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Archive - 2011

October 18th

Two New Bee Species May Shed Light on Panama’s History

Smithsonian scientists have discovered two new, closely related bee species: one from Coiba Island in Panama and another from northern Colombia. Both descended from of a group of stingless bees that originated in the Amazon and moved into Central America, the ancestors of Mayan honeybees. The presence of one of these new species on Coiba and Rancheria Islands, and its absence from the nearby mainland, is a mystery that may ultimately shed light on Panama's history and abundant biodiversity. The new findings were published online on September 8, 2011 in Systematic Entomology. At almost 200 square miles, Coiba Island is the largest offshore island along the Pacific coast of Latin America. Rancheria Island is a much smaller neighbor. The species name, insularis, of the new bee from Coiba, Melipona insularis, means "island." This is the first species in its group to be found on islands near the mainland. "These forest bees have a small range over which they can establish new nests and colonies," says Dr. David Roubik, staff scientist at the Smithsonian Tropical Research Institute. "They can't establish a new nest across more than a short stretch of open water because workers from the original nest have to build and supply the new nest before the new queen moves in." Either several entire tree-cavity nests arrived on Coiba and Rancheria in floating mats of vegetation or a land connection existed between the island and the mainland before the bees disappeared from the mainland. Sea level has risen and fallen dramatically in the past. During ice ages, when much of the Earth's water is locked up in polar caps and glaciers, sea level drops in Panama.

First Phase III Results Suggest Promise of New Malaria Vaccine

First results from a large-scale Phase III trial of RTS,S, published online on October 18, 2011 in the New England Journal of Medicine (NEJM), show the malaria vaccine candidate to provide young African children with significant protection against clinical and severe malaria with an acceptable safety and tolerability profile. The results were announced today at the Malaria Forum hosted by the Bill & Melinda Gates Foundation in Seattle, Washington. Half the world's population is at risk of malaria. The disease is responsible for close to 800,000 deaths each year, most of whom are children under five in sub-Saharan Africa The trial, conducted at eleven trial sites in seven countries across sub-Saharan Africa, including a University of North Carolina-led site in Lilongwe, Malawi, showed that three doses of RTS,S reduced the risk of children experiencing clinical malaria and severe malaria by 56 percent and 47 percent, respectively. This analysis was performed on data from the first 6,000 children aged 5 months to 17 months, over a 12-month period following vaccination. Clinical malaria results in high fevers and chills. It can rapidly develop into severe malaria, typified by serious effects on the blood, brain, or kidneys that can prove fatal. These first Phase III results are in line with those from previous Phase II studies. The widespread coverage of insecticide-treated bed nets (75 percent) in this study indicated that RTS,S can provide protection in addition to that already offered by existing malaria control interventions. The trial is ongoing and efficacy and safety results in 6 week- old to 12 week-old infants are expected by the end of 2012. These data will provide an understanding of the efficacy profile of the RTS,S malaria vaccine candidate in this age group, for both clinical and severe malaria.

First-Ever Sequence of a Particular Biologically Important Complex Carbohydrate

If genes provide the blueprint for life and proteins are the machines that do much of the work for cells, then carbohydrates that are linked to proteins are among the tools that enable cells to communicate with the outside world and each other. But until now, scientists have been unable to determine the structure of a biologically important so-called GAG proteoglycan-or even to agree whether these remarkably complex molecules have well-defined structures. In a paper published online on October 9, 2011 in the journal Nature Chemical Biology, however, a team of scientists from the University of Georgia (UGA), Rensselaer Polytechnic Institute, and Chiba University in Japan announced that it has, for the first time, determined the sequence and structure of a glycosaminoglycan, or GAG, proteoglycan. "The fact that a structure even exists is surprising, because people had the sense that the complexity of these molecules pointed to a randomness," said study co-author Dr. Jonathan Amster, professor and head of the department of chemistry in the UGA Franklin College of Arts and Sciences. "There are many different areas in medicine that will be enabled by understanding carbohydrates at this fundamental level." Modifications to the GAG, or carbohydrate biopolymer, portion of proteoglycans have been associated with the presence and malignancy of certain cancers, for example, and the researchers noted that the identification of carbohydrates that are involved in disease opens the door to the development of drugs that can block their action. The field of glycobiology is still in its infancy, largely because attempts to sequence proteoglycans have, until now, ended in frustration and failure.

