together, they reveal distinct stages in Alzheimer's disease with a specific order in time. In addition to its well-known, devastating effects on memory and learning, Alzheimer's disease can also impair a person's sense of smell or vision. Typically, these changes in sensory cognition only show themselves behaviorally when the disease is more advanced. A new study sheds light on what is happening in the brain throughout the disease process, specifically with respect to the part of the cerebral cortex responsible for integrating visual information. A team led by Professor Arthur Konnerth, a Carl von Linde Senior Fellow of the TUM Institute for Advanced Study, has observed Alzheimer's-related changes in the visual cortex at the single-cell level. Using a technique called two-photon calcium imaging, the researchers recorded both spontaneous and stimulated signaling activity in cortical neurons of living mice: transgenic mice carrying mutations that cause Alzheimer's disease in humans, and wild-type mice as a control group. By observing how neuronal signaling responded to a special kind of vision test – in which a simple grating pattern of light and dark bars moves in front of the mouse's eye – the scientists could characterize the visual circuit as being more or less "tuned" to specific orientations and directions of movement. Dr.

Researchers ID Potential Weakness in Life-Threatening Malaria Parasites

Scientists have identified a link between different strains of malaria parasites that cause severe disease, which could aid the development of vaccines or drugs against life-threatening cases of the infection. Researchers have identified a key protein that is common to many potentially fatal forms of the condition, and found that antibodies that targeted this protein were effective against these severe malaria strains. The protein has sticky properties that enable it to bind to red blood cells and form dangerous clumps that can block blood vessels. These clumps, or rosettes, can cause severe illness, including coma and brain damage. Presently, between 10 and 20 per cent of people with severe malaria die from it, and the disease – which is spread by blood-sucking mosquitoes – claims about one million lives per year. Malaria parasites, once in the bloodstream, are able to alter the protein molecules on their surfaces to evade attack by the immune system. These surface proteins are usually poor targets for treatments or vaccines because they are highly variable between different malaria parasite strains. Now, researchers have found that the surface proteins of rosette-forming parasites share similarities that may allow them to act as a target for treatments to block progress of the disease. Scientists from the University of Edinburgh worked with collaborators from Cameroon, Mali, Kenya, and Gambia to test their antibodies against parasites collected from patients. The study, published on April 19, 2012 in PLoS Pathogens, was supported by the Wellcome Trust.

New Sequencing Approach Reveals 22 New Genes for Autism and Related Disorders

A new approach to investigating hard-to-find chromosomal abnormalities has identified 33 genes associated with autism and related disorders, 22 for the first time. Several of these genes also appear to be altered in different ways in individuals with psychiatric disorders such as schizophrenia, symptoms of which may begin in adolescence or adulthood. Results of the study by a multi-institutional research team were published online on April 19, 2012 in Cell. "By sequencing the genomes of a group of children with neurodevelopmental abnormalities, including autism, who were also known to have abnormal chromosomes, we identified the precise points where the DNA strands are disrupted and segments exchanged within or between chromosomes. As a result, we were able to discover a series of genes that have a strong individual impact on these disorders," says James Gusella, Ph.D., director of the Massachusetts General Hospital Center for Human Genetic Research (MGH CHGR) and senior author of the Cell paper. "We also found that many of these genes play a role in diverse clinical situations – from severe intellectual disability to adult-onset schizophrenia – leading to the conclusion that these genes are very sensitive to even subtle perturbations." Physicians evaluating children with neurodevelopmental abnormalities often order tests to examine their chromosomes, but while these tests can detect significant abnormalities in chromosomal structure, they typically cannot identify a specific gene as being disrupted.

