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Archive - 2011 - Story

November 26th

Drug Protects Neurons in Huntington’s Disease Model

Huntington's disease (HD) is characterized by ongoing destruction of specific neurons within the brain. It affects a person's ability to walk, talk, and think - leading to involuntary movement and loss of muscle coordination. New research, published on November 25, 2011 in BioMed Central's open access journal Molecular Neurodegeneration, shows that the RyanR inhibitor Dantrolene is able to reduce the severity of walking and balance problems in a mouse model of HD. Progressive damage to medium spiny neurons (MSN) in the brain of a person with HD is responsible for many of the symptoms and is caused by an inherited recessive mutation in the gene 'Huntingtin.’ The mutated version of this protein leads to abnormal release of calcium from stores within the neurons which in turn disrupts the connections between neurons firing and muscle contractions, and eventually kills the neurons. Researchers from the University of Texas Southwestern Medical Center, and colleagues, tested Dantrolene, a muscle relaxant which works by stabilizing calcium signaling, and showed that this drug could prevent calcium-dependent toxicity in laboratory-grown neurons. The team led by Dr. Ilya Bezprozvanny also found that Dantrolene could prevent destruction of coordination, measured by beam walking and footprint patterns, in mice with Huntington's-like disease. Dr. Bezprozvanny explained, "One of the features of HD mice is the progressive loss of their NeuN-positive neurons. Dantrolene was not only able to protect muscle coordination in mice with HD, but also prevented destruction of NeuN-positive neurons.

November 17th

Drugs May Be Developed to Treat Malaria in Both the Liver and Blood Stages

Researchers have discovered a group of chemical compounds that might one day be developed into drugs that can treat malaria infection in both the liver and the bloodstream. The study, which was published online on November 17, 2011 in Science, was led by Elizabeth A. Winzeler, Ph.D., of the Scripps Research Institute in La Jolla, California, and was partially funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health. Caused by four related parasites in the genus Plasmodium, malaria is transmitted to humans via the bite of an infected mosquito. Once the bite occurs, the parasites travel to the liver, where they usually multiply rapidly for about a week without causing symptoms. Symptoms begin when the parasites spread from the liver to the rest of the body through the bloodstream. However, the parasites can lie dormant in the liver for periods ranging from several months to years before an infected person demonstrates symptoms. Most of the malaria drugs currently in development target the symptomatic, blood stage of infection. To help achieve malaria eradication, however, a drug would ideally treat infection during both the liver and blood stages. Currently, the World Health Organization recommends only one treatment, primaquine, for the initial, liver stage of certain types of malaria infection; however, primaquine and related drugs can cause a dangerous blood disorder among patients with a genetic condition that is common in malaria-endemic regions of the world. Additionally, drug resistance has been reported, which amplifies the need to find new treatment alternatives.

November 16th

New Clues to Molecular Links Between Psoriasis and Heart Disease

Collaborative research from Perelman School of Medicine at the University of Pennsylvania has shown that psoriasis patients have an increased risk of heart attack, stroke, and cardiovascular death, especially if the psoriasis is moderate to severe. Now, Penn researchers have discovered the potential underlying mechanism by which the inflammatory skin disease impacts cardiovascular health. In two new studies presented at the 2011 American Heart Association Scientific Sessions (November 12-16, 2011) in Orlando, Florida, Penn researchers show that the systemic inflammatory impact of psoriasis may alter both the makeup and numbers of cholesterol particles, as well as impair the function of high-density lipoprotein (HDL), the "good" cholesterol. "Anecdotally, many researchers have observed that HDL levels may be lower in states of inflammation, such as rheumatoid arthritis, psoriasis, and even obesity," said lead study author Dr. Nehal Mehta, director of Inflammatory Risk in Preventive Cardiology at Penn. "However, these new findings suggest that in addition to lower levels, chronic inflammation associated with conditions like psoriasis may change the composition and decrease the function of HDL as well." In the current studies, researchers enrolled 78 patients with psoriasis and 84 control subjects. In the first study, the authors measured fasting lipid levels and examined the number and size of cholesterol particles using nuclear magnetic resonance (NMR) spectroscopy. This analysis revealed that patients with psoriasis had a higher number of smaller LDL particles, or "bad" cholesterol, which was independent of traditional risk factors and obesity.

