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Archive - 2011

September 29th

“Alarm Clock” Gene Identified

Ever wondered why you wake up in the morning ---- even when the alarm clock isn't making jarring noises? Wonder no more. Researchers at the Salk Institute for Biological Studies have identified a new component of the biological clock, a gene responsible for starting the clock from its restful state every morning. The biological clock ramps up our metabolism early each day, initiating important physiological functions that tell our bodies that it's time to rise and shine. Discovery of this new gene and the mechanism by which it starts the clock everyday may help explain the genetic underpinnings of sleeplessness, aging, and chronic illnesses, such as cancer and diabetes, and could eventually lead to new therapies for these illnesses. "The body is essentially a collection of clocks," says Dr. Satchindananda Panda, an associate professor in Salk's Regulatory Biology Laboratory, who led the research along with Dr. Luciano DiTacchio, a post-doctoral research associate. "We roughly knew what mechanism told the clock to wind down at night, but we didn't know what activated us again in the morning. Now that we've found it, we can explore more deeply how our biological clocks malfunction as we get older and develop chronic illness." In a report published online on September 30, 2011, in the journal Science, the Salk researchers and their collaborators at McGill University and Albert Einstein College of Medicine describe how the gene KDM5A encodes a protein, JARID1a, that serves as an activation switch in the biochemical circuit that maintains our circadian rhythm. The discovery fills in a missing link in the molecular mechanisms that control our daily wake-sleep cycle. The central player of our biological clock is a protein called PERIOD (PER). The number of PER proteins in each of our cells rises and falls every 24 hours.

September 28th

A Micro-RNA Is Key Regulator of Learning and May Play Role in Alzheimer’s

Among many different functions, proteins serve as the molecular machines of the cell. They transport materials, cleave products, or transmit signals – and for a long time, they have been a main focus of attention in molecular biology research. In the last two decades, however, another class of critically important molecules has emerged: small RNA molecules, including micro-RNAs. It is now well established that micro-RNAs play a key role in the regulation of cell function. "A micro-RNA regulates the production of an estimated 300-400 proteins. This class of molecules can be regarded as a switch that coordinates the transition of cells from one state to another," explains Professor André Fischer, scientist at the German Center for Neurodegenerative Diseases (DZNE) and Speaker of the DZNE site Göttingen. He and his team have identified a micro-RNA that regulates the learning processes and probably plays a central role in Alzheimer's disease. The researchers have shown that there is too much of a micro-RNA called "miRNA 34c" in mouse models of Alzheimer's disease, and decreasing the level of miRNA 34c in these mice can restore their learning ability. The scientists have identified a new target molecule that might be important for diagnosis and treatment of Alzheimer's disease. The studies were carried out in collaboration with scientists at the European Neuroscience Institute Göttingen, the Göttingen University, and the DZNE site in Munich, and with researchers from Switzerland, USA and Brazil. The results were published online on September 23, 2011, in The EMBO Journal.

Scientists ID Key Protein Causing Excess Liver Production of Glucose in Diabetes

Researchers at the John G. Rangos Sr. Research Center at Children's Hospital of Pittsburgh of the University of Pittsburgh Medical Center, and the University of Pittsburgh School of Medicine have identified a powerful molecular pathway that regulates the liver's management of insulin and new glucose production, which could lead to new therapies for diabetes. The findings were published online on September 22, 2011, in Diabetes, a journal of the American Diabetes Association. Usually, the liver stores excess blood sugar as glycogen, which it doles out overnight during sleep and other periods of fasting to keep glucose levels within a normal physiological range, explained Dr. H. Henry Dong, associate professor of pediatrics, Pitt School of Medicine. But in diabetes, the liver continues to pump out glucose even when insulin is provided as a treatment. "Scientists have been trying to find the factors that contribute to this liver overproduction of glucose for decades," Dr. Dong said. "If we can control that pathway, we should be able to help reduce the abnormally high blood sugar levels seen in patients with diabetes." He and his team have been studying a family of proteins called forkhead box or FOX, and for the current project focused on one called FOX06. They found that mice engineered to make too much FOX06 developed signs of metabolic syndrome, the precursor to diabetes, including high blood sugar and high insulin levels during fasting, as well as impaired glucose tolerance, while mice that made too little FOX06 had abnormally low blood sugars during fasting. "In a normal animal, a glucose injection causes blood sugar level to rise initially and then it goes back to normal range within two hours," Dr. Dong said. "In animals that made too much FOX06, blood sugar after a glucose injection doesn't normalize within two hours.

