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Archive - 2012

December 5th

Nuclear Import of Transcriptional Repressor in Jasmonate Signaling

Researchers examining how the hormone jasmonate works to protect plants and promote their growth have discovered how a transcriptional repressor of the jasmonate signaling pathway makes its way into the nucleus of the plant cell. The scientists hope that this recently published discovery will eventually help farmers experience better crop yields with less use of potentially harmful chemicals. “This is a small piece of a bigger picture, but it is a very important piece,” said Dr. Maeli Melotto, a University of Texas at Arlington (UT Arlington) assistant professor of biology. Dr. Melotto recently co-authored a paper that advances current understanding of plant defense mechanisms with her collaborator Dr. Sheng Yang and his team at Michigan State University’s Department of Energy Plant Research Laboratory (DOE-PRL). Dr. Yeng is a Howard Hughes Medical Institute-Gordon and Betty Moore Foundation investigator. The collaborative paper was published in the December 4, 2012 issue of PNAS. Jasmonate signaling has been a target of intense research because of its important role in maintaining the balance between plant growth and defense. In healthy plants, jasmonates play a role in reproductive development and growth responses. But, when stressors such as herbivorous insects, pathogen attack, or drought come into play, jasmonate signaling shifts to defense-related cellular processes. The team from UT Arlington and Michigan State focused on the role of jasmonate signaling repressors referred to as JAZ. Specifically, the scientists looked at how JAZ interacts with a major transcription factor called MYC2 and a protein called COI1, which is a receptor necessary for jasmonate signaling.

Novel Drug Reduces Depression Scores within Hours in Phase IIa Trial

Naurex Inc., a clinical stage company developing innovative treatments to address unmet needs in psychiatry and neurology, today reported positive results from a Phase IIa clinical trial of its lead antidepressant compound, GLYX-13. GLYX-13 is a novel partial agonist of the NMDA receptor. The Phase Ila results are being presented at the 51st Annual Meeting of the American College of Neuropsychopharmacology (ACNP), being held December 2-6, 2012 in Hollywood, Florida. The Phase IIa results show that a single administration of GLYX-13 produced statistically significant reductions in depression scores in subjects who had failed treatment with one or more antidepressant agents. The reductions were evident within 24 hours and persisted for an average of seven days. Importantly, the effect size, a measure of the magnitude of the drug's antidepressant efficacy, observed at 24 hours and at seven days after a single administration of GLYX-13, was nearly double the effect size seen with most other antidepressant drugs after 4-6 weeks of repeated dosing. In the Phase IIa trial, GLYX-13 was well tolerated. Reported side effects were mild to moderate and were consistent with those observed in subjects receiving placebo. Consistent with previous studies, GLYX-13 did not produce any of the schizophrenia-like psychotomimetic effects associated with other drugs that modulate the NMDA receptor. "These data are an important step in validating Naurex's mission of developing breakthrough therapies for depression and other CNS disorders," said Derek Small, CEO of Naurex. "Our founder discovered a new class of drugs that appeared to have the remarkable antidepressant efficacy of ketamine-like compounds, but without their limiting side effects.

