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Archive - 2011

October 12th

Diabetes Advance: Scientists Breathe New Life into Aging Beta Cells

As a person ages, the ability of his or her beta cells to divide and make new beta cells declines. By the time children reach the age of 10 to 12 years, the ability of these insulin-producing cells to replicate greatly diminishes. If these beta cells are destroyed—as they are in type 1 diabetes—treatment with the hormone insulin becomes essential to regulate blood glucose levels and allow energy to be obtained from food. Now, longtime JDRF (Juvenile Diabetes Research Foundation)-funded researchers at Stanford University have identified a pathway responsible for this age-related decline, and have shown that they can manipulate it to make older beta cells act young again—and start dividing. The research, published online on October 12, 2011 in Nature, provides the most complete picture to date of the molecular and biochemical mechanisms that bring beta cell regeneration to a near halt as beta cells age. These findings may help pave a path for developing strategies to restore beta cell number to treat both type 1 and type 2 diabetes. In their study, the researchers, led by Dr. Seung Kim of Stanford University, found that a protein called PDGF, or platelet-derived growth factor, and its receptor send beta cells signals to start dividing via an intricate pathway that controls the levels of two proteins in the beta cell nucleus, where cell division is orchestrated. Working with young mice, Dr. Kim and his team found that PDGF binds to its receptor on the beta cell's surface and controls the level of these regulating proteins allowing cells to divide. However, in older mice, they discovered that beta cells lose PDGF receptors, and that this age-related change prevents beta cells from dividing. Dr.

First Practical Test to Date and Authenticate Priceless Silk Treasures

Scientists are reporting development of the first fast and reliable scientific method to determine the age and authenticity of priceless silk tapestries and other silk treasures -- such as Civil War General Phillip Sheridan's famous red-and-white battle flag -- in museums and other collections around the world. A report on the work appears in the October 1, 2011 issue of the American Chemical Society’s journal Analytical Chemistry. Dr. Mehdi Moini and colleagues at the Smithsonian Institution point out that for thousands of years, silk fibers, consisting of natural protein unwound from the cocoons of the silkworm, have been woven into not just garments, but wall hangings, tapestries, carpets, and painted silk artworks. Until now, however, there has been no practical scientific way to tell whether a silk tapestry is a well-preserved example from the Fontainebleu series from the 1540s or a copy made just last week. In many cases, scientists could not use the familiar carbon-14 dating process, because it involves taking samples of material large enough to cause visible damage to the silk object. The scientists’ solution is a new test that tracks time-related deterioration of the amino acid building blocks in silk protein. As silk ages, the so-called L-amino acids in its protein change into so-called D-amino acids. The D/L ratio provides a highly accurate measure of a silk object's age, to within 50-100 years, and indicates whether it is deteriorating and needs conservation work. Archaeologists have previously used the D/L approach to date ancient teeth and bone, but Dr. Moini's team simplified the technique and adapted it for silk. The researchers demonstrated the test, called "CE-MS," on Sheridan's flag, a Fontainebleu tapestry, ancient silks from China, and other old samples from masterpieces in museums around the world.

October 11th

Most Vertebrates Descended from Ancestor with Sixth Sense

People experience the world through five senses, but sharks, paddlefishes, and certain other aquatic vertebrates have a sixth sense: they can detect weak electrical fields in the water and use this information to detect prey, communicate, and orient themselves. A study published online on October 11, 2011 in Nature Communications caps more than 25 years of work and finds that the vast majority of vertebrates – some 30,000 species of land animals (including humans) and a roughly equal number of ray-finned fishes – descended from a common ancestor that had a well-developed electroreceptive system. This ancestor was probably a predatory marine fish with good eyesight, jaws, and teeth, and a lateral line system for detecting water movements, visible as a stripe along the flank of most fishes. It lived around 500 million years ago. The vast majority of the approximately 65,000 living vertebrate species are its descendants. "This study caps questions in developmental and evolutionary biology, popularly called 'evo-devo,' that I've been interested in for 35 years," said Dr. Willy Bemis, Cornell professor of ecology and evolutionary biology and a senior author of the paper. Dr. Melinda Modrell, a neuroscientist at the University of Cambridge who did the molecular analysis, is the paper's lead author. Hundreds of millions of years ago, there was a major split in the evolutionary tree of vertebrates. One lineage led to the ray-finned fishes, or actinopterygians, and the other to lobe-finned fishes, or sarcopterygians; the latter gave rise to land vertebrates, Dr. Bemis explained. Some land vertebrates, including such salamanders as the Mexican axolotl, have electroreception and, until now, offered the best-studied model for early development of this sensory system.