October 17th

Common RNA Modification Linked to Obesity and Type II Diabetes

An international research team has discovered that a pervasive human RNA modification provides the physiological underpinning of the genetic regulatory process that contributes to obesity and type II diabetes. European researchers previously showed, in 2007, that the FTO gene was the major gene associated with obesity and type II diabetes, but the details of the gene’s physiological and cellular functioning remained unknown. Now, a team led by University of Chicago chemistry professor Dr. Chuan He has demonstrated experimentally the importance of a reversible RNA modification process mediated by the FTO protein upon biological regulation. Dr. He and ten co-authors from Chicago, China and England published the details of their findings in the October 16, 2011 advance online edition of Nature Chemical Biology. Dr. He and his colleagues have shown, for the first time, the existence of the reversible RNA modification process — called methylation — and that it potentially impacts protein expression and function through its action on a common RNA base: adenosine. The process is reversible because it can involve the addition or removal of a methyl group from adenosine. The team found that the FTO protein mediates cellular removal of the methyl group. "An improved understanding of the normal functions of FTO, as exemplified by this work, could aid the development of novel anti-obesity therapies," said Dr. Stephen O'Rahilly, professor of clinical biochemistry and director of the Metabolic Research Laboratories at the University of Cambridge. Dr. O'Rahilly, a leading researcher in obesity and metabolic disease who also has studied FTO, was not directly involved in Dr. He's project.

October 14th

Vast New Regulatory Network Discovered in Mammalian Cells

Researchers at Columbia University Medical Center (CUMC) and other institutions have uncovered a vast new gene regulatory network in mammalian cells that could explain genetic variability in cancer and other diseases. Four studies bearing on this new regulatory network appear in the October 14, 2011 issue of Cell. "The discovery of this regulatory network fills in a missing piece in the puzzle of cell regulation and allows us to identify genes never before associated with a particular type of tumor or disease," said Dr. Andrea Califano, professor of systems biology, director of the Columbia Initiative in Systems Biology, and senior author of the CUMC research team’s article. For decades, scientists have thought that the primary role of messenger RNA (mRNA) is to shuttle information from the DNA to the ribosomes, the sites of protein synthesis. However, these new studies suggest that the mRNA of one gene can control, and be controlled by, the mRNA of other genes via a large pool of microRNA molecules, with dozens to hundreds of genes working together in complex self-regulating sub-networks. The findings have the potential to broaden investigations into how tumors develop and grow, who is at risk for cancer, and how to identify and inactivate key molecules that encourage the growth and spread of cancer. For example, in the case of the phosphatase and tensin homolog gene (PTEN), a major tumor suppressor, deletions of its mRNA network regulators in patients appear to be as damaging as mutations of the gene itself in several types of cancer, the studies show. The newly identified regulatory network (called the mPR network by the CUMC investigators) allows mRNAs to communicate through small bits of RNA called microRNAs.

Innate Immune Response Illuminated by New Study of RIG-I

When a thief breaks into a bank vault, sensors are activated and the alarm is raised. Cells have their own early-warning system for intruders, and scientists at the European Molecular Biology Laboratory (EMBL) in Grenoble, France, have discovered how a particular protein sounds that alarm when it detects invading viruses. The study, published in the October 14, 2011 issue of Cell, is a key development in our understanding of the innate immune response, shedding light on how cells rapidly respond to a wide range of viruses including influenza, rabies, and hepatitis. To sense invading agents, cells use proteins called pattern recognition receptors, which recognize and bind to molecular signatures carried only by the intruder. This binding causes the receptors to change shape, starting a chain-reaction that ultimately alerts the surrounding cells to the invasion. How these two processes ¬– sensing and signalling – are connected, has until now remained unclear. The EMBL scientists have now discovered the precise structural mechanism by which one of these receptors, RIG-I, converts a change of shape into a signal. “For a structural biologist, this is a classic question: how does ligand binding to a receptor induce signalling?” says Dr. Stephen Cusack, who led the work. “We were particularly interested in answering it for RIG-I, as it targets practically all RNA viruses, including influenza, measles, and hepatitis C.” In response to a viral infection, RIG-I recognizes viral genetic material – specifically, viral RNA – and primes the cell to produce the key anti-viral molecule, interferon. Interferon is secreted and picked up by surrounding cells, causing them to turn on hundreds of genes that act to combat the infection.

October 13th

Black Death Genome Reconstructed; Likely Ancestor of All Modern Plague

An international team, led by researchers at McMaster University in Canada and the University of Tubingen in Germany, has sequenced the entire genome of the organism causing the Black Death, one of the most devastating epidemics in human history. This marks the first time that scientists have been able to draft a reconstructed genome of any ancient pathogen, and it should allow researchers to track changes in the pathogen’s evolution and virulence over time. This new work, published online on October 12, 2011 in Nature, could lead to a better understanding of modern infectious diseases. Geneticists Hendrik Poinar and Kirsten Bos of McMaster University and Johannes Krause and Verena Schuenemann of the University of Tubingen collaborated with Brian Golding and David Earn of McMaster University, Hernan A. Burbano and Matthias Meyer of the Max Planck Institute for Evolutionary Anthropology, and Sharon DeWitte of the University of South Carolina, among others. In a separate study published recently, the team described a novel method to extract tiny degraded DNA fragments of the causative agent of the Black Death, and showed that a specific variant of the Yersinia pestis bacterium was responsible for the plague that killed 50 million Europeans between 1347 and 1351. After this success, the next major step was to “capture” and sequence the entire bacterial genome, explains Dr. Poinar, associate professor of anthropology and director of the McMaster Ancient DNA Centre and an investigator with the Michael G. DeGroote Institute of Infectious Disease Research, also at McMaster University. “The genomic data show that this bacterial strain, or variant, is the ancestor of all modern plagues we have today worldwide. Every outbreak across the globe today stems from a descendant of the medieval plague,” he says.