December 5th

X-Ray Laser Reveals Structure of Key Sleeping Sickness Enzyme

An international team of scientists, using the world’s most powerful X-ray laser, has revealed the three-dimensional structure of a key enzyme that contributes to the pathogenicity of the single-celled parasite that causes African trypanosomiasis (or sleeping sickness) in humans. With the elucidation of the 3D structure of the cathepsin B enzyme, it should be possible to design new drugs to inhibit the parasite (Trypanosoma brucei) that causes sleeping sickness, leaving the infected human unharmed. The research team, including several Arizona State University (ASU) scientists, was led by the German Electron Synchrotron (DESY) scientist Dr. Henry Chapman from the Center of Free-Electron Laser Science (CFEL), professor Christian Betzel from the University of Hamburg and Dr. Lars Redecke from the SIAS joint Junior Research Group at the Universities of Hamburg and Lübeck. The team reported its findings on November 29, 2012 in Science. "This is the first new biological structure solved with a free-electron laser," said Dr. Chapman of the development. "These images of an enzyme, which is a drug target for sleeping sickness, are the first results from our new ‘diffract-then-destroy’ snapshot X-ray laser method to show new biological structures which have not been seen before,” explained Dr. John Spence, ASU Regents’ Professor of Physics. “The work was led by the DESY group and used the Linac Coherent Light Source at the U.S. Department of Energy’s SLAC National Accelerator Laboratory." Transferred to its mammalian host by the bite of the tsetse fly, the effects of the parasite are almost always fatal if treatment is not received. The sleeping sickness parasite threatens more than 60 million people in sub-Saharan Africa and annually kills an estimated 30,000 people.

November 28th

First Success of Targeted Therapy in Most Common Non-Small-Cell Lung Cancer

A new study by an international team of investigators led by Dana-Farber Cancer Institute scientists is the first to demonstrate that chemotherapy and a new, targeted therapy work better in combination than chemotherapy alone in treating patients with the most common genetic subtype of lung cancer. Published online on November 28, 2012 in The Lancet Oncology, the combination of chemotherapy and the targeted drug selumetinib was more effective than chemotherapy alone in a clinical trial involving patients with a form of non-small-cell lung cancer (NSCLC) that carries a mutation in the gene KRAS – a variety that represents about 20 percent of all NSCLC cases. Previously, no targeted agent, either alone or in combination with another drug, had proven beneficial in a trial involving patients with this type of NSCLC. The 87 patients who participated in the new, phase II trial – conducted at 67 sites around the world – had advanced, KRAS-mutant NSCLC that had failed initial chemotherapy. The participants were randomly assigned to receive either selumetinib and the chemotherapy agent docetaxel or docetaxel alone. Investigators found that while 37 percent of the patients in the selumetinib group experienced some shrinkage of their tumor, none of the patients in the docetaxel-only group did. Of particular significance, patients receiving selumetinib lived a median of 5.3 months before their cancer began to worsen, compared to 2.1 months for those receiving chemotherapy alone. (Patients in the selumetinib group also survived longer, on average, than those in the docetaxel group – 9.4 months compared to 5.2 months – but the improvement was not considered statistically significant.) "Our findings suggest that selumetinib and docetaxel work synergistically – each enhancing the effect of the other," says the study's lead author, Pasi A.

November 26th

Watermelon Genome Decoded

Are juicier, sweeter, more disease-resistant watermelons on the way? An international consortium of more than 60 scientists from the United States, China, and Europe has published the genome sequence of watermelon (Citrullus lanatus) — information that could dramatically accelerate watermelon breeding toward production of a more nutritious, tastier, and more disease-resistant fruit. The watermelon genome sequence was published in the November 25, 2012 online version of Nature Genetics. The researchers discovered that a large portion of disease-resistance genes were lost in the domestication of watermelon. With the high-quality watermelon sequence now complete, it is hoped that breeders can now use the information to recover some of these natural disease defenses. The authors reported that the genome of the domesticated watermelon contained 23,440 genes, roughly the same number of genes as in humans. The group compared the genomes of 20 different watermelons and developed a first-generation genetic variation map for watermelon. This information allowed them to identify genomic regions that have been under human selection, including those associated with fruit color, taste, and size. “Watermelons are an important cash crop and among the top five most consumed fresh fruits; however, cultivated watermelons have a very narrow genetic base, which presents a major bottleneck to its breeding. Decoding the complete genome of the watermelon and resequencing watermelons from different subspecies provided a wealth of information and toolkits to facilitate research and breeding,” said Dr. Zhangjun Fei, a scientist at the Boyce Thompson Institute (BTI) for Plant Research at Cornell University, and one of the leaders of this project. Dr. Fei worked with BTI scientists on different aspects of the research, including Dr.