April 19th

Ravens Remember Relationships with Others

In daily life, we remember faces and voices of several known individuals. Similarly, mammals have been shown to remember calls and faces of known individuals after a number of years. Dr. Markus Boeckle and Dr. Thomas Bugnyar from the Department of Cognitive Biology of the University of Vienna show in a new article, published online on April 19, 2012 in Current Biology, that ravens differentiate individuals based on familiarity. Additionally, they discovered that ravens memorize relationship valence and affiliation. So far it has been unknown whether relationship valence can be remembered based on former positive or negative interactions. As response to calls of formerly known individuals ravens not only increase the number of calls but also change call characteristics dependent on whether they hear former "friends" or "foes." This suggests that ravens remember specific individuals at least for three years. The ability to change call characteristics is especially interesting. In the event they hear a "friendly" individual, they respond with a "friendly" call, whereas when listening to a "foe," they exhibit lower frequencies and rougher characteristics, an effect already described for other animal species. Ravens respond to calls from previously unknown individuals with even lower and rougher calls and thus try to increase their acoustically perceivable body size – also in humans, larger people have lower voices than smaller ones and angry humans rougher voices. While it was known that mammals change their voices based on the relationship they share with others, the researchers here were able to show for the first time that birds also change their calls according to relationship quality.

Scientists Develop Effective Treatment for Deadly Cat Disease

Lone Star ticks, which are notorious carriers of many diseases including cytauxzoonosis, or "bobcat fever," have been spreading across the nation in recent years. As a result, cats across much of the country are now exposed to the deadly disease. University of Missouri veterinarian Dr. Leah Cohn, a small animal disease expert, and Dr. Adam Birkenheuer from North Carolina State University, have found an effective treatment for the dangerous disease. "Previous treatment methods have only been able to save less than 25 percent of infected cats, but our method, which is now being used by veterinarians across the country, has been shown to save about 60 percent of infected cats," Dr. Cohn said. "While that number isn't as high as we'd like due to the deadly nature of the disease, our method is the first truly effective way to combat the disease." Routinely carried by bobcats and mountain lions, Dr. Cohn and Dr. Birkenheuer also found that bobcat fever can even infect tigers. All types of cats, but only cats, can catch bobcat fever. Dr. Cohn calls the disease the "Ebola virus for cats," saying that it is a very quick and painful death for cats that succumb from the infection. Bobcat fever is easily spread between cats through tick bites, but Dr. Cohn and Dr. Birkenheuer found that the disease is not readily passed down through birth like malaria and many other protozoan diseases. "Bobcat fever affects healthy outdoor cats the most, because they are the most likely to get bitten by ticks," Dr. Cohn said. "The disease acts very quickly and can kill a cat less than a week after it begins to show signs of being sick, so it is important to get treatment from a veterinarian as soon as the cat appears ill." Dr.

Landmark Breast Cancer Study Could Revolutionize Diagnosis & Treatment

A major study carried out by Cancer Research UK scientists and collaborators around the world could revolutionize the way women with breast cancer will be diagnosed and treated in the future, by reclassifying the disease into ten completely new categories based on the genetic fingerprint of a tumor. Doctors should one day be able to predict survival more accurately in women with breast cancer based on these new subtypes, and better tailor treatment to the individual patient. The research, published online on April 18, 2012 in Nature, is the largest global gene study of breast cancer tissue ever performed and represents the culmination of decades of research into the disease. The team at Cancer Research UK’s Cambridge Research Institute, in collaboration with the British Columbia (BC) Cancer Agency in Vancouver, Canada, and multiple institutions around the world, analyzed the DNA and RNA of 2,000 tumor samples taken from women diagnosed with breast cancer between five and ten years ago. The scientists classified breast cancer into at least ten subtypes grouped by common genetic features that correlate with survival. This new classification could change the way drugs are tailored to treat women with breast cancer. The investigators also discovered several completely new breast cancer genes that drive the disease. These genes are all potential targets for the development of new types of drugs. This information will be available to scientists worldwide to boost drug discovery and development. The research also revealed the relationship between these genes and known cell signaling pathways, networks that control cell growth and division. This could pinpoint how these gene faults cause cancer, by disrupting important cell processes.

