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March 29th, 2011

Cancer Drug Gleevec Shows Promise for Treating Sclerodoma

A drug approved to treat certain types of cancer has shown promising results in the treatment of patients with scleroderma, according to results from an open-label Phase II trial. While the drug's efficacy must be demonstrated in a Phase III trial, the gold standard for testing a drug, researchers are optimistic that Gleevec (imatinib) could potentially be a weapon against the chronic connective tissue disease for which a treatment has remained elusive. "This trial showed Gleevec has acceptable safety and tolerability, and there are hints of efficacy or suggestions the drug may work," said Robert Spiera, M.D., an associate attending rheumatologist at Hospital for Special Surgery who led the study. "This study strongly suggests that a randomized placebo-controlled trial is warranted." The study appeared online on March 11, 2011, in Annals of the Rheumatic Diseases. Systemic scleroderma affects not only the skin, but also underlying blood vessels, and often muscles and joints, as well as the gastrointestinal tract, kidneys, lungs and heart. According to the Scleroderma Foundation, roughly 300,000 individuals have scleroderma in the United States and roughly a third of these have the systemic kind. The disease typically strikes in the prime of patients' lives, when they are 30-50 years old. To date, there has never been a drug that has been shown to be effective for scleroderma. For the study, investigators at Hospital for Special Surgery enrolled 30 patients with diffuse scleroderma, a widespread severe form of the disease, and gave them 400 mg of Gleevec per day. Patients were evaluated monthly for 12 months during treatment and were seen for follow-up three months after discontinuing the drug.

New Imaging Capability for Chemical Mapping of Nanoscale Materials

Scientists at Berkeley Lab’s Molecular Foundry and colleagues have pioneered a new chemical mapping method that provides unprecedented insight into materials at the nanoscale. Moving beyond traditional static imaging techniques, which provide a snapshot in time, these new maps will guide researchers in deciphering molecular chemistry and interactions at the nanoscale—critical for artificial photosynthesis, biofuels production, and light-harvesting applications such as solar cells. “This new technique allows us to capture very high-resolution images of nanomaterials with a huge amount of physical and chemical information at each pixel,” said Dr. Alexander Weber-Bargioni, a postdoctoral scholar in the Imaging and Manipulation of Nanostructures Facility at the Foundry. “Usually when you take an image, you just get a picture of what this material looks like, but nothing more. With our method, we can now gain information about the functionality of a nanostructure with rich detail.” The Molecular Foundry is a U.S. Department of Energy (DOE) Office of Science nanoscience center and national user facility. With the Foundry’s state-of-the-art focused ion beam tool at its disposal, Dr. Weber-Bargioni and his team designed and fabricated a coaxial antenna capable of focusing light at the nanoscale, – a harnessing of light akin to wielding a sharp knife in a thunderstorm, Dr. Weber-Bargioni said. Consisting of gold wrapped around a silicon nitride atomic force microscope tip, this coaxial antenna serves as an optical probe for structures with nanometer resolution for several hours at a time. What’s more, unlike other scanning probe tips, it provides enough enhancement, or light intensity, to report the chemical fingerprint at each pixel while collecting an image (typically 256 pixels x 256 pixels).

March 28th

Scientists ID Gene Region Associated with Attempted Suicide

A genome-wide association study of thousands of people with bipolar disorder suggests that genetic risk factors may influence the decision to attempt suicide. Johns Hopkins scientists and an international team of collaborators, reporting online on March 22, 2011, in the journal Molecular Psychiatry, have identified a small region on chromosome 2 that is associated with increased risk for attempted suicide. This small region contains four genes, including the ACP1 gene, and the researchers found above normal levels of the ACP1 protein in the brains of people who had committed suicide. This protein is thought to influence the same biological pathway as lithium, a medication known to reduce the rate of suicidal behavior. The researchers said the findings could lead to better suicide prevention efforts by providing new directions for research and drug development. "We have long believed that genes play a role in what makes the difference between thinking about suicide and actually doing it," said study leader Dr. Virginia L. Willour, Ph.D., an assistant professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine. Dr. Willour and her colleagues studied DNA samples from nearly 2,700 adults with bipolar disorder, 1,201 of them with a history of suicide attempts and 1,497 without. They found that those with one copy of a genetic variant in the region of chromosome 2 where ACP1 is located were 1.4 times more likely to have attempted suicide, and those with two copies were almost 3 times as likely. Dr. Willour and her colleagues were able to replicate their findings in another group of samples: This one comprised DNA from more than 3,000 people with bipolar disorder.

