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Archive - Dec 13, 2019

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DNA Stress Sensed by Mitochondria Can Cause Them to Activate Innate Immune System, Including Interferon-Stimulated Genes (ISGs) That Act to Protect Nuclear DNA and This May Support Development of Resistance to DNA-Damaging Chemotherapy

Mitochondria, tiny structures present in most cells, are known for their energy-generating machinery. Now, Salk researchers have discovered a new function of mitochondria: they set off molecular alarms when cells are exposed to stress or chemicals that can damage DNA, such as chemotherapy. The results, published online in Nature Metabolism on December 9, 2019, could lead to new cancer treatments that prevent tumors from becoming resistant to chemotherapy. The article is titled “Mitochondrial DNA Stress Signalling Protects the Nuclear Genome.” "Mitochondria are acting as a first line of defense in sensing DNA stress. The mitochondria tell the rest of the cell, 'Hey, I'm under attack, you better protect yourself,'" says Gerald Shadel, PhD, a Professor in Salk's Molecular and Cell Biology Laboratory and the Audrey Geisel Chair in Biomedical Science. Most of the DNA that a cell needs to function is found inside the cell's nucleus, packaged in chromosomes and inherited from both parents. But mitochondria each contain their own small circles of DNA (called mitochondrial DNA or mtDNA), passed only from a mother to her offspring. And most cells contain hundreds--or even thousands--of mitochondria. Dr. Shadel's lab group previously showed (in “Mitochondrial DNA Stress Primes the Antiviral Innate Immune Response” at https://www.nature.com/articles/nature14156) that cells respond to improperly packaged mtDNA similarly to how they would react to an invading virus--by releasing it from mitochondria and launching an immune response that beefs up the cell's defenses.

Why Giant Pandas Are Born So Tiny; Short Gestation Period May Be Cause

Born pink, blind, and helpless, giant pandas typically weigh about 100 grams at birth -- the equivalent of a stick of butter. Their mothers are 900 times more massive than that. This unusual size difference has left researchers puzzled for years. With a few exceptions among animals such as echidnas and kangaroos, no other mammal newborns are so tiny relative to their mothers. No one knows why, but a Duke University study of bones across 10 species of bears and other animals finds that some of the current theories don't hold up. Duke biology professor Kathleen Smith, PhD, and her former student Peishu Li published their findings this month in the Journal of Anatomy. The article was published online on December 2, 2019 and is titled "Comparative Skeletal Anatomy of Neonatal Ursids and the Extreme Altriciality of the Giant Panda.” Baby panda skeletons are hard to come by, but the researchers were able to study the preserved remains of baby pandas born at the Smithsonian's National Zoo in Washington, D.C. The National Zoo's first panda couple, Ling-Ling and Hsing-Hsing, had five full-term cubs in the 1980s, but none of them survived long after birth. The researchers took micro-CT scans of two of those cubs, along with newborn grizzlies, sloth bears, polar bears, dogs, a fox, and other closely related animals from the Smithsonian National Museum of Natural History and the North Carolina State College of Veterinary Medicine. They used the scans to create 3-D digital models of each baby's bony interior at birth. As a baby animal grows and develops inside the womb, its bones and teeth do also. The researchers examined the degree of ossification, or how much the skeleton has formed by the time of birth.

Multiple Distinct Psychiatric Diseases Share Common Genetic Structure, According to Large MGH Study Published in Cell; Results May Provide New Clues for Treatment and Prevention of Psychiatric Disorders

Many distinct psychiatric diseases share a common genetic structure, according to new research by scientists at Massachusetts General Hospital (MGH) and the Psychiatric Genomics Consortium, an international team of investigators. Psychiatric disorders affect more than 25 percent of the population in a given year. In the largest-ever study of its kind, published in the December 12, 2019 issue of Cell, researchers identified more than 100 genetic variants that affect the risk for more than one mental health condition. The article is titled “Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms Across Eight Psychiatric Disorders.” A gene is made up of segments of DNA; an alteration in the DNA sequence produces a gene variant, which can increase or decrease the risk for disease. Many individual gene variants that affect the risk for specific psychiatric disorders have been identified. However, genes are often pleiotropic, meaning they produce multiple effects in the body. Identifying gene variants that influence the risk for more than one psychiatric disorder is an important step toward improving the diagnosis and treatment of these conditions, says the study’s senior author, Jordan W. Smoller, MD, ScD, Director of MGH’s Psychiatric and Neurodevelopmental Genetics Unit and a Professor of Psychiatry at Harvard Medical School (HMS). “Understanding how specific genetic variations may contribute to a broad spectrum of illnesses can tell us something about the degree to which these disorders may have a shared biology,” says Dr. Smoller. To identify these multi-purpose gene variants, the researchers used a technique called genome-wide association to analyze genetic data from 494,162 healthy control subjects and 232,964 people diagnosed with at least one of eight common psychiatric disorders.