Schizophrenia Genetics Linked to Disruption in How Brain Processes Sound

Recent studies have identified many genes that may put people at risk for schizophrenia. But what links genetic differences to changes in altered brain activity in schizophrenia is not clear. Now, three laboratories at the Perelman School of Medicine at the University of Pennsylvania have come together, using electrophysiological, anatomical, and immunohistochemical approaches - along with a unique high-speed imaging technique - to understand how schizophrenia works at the cellular level, especially in identifying how changes in the interaction between different types of nerve cells lead to symptoms of the disease. The findings were reported online on October 3, 2011 in the Proceedings of the National Academy of Sciences. "Our work provides a model linking genetic risk factors for schizophrenia to a functional disruption in how the brain responds to sound, by identifying reduced activity in special nerve cells that are designed to make other cells in the brain work together at a very fast pace," explains lead author Dr. Gregory Carlson, assistant professor of Neuroscience in Psychiatry. "We know that in schizophrenia this ability is reduced, and now, knowing more about why this happens may help explain how loss of a protein called dysbindin leads to some symptoms of schizophrenia." Previous genetic studies had found that some different forms of the gene for dysbindin were found in people with schizophrenia. Most importantly, a prior finding at Penn showed that the dysbindin protein is reduced in a majority of schizophrenia patients, suggesting it is involved in a common cause of the disease. For the current PNAS study, Dr. Carlson, Dr. Steven J. Siegel, associate professor of Psychiatry, director of the Translational Neuroscience Program; and Dr. Steven E.

Breakthrough Approach to Allergy Treatment

Researchers from the University of Notre Dame and Harvard University have announced a breakthrough approach to allergy treatment that inhibits food allergies, drug allergies, and asthmatic reactions without suppressing a sufferer's entire immunological system. The therapy centers on a special molecule the researchers designed, a heterobivalent ligand (HBL), which when introduced into a person's bloodstream can, in essence, out-compete allergens like egg or peanut proteins in the race to attach to mast cells, a type of white blood cell that is the source of type-I hypersensitivity (that is, allergy). The new work is published as the cover article of the September 23, 2011 issue of Chemistry & Biology. "Unlike most current treatments, this approach prevents allergic reactions from occurring in the first place," says Dr. Basar Bilgicer, senior author of the paper and assistant professor of Chemical and Biomolecular Engineering and Chemistry and Biochemistry and principal investigator in Notre Dame's Advanced Diagnostics & Therapeutics initiative. Michael Handlogten, lead author on the paper and a graduate student in Dr. Bilgicer's group, explained that among the various chemical functionalities he analyzed to be used as the scaffold in HBL synthesis, ethylene glycol, an FDA-approved molecule, proved to be the most promising. Mast cells are part of the human body's defense against parasites (such as tapeworms), and, when working normally, they are attracted to, attach to, and annihilate these pathogens. But type-I hypersensitivity occurs when the cells react to non-threatening substances. More common allergies are due to ambient stimulants, and an allergic response may range from a mild itch to life-threatening anaphylactic shock. Dr.

October 12th

Naked Mole Rat Genome Sequenced; Clues to Longevity Sought

Scientists have sequenced the complete genome of the naked mole rat, a pivotal step to understanding the animal's extraordinarily long life and good health. A colony of more than 2,000 naked mole rats at The University of Texas (UT) Health Science Center at San Antonio contributed to the findings, published online on October 12, 2011 in the journal Nature. "If we understand which genes are different or are expressed differently in naked mole rats — compared to short-lived mice that clearly have poor defenses against aging and cancer — we might find clues as to why the naked mole rat is able to extend both health span and longevity, as well as fight cancer, and this information could be directly relevant and translatable to humans," said Dr. Rochelle Buffenstein, professor of physiology at the Barshop Institute for Longevity and Aging Studies, part of the UT Health Science Center San Antonio. Dr. Buffenstein worked on the study with Dr. Thomas Park, of the University of Chicago; Dr. Vadim Gladyshev, of Harvard Medical School; scientists at the Beijing Genomics Institute; and other collaborators. The mouse-sized naked mole rat is the longest-lived rodent known, surviving up to 31 years in captivity. This is much longer than its laboratory rodent relatives, and the naked mole rat maintains good health and reproductive potential well into its third decade. Naked mole rats live underground in large family groups, like termites and bees, with only a single breeding female. These social rodents are extremely tolerant of life in low oxygen and high levels of carbon dioxide. The naked mole rat's capacity to resist cancer and maintain protein integrity in the face of oxidative damage makes it an ideal animal model for aging and biomedical research, Dr. Buffenstein said.