Deciphering Bacterial Doomsday Decisions

As a homeowner prepping for a hurricane, the bacterium Bacillus subtilis uses a long checklist to prepare for survival in hard times. In a new study, scientists at Rice University and the University of Houston uncovered an elaborate mechanism that allows B. subtilis to begin preparing for survival, even as it delays the ultimate decision of whether to “hunker down” and withdraw into a hardened spore. The new study by computational biologists at Rice and experimental biologists at the University of Houston was published online on November 19, 2012 in PNAS. “The gene-expression program that B. subtilis uses to form spores involves hundreds of genes,” said Dr. Oleg Igoshin, lead scientist on the study and professor of bioengineering at Rice. “Many of these genes are known and have been studied for decades, but the exact mechanism that B. subtilis uses to make the decision to form a spore has remained a mystery.” B. subtilis is a common soil bacterium that forms a spore when food runs short. Spore formation involves dramatic changes. The cell first asymmetrically divides within its outer wall, forming one large chamber and one small one. As spore formation progresses, one chamber envelopes the other, which becomes a vault for the organism’s DNA and a small set of proteins that can “reboot” the organism when it senses that outside conditions have improved. B. subtilis is harmless to humans, but some dangerous bacteria like anthrax also form spores. Scientists are keen to better understand the process, both to protect public health and to explore the evolution of complex genetic processes. During spore formation, scientists know that a bacterium channels its energy into producing proteins that help prepare the cell to become a spore.

Possible New Treatment for Ewing Sarcoma

Discovery of a new drug with a high potential to treat Ewing sarcoma, an often deadly cancer of children and young adults, and the previously unknown mechanism behind it, come hand-in-hand in a new study by researchers from Huntsman Cancer Institute (HCI) at the University of Utah. The report appeared November 26, 2012 online in the journal Oncogene. “Ewing sarcoma is almost always caused by a cancer-causing protein called EWS/FLI," said Stephen Lessnick, M.D., Ph.D., director of HCI's Center for Children's Cancer Research, professor in the Department of Pediatrics at the University of Utah School of Medicine, and an HCI investigator. In the lab, Dr. Lessnick and his colleagues found that an enzyme, called lysine-specific demethylase (LSD-1), interacts with EWS/FLI to turn off gene expression in Ewing sarcoma. By turning off specific genes, the EWS/FLI-LSD1 complex causes Ewing sarcoma development. "This makes LSD-1 an important target for the development of new drugs to treat Ewing sarcoma," Dr. Lessnick said. "For a long time, we've known that EWS/FLI works by binding to DNA and turning on genes that activate cancer formation," said Dr. Lessnick. "It was a surprise to find out that it turns genes off as well. The beauty, if there's anything beautiful about a nasty disease like this, is that if we can inhibit EWS/FLI, we can inhibit this cancer, because EWS/FLI is the master regulator of Ewing sarcoma," Dr. Lessnick added. While Dr.

November 23rd

Progress in Worldwide Study of New Drug Combination for Pancreatic Cancer

A new cancer drug combination demonstrated significant improvement in overall survival of late-stage pancreatic cancer patients compared to those receiving standard treatment, according to results of a Phase III clinical trial led by physicians from Scottsdale Healthcare's Virginia G. Cancer Center Clinical Trials, a partnership with the Translational Genomics Research Institute (TGen). Physicians at the Virginia G. Piper Cancer Center at Scottsdale Healthcare were first to design a clinical trial to determine the safety, tolerability, and effectiveness of nab-paclitaxel (Abraxane) in combination with the standard drug gemcitabine in patients with advanced pancreatic cancer. Results of that multicenter study chaired by Dr. Daniel Von Hoff were encouraging enough that it led to one of the largest international studies ever done in pancreatic cancer, with 861 patients. Full results are expected to be presented at the American Society of Clinical Oncology (ASCO) 2013 Gastrointestinal Cancers Symposium January 24-26, 2013 in San Francisco. "This is a great example of rapid bench-to-bedside development of new treatments for cancer. We're ecstatic that we will have a new treatment for patients with late stage pancreatic cancer," said Dr. Von Hoff, international lead investigator and Chief Scientific Officer for the Virginia G. Cancer Center Clinical Trials at Scottsdale Healthcare and TGen's Physician-in-Chief. The pancreas is a gland behind the stomach that secretes enzymes into the upper part of the small intestine to help digestion. It also produces hormones, including insulin, which helps regulate the metabolism of sugars. Advanced pancreatic cancer is the fourth most common cause of cancer death in the United States and throughout the world. It is a difficult to diagnose and treat cancer with the lowest survival rates among all cancer types.

