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Archive - Nov 13, 2014


Beetle and Longtime Fungal Associate Go Rogue

Scientists with the U.S. Forest Service and Colorado State University examined a fungus native to North America, the native beetle that carries it, and their host tree and found something surprising: Geosmithia morbida (the fungus) and the walnut twig beetle co-evolved and, while the beetle/fungus complex was once the equivalent of a hang nail for a black walnut tree, it has now become lethal. Research published on November 13, 2014 in PLOS ONE by U.S. Forest Service scientist Dr. Keith Woeste, Colorado State University scientists Dr. Marcelo M. Zerillo and Dr. Jorge Ibarra Caballero, and colleagues, details the origins and spread of Thousand Cankers Disease (TCD), a fungal disease that is threatening the health of black walnut in the Eastern United States. The study provides a detailed look at the genetic diversity of the fungus and how that diversity is distributed on the landscape, allowing scientists to make much stronger conclusions about the sources of TCD spread in the past and in the future. "Black walnut is a species with tremendous economic and cultural significance," said Dr. Michael T. Rains, Director of the Northern Research Station and the Forest Products Laboratory. "To help ensure this species sustains it vibrancy, Forest Service scientists are working with state agencies, other federal agencies, and university partners to advance survey and detection efforts and to understand the genetics of the disease, as well as resistance to TCD." When black walnut trees in California and Arizona began dying of TCD two decades ago, some scientists believed that the walnut twig beetle (image) had acquired a new and probably non-native fungus that was killing the trees. "That wasn't the case," said Dr. Woeste, a research plant molecular geneticist with the U.S.

Common Cholesterol-Fighting Drug May Prevent Hysterectomies in Women with Uterine Fibroids

Researchers at the University of Texas Medical Branch (UTMB) at Galveston, in collaboration with scientists at The University of Texas Health Science Center at Houston (UTHealth), the Baylor College of Medicine, and the Georgia Regents University, report for the first time that the cholesterol-lowering drug simvastatin inhibits the growth of human uterine fibroid tumors. These new data were published online on October 30, 2014, and are scheduled to appear in the January print edition of the Journal of Biological Chemistry (JBC). Statins, such as simvastatin, are commonly prescribed to lower high cholesterol levels. Statins work by blocking an early step in cholesterol production. Beyond these well-known cholesterol-lowering abilities, statins also combat certain tumors. Statins have previously been shown to have anti-tumor effects on breast, ovarian, prostate, colon, leukemia, and lung cancers. The effect of statins on uterine fibroids was previously unknown. “Non-cancerous uterine fibroids are the most common type of tumor in the female reproductive system, accounting for half of the 600,000 hysterectomies done annually in the U.S. Their estimated annual cost is up to $34 billion in the U.S. alone,” said UTMB’s Dr. Mostafa Borahay, assistant professor in the department of obstetrics and gynecology and lead author of the JBC article. “Despite this, the exact cause of these tumors is not well understood, as there are several genetic, familial, and hormonal abnormalities linked with their development.” The current study investigated the impact of simvastatin on human uterine fibroid cell growth. The researchers revealed that simvastatin impedes the growth of uterine fibroid tumor cells. The researchers also studied the way simvastatin works to suppress these tumors.

Cold-Induced Pain Linked to the Garlic and Mustard Receptor

Some people experience cold not only as feeling cold, but actually as a painful sensation. This applies even to fairly mild temperatures - anything below 20°C. A group of researchers from Lund University in Sweden has now identified the mechanism in the body that creates this connection between cold and pain. It turns out that it is based on the same receptor (TRP subtype A1) that reacts to the pungent substances in mustard and garlic. This result was reported online on November 11, 2014 in PNAS. Professor of Pharmacology Peter Zygmunt and Professor of Clinical Pharmacology Edward Högestätt have long conducted research on pain and the connection between pain and irritant substances in mustard, garlic, and chilli. In large quantities, these strong spices can cause burning or irritant sensations in the mouth and throat, and can also cause rashes and swelling. When the eyes are exposed, these spices produce strong pain and lacrimation, a property that has been exploited in pepper spray and tear gas. The reason is that the substances affect nerves that are part of the pain system and that are activated by inflammation. Ten years ago, the Lund research group identified the receptor for mustard and garlic, i.e. the way in which the pungent substances in the spices irritate the nerve cells. Since then, the question of whether this receptor also responds to cold has been a matter of debate. However, the researchers have now demonstrated that this is the case. "We have worked with Professors of Biochemistry Urban Johanson and Per Kjellbom here in Lund to extract the human receptor protein and insert it into an artificial cell membrane. There we could see that it reacted to cold," explained Professor Zygmunt. The findings increase our knowledge of the human body's temperature senses.

