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Archive - May 2011

Date

May 20th

New Organic Catalyst Should Enhance Drug Research and Development

A new "organocatalyst" developed at Oregon State University is now available for commercial use. Produced by an Albany, Ore., pharmaceutical company, it should make new drug development around the world less costly, more efficient, and more environmentally friendly. This catalyst, named "Hua Cat," is also one of the first products to reach the marketplace as a result of support from the University Venture Development Fund, an initiative finalized in 2007 by the Oregon Legislature to create jobs and aid business by bringing university-based discoveries to commercial use. The product itself is a new and important part of the field of organocatalysis, which experts believe offers a better and more affordable avenue for research and commercial production of new drugs, while eliminating the need for toxic heavy metals often used in the past. "Organocatalysis is a very young science, but we believe it's about ready to take off and provide improved methods for drug research and development," said Dr. Rich Carter, an OSU professor of chemistry, a national leader in this field and co-inventor of the new catalyst along with Dr. Hua Yang, an OSU postdoctoral research associate. "These types of catalysts can be used in the development of almost any type of drug, whether they are for treating cancer, heart disease, infectious disease, or other health problems," Dr. Carter said. "At the same time, OSU students are now gaining an edge in the new era of environmentally-friendly medicinal chemistry." The catalyst was developed in close collaboration and with the support of Synthetech, an Albany, Ore., contract manufacturer of pharmaceutical products, and a wholly-owned subsidiary of W.R. Grace, Inc. OSU patented the technology and is licensing its use to private industry.

Genetic Study Clarifies Evolutionary Origin of Elusive Montane Red Fox

North American red foxes originated from two separate genetic lineages that were isolated from each other by glaciers some half a million years ago, according to a U.S. Forest Service Pacific Northwest Research Station study. The research—featured in the April/May 2011 issue of Science Findings, a monthly publication of the station—can assist efforts aimed at conserving potentially imperiled montane populations of the species. "When most people think of the red fox, they envision the ones that thrive in low-elevation, human-dominated landscapes," said Dr. Keith Aubry, a research wildlife biologist at the station who led the study. "But there are other extremely elusive and rarely seen populations that live only in isolated alpine and subalpine areas in the mountains of the Western United States." The latter group—the montane red foxes—may be imperiled by climate change and other contemporary pressures and were the focus of Aubry's doctoral work in the early 1980s. Contrary to prevailing theory at the time, Dr. Aubry hypothesized that native North American red foxes were descended from two distinct lineages, not one, that were isolated from each other in both northern and southern ice-free areas during the most recent Ice Age. Such an evolutionary history would help explain the unique ecological adaptations of the montane foxes, and why native red foxes in southern British Columbia are so much bigger than the montane foxes that occupy nearly adjacent areas in Washington's Cascade Range. "If all of North America's foxes originated from a single lineage that had expanded its distribution in a wave across the continent, you'd expect to see a more or less continuous gradient in size," Dr. Aubry said.

May 18th

New Mouse Model of Depression

Researchers at the University of Pittsburgh School of Medicine have developed a mouse model of major depressive disorder (MDD) that is based on a rare genetic mutation that appears to cause MDD in the majority of people who inherit it. The findings, which were published online on May 19, 2011, in the American Journal of Medical Genetics Part B: Neuropsychiatric Genetics EarlyView, could help to clarify the brain events that lead to MDD, and contribute to the development of new and better means of treatment and prevention. This report also illustrates an advance in the design of recombinant mouse models that should be applicable to many human diseases. "Major depressive disorder is a leading cause of suffering, disability, and premature death from all causes including suicide. While the cause currently is unknown, twin and adoption studies indicate that genetic factors account for 40 to 70 percent of the risk for developing this common disorder," explained lead author Dr. George Zubenko, professor of psychiatry, Pitt School of Medicine. "In this report, we describe how we constructed a laboratory mouse strain that mimics the brain mechanism that leads to major depression in humans, rather than symptoms," he said. "Nonetheless, in our initial characterization, the mutant mice exhibited several features that were reminiscent of the human disorder, including alterations of brain anatomy, gene expression, behavior, as well as increased infant mortality. These findings support the role of the genetic variant in the development of MDD, and affirm the mutant mouse strain as a model of MDD worthy of further study," Dr. Zubenko said. Hugh B. Hughes, III, M.S., served as the co-author of this report.

