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Archive - Jun 12, 2019

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Transgenerational Exposure to Bisphenol A (BPA) Causes Autism-Like Behavior in Mouse Model—Unexposed Mice Descended from Great-Grandmother Exposed to BPA During Pregnancy Show Evidence of Autism-Like Behavior

Transgenerational bisphenol A (BPA) exposure may contribute to autism, according to a mouse study that was published online on June 12, 2019 in the Endocrine Society's journal Endocrinology. The article is titled “Endocrine Disrupting Chemicals (EDCs) Are Chemicals or Mixtures of Chemicals That Interfere with the Way the Body's Hormones Work.” BPA is a common EDC used in plastics and food storage material, and it is already present in most humans' urine or blood. Animal studies have linked BPA to anxiety, aggression, and poor learning and social interactions. Studies of human populations report associations between BPA and neurobehavioral issues like attention deficit hyperactivity disorder and autism. "Exposure of mouse fetuses to BPA disrupts formation of nerve cell connections in the brain, and this is a transgenerational effect," said the study's senior author, Emilie F. Rissman, PhD, of the University of Virginia School of Medicine in Charlottesville, Virginia, and North Carolina State University in Raleigh, North Carolina. "To put this in human terms, if your great-grandmother was exposed to BPA during her pregnancy and none of your other relatives ever came into contact with BPA, your brain would still show these effects." In this mouse study, researchers tested mice descended from those exposed to BPA for social recognition and found that they showed a social behavioral deficient like autistic behavior. Mice whose great-grandmothers were exposed to BPA during pregnancy were more active and took longer to habituate to strangers than other mice. More strikingly, they didn't explore the new mice that were introduced to the group. Mice are normally very social and curious, so this is an exciting finding. "Even if we ban all BPA right now, that will not change these long-term effects on the brain," Dr. Rissman said.

Existing Acne Drug (Minocycline) Found Highly Effective in Preventing/Treating Hardening of the Arteries; Finding Culminates 12 Years of Research

A team of UK scientists has identified the mechanism behind hardening of the arteries, and shown in animal studies that a generic medication normally used to treat acne could be an effective treatment for the condition. The team, led by the University of Cambridge and King's College London, found that a molecule once thought only to exist inside cells for the purpose of repairing DNA is also responsible for hardening of the arteries, which is associated with dementia, heart disease, high blood pressure, and stroke. There is no current treatment for hardening of the arteries, which is caused by build-up of bone-like calcium deposits, stiffening the arteries and restricting blood flow to organs and tissues. Supported by funding from the British Heart Foundation, the researchers found that poly(ADP ribose), or PAR, a molecule normally associated with DNA repair, also drives the bone-like calcification of arteries. Additionally, using rats with chronic kidney disease, the researchers found that minocycline -- a widely-prescribed antibiotic often used to treat acne -- could treat hardening of the arteries by preventing the build-up of calcium in the circulatory system. The study, the result of more than a decade of fundamental research, was published online on June 11, 2019 in Cell Reports. The open-access article is titled “Poly(ADP-Ribose) Links the DNA Damage Response and Biomineralization.” "Artery hardening happens to everyone as they age, and is accelerated in patients on dialysis, where even children develop calcified arteries. But, up until now, we haven't known what controls this process and therefore how to treat it," said Professor Melinda Duer, PhD, from Cambridge's Department of Chemistry, who co-led the research as part of a long-term collaboration with Professor Cathy Shanahan, PhD, from King's College London.

New-Found Vulnerability in Major Human Viruses; Rhinoviruses (e.g., Colds) and Enteroviruses (e.g., Polio) Shown to Have Functionally Key Capsid Pocket That Can Be Blocked to Likely Prevent Replication

Discovery of a new feature of a large class of pathogenic viruses may allow development of new antiviral medications for the common cold, polio, and other illnesses, according to a new study published online on June 11 in the open-access journal PLOS Biology by Rana Abdelnabi, PhD, and Johan Neyts of the University of Leuven, Belgium, and James Geraets, PhD, and Sarah Butcher, PhD, of the University of Helsinki and their colleagues. The article is titled “A Novel Druggable Interprotomer Pocket in the Capsid of Rhino- and Enteroviruses.” Picornaviruses include rhinoviruses and enteroviruses. Rhinoviruses cause millions of cases of upper respiratory infections ("colds") yearly and contribute to asthma, while enteroviruses are responsible for millions of infections including cases such as meningitis, encephalitis, and polio. There are currently no antivirals that can be used for the