September 23rd

Aborigine Genome Sequence Suggests Direct Descent from First Human Explorers

In an exciting development, an international team of researchers has, for the first time, pieced together the human genome from an Aboriginal Australian. The results, published online on September 22, 2011, in the international journal Science, suggest a re-interpretation of the prehistory of our species. By sequencing the genome, the researchers demonstrate that Aboriginal Australians descend directly from an early human expansion into Asia that took place some 70,000 years ago, at least 24,000 years before the population movements that gave rise to present-day Europeans and Asians. The results imply that modern-day Aboriginal Australians are, in fact, the direct descendents of the first people who arrived in Australia as early as 50,000 years ago. The study derived from a lock of hair donated to a British anthropologist by an Aboriginal man from the Goldfields region of Western Australia in the early 20th century. One hundred years later, researchers have isolated DNA from this same hair, using it to explore the genetics of the first Australians and to provide insights into how humans first dispersed across the globe. The genome, shown to have no genetic input from modern European Australians, reveals that the ancestors of the Aboriginal man separated from the ancestors of other human populations some 64-75 thousand years ago. Aboriginal Australians therefore descend directly from the earliest modern explorers, people who migrated into Asia before finally reaching Australia about 50,000 years ago. In showing this, the study establishes Aboriginal Australians as the population with the longest association with the land on which they live today. This research is presented with the full endorsement of the Goldfields Land and Sea Council, the organization that represents the Aboriginal traditional owners for the region.

DNA Study Suggests Asia Was Settled in Multiple Waves of Migration

An international team of researchers studying DNA patterns from modern and archaic humans has uncovered new clues about the movement and intermixing of populations more than 40,000 years ago in Asia. Using state-of-the-art genome analysis methods, scientists from Harvard Medical School and the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, have found that Denisovans—a recently identified group of archaic humans whose DNA was extracted last year from a finger bone excavated in Siberia—contributed DNA, not just to present-day New Guineans, but also to aboriginal Australian and Philippine populations. The study demonstrates that contrary to the findings of the largest previous genetic studies, modern humans settled Asia in more than one migration. According to Dr. David Reich, a professor of genetics at Harvard Medical School, "Denisova DNA is like a medical imaging dye that traces a person's blood vessels. It is so recognizable that you can detect even a little bit of it in one individual. In a similar way, we were able to trace Denisova DNA in the migrations of people. This shows the power of sequencing ancient DNA as a tool for understanding human history." The patterns the researchers found can only be explained by at least two waves of human migration: the first giving rise to the aboriginal populations that currently live in Southeast Asia and Oceania, and later migrations giving rise to relatives of East Asians, who now are the primary population of Southeast Asia. The study also provides new insights about where the ancient Denisovans lived. According to Dr. Mark Stoneking, a professor at the Max Planck Institute who is senior author of the paper, Denisovans must have inhabited an extraordinarily large ecological and geographic range, from Siberia to tropical Southeast Asia.

Insulin Master Switch Discovered—May Signal Hope for Reversing Type 2 Diabetes

Australian scientists have discovered that a single gene controls a very complex process, apparently forming the crucial link between eating a high-fat diet and developing diabetes. Compounds are already being developed for blocking the gene – known as Id1 – as it has known adverse effects in cancer. This drug development work would very much shorten the path from discovery to prospective treatment in the case of diabetes. Type 2 diabetes occurs when the body becomes less able to produce and use insulin, a hormone essential for maintaining normal metabolism of food. The disorder is associated with a high-sugar, high-fat diet combined with lack of exercise. Insulin is produced in the pancreas by highly specialized “beta cells,” and then carried around our bodies in the bloodstream, helping cells metabolize food. While cells in our bodies contain the same DNA, different cells express different genes, depending on the cell’s function. Beta cells predominantly express genes that help them secrete insulin. When diabetes develops, the gene expression pattern in a beta cell changes, ultimately making the cell incapable of doing its job. Ph.D. scholar Mia Akerfeldt and Dr. Ross Laybutt from Sydney’s Garvan Institute of Medical Research have found that Id1 appears to be the master regulator of other genes in a beta cell, and it is “switched on” when people consume a high-fat diet. This finding was reported online on September 22, 2011, in the journal Diabetes. “We’re saying that Id1 is the molecular link between environmental factors, such as high-fat diet, and beta cell dysfunction,” said Dr Laybutt. “Not only does the presence of Id1 appear to initiate all the other gene expression changes that take place in dysfunctional beta cells, its absence completely protects the beta cell.

New Treatment for Leishmaniasis, a Deadly Parasitic Disease

East Africa is fighting the worst kala azar outbreak in a decade. Kala azar is another name given to visceral leishmaniasis (VL), a parasitic disease endemic in around 70 countries worldwide. South Sudan has the second highest number of cases after India. The disease is spread through the bite of a sandfly and is fatal without treatment. Approximately half a million people are infected with the disease and 50,000-60,000 die every year as a result of the infection. Patients suffer from irregular bouts of fever, substantial weight loss, swelling of the spleen and liver, and anemia. Collaboration across the East Africa region through the Leishmaniasis East Africa Platform (LEAP) has resulted in the development of a new combination therapy (SSG&PM) which is cheaper and nearly halves the length of treatment from a 30-day course of injections to 17 days. East African endemic countries are taking the necessary regulatory measures to use it in their programmes, but experts warn that without international funding or interest in supporting governments in the roll out, too few patients will benefit. “The poorest of the poor, in the most remote villages are the ones who are wasting away from kala azar and who could benefit the most from a shorter more affordable treatment,” said Dr. Monique Wasunna, Assistant Director, KEMRI, and Head, DNDi Africa. “Neglected diseases and patients mean that even when there are new treatments and hope, they are too far from the headlines and donor priorities to get support to governments.