New Nano-Based Device Can Detect Single Cancer Cells

A Harvard bioengineer and an MIT aeronautical engineer have created a new device that can detect single cancer cells in a blood sample, potentially allowing doctors to quickly determine whether cancer has spread from its original site. The microfluidic device, described in the March 17, 2011 online edition of the journal Small, is about the size of a dime, and might also detect viruses such as HIV. It could eventually be developed into low-cost tests for doctors to use in developing countries where expensive diagnostic equipment is hard to come by, said Dr. Mehmet Toner, professor of biomedical engineering at Harvard Medical School and a member of the Harvard-MIT Division of Health Sciences and Technology. Dr. Toner built an earlier version of the device four years ago. In that original version, blood taken from a patient flows past tens of thousands of tiny silicon posts coated with antibodies that stick to tumor cells. Any cancer cells that touch the posts become trapped. However, some cells might never encounter the posts at all. Dr. Toner thought if the posts were porous instead of solid, cells could flow right through them, making it more likely they would stick. To achieve that, he enlisted the help of Dr. Brian Wardle, an MIT associate professor of aeronautics and astronautics, and an expert in designing nano-engineered advanced composite materials to make stronger aircraft parts. Out of that collaboration came the new microfluidic device, studded with carbon nanotubes, that collects cancer cells eight times better than the original version. Circulating tumor cells (cancer cells that have broken free from the original tumor) are normally very hard to detect, because there are so few of them — usually only several cells per 1-milliliter sample of blood, which can contain tens of billions of normal blood cells.

Plant Pathologists ID Key Metabolite in Systemic Immunity

University of Kentucky plant pathologists recently discovered a metabolite that plays a critical role early on in the ability of plants, animals, humans and one-celled microorganisms to fend off a wide range of pathogens at the cellular level, which is known as systemic immunity. This mode of resistance has been known for more than 100 years, but the key events that stimulate that resistance have remained a mystery. The findings of the UK College of Agriculture researchers, led by Dr. Pradeep Kachroo and Dr. Aardra Kachroo, were published online in Nature Genetics on March 27, 2011. Researchers from the UK Department of Statistics and Washington State University also contributed to the article. "If you can generate systemic immunity, you can have great benefits in disease resistance," Dr. Kachroo said. "It is particularly gratifying to be able to describe a mechanism for a type of immunity; pioneering studies were incidentally carried out by our own emeritus faculty, Joe Kuc." Using soybeans and Arabidopsis, a model laboratory plant, the scientists were able to identify the metabolite glycerol-3-phosphate as a key mobile regulator of systemic immunity. A metabolite is a substance produced in the body through normal metabolic processes. The glycerol-3-phosphate is transformed into an unknown compound and uses a protein, called DIR1 to signal systemic immunity. Scientists already identified the protein as a necessary component to trigger systemic immunity. "The metabolite and protein are dependent on each other to transport immunity from one location in the plant tissue to the other," Dr. Kachroo said. "Metabolite levels increase in plant tissues after the plant has been inoculated by a pathogen." While the research was conducted on plants, Dr.

Infrared Light Activates Heart and Ear Cells; Great Clinical Potential

University of Utah scientists and colleagues have used invisible infrared light to make rat heart cells contract and toadfish inner-ear cells send signals to the brain. The discovery someday might improve cochlear implants for deafness and lead to devices to restore vision, maintain balance and treat movement disorders like Parkinson's. "We're going to talk to the brain with optical infrared pulses instead of electrical pulses," which now are used in cochlear implants to provide deaf people with limited hearing, said Dr. Richard Rabbitt, a professor of bioengineering and senior author of the heart-cell and inner-ear-cell studies published in the March 15, 2011 issue of The Journal of Physiology. The studies also raise the possibility of developing cardiac pacemakers that use optical signals rather than electrical signals to stimulate heart cells. But Rabbitt says that because electronic pacemakers work well, "I don't see a market for an optical pacemaker at the present time." The scientific significance of the studies is the discovery that optical signals – short pulses of an invisible wavelength of infrared laser light delivered via a thin, glass optical fiber – can activate heart cells and inner-ear cells related to balance and hearing. In addition, the research showed infrared activates the heart cells, called cardiomyocytes, by triggering the movement of calcium ions in and out of mitochondria, the organelles or components within cells that convert sugar into usable energy. The same process appears to occur when infrared light stimulates inner-ear cells. Infrared light can be felt as heat, raising the possibility the heart and ear cells were activated by heat rather than the infrared radiation itself.

Sindbis Virus Replicase May Be Potential Cancer Therapy

Alpha viruses, such as Sindbis virus, carry their genetic information on a single strand of RNA. On infection they use a protein, replicase, to produce double-stranded RNA (dsRNA) which is used as genetic material to make more viruses. However, the body recognizes dsRNA as foreign, and infected cells initiate an immune response. New research published on March 28, 2011, in BioMed Central's open-access journal BMC Cancer demonstrates that an artificial plasmid coding for the replicase genes of Sindbis virus causes regression and destruction of lung cancer and melanoma cells in mice. Previous attempts to use synthetic dsRNA to destroy tumor cells have met with problems, including side effects at an effective dose, but there are also concerns about using attenuated viruses, to deliver dsRNA inside cells. Researchers from the University of Texas at Austin and collaborating institutions have instead used a plasmid containing Sindbis replicase genes (nsp1-4) to force cells to produce dsRNA themselves. For ten days, mice were given daily injections of plasmid into the site of a tumor. After another 15 days most of the tumors had begun to regress, and by day 37 all of the tumors had either regressed or been destroyed. Professor Zhengrong Cui, senior author of the study, said, "The anti-cancer action of the plasmid seemed to be two-fold. Firstly, accumulation of dsRNA resulted in cell death and secondly the presence of dsRNA, and the foreign, unmethylated, plasmid DNA, inside a cell activated both innate and adaptive immune responses." Professor Cui continued, "In our study both highly immunogenic and poorly immunogenic tumors were receptive to treatment with an RNA replicase-based plasmid.