Viagra Reduces Multiple Sclerosis Symptoms in Animal Model

Universitat Autònoma de Barcelona researchers have discovered that Viagra® drastically reduces multiple sclerosis symptoms in animal models with the disease. The research, published in Acta Neuropathologica, demonstrates that a practically complete recovery occurs in 50% of the animals after eight days of treatment. Researchers are confident that clinical trials soon will be carried out in patients given that the drug is well tolerated and has been used to treat sexual dysfunction in some multiple sclerosis patients. Multiple sclerosis is the most common chronic inflammatory disease of the central nervous system and one of the main causes of disability among young adults. The disease is caused by the presence of multiple focuses of demyelination (loss of myelin sheaths around the axons, affecting the ability of neurons to communicate) and neurodegeneration in different areas of the central nervous system. There is currently no cure for the disease, although some drugs have proven effective in fighting symptoms and preventing it from progressing. A research team from the UAB Institute of Biotechnology and Biomedicine directed by Dr. Agustina García, in collaboration with the research team directed by Dr. Juan Hidalgo from the UAB Institute of Neurosciences, has studied the effects of a treatment using sildenafil, sold as Viagra®, in an animal model of multiple sclerosis known as experimental autoimmune encephalomyelitis (EAE). Researchers demonstrated that a daily treatment with sildenafil after disease onset quickly reduced clinical signs, with a practically complete recovery in 50% of the cases after eight days of treatment.

May 17th

Stat5 Marker IDs Breast Cancer Patients Likely to Respond to Tamoxifen

Cancer researchers at the Kimmel Cancer Center at Thomas Jefferson University and an international team of collaborators have discovered a biomarker in breast cancer that may help identify which women will respond to anti-estrogen therapy. The research appeared online on May 16, 2011, in the Journal of Clinical Oncology. Anti-estrogen drugs, most notably tamoxifen, are widely used in patients diagnosed with estrogen receptor-positive breast cancer. However, as many as a third of the women given tamoxifen fail to respond. In this new study, the investigators found that women whose tumors retain the active form of the protein biomarker Stat5 have an increased likelihood of responding to tamoxifen. In contrast, women treated with tamoxifen whose tumors lacked active Stat5 had up to a 20-fold increased risk of dying from breast cancer after adjustment for effects of standard hormone receptor markers and other pathology data. "Identification of predictive biomarkers present in breast cancer will lead to improved individualized therapies tailored specifically towards each woman's cancer," said Dr. Hallgeir Rui, professor of oncology, Kimmel Cancer Center at Thomas Jefferson University, and principal investigator of the study. "Absence of the active form of Stat5 could help identify a group of patients unlikely to respond to tamoxifen so they may be offered alternative and more aggressive treatments." Stat5 protein is a DNA-binding factor that regulates expression of certain genes, many of which remain unknown. During pregnancy, Stat5 is activated by the hormone prolactin, and stimulates milk production in the breast. Active Stat5 is also detectable at lower levels in healthy breast tissue of non-pregnant women.

Imaging Technology Reveals Details of 49-Million-Year-Old Spider

Scientists have used the latest computer-imaging technology to produce stunning three-dimensional pictures of a 49-million-year-old spider trapped inside an opaque piece of fossilized amber resin. University of Manchester researchers, working with colleagues in Germany, created the intricate images using X-ray computed tomography to study the remarkable spider, which can barely be seen under the microscope in the old and darkened amber. Writing in the international journal Naturwissenschaften, the scientists showed that the amber fossil – housed in the Berlin Natural History Museum – is a member of a living genus of the Huntsman spiders (Sparassidae), a group of often large, active, free-living spiders that are hardly ever trapped in amber. As well as documenting the oldest ever Huntsman spider, especially through a short film revealing astounding details, the scientists showed that even specimens in historical pieces of amber, which at first look very bad, can yield vital data when studied by computed tomography. “More than 1,000 species of fossil spider have been described, many of them from amber,” said Dr David Penney, from Manchester’s Faculty of Life Sciences. “The best-known source is Baltic amber which is about 49 million years old, and which has been actively studied for over 150 years. “Indeed, some of the first fossil spiders to be described back in 1854 were from the historically significant collection of Georg Karl Berendt, which is held in the Berlin Natural History museum.

May 17th

Mass Spec Technology Reveals Dynamics of Crucial Protein Switch

Researchers at the University of Texas Medical Branch at Galveston and the University of California-San Diego School of Medicine have published a study that offers a new understanding of a protein critical to physiological processes involved in major diseases such as diabetes and cancer. This work could help scientists design drugs to battle these disorders. The article was deemed a "Paper of the Week" by the Journal of Biological Chemistry and will be featured on the cover of that journal. The article is scheduled for publication in the May 20, 2011 issue and is now available online. "This study applied a powerful protein structural analysis approach to investigate how a chemical signal called cAMP turns on one of its protein switches, Epac2," said principal investigator Dr. Xiaodong Cheng, professor in the Department of Pharmacology and Toxicology and member of the Sealy Center for Structural Biology and Molecular Biophysics at UTMB. The cAMP molecule controls many physiological processes, ranging from learning and memory in the brain and contractility and relaxation in the heart to insulin secretion in the pancreas. cAMP exerts its action in cells by binding to and switching on specific receptor proteins, which, when activated by cAMP, turn on additional signaling pathways. Errors in cell signaling are responsible for diseases such as diabetes, cancer, and heart failure. Understanding cAMP-mediated cell signaling, in which Epac2 is a major player, likely will facilitate the development of new therapeutic strategies specifically targeting the cAMP-Epac2 signaling components, according to the researchers. The project involved an ongoing collaboration between Dr. Cheng's research group at UTMB, experts in the study of cAMP signaling, and UCSD professor of medicine Virgil Woods Jr.