November 14th

Conservation Success Reported for Scarlet Macaw in Guatemala

Researchers and conservationists from the Wildlife Conservation Society's Guatemala Program, WCS's Bronx Zoo, the National Park Service of Guatemala, and other groups report a major conservation victory from Central America: a bumper crop of magnificent scarlet macaw fledglings that have now taken flight over the forests of Guatemala. The newly fledged birds total 29 macaws, a big success for conservationists working in the Maya Biosphere Reserve who were hoping to record at least one fledgling from each monitored nest (24 nests in total) during the 2011 season. The monitoring program focused on helping weak and at-risk chicks—some of which were removed from tree cavity nests and hand-reared in a jungle hospital—with guidance from the Bronx Zoo's Department of Ornithology and veterinarians from the Global Health Program. The rehabilitated chicks were then fostered back in nests with chicks of the same age, a procedure that greatly increased the chances of survival for these rare birds. "The success in increasing the nesting success of scarlet macaws through intensive chick management and fostering is a great step forward for macaw conservation," said WCS Conservationist Rony Garcia. "We believe the lessons learned can not only help save the scarlet macaw in Guatemala, but be extended to help other threatened species of parrots and cavity nesters across the globe." With a total estimated population of some 300 macaws in the country, each successfully fledged bird is critical for the survival of the species. The bumper crop of fledglings in the 2011 season stands in stark contrast to the 2003 season that registered only one fledgling from 15 nests. Monitoring scarlet macaw nests is not for the faint of heart.

Good, Early Blood Glucose Control Can Delay Kidney Disease in Type 1 Diabetes

Maintaining good glucose control early in the course of type 1 diabetes could lessen the long-term risk of kidney disease, as measured by a common test of kidney function. This finding comes from more than two decades of research on preventing life-shortening complications of type 1 diabetes. The National Institutes of Health (NIH) funded the longitudinal study. Results were published online on November 12, 2011 in the New England Journal of Medicine and presented November 12, 2011 at the American Society of Nephrology Kidney Week in Philadelphia. Researchers at the University of Washington (UW) in Seattle and several collaborating institutions in the United States and Canada examined the effects of early, intensive glucose-lowering therapy on glomerular filtration rates (GFR). This measurement estimates how much blood passes each minute through tiny filters in the kidneys. A GFR blood test checks the kidney's ability to rid the body of a muscle-generated waste product, creatinine. If the kidneys can't filter fast enough, the substance builds up in the blood. A low GFR is a dangerous sign of existing diabetic kidney disease that can progress to kidney failure, also called end-stage kidney disease, which requires dialysis or kidney transplantation. Moreover, a low GFR also can contribute to the heart and blood vessel complications of diabetes, the researchers explained. People with type 1 diabetes are prone to kidney disease and related complications resulting in disability and premature death. Until this study, no interventions for this population have been shown to prevent impaired GFR. According to Dr.

November 13th

Newly Identified Gene Mutation Adds to Melanoma Risk

A major international study has identified a novel gene mutation that appears to increase the risk of both inherited and sporadic cases of malignant melanoma, the most deadly form of skin cancer. The identified mutation occurs in the gene encoding MITF, a transcription factor that induces the production of several important proteins in melanocytes, the cells in which melanoma originates. While previous research has suggested that MITF may act as a melanoma oncogene, the current study identifies a mechanism by which MITF mutation could increase melanoma risk. The report from researchers from the U.S., the U.K., and Australia was published online in Nature on November 13, 2011. It is expected to appear in a print issue along with a study from French researchers finding that the same mutation increased the risk for the most common form of kidney cancer, for melanoma, or for both tumors. "We previously knew that MITF is a master regulator for production of the pigment melanin; and several years ago we identified a chemical modification, called sumoylation, that represses MITF activity," says Dr. David Fisher, chief of Dermatology at Massachusetts General Hospital (MGH), director of the MGH Cutaneous Biology Research Center and co-senior author of the Nature paper. "The currently discovered mutation appears to block sumoylation of MITF, and the resulting overactivity of MITF significantly increases melanoma risk." While approximately 10 percent of patients with melanoma report a family history of the disease, true hereditary melanoma, involving multiple cases across many generations, probably accounts for 1 percent or less of all cases, says co-senior author Dr. Hensin Tsao, of MGH Dermatology and the Wellman Center for Photomedicine.

HDAC Inhibitor May Overcome Resistance to Tamoxifen in ER+ Breast Cancer

Researchers have shown how estrogen receptor (ER)-positive breast cancer tumors become resistant to tamoxifen, the only approved hormonal therapy for premenopausal patients with this type of breast cancer. They also found that introducing a novel histone deacetylase (HDAC) inhibitor in hormone therapy treatment can overcome resistance to hormonal therapy. "We always thought that resistance was primarily an inborn or genetic effect," said Dr. Pamela N. Munster, director of the Early-Phase Clinical Trials Program at the University of California, San Francisco (UCSF). "But this is not the case. Tumors have found a way to modify their genes to become resistant. This process is called 'epigenetics,' where genes are turned on and off, but the sequence of DNA is not altered. We have also found that with this kind of breast cancer, we can prevent that resistance with histone deacetylase inhibitors." Dr. Munster presented the findings at the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics, held November 12-16, 2011 in San Francisco, California. She and her colleagues found that ER-positive breast cancer tumors alter their genes to create more AKT, a protein that spurs actions within the cell to keep it alive — the opposite of what tamoxifen is designed to do. In a preclinical study, researchers introduced the HDAC inhibitor PCI-24781 at an early phase of tamoxifen treatment and found that it reverses the tumor's survival strategy of increasing production of AKT, thus stopping the tumor cells from developing resistance and leading to higher levels of cell death. "The HDACs regulate the response of AKT to tamoxifen, and together, the effects of HDAC inhibitors and tamoxifen lead to more cell death if introduced with hormonal therapy," said Dr. Munster.