HFE Gene Variant, Found in 30 percent of ALS Patients, Speeds Up Disease Progression

Mice bred to carry a gene variant found in a third of ALS patients have a faster disease progression and die sooner than mice with the standard genetic model of the disease, according to Penn State College of Medicine researchers. Understanding the molecular pathway of this accelerated model could lead to more successful drug trials for all ALS patients. Amyotrophic lateral sclerosis (ALS), commonly known as Lou Gehrig's disease, is a degeneration of lower and upper motor neurons in the brainstem, spinal cord, and the motor cortex. The disease, which affects 12,000 Americans, leads to loss of muscle control. People with ALS typically die of respiratory failure when the muscles that control breathing fail. Penn State researchers were the first to discover increased iron levels in the brains of some patients with the late-onset neurodegenerative disorders Parkinson's disease and Alzheimer's disease. A decade ago, they also identified a relationship between ALS and excess iron accumulation when they found that 30 percent of ALS patients in their clinic carried a variant of a gene known as HFE [high iron (Fe)] that is associated with iron overload. For this study, the researchers crossbred mice with the H63D HFE gene variant with the standard mice used in ALS research. "When we followed the disease progression and the behavior of our crossbred mice compared to the standard mice, we saw significant differences," said Dr. James Connor, vice chair of neurosurgery research and director of the Center for Aging and Neurodegenerative Diseases. The crossbred mice performed significantly worse on tests of forelimb and hindlimb grip strength and had a 4 percent shorter life span. The researchers published their findings in the December 2014 issue of the BBA Molecular Basis of Disease.

Scientists Discover Additional Properties of S. pneumoniae That Cause Conjunctivitis

Scientists from Massachusetts Eye and Ear/Harvard Medical School Department of Ophthalmology have used the power of new genomic technology to discover that particular microbes that commonly infect the eye have special, previously unknown properties. These properties are predicted to allow the bacterium --Streptococcus pneumoniae -- to specifically stick to the surface of the eye, grow, and cause damage and inflammation. Researchers are now using this information to develop new ways to treat and prevent infections with this bacterium, which is becoming increasingly resistant to antibiotics. Their findings were published in the current issue of Nature Communications in an article entitled, “"Unencapsulated Streptococcus pneumoniae from Conjunctivitis Encode Variant Traits and Belong to a Distinct Phylogenetic Cluster." S. pneumoniae is a leading cause of infection and is responsible for diseases ranging from infection of the lungs, pneumonia, to infection of the brain, to infection of the surface of the eye, known as conjunctivitis. Although infection of the eye can usually be safely treated, S. pneumoniae infection is a leading cause of illness and death worldwide. According to Massachusetts Eye and Ear researcher Dr. Michael S. Gilmore, Sir William Osler Professor of Ophthalmology, Harvard Medical School, an effective vaccine is available that helps prevent many of the most severe types of infection. "I believe it is especially important for children and the elderly to be vaccinated. The vaccine causes the body to react to a slimy coating on the bacterial surface called a "capsule." The capsule allows S. pneumoniae to escape from white blood cells that try to eliminate it, and S. pneumoniae goes on to cause lung and other infections." However, the strains of S.

Two Mutations Linked to Ewing Sarcoma Subtype with Poor Prognosis; New Combination Therapy May Be Effective

An international collaboration has identified frequent mutations in two genes that often occur together in Ewing sarcoma (ES) and that define a subtype of the cancer associated with reduced survival. The research, conducted by the St. Jude Children's Research Hospital-Washington University Pediatric Cancer Genome Project and the Institut Curie-Inserm through the International Cancer Genome Consortium, appears in the November 2014 issue of Cancer Discovery. Mutations in the genes STAG2 and TP53 have previously been linked to ES. This is the first study, however, to show that patients whose tumors carry alterations in both genes are less likely to survive than are patients without the changes. The discovery stems from the most comprehensive analysis yet of the genetic makeup of ES, a cancer of the bone and soft tissue that primarily strikes children and adolescents. The findings come as St. Jude finalizes plans for clinical trials of an ES combination therapy. A recent St. Jude study showed that the combination therapy was effective in mice with ES that included both mutations. The agents work by damaging DNA or interfering with cellular repair mechanisms. "The current study used whole genome sequencing to define the most comprehensive landscape yet of the genetic alterations that contribute to the growth and recurrence of Ewing sarcoma," said Jinghui Zhang, Ph.D., a member of the St. Jude Department of Computational Biology. Dr. Zhang and Olivier Delattre, M.D., Ph.D., head of the genetic and biology of pediatric cancer group of Institut Curie, Paris, are the study's corresponding authors. "With the combined expertise of St. Jude and Institut Curie, we were able to identify a subtype with a dismal prognosis based on a tumor's genetic profile.