Sodium Channels Evolved Before Animal Nervous Systems

An essential component of animal nervous systems—sodium channels—evolved prior to the evolution of those systems, researchers from The University of Texas at Austin have discovered. "The first nervous systems appeared in jellyfish-like animals six hundred million years ago or so," says Dr. Harold Zakon, professor of neurobiology, "and it was thought that sodium channels evolved around that time. We have now discovered that sodium channels were around well before nervous systems evolved." Dr. Zakon and his coauthors, Professor David Hillis and graduate student Benjamin Liebeskind, published their findings online in PNAS on May 16, 2011. Nervous systems and their component neuron cells were a key innovation in the evolution of animals, allowing for communication across vast distances between cells in the body and leading to sensory perception, behavior, and the evolution of complex animal brains. Sodium channels are an integral part of a neuron's complex machinery. The channels are like floodgates lodged throughout a neuron's levee-like cellular membrane. When the channels open, sodium floods through the membrane into the neuron, and this generates nerve impulses. Zakon, Hillis and Liebeskind discovered the genes for such sodium channels hiding within an organism that isn't even made of multiple cells, much less any neurons. The single-celled organism is a choanoflagellate, and it is distantly related to multi-cellular animals such as jellyfish and humans. The researchers then constructed evolutionary trees, or phylogenies, showing the relationship of those genes in the single-celled choanoflagellate to those in multi-cellular animals, including jellyfish, sponges, flies, and humans.

Mechanism of Stem Cell to Skeletal Muscle Cell Differentiation

A team led by developmental biologist Professor Christophe Marcelle of Monash University in Australia has determined the mechanism that causes stem cells in the embryo to differentiate into specialized cells that form the skeletal muscles of animals’ bodies. The scientists published their results online in Nature on May 15, 2011. Scientists worldwide are racing to pin down the complex molecular processes that cause stem cells in the early embryo to differentiate into specialist cells such as muscle or nerve cells. The field has the potential to revolutionize medicine by delivering therapies to regenerate tissue damaged by disease or injury. Differentiation happens soon after fertilization, when embryonic cells are dividing rapidly and migrating as the animal’s body takes shape. Professor Marcelle’s team analyzed the differentiation of muscle stem cells in chicken embryos. The mechanisms in birds are identical to those in mammals, so the chick is a good model species for understanding the mechanisms in humans, says team member and the paper’s lead author Anne Rios. The scientists investigated the effect of a known signaling pathway called NOTCH on muscle differentiation. They found that differentiation of stem cells to muscle was initiated when NOTCH signalling proteins touched some of the cells. These proteins were carried by passing cells migrating from a different tissue–the neural crest–the progenitor tissue of sensory nerve cells. Muscle formation in the target stem cells occurred only when the NOTCH pathway was triggered briefly by the migrating neural crest cells. “This kiss-and-run activation of a pathway is a completely novel mechanism of stem cell specification which explains why only some stem cells adopt a muscle cell fate,” Ms. Rios said.

Four New Species of Mysterious Purse-Web Spiders Described

A team of researchers from the University of the Free State in South Africa (Drs. René Fourie and Charles Haddad) and the Royal Museum for Central Africa in Belgium (Dr. Rudy Jocqué) discovered very poorly known purse-web spiders of the genus Calommata in Africa. Four of the species described are new to science. The study was published in the open access journal ZooKeys. What is really unique about purse-web spiders is that, in contrast to trapdoor spiders, they do not construct a structure to close the burrow. Instead, they build a purse-shaped web of dense silk that covers a chamber in which the spider waits for wandering prey to step on the web, before impaling it from beneath with its exceptionally long fangs. Little is known on the biology of these small spiders as they are extremely difficult to locate in nature. The burrows of the African species have never been photographed, and the first ever photograph of a live African Calommata male, captured in a pitfall trap, was taken only last year by Ian Engelbrecht. “While Calommata spiders have been collected elsewhere in Africa throughout the last century, albeit on rare occasions, our study was prompted by the recent rediscovery of these spiders in South Africa, nearly eight decades since the last specimen was collected here in 1923. Currently six African species are recognized, with an additional six species from East Asia and Israel,“ Dr. Haddad said. The new discovery is expected to shed light on the evolutionary history of these spiders, known from two distant geographical regions, and to draw attention to the urgent need for their conservation. These spiders are mostly threatened by habitat loss and urbanization.