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Archive - Nov 2011 - Story

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November 30th

Simple Blood Test Detects Parkinson’s Disease Before Symptoms Appear

A new research report appearing in the December 2011 issue of the FASEB Journal shows how scientists from the United Kingdom have developed a simple blood test to detect Parkinson's disease even at the earliest stages. The test is possible because scientists found a substance in the blood, called "phosphorylated alpha-synuclein," which is common in people with Parkinson's disease, and then developed a way to identify its presence in blood. "A blood test for Parkinson's disease would mean you could find out if a person was in danger of getting the disease, before the symptoms started," said Dr. David Allsop, a researcher involved in the work from the Division of Biomedical and Life Sciences and the School of Health and Medicine at the University of Lancaster, in Lancaster, UK. "This would help the development of medicines that could protect the brain, which would be better for the quality of life and future health of older people." To develop the blood test for Parkinson's disease, Dr. Allsop and colleagues studied a group of people diagnosed with the disease and a second group of healthy people of a similar age. Blood samples from each group were analyzed to determine the levels of phosphorylated alpha-synuclein present. They found those with Parkinson's disease had increased levels of the substance. Based upon these findings, researchers developed a blood test that detects the presence of phosphorylated alpha-synuclein, which could allow for diagnosis of the disease well before symptoms appear, but when brain damage has already begun to occur. "When most people think of Parkinson's disease, they think of the outward symptoms, such as involuntary movements," said Dr.

November 29th

Research Sheds Light on “Dark Matter” of Genome

Most of the time, Dr. Stefano Torriani is a plant pathologist. His most recent research project revolved around the fungus Mycosphaerella graminicola where he analyzed a special class of genes that encode cell-wall-degrading enzymes. A virulent fungus relies heavily on these enzymes when attacking a plant. But while investigating these genes, Dr. Torriani came across something odd; one gene came in different sizes in different individuals. To further explore and better understand this phenomenon, the researcher deviated from his original plan and drew in other experts, including Drs. Daniel Croll, Patrick Brunner, and Eva Stukenbrock from the research group led by Dr. Bruce McDonald, Professor of Plant Pathology, ETH Zurich. What the collaborators discovered after a year of feverish research throws new light on genome evolution - but still leaves many questions unanswered. The plant pathologists quickly answered the question of why the same gene came in different lengths in different individuals. In some strains, the gene "ID-60105," which encodes for a cell-wall-digesting enzyme, had an intron; in other strains, the same gene did not have an intron. Thus, the researchers stepped into a relatively young field in biology. So-called "spliceosomal introns" were discovered only 30 years ago. Because they are non-coding regions of a gene, they provide no information on the structure of the encoded protein. Introns are separated by the coding regions, called exons. A gene, including both exons and introns, is read by the cellular machinery and transcribed into a messenger RNA. In a next step, the noncoding introns are cut away and the coding exons are spliced together. This creates the blueprint for the corresponding protein encoded by a gene.

November 26th

Surprise Role of Nuclear Structure Protein in Organ Development

Scientists have long held theories about the importance of proteins called B-type lamins in the process of embryonic stem cells replicating and differentiating into different varieties of cells. New research from a multi-institutional team led by the Carnegie Institution for Science’s Dr. Yixian Zheng indicates that, counter to expectations, these B-type lamins are not necessary for stem cells to renew and develop, but are necessary for proper organ development. The team’s work was published on November 24, 2011 in Science Express. Nuclear lamina is the material that lines the inside of a cell's nucleus. Its major structural component is a family of proteins called lamins, of which B-type lamins are prominent members and thought to be absolutely essential for a cell's survival. Mutations in lamins have been linked to a number of human diseases. Lamins are thought to suppress the expression of certain genes by binding directly to the DNA within the cell's nucleus. The role of B-type lamins in the differentiation of embryonic stem cells into various types of cells, depending on where in a body they are located, was thought to be crucial. The lamins were thought to use their DNA-binding suppression abilities to tell a cell which type of development pathway to follow. But the research team--including Carnegie's Drs. Youngjo Kim, Katie McDole, and Chen-Ming Fan--took a hard look at the functions of B-type lamins in embryonic stem cells and in live mice. They found that, counter to expectations, B-type lamins were not essential for embryonic stem cells to survive, nor did their DNA binding directly regulate the genes to which they were attached. However, mice deficient in B-type lamins were born with improperly developed organs—including defects in the lungs, diaphragms, and brains—and were unable to breathe.

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.