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New Target For Dystonia Therapy

New Target For Dystonia Therapy—Dystonia—when someone’s muscles contract uncontrollably—is the third most common movement disorder (after Parkinson’s and essential tremor), affecting about 250,000 Americans. Research and treatment for the most common inherited form of dystonia, called DYT1, has focused mainly on the basal ganglia region of the brain. But new animal research by Einstein scientists implicates a different part of the brainthe cerebellumas the site of the problem. The study, published in the February 15 online issue of eLife, was led by Kamran Khodakhah, Ph.D., professor and chair of the Dominick P. Purpura Department of Neuroscience and the Harold and Muriel Block Chair in Neuroscience. He and his colleagues made their discovery after generating the first mouse model of DYT1 to exhibit the overt symptoms of dystonia seen in patients. Previous research in Dr. Khodakhah’s lab has shown that severing the link between the cerebellum and the basal ganglia might be an effective way to treat cerebellar-induced dystonias.

Monday, March 20, 2017
 
Putting the Brakes on Cancer

Putting the Brakes on Cancer—Stimulation of the PD-1 (Programmed Cell Death-1) receptor on the surface of T cells puts the brakes on T cells’ immune response. Tumors manage to avoid T-cell attack by using their cell-surface proteins PD-L1 and PD-L2 to activate PD-1. Einstein researchers led by Steven C. Almo, Ph.D., and Chandan Guha, M.B.B.S, Ph.D., developed a PD-1 receptor variant that binds strongly to PD-L1 and PD-L2 tumor proteins, rendering them unable to bind PD-1 receptors on T cells. As described in the February 6 issue of EBioMedicine, using the PD-1 receptor variant combined with radiation therapy in a mouse model of lung cancer caused decreases in both tumor burden and tumor recurrence. Radiation therapy fragments tumor cells, releasing tumor proteins that stimulate the immune system much as a vaccine would. Dr. Almo is professor and chair of biochemistry, professor of physiology & biophysics, and Wollowick Family Foundation Chair in Multiple Sclerosis and Immunology. Dr. Guha is professor and vice chair of radiation oncology.

Friday, March 17, 2017
 
Focusing on RNA-protein Interactions

Focusing on RNA-protein Interactions—Gene expression relies on interactions between messenger RNA molecules and RNA-binding proteins.  Insufficient resolution means that today’s microscopes tend to “see” molecular interactions that actually don’t occur. In a paper published on February 21 in the journal Proceedings of the National Academy of Sciences, Robert Singer, Ph.D., along with Carolina Eliscovich, Ph.D., and Shailesh Shenoy, B.S., describe their high-resolution methodology for detecting whether two molecules are physically interacting or are close to each other merely due to chance. Surprisingly, the methodology showed that certain proteins thought to bind mRNAs actually don’t. The new methodology could reveal dysfunctional RNA-protein interactions that can cause genetic disorders including neurodevelopmental and neurodegenerative diseases and cancer. Dr. Singer is professor and co-chair of anatomy & structural biology, as well as co-director of the Gruss-Lipper Biophotonics Center and of the Integrated Imaging Program. He also is professor in the Dominick P. Purpura Department of Neuroscience and of cell biology and the Harold and Muriel Block Chair in anatomy & structural biology.

Monday, March 06, 2017
 
Mixed Results from Testosterone Treatment

Mixed Results from Testosterone Treatment—For older men with low testosterone levels, supplementary testosterone can have both positive and negative health effects. The findings, published on February 21 in the Journal of the American Medical Association (JAMA) and JAMA Internal Medicine, come from clinical trials carried out at Einstein and 11 other centers around the country. The Einstein senior principal investigator was Jill P. Crandall, M.D., professor of clinical medicine and attending physician, endocrinology at Montefiore. Researchers at the Perlman School of Medicine at the University of Pennsylvania oversaw the trials, which involved 788 men with low testosterone, age 65 and over, who were randomized into two groups: one used a testosterone gel daily for one year and the other used a daily placebo gel. The four papers published report on four different health effects from testosterone treatment:

Bone: improved bone density and estimated bone strength. (JAMA Internal Medicine)

Anemia: improved red blood cell count in men with some types of anemia. (JAMA Internal Medicine)

Cognition: did not improve memory or any other measure of cognition. (JAMA)

Cardiovascular: more coronary artery plaque buildup in testosterone-treated men (as assessed by CT angiography), although the number of major adverse cardiovascular events (such as heart attacks or strokes) was similar in both groups. (JAMA)

Other results from this trial, published in February 2016 in the New England Journal of Medicine, showed that testosterone treatment resulted in modest improvements in sexual function, walking ability and mood.