April 17th

First Blood Test to Diagnose Major Depression in Teens

With collaborators, a Northwestern University scientist has developed the first blood test to diagnose major depression in teens, a breakthrough approach that allows an objective diagnosis by measuring a specific set of genetic markers found in a patient's blood. The current method of diagnosing depression is subjective. It relies on the patient's ability to recount his symptoms and the physician's ability and training to interpret them. Diagnosing teens is an urgent concern because they are highly vulnerable to depression and difficult to accurately diagnose due to normal mood changes during this age period. The test also is the first to identify subtypes of depression. It distinguished between teens with major depression and those with major depression combined with anxiety disorder. This is the first evidence that it's possible to diagnose subtypes of depression from blood, raising the hope for tailoring care to the different types. "Right now depression is treated with a blunt instrument," said Dr. Eva Redei, a professor of psychiatry and behavioral sciences at the Northwestern University Feinberg School of Medicine and lead investigator of the study, published online on April 17, 2012 in Translational Psychiatry. "It's like treating type 1 diabetes and type 2 diabetes exactly the same way. We need to do better for these kids. This is the first significant step for us to understand which treatment will be most effective for an individual patient," added Dr. Redei, also the David Lawrence Stein Professor of Psychiatric Diseases Affecting Children and Adolescents. "Without an objective diagnosis, it's very difficult to make that assessment.

April 16th

DNA Sequencing Allows ID of Unusual, Oft-Fatal Pathogen in Patient

A 14-year-old Texas girl was finally cured of an oft-fatal emerging disease when doctors amputed her lower leg, where the infection arose, after various antimicrobials proved ineffective. The culprit was Pythium insidiosum, a fungus-like microbe which rarely causes disease in humans and then primarily in Thailand. The case "clearly highlights the need for clinicians to have the best support possible from the clinical microbiology lab," says Dr. Don Murphey of Cook Children's Medical Center, who served as attending physician during the case. The case report is published in the April 2012 issue of the Journal of Clinical Microbiology. The girl, otherwise healthy, presented to an urgent care facility with a 2-week history of a continuously enlarging erythematous bump on her lower leg, having reported recently swimming in an algae-filled pool. "Over the course of several weeks, what started as a very small lesion grew to involve most of her leg," says first author Dr. Stephen J. Salipante, of the University of Washington, Seattle. "Initial cultures of the wound suggested that this was a bacterial infection, and it was treated as such, but without success. She eventually needed to be hospitalized," says Dr. Salipante. Her treatment team at Cook Children's hospital tried increasingly aggressive medical and surgical management, including different antibiotic regimens, antifungals, and surgical debridements, but the infection simply didn't respond. "Given the microscopic appearance of the organism, our working hypothesis was that this was some kind of unusual, and very aggressive fungus," says Dr. Salipante. However, sequencing a segment of DNA that is useful for categorizing fungi, the ITS1 sequence, "revealed that this was not a fungus at all—rather, the DNA sequence very closely matched… P. insidiosum," says Dr.

Promiscuous Queen Bees Maintain Genetic Diversity in Island Environment

By mating with nearly 100 males, queen bees on isolated islands avoid inbreeding and keep colonies healthy. The results, published online in PLoS ONE, focused on giant honey bee colonies on Hainan Island, off the coast of China. Because these bees have long been separated from their continental cousins, it was thought that the island bees would be prime candidates for inbreeding as well as having very different genes, said Dr. Zachary Huang, Michigan State University (MSU) entomologist. “We believed that the island bees would show evidence of the founder effect, or random genetic changes in an isolated population, on a unique sex determination gene from the mainland bees,” he said. “At first we were surprised when we couldn’t document this effect. Looking at it further, I asked myself, ‘Why didn’t I think of this before?’” When compared to bees, humans have a rather simplistic sex-determination process. In females, the two sex-determination chromosomes are the same, and in males the two chromosomes are different. With bees, however, the combinations of complementary sex determination genes, or CSDs, determine the sex and the societal role of the bees. One particular gene can have alleles – the “flavor” of genes. In humans, they dictate hair and eye color. In bees, though, they are responsible for creating females (worker bees), fertile males (that mate with the queen) or infertile males (diploid males which serve no purpose). The “voila” moment came once Dr. Huang estimated the bees’ mating habits and the potential of CSD allele combinations. That’s when he understood why he couldn’t confirm the founder effect. Keeping the CSD mix diverse is one of the keys to maintaining a healthy hive, he said. The island queens carry around 40 CSD alleles.