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Archive - Sep 2019

Date

September 4th

Scientists Identify Four Genetic Regions Associated with Left-Handedness

A new study has, for the first time, identified regions of the genome associated with left-handedness in the general population and linked their effects with brain architecture. The study linked these genetic differences with the connections between areas of the brain related to language. It was already known that genes have a partial role in determining handedness - studies of twins have estimated that 25% of the variation in handedness can be attributed to genes - but which genes these are had not been established in the general population. The new study, led by researchers at the University of Oxford who were funded by the Medical Research Council and Wellcome, was published online on September 5, 2019 in Brain. The study identified some of the genetic variants associated with left-handedness by analyzing the genomes of approximately 400,000 people from UK Biobank, which included 38,332 left-handers. The open-access article is titled “'Handedness, Language Areas, and Neuropsychiatric Diseases: Insights from Brain Imaging and Genetics,” Of the four genetic regions the scientists identified, three of these were associated with proteins involved in brain development and structure. In particular, these proteins were related to microtubules, which are part of the scaffolding inside cells, called the cytoskeleton, which guides the construction and functioning of the cells in the body. Using detailed brain imaging from approximately 10,000 of these participants, the researchers found that these genetic effects were associated with differences in brain structure, in white matter tracts - which contain the cytoskeleton of the brain - that joins language-related regions.

September 4th

Immune Cells (Neutrophils) Drive Gallstone Formation; Finding May Open Door to New Therapeutic Interventions

Sticky meshworks of DNA and proteins extruded by white blood cells called neutrophils act as the glue that binds together calcium and cholesterol crystals during gallstone formation, researchers in Germany report in an article published online on August 15, 2019 in Immunity. The article is titled “"Neutrophil Extracellular Traps Initiate Gallstone Formation.” Both genetic and pharmacological approaches that inhibited the formation of these so-called neutrophil extracellular traps (NETs) reduced the formation and growth of gallstones in mice. "Neutrophils have long been considered the first line of defense against infection and have been shown to generate NETs that entangle and kill pathogens," says senior study author Martin Herrmann, MD, PhD, an immunologist at Universitätsklinikum Erlangen in Germany. "Here, we provide additional evidence for the double-edged-sword nature of these NETs by showing that they play an important role in the assembly and growth of gallstones. Targeting neutrophils and NET formation may become an attractive instrument to prevent gallstones in high-risk populations." Gallstones (image) are hard, pebble-like pieces of material that may be as small as a grain of sand or as large as a golf ball. They form in a pear-shaped organ called the gallbladder, which releases bile to the small intestine through the bile ducts during meals to help break down fat. Although most people with gallstones do not have symptoms, they can cause abdominal pain, nausea, and vomiting, and they are a leading cause of hospital admissions worldwide. Surgery to remove the gallbladder is one of the most common operations performed on adults in the United States.

Normal Cells Show Transient Induction of Telomerae Just Before Cell Death, Mediating Senescence and Reducing Tumorigenesis

New research from the University of Maryland (UMD) and the National Institutes of Health reveals a new role for the enzyme telomerase. Telomerase's only known role in normal tissue was to protect certain cells that divide regularly, such as embryonic cells, sperm cells, adult stem cells, and immune cells. Scientists thought telomerase was turned off in all other cells, except in cancerous tumors where it promotes unlimited cell division. The new study found that telomerase reactivates in normal adult cells at a critical point in the aging process. Just before cell death, a burst of telomerase buffers cells from the stresses of aging, slowing the process and reducing DNA damage that could lead to cancer. The study was published in the Proceedings of the National Academy of Sciences on September 2, 2019. The open-access article is titled” Transient Induction of Telomerase Expression Mediates Senescence and Reduces Tumorigenesis in Primary Fibroblasts.” "This study reshapes the current understanding of telomerase's function in normal cells,"said Kan Cao, PhD, senior author of the study and an Associate Professor of Cell Biology and Molecular Genetics at UMD. "Our work shows, for the first time, that there is a role for telomerase in adult cells beyond promoting tumor formation. We can now say that regulated activation of telomerase at a critical point in a cell's life cycle serves an important function." Telomerase prevents the shortening of telomeres--a specialized DNA-protein structure at the end of a cell's chromosomes that protect the chromosomes from damage (shown lighted up in image). Telomerase plays a critical role during embryonic development and stem cell differentiation, when cells divide profusely.