Friday, March 03, 2017
 
Investigating Enzymes

Investigating Enzymes—Sulfotransferases (SULT) are enzymes that regulate the activities of hundreds of metabolites, including the activity of many drugs.  Dr. Leyh and his group have discovered that SULTS are regulated by allosteres — small-molecule metabolites that bind to SULTS at pockets distinct from their catalytic sites. These findings have increased understanding of the molecular basis of SULT function and may lead to ways of designing allosteres that can control SULT function. Such man-made allosteres could potentially help in treating diseases including addiction, depression, Parkinson’s disease, HIV infection and obesity. To that end, the National Institute of General Medical Sciences has awarded Thomas S. Leyh, Ph.D., a four-year, $1.5 million grant to characterize SULT-allostere binding structures. Dr. Leyh is professor of microbiology & immunology. (1R01GM121849-01)

Thursday, March 02, 2017
 
Probing Autophagy

Probing Autophagy—Cells use several kinds of autophagy—a process for breaking down and recycling proteins and other cellular components. Defects in autophagy can lead to liver and kidney diseases as well as neurodegenerative diseases including Alzheimer’s. One type of autophagy, called endosomal microautophagy (eMI), has been characterized in mammalian cell culture, but lacked a genetic system in an easily managed model organism. The National Institute of General Medical Sciences has awarded Andreas Jenny, Ph.D., a four-year, $1.8 million grant that his group will use to characterize eMI in fruit flies. Dr. Jenny and colleagues previously established a system in fruit flies for monitoring eMI and the proteins that it selectively degrades. They plan to use their system to identify components that regulate eMI in fruit flies. Dr. Jenny is associate professor of developmental and molecular biology and of genetics. (1R01GM119160-01A1)

Wednesday, February 22, 2017
 
Understanding Latino Heart Health

Understanding Latino Heart Health—The National Heart, Lung and Blood Institute awarded a four-year, $3.1 million grant to Yasmin Mossavar-Rahmani, Ph.D., and Robert Kaplan, Ph.D., to study the health of Hispanic & non-Hispanic prediabetics (individuals whose blood sugar level is higher than normal but not high enough for a type 2 diabetes diagnosis). Hispanic adults are at a greater risk of diabetes compared to the general U.S. population. Paradoxically, however, Hispanics live longer than people in the general population and may have a lower risk of cardiovascular disease, a common complication of diabetes. The study will monitor physical activity, among a diverse group of 5,500 prediabetics, and will look for explanations for the unique health profile of Hispanics.Dr. Mossavar-Rahmani is associate professor of clinical epidemiology & population health. Dr. Kaplan is professor of epidemiology & population health and holds the Dorothy and William Manealoff Foundation and Molly Rosen Chair in Social Medicine. (1R01HL136266-01)

Friday, February 17, 2017
 
Asthma Risk After Moving to the U.S.

Asthma Risk After Moving to the U.S.—The prevalence of asthma reportedly is higher among U.S.-born Hispanics/Latinos than those who’ve relocated here. But it’s not known whether these findings are consistent across Hispanic/Latino groups. In a retrospective study published online on February 2 in the American Journal of Preventive Medicine, lead authors Elina Jerschow, M.D., and Garrett Strizich, M.P.H., found that the effect on asthma risk from relocating to the U.S. differs among various Hispanic/Latino groups. The study involved more than 15,000 U.S.-dwelling participants in the NIH-funded Hispanic Community Health Study (HCHS)/Study of Latinos (SOL). They were questioned about their asthma histories from birth through age 30. Foreign-born Dominicans and Mexicans (and to a lesser extent Puerto Ricans) had higher rates of asthma after relocating to the U.S. compared with counterparts the same age who relocated to the U.S. when they were older. Dr. Jerschow is associate professor of medicine and attending physician at Montefiore.

Thursday, February 02, 2017
 
Preventing Drug-Resistant Tuberculosis

Preventing Drug-Resistant Tuberculosis—Efforts to prevent extensively drug-resistant (XDR) tuberculosis (TB) from spreading have traditionally relied on improving patient treatment. But a study co-authored by James Brust, M.D., and published in the January 18 online issue of The New England Journal of Medicine suggests that efforts to halt TB transmission in hospitals and community settings may be a better strategy. The study, conducted with collaborators at Emory University, the U.S. CDC, and the University of KwaZulu-Natal, enrolled 404 TB patients from South Africa’s KwaZulu-Natal province. All had XDR-TB, meaning their infections were resistant to at least four first-line and second-line TB drugs. South Africa is experiencing a widespread epidemic of XDR-TB, and many people there are co-infected with HIV, which weakens their immunity. The study found that transmission of XDR-TB was responsible for at least 69 percent of cases. By contrast, only 31 percent of cases involved patients who developed XDR-TB during treatment. Dr. Brust is an associate professor of medicine.

Friday, January 20, 2017
 
Gender Differences in Walking Among Seniors

Gender Differences in Walking Among Seniors—Albert Einstein College of Medicine scientists had previously shown that older people who do poorly on dual-task walking tests (walking while talking) face an increased risk for falls, disability and death. But it wasn’t known whether gender and stress influence how the brain responds to the demands of dual-task walking. A study by Roee Holtzer, Ph.D., and colleagues assessed older men and women during both walking and dual-task walking. When confronted with the demands of dual-task walking, older men were more vulnerable than older women to the effect that perceived stress has on their walking velocity and the oxygenation levels in their pre-frontal cortex (which controls executive functions). The study, published online on December 28, 2016, in the European Journal of Neuroscience, suggests that tests for assessing whether people prone are to mobility impairments should include measures of stress. Dr. Holtzer is a professor in the Saul R. Korey Department of Neurology.

Thursday, January 19, 2017
 
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