Personalized Medicine Advance: Protein Level Test and Related Treatment Help Reduce Risk of Death Over Specified Period in Certain Patients with Advanced Lung Cancer

Researchers at the University of Colorado Cancer Center have developed a test that identifies a key biomarker in advanced lung cancer that helped reduce the risk of death by 36 percent over a 30- month period in a recent clinical trial. "We are moving from a one-size-fits-all model to more personalized medicine in lung cancer," said University of Colorado School of Medicine Professor Fred R. Hirsch, a Cancer Center investigator who developed the test along with colleague Dr. Wilbur Franklin. "This is a completely new paradigm in treating cancer." The test was developed in 2003 when Dr. Hirsch and his colleagues created a scoring system ranging from 0 to 400 that identified patients with the highest levels of the protein Epidermal Growth Factor Receptor (EGFR). Those scoring over 200 had a better prognosis. A clinical trial held in Europe known as the FLEX-study, found that 30 percent of the advanced lung cancer patients who took part had high levels of the EGFR protein identified by the University of Colorado Cancer Center test. The trial consisted of 1,125 advanced lung cancer patients separated into two groups. One group received standard chemotherapy while the other had chemotherapy along with the drug cetuximab, an antibody that attaches to EGFR receptors atop lung cancer cells and often inhibits their growth. The results were announced at the 2011 European Multidisciplinary Cancer Conference in Stockholm. Using the Cancer Center test, the trial showed that Caucasian patients with an over expression of EGFR and treated with chemotherapy and cetuximab had a 36 percent reduction in deaths compared to the other group. Cetuximab, or Erbitux, is primarily used to fight colo-rectal and head and neck cancers. Dr.

New Review of TAL Effector Proteins Published in Science

In the two years since Iowa State University's Dr. Adam Bogdanove, along with student Matthew Moscou, published their groundbreaking gene research in the cover story of the journal Science, researchers around the world have built on those findings to explore further breakthroughs. Science has published another article by Dr. Bogdanove in its September 30, 2011 issue that updates the scientific community on where the research has been since 2009 and where it is heading. "In the past two years, an extraordinary number of things have happened in this field," said Dr. Bogdanove, a professor of plant pathology. "This is really pretty revolutionary." Dr. Bogdanove's research published in 2009 uncovered how so-called TAL (transcription activator-like) effector proteins bind to different DNA locations, and how particular amino acids in each protein determine those locations -- called binding sites -- in a very straightforward way. Knowing this, scientists are using the proteins to target and manipulate specific genes, something that was much more difficult to accomplish prior to this research. That could lead to breakthroughs in understanding gene function and improving traits in livestock and plants, and even treating human genetic disorders, according to Dr. Bogdanove. He says that in the two years since his and Moscou's work was published, nearly two dozen research papers have been published using this discovery. "We are so excited about the potential of these proteins. Just in the past six months, they have been used successfully in model organisms such as yeast, zebrafish, and C. elegans, and even in human stem cells. There is some really innovative stuff going on," he said. Dr. Bogdanove collaborated on this Science article with Dr.

October 10th

Loss of a Sialic Acid May Have Increased Disease Protection and Influenced Evolution of Early Man

Researchers at the University of California, San Diego School of Medicine say that losing the ability to make a particular kind of sugar molecule boosted disease protection in early hominids, and may have directed the evolutionary emergence of our ancestors, the genus Homo. The findings, published online on October 10, 2011 in the Proceedings of the National Academy of Sciences, are among the first to show a novel link between cell surface sugars, Darwinian sexual selection, and immune function in the context of human origins. Sialic acids are sugar molecules found on the surfaces of all animal cells, where they serve as vital contact points for interaction with other cells and with the surrounding environment, including as targets for invasive pathogens. For millions of years, the common ancestors of humans and other apes shared a particular kind of sialic acid known as N-glycolylneuraminic acid or Neu5Gc. Then, for reasons possibly linked to a malarial parasite that bound Neu5Gc, a gene mutation three million or so years ago inactivated the human enzyme involved in making the molecule. Instead, humans began producing more of a slightly different form of sialic acid called Neu5Ac, the precursor of Neu5Gc. "This occurred at about the same time as early humans were apparently becoming major predators in their environment," said Dr. Pascal Gagneux, an evolutionary biologist and associate professor of cellular and molecular medicine at UC San Diego. "It's hard to be sure exactly what happened because evolution works on so many things simultaneously, but the change in sialic acid meant that early humans developed an immune response to Neu5Gc. It became viewed by their immune systems as foreign, something to be destroyed.

October 7th

New Imaging Agents May Enable Early Visualization of Cancer

A series of novel imaging agents could make it possible to "see" tumors in their earliest stages, before they turn deadly. The compounds, derived from inhibitors of the enzyme cyclooxygenase-2 (COX-2) and detectable by positron emission tomography (PET) imaging, may have broad applications for cancer detection, diagnosis, and treatment. Vanderbilt University investigators describe the new imaging agents in a paper featured on the cover of the October 2011 issue of Cancer Prevention Research. "This is the first COX-2-targeted PET imaging agent validated for use in animal models of inflammation and cancer," said Dr. Lawrence Marnett, director of the Vanderbilt Institute of Chemical Biology and leader of the team that developed the compounds. COX-2 is an attractive target for molecular imaging. It's not found in most normal tissues, and then it is "turned on" in inflammatory lesions and tumors, Dr. Marnett explained. "As a tumor grows and becomes increasingly malignant, COX-2 levels go up," Dr. Marnett said. To develop compounds that target COX-2 and can be detected by PET imaging, Dr. Jashim Uddin, research assistant professor of biochemistry, started with the "core" chemical structures of the anti-inflammatory medicines indomethacin and celecoxib and modified them to add the element fluorine in various chemical configurations. After demonstrating that the fluorinated compounds were selective inhibitors of COX-2, the investigators incorporated radioactive fluorine (18-F) into the most promising compound. Intravenous injection of this 18-F compound into animal models provided sufficient signal for PET imaging. The researchers demonstrated the potential of this 18-F compound for in vivo PET imaging in two animal models: irritant-induced inflammation in the rat footpad and human tumors grafted into mice.