September 22nd

First-Ever Multi-Cellular Model of Zellweger’s Syndrome

Research groups worldwide have tried to develop a simple model of a rare, fatal disease called Zellweger's syndrome but none has succeeded, until researchers at the Faculty of Medicine & Dentistry at the University of Alberta in Canada did so in fruit flies. Zellweger's syndrome is a form of peroxisome biogenesis disorder, a group of deadly genetic diseases that claim the lives of children usually before they reach their first birthday. Researchers have been stumped as to how to make a multi-cellular model they can use to develop treatments. The chair of the Department of Cell Biology, Dr. Richard Rachubinksi, and his Ph.D student Fred Mast, with the help of Drosophila expert Dr. Andrew Simmonds, have been successful in developing a model of Zellweger's syndrome. This syndrome is the most common type of peroxisome biogenesis disorder. "Mating two parents that have the mutated gene gave us a mutant fly that mimicked the human phenotype," said Dr. Rachubinski. The fruit fly is ideal for medical research because its development can be studied from fertilization through to adulthood, and the development is much more rapid than in mice or humans. "The periods that you can allow for development are much shorter in flies so you can look at things much more quickly," said Dr. Rachubinski. "You get two generations per month." It is also less expensive to use Drosophila. As the research group moves forward testing compounds that could be used as pharmaceuticals to treat Zellweger's syndrome, they only have to use minute amounts compared to what would be needed for other laboratory models.

Mayo Scientists Investigate Genetics of Responses to Measles Vaccine

Researchers at the Mayo Clinic are cracking the genetic code that controls the human response to disease vaccination, and they are using this new cipher to answer many of the deep-seated questions that plague vaccinology, including why patients respond so differently to identical vaccines and how to minimize the side effects of vaccination. Led by Dr. Gregory Poland, researchers in Mayo's Vaccine Research Group have published results of two genetic studies that identify mutations linked to immune response to the measles vaccine. The studies were published online (August 26 and August 27, 2011) in the journal Vaccine. "We are trying to understand, to the maximum extent possible, how a person's individual genetic makeup affects response to vaccination," says Dr. Poland. These and similar studies will likely allow physicians to prescribe appropriate doses and timing of vaccines based on routine genetic screening blood tests in the near future. Longer-reaching implications of the vaccine group's work include the development of more effective vaccines and, perhaps someday, the ability to construct personalized vaccines. "Vaccination is the single most important and far-reaching practice in medicine. By the time a child enters school in the United States, they have received upwards of 20 shots," says Dr. Poland. "In no other field of medicine do we do exactly the same thing to everyone — and we do it everywhere in the world." Doctors and epidemiologists have long been puzzled about the genetic underpinnings of the fact that up to 10 percent of recipients fail to respond to the first dose of the measles vaccine, while another 10 percent generate extremely high levels of measles antibodies. The remaining 80 percent fall somewhere in the middle.

September 21st

Genetic Overlap Found Between Schizophrenia and Bipolar Disorder

Knowledge about the biological origin of diseases like schizophrenia, bipolar disorder, and other psychiatric conditions is critical to improving diagnosis and treatment. In an effort to push the field forward, three UCLA researchers, along with scientists from more than 20 countries, have been taking part in one of the largest collaborative efforts in psychiatry — a genome-wide study involving more than 50,000 study participants aimed at identifying which genetic variants make people susceptible to psychiatric disease. This collaborative, the Psychiatric Genome-Wide Association Study Consortium (PGC), now reports, in two articles in the September 18, 2011 online edition of Nature Genetics, that it has discovered that common genetic variants contribute to a person's risk of schizophrenia and bipolar disorder. The PGC's studies provide new molecular evidence that 11 regions on the genome are strongly associated with these diseases, including six regions not previously observed. The researchers also found that several of these DNA variations contribute to both diseases. The findings, the researchers say, represent a significant advance in understanding the causes of these chronic, severe, and debilitating disorders. The UCLA researchers who contributed to the schizophrenia study are Dr. Roel A. Ophoff, a professor of psychiatry and human genetics and one of the founding principal investigators of the schizophrenia portion of the study; Dr. Nelson Freimer, a professor of psychiatry and director of the Center for Neurobehavioral Genetics at the Semel Institute for Neuroscience and Human Behavior at UCLA; and Dr. Rita Cantor, a professor of psychiatry and human genetics. Schizophrenia and bipolar disorder are common and often devastating brain disorders.