Syndicate content

Archive - Oct 16, 2020

Study Suggests Higher Dopamine Levels May Be Associated with Better Mobility in Frail & Elderly Adults

Variations in a gene that regulates dopamine levels in the brain may influence, positively or negatively, the mobility of elderly and frail adults, according to new research from the University of Pittsburgh (Pitt) Graduate School of Public Health. These results, published online on October 12, 2020 in the Journal of The American Geriatrics Society, add to a growing body of evidence hinting that lower dopamine levels can contribute to the slower, often disabling walking patterns seen in some elderly populations. The article is titled “Catechol‐O‐Methyltransferase Genotype, Frailty, and Gait Speed in a Biracial Cohort of Older Adults.” "Most people think about dopamine's role in mobility in the context of Parkinson's disease, but not in normal aging," said senior author Caterina Rosano, MD, MPH, Professor of Epidemiology at Pitt Public Health. "We were curious to see if a genetic predisposition to produce more or less dopamine was related to mobility in individuals who had some level of frailty, yet did not have dementia, parkinsonism or any other neurological condition." While several genetic elements control dopamine signaling, Dr. Rosano and her team focused on a gene called COMT (catechol-O-methyltransferase), which breaks down dopamine to control its levels within the brain. They also considered the frailty status of participants, which is a common consequence of aging marked by a decline in physiological function, poor adjustment to stressors and a susceptibility toward adverse health outcomes. The researchers suspected that frail participants could be particularly vulnerable to COMT-driven differences in dopamine levels. Dr.

How Deadly Parasites “Glide” Along and Into Human Cells

In biological terms, gliding refers to the type of movement during which a cell moves along a surface without changing its shape. This form of movement is unique to parasites from the phylum Apicomplexa, such as Plasmodium and Toxoplasma. Both parasites, which are transmitted by mosquitoes and cats, have an enormous impact on global heath. Plasmodium causes 228 million malaria infections and approximately 400,000 deaths per year. Toxoplasma, which infects an estimated one third of the human population, can cause severe symptoms in some people, and is particularly dangerous during pregnancy. Gliding enables the Apicomplexa parasites to enter and move between host cells. For example, upon entering the human body through a mosquito bite, Plasmodium glides through human skin before crossing into human blood vessels. This type of motion relies on actin and myosin, which are the same proteins that enable muscle movement in humans and other vertebrates. Myosin has a form of molecular 'legs' that 'march' along actin filaments and thereby create movement. In Apicomplexa, myosin interacts with several other proteins, which together form a complex called the “glideosome.” The exact mechanism by which the glideosome works is not well understood, among other reasons because the molecular structure of most glideosome proteins are unknown. Yet understanding this mechanism could aid the development of drugs that prevent the assembly of the glideosome and thereby stop the progression of diseases such as malaria and toxoplasmosis. Scientists at European Molecular Biology Laboratory (EMBL) Hamburg analyzed the molecular structure of essential light chains (ELCs), which are glideosome proteins that bind directly to myosin.

Scientists Develop “Unprecedented” 3-D Model of Molecular Machine (BAF Complex) That Regulates Expression of Genes by Modifying Chromatin; Model Has Enabled Investigators to Map Many Cancer-Related Mutations to Locations in BAF Complex

Scientists have created an unprecedented 3-dimensional structural model of a key molecular “machine” known as the BAF complex (mammalian SWI/SNF complex) (https://en.wikipedia.org/wiki/SWI/SNF), which modifies DNA architecture and is frequently mutated in cancer and some other diseases. The researchers, led by Cigall Kadoch (photo), PhD, (http://www.kadochlab.org/ of Dana-Farber Cancer Institute, have reported the first 3-D structural “picture” of BAF complexes purified directly from human cells in their native states--rather than artificially synthesized in the laboratory--providing an opportunity to spatially map thousands of cancer-associated mutations to specific locations within the complex. “A 3-D structural model, or ‘picture,’ of how this complex actually looks inside the nucleus of our cells has remained elusive--until now,” says Dr. Kadoch. The newly obtained model represents “the most complete picture of the human BAF complex achieved to date,” said the investigators, reporting in the journal Cell. The article is titled “A Structural Model of the Endogenous Human BAF Complex Informs Disease Mechanisms.” Dr. Kadoch is Associate Professor of Pediatric Oncology, Dana-Farber Cancer Institute; Affiliated Faculty, Biological Chemistry and Molecular Pharmacology, Harvard Medical School; and Institute Member and Epigenomics Program Co-Director, Broad Institute of MIT and Harvard. The new findings “provide a critical foundation for understanding human disease-associated mutations in components of the BAF complex, which are present in over 20% of human cancers and in several intellectual disability and neurodevelopomental disorders,” the authors said.