Potential New Targets for Treatment of Inflammatory and Autoimmune Diseases

Researchers have discovered a cellular pathway that promotes inflammation in diseases like asthma, rheumatoid arthritis, psoriasis, inflammatory bowel disease, and multiple sclerosis. Understanding the details of this pathway may provide opportunities for tailored treatments of inflammatory and autoimmune diseases. Discovery of this pathway was the work of an active collaboration between Dr. Xiaoxia Li and Dr. Thomas Hamilton, Department Chair, both of the Department of Immunology at Lerner Research Institute of the Cleveland Clinic. Their two publications in the September 2011 issue of Nature Immunology, selected for a News and Views article in the same issue, portray how a protein molecule known as interleukin-17 (IL-17) spurs inflammation by recruiting specific white blood cells to sites of infection and injury, producing a strong, pathogenic response. Being able to block this pathway may allow treatment of IL-17-induced inflammatory diseases. Molecular factors discovered by Drs. Li and Hamilton make this concept a potential strategy. "We are excited by the possibilities that this new research opens up for developing improved therapeutics for these difficult diseases," Dr. Hamilton said. "Being able to collaborate like this really expedites the science," Dr. Li added, "ultimately leading, we hope, to profound improvement for those suffering from these autoimmune and inflammatory conditions." [Press release] [Nature Immunology abstract 1] [Nature Immunology abstract 2] [Nature Immunology News & Views article]

Study Confirms Genetic Link to Suicidal Behavior

A new study from the Centre for Addiction and Mental Health in Canada has found evidence that a specific gene is linked to suicidal behaviour, adding to our knowledge of the many complex causes of suicide. This research may help doctors one day target the gene in prevention efforts. In the past, studies have implicated the gene for brain-derived neurotrophic factor (BDNF) in suicidal behaviour. BDNF is involved in the development of the nervous system. After pooling results from eleven previous studies and adding their own study data involving people with schizophrenia, CAMH scientists confirmed that among people with a psychiatric diagnosis, those with the methionine ("met") variation of the BDNF gene had a higher risk of suicidal behavior compared to those with the valine variation. The review, published online on August 30, 2011 in the International Journal of Neuropsychopharmacology, included data from 3,352 people, of whom 1,202 had a history of suicidal behavior. The news coincides with Mental Illness Awareness Week, October 2-8, and World Mental Health Day, October 10. "Our findings may lead to the testing and development of treatments that target this gene in order to help prevent suicide," says Dr. James Kennedy, director of CAMH's Neuroscience Research Department. "In the future, if other researchers can replicate and extend our findings, then genetic testing may be possible to help identify people at increased risk for suicide." As the low-functioning BDNF met variation is a risk factor for suicidal behavior, it may also be possible to develop a compound to increase BDNF functioning, Dr. Kennedy says. About 90 percent of people who have died by suicide had at least one mental health disorder, the researchers note.

September 29th

Australian Tree Frogs Endure Cold to Collect Precious Water

Research published in the October issue of The American Naturalist shows that Australian green tree frogs survive the dry season with the help of the same phenomenon that fogs up eyeglasses in the winter. According to researchers from Charles Darwin University in Australia, tree frogs often plop themselves down outside on cool nights during the dry season in tropical Australia. When they return to their dens, condensation forms on their cold skin—just like it does on a pair of glasses when we come in from the cold. The researchers found that frogs absorb this moisture through their skin, which helps to keep them hydrated during periods of little or no rain. Before this study, the frogs' dry-season excursions were a bit mysterious. "Every once in a while, we would find frogs sitting on a stick under the open sky, on nights when it was so cold they could barely move," said Dr. Chris Tracy, who led the research. "It was a real puzzle." Dr. Tracy and his colleagues thought this behavior might enable the frogs to collect condensation, but the hypothesis had never been tested. The researchers designed a series of experiments using real frog dens in eucalyptus trees and artificial ones made from PVC pipe. They wanted to see if the frogs could collect enough moisture through condensation to compensate for what they lost being in the cold. They found that a cold night out cost a frog as much as .07 grams of water. However, a frog could gain nearly .4 grams, or nearly 1 percent of its total body weight, in water upon returning to the warm den. The researchers also tested how well a frog's skin could absorb water, and found that as much as 60 percent of each water drop could be absorbed. The results show that frogs can use condensation to hydrate themselves.