September 2nd

Scientists Locate RNA of Persistent Arthritis-Causing Chikungunya Virus Hidden in Dermal and Muscle Fibroblasts and Skeletal Myofibers

Since chikungunya virus emerged in the Americas in 2013, it has infected millions of people, causing fever, headache, rash, and muscle and joint pain. For some people, painful, debilitating arthritis lasts long after the other symptoms have resolved. Researchers have suspected that the virus or its genetic material - in this case, RNA - persist in the body undetected, but they have been unable to find its hiding places. Now, researchers at Washington University School of Medicine in St. Louis have figured out a way to detect cells infected with chikungunya virus that survive the infection. The scientists genetically modified the virus such that it activated a fluorescent tag within cells during infection. Months after the initial infection, the researchers could detect glowing red cells still harboring viral RNA. The study, in mice, opens up new ways to understand the cause of - and find therapies for - chronic viral arthritis. The findings were published August 29, 2019 in PLOS Pathogens. The open-access article is titled “Dermal and Muscle Fibroblasts and Skeletal Myofibers Survive Chikungunya Virus Infection and Harbor Persistent RNA.” Senior author Deborah Lenschow, MD, PhD, an Associate Professor of Medicine and of Pathology and Immunology, and co-first author and graduate student Marissa Locke answered questions about the research, which was conducted in collaboration with co-first author Alissa Young, PhD, co-author Michael S. Diamond, MD, PhD, the Herbert S. Gasser Professor of Medicine, and others. How common is chronic arthritis caused by chikungunya infection? Dr. Lenschow: Between 30% and 60% of people infected with chikungunya virus go on to develop chronic arthritis that can last up to three or four years after infection.

Promising Gene Replacement Therapy for Niemann-Pick Type A Disease Moves Forward at Ohio State

Research led by Krystof Bankiewicz (photo), MD, PhD, who recently joined The Ohio State University College of Medicine, shows that gene replacement therapy for Niemann-Pick type A disease is safe for use in nonhuman primates and has therapeutic effects in mice. These research findings were published online on August 21, 2019, in the journal Science Translational Medicine. The article is titled “Adeno-Associated Viral Vector Serotype 9–Based Gene Therapy for Niemann-Pick Disease Type A.” Prior to joining Ohio State as a Professor of Neurosurgery, Dr. Bankiewicz conducted this translational gene therapy research at the University of California at San Francisco, in conjunction with researchers in New York, Massachusetts, and Spain. Niemann-Pick disease type A (NPD-A) is a lysosomal storage disorder characterized by neurodegeneration and early death. It is caused by loss-of-function mutations in the gene coding for the enzyme acid sphingomyelinase (ASM), which hydrolyzes sphingomyelin into ceramide. With this disease, the body's ability to metabolize fat within cells is affected, causing these cells to malfunction and, eventually, die. This inherited disease can affect the brain, nerves, liver, spleen, bone marrow, and lungs. The three main types of Niemann-Pick disease are types A, B and C. The signs and symptoms experienced depend on the type and severity of the condition. Some infants with type A will show signs and symptoms within the first few months of life. Those with type B may not show signs for years and have a better chance of surviving to adulthood. People with type C may not experience any symptoms until adulthood. Dr.

September 1st

Screening for Genetic High Cholesterol (Familial Hypercholinesterolemia) Could Help Patients and Families Avoid Heart Attack

Genetic high cholesterol is underdiagnosed and undertreated, according to research presented on September 1, 2019 at the ESC (European Society of Cardiology) Congress 2019 together with the World Congress of Cardiology in Paris, France (August 31-September 4). The presentation abstract was titled "Prevalence and Severity of Coronary Disease In Patients with Familial Hypercholesterolemia Hospitalized for an Acute Myocardial Infarction: Data from the RICO Survey.” Screening could identify patients and family members affected by the condition so that lifestyle changes and treatments can be started to prevent heart attack and stroke. Heterozygous familial hypercholesterolaemia (FH) is a life-threatening genetic condition linked with a high risk of premature cardiovascular disease, including heart attack and stroke. FH is one of the most common potentially fatal family disorders, with a prevalence estimated at 1/250 to 1/200, corresponding to 3.6 to 4.5 million individuals in Europe. Patients with FH have high levels of "bad" cholesterol (low-density lipoprotein; LDL) due to a mutation in genes that clear cholesterol from the body. LDL particles accumulate in the blood and can ultimately build up in the coronary artery walls. Children of patients with heterozygous FH have a 50% chance of inheriting the disorder. As LDL cholesterol levels are elevated as early as birth, the risk of heart attack in patients with FH is 10 to 13 times greater than that of the general population. Elevated LDL cholesterol plus family or personal history of early heart disease are key criteria for diagnosis, which may be confirmed by genetic testing. Management of FH includes a healthy lifestyle and medication.