November 11th

Two Mayo Clinic Studies Focus on High Blood Pressure and Pregnancy

Two studies from the Mayo Clinic presented during the this year’s American Society of Nephrology's Annual Kidney Week (November 8-November 13, 2011) provide new information related to high blood pressure during pregnancy. In one study, Dr. Vesna Garovic and her team examined the potential of a test done mid-pregnancy to predict which women will later develop preeclampsia, a late-pregnancy disorder that is characterized by high blood pressure and excess protein in the urine and that affects 3% to 5% of pregnancies. Left untreated, preeclampsia can lead to serious -- even fatal -- complications for a pregnant woman and her baby. Among a group of 315 patients, 15 developed preeclampsia and 15 developed high blood pressure (but not preeclampsia) during pregnancy. All of the patients who developed preeclampsia tested positive in mid-pregnancy in a test that detects the shedding of certain kidney cells called podocytes in the urine. None of those with only high blood pressure tested positive, and none of 44 women with normal pregnancies tested positive. Therefore, this test is highly accurate for predicting preeclampsia, which could alert clinicians to take steps to safeguard against the condition. In another study, Dr. Garovic's team looked at the long-term health effects of high blood pressure during pregnancy. They identified female residents of Rochester, Minnesota, and the surrounding townships in Olmsted County who delivered between 1976 and 1982. The investigators divided the women into two groups -- those with high blood pressure during pregnancy and those without -- and followed them after they reached 40 years of age to monitor their heart and kidney health. A total of 6,051 mothers delivered between 1976 and1982, and 607 women had high blood pressure at the time while 5,444 did not.

Insight into 100-Year-Old Haber-Bosch Process for Producing Ammonia

For the past 100 years, the Haber-Bosch process has been used to convert atmospheric nitrogen into ammonia, which is essential in the manufacture of fertilizer. Despite the longstanding reliability of the process, scientists have had little understanding of how it actually works. But now a team of chemists, led by Dr. Patrick Holland of the University of Rochester, has gained new insight into how the ammonia is formed. Their findings are published in the November 11, 2011 issue of Science. Dr. Holland calls nitrogen molecules "challenging." While they're abundant in the air around us, which makes them desirable for research and manufacturing, their strong triple bonds are difficult to break, making them highly unreactive. For the last century, the Haber-Bosch process has made use of an iron catalyst at extremely high pressures and high temperatures to break those bonds and produce ammonia, one drop at a time. The question of how this works, though, has not been answered to this day. "The Haber-Bosch process is efficient, but it is hard to understand because the reaction occurs only on a solid catalyst, which is difficult to study directly," said Dr. Holland. "That's why we attempted to break the nitrogen using soluble forms of iron." Dr. Holland and his team, which included Dr. Meghan Rodriguez and Dr. William Brennessel at the University of Rochester and Dr. Eckhard Bill of the Max Planck Institute for Bioinorganic Chemistry in Germany, succeeded in mimicking the process in solution. They discovered that an iron complex combined with potassium was capable of breaking the strong bonds between the nitrogen (N) atoms and forming a complex with an Fe3N2 core, which indicates that three iron (Fe) atoms work together in order to break the N-N bonds.

“1000 Fungal Genomes” Project Funded

With an estimated 1.5 million species, fungi represent one of the largest branches of the Tree of Life. They have an enormous impact on human affairs and ecosystem functioning due to their diverse activities as decomposers and pathogens, and their partnership with host organisms for mutual benefit. To use fungi for the benefit of humankind, an accurate understanding of what exactly they do, how they function, and how they interact in natural and synthetic environments is required. Dr. Jason Stajich, an assistant professor of plant pathology and microbiology at the University of California, Riverside, is a member of an international research team that, in collaboration with the Joint Genome Institute of the U.S. Department of Energy, has embarked on a five-year project to sequence 1000 fungal genomes from across the Fungal Tree of Life. Called the "1000 Fungal Genomes" project, the research endeavor aims to bridge the gap in our understanding of fungal diversity and is one of 41 projects funded through the U.S. Department of Energy's 2012 Community Sequencing Program. The funding awards were announced on November 3, 2011 by the DOE. "The overall plan is to fill in gaps in the Fungal Tree of Life by sequencing at least two species from every known fungal family," said Dr. Stajich, a member of UCR's Institute for Integrative Genome Biology. "Once the data is compiled, the project scientists will make use of the data as a starting point for interpreting how these organisms change and use their environment to make a living." Dr. Stajich is co-leading the Fungal Genomes project with Dr. Joey Spatafora, a professor of botany and plant pathology at Oregon State University.