How the Black Dahlia Gets Its Distinctive Color

The molecular mechanisms whereby a spectrum of dahlias, from white to yellow to red to purple, get their color are already well known, but the black dahliahas hitherto remained a mystery. Now, a study published November 23, 2012 in BioMed Central's open-access journal BMC Plant Biology reveals for the first time that the distinctive black-red coloring is based on an increased accumulation of anthocyanins as a result of drastically reduced concentrations of flavones. Dahlia variabilis hort. is a popular garden flower. Continuous dahlia breeding worldwide has led to the availability of a huge number of cultivars – 20,000 varieties – many of them showing red hues. However, black hues of dahlia flowers occur rarely, in comparison. Flower color in dahlias is exclusively based on the accumulation of a group of metabolites called flavonoids, for example anthocyanins, flavones, and flavonols. It's known that red tones arise from anthocyanins, whilst white and yellow tones lack anthocyanins but contain large amounts of flavones and chalcones respectively. Flavones and flavonoids are colorless, but they influence flower coloration by acting as co-pigments, interacting with anthocyanins to stabilize their structures. It is assumed that flavones rather than flavonols are the predominant co-pigments present in dahlias because all cultivars show high flavone synthase II (FNS) enzyme activity and low flavonol synthase activity. To examine the biochemical basis for the distinctive dark coloring of the black dahlia, the research team from the Vienna University of Technology in Austria used pigment, enzyme, and gene expression analyses. They determined that the majority of black cultivars have very low concentrations of flavones, as confirmed by low FNS II expression.

November 19th

Breakthrough Nanoparticle Halts Multiple Sclerosis in Animal Model

In a breakthrough for nanotechnology and multiple sclerosis, a biodegradable nanoparticle turns out to be the perfect vehicle to stealthily deliver an antigen that tricks the immune system into stopping its attack on myelin and halt a model of relapsing remitting multiple sclerosis (MS) in mice, according to new Northwestern Medicine research. The new nanotechnology also can be applied to a variety of immune-mediated diseases including type 1 diabetes, food allergies, and airway allergies such as asthma. In MS, the immune system attacks the myelin membrane that insulates nerves cells in the brain, spinal cord, and optic nerve. When the insulation is destroyed, electrical signals can't be effectively conducted, resulting in symptoms that range from mild limb numbness to paralysis or blindness. About 80 percent of MS patients are diagnosed with the relapsing remitting form of the disease. The Northwestern nanotechnology does not suppress the entire immune system as do current therapies for MS, which make patients more susceptible to everyday infections and higher rates of cancer. Rather, when the nanoparticles are attached to myelin antigens and injected into the mice, the immune system is reset to normal. The immune system stops recognizing myelin as an alien invader and halts its attack on it. "This is a highly significant breakthrough in translational immunotherapy," said Dr. Stephen Miller, a corresponding author of the study and the Judy Gugenheim Research Professor of Microbiology-Immunology at Northwestern University Feinberg School of Medicine. "The beauty of this new technology is it can be used in many immune-related diseases. We simply change the antigen that's delivered. The holy grail is to develop a therapy that is specific to the pathological immune response, in this case the body attacking myelin," Dr.