March 27th

Scientists Create Artificial Leaf

Researchers today (March 27, 2011) claimed one of the milestones in the drive for sustainable energy — development of the first practical artificial leaf. Speaking at the 241st National Meeting of the American Chemical Society, they described an advanced solar cell the size of a playing card that mimics the process of photosynthesis that green plants use to convert sunlight and water into energy. "A practical artificial leaf has been one of the Holy Grails of science for decades," said Dr. Daniel Nocera, who led the research team. "We believe we have done it. The artificial leaf shows particular promise as an inexpensive source of electricity for homes of the poor in developing countries. Our goal is to make each home its own power station," he said. "One can envision villages in India and Africa not long from now purchasing an affordable basic power system based on this technology." The device bears no resemblance to Mother Nature's counterparts on oaks, maples, and other green plants, which scientists have used as the model for their efforts to develop this new genre of solar cells. About the shape of a playing card but thinner, the device is fashioned from silicon, electronics and catalysts. Placed in a single gallon of water in bright sunlight, the device could produce enough electricity to supply a house in a developing country with electricity for a day, Dr. Nocera said. It does so by splitting water into its two components, hydrogen and oxygen. The hydrogen and oxygen gases would be stored in a fuel cell, which uses those two materials to produce electricity, located either on top of the house or beside it. Dr. Nocera, who is with the Massachusetts Institute of Technology, points out that the "artificial leaf" is not a new concept. The first artificial leaf was developed more than a decade ago by Dr. John Turner of the U.S.

Insights into Molecular Motor Inside DNA Repair Complex

Over the last years, two teams of researchers at The Scripps Research Institute have steadily built a model of how a powerful DNA repair complex works. Now, their latest discovery provides revolutionary insights into the way the molecular motor inside the complex functions – findings they say may have implications for treatment of disorders ranging from cancer to cystic fibrosis. In a paper published online on March 27, 2011, in Nature Structural & Molecular Biology, the scientists say that the complex's motor molecule, known as Rad50, is a surprisingly flexible protein that can change shape and even rotate depending on the task at hand. The finding solves the long-standing mystery of how a single protein complex known as MRN (Mre11-Rad50-Nbs1) can repair DNA in a number of different, and tricky, ways that seem impossible for "standard issue" proteins to do, said team leaders Scripps Research Professor John Tainer and Scripps Research Professor Paul Russell, who also collaborated with members of the Lawrence Berkeley National Laboratory on the study. The scientists said the finding also provides a critical insight into the ABC-ATPase superfamily of molecular motors, of which Rad50 is a member. "Rad50 and its brethren proteins in this superfamily are biology's general motors," said Dr. Tainer, "and if we know how they work, we might be able to control biological outcomes when we need to." For example, knowing that Rad50 changes its contour to perform a function suggests it might be possible to therapeutically target unique elements in that specific conformation. "There could be a new generation of drugs that are designed not against an active site, like most drugs now (an approach that can cause side effects), but against the shape the protein needs to be in to work," Dr. Tainer said. Dr.

Walnut Is Top Nut for Antioxidants

A new scientific study positions walnuts in the No. 1 slot in a family of foods that lays claim to being among Mother Nature's most nearly perfect packaged foods: Tree and ground nuts. In a report presented on March 27, 2011, at the 241st National Meeting & Exposition of the American Chemical Society, scientists presented an analysis showing that walnuts have a combination of more healthful antioxidants and higher-quality antioxidants than any other nut. "Walnuts rank above peanuts, almonds, pecans, pistachios and other nuts," said Dr. Joe Vinson, who did the analysis. "A handful of walnuts contains almost twice as much antioxidants as an equivalent amount of any other commonly consumed nut. But unfortunately, people don't eat a lot of them. This study suggests that consumers should eat more walnuts as part of a healthy diet." Vinson noted that nuts in general have an unusual combination of nutritional benefits — in addition to those antioxidants — wrapped into a convenient and inexpensive package. Nuts, for instance, contain plenty of high-quality protein that can substitute for meat; vitamins and minerals; dietary fiber; and are dairy- and gluten-free. Years of research by scientists around the world link regular consumption of small amounts of nuts or peanut butter with decreased risk of heart disease, certain kinds of cancer, gallstones, Type 2 diabetes, and other health problems. Despite all the previous research, scientists until now had not compared both the amount and quality of antioxidants found in different nuts, Dr. Vinson said. He filled that knowledge gap by analyzing antioxidants in nine different types of nuts: walnuts, almonds, peanuts, pistachios, hazelnuts, Brazil nuts, cashews, macadamias, and pecans. Walnuts had the highest levels of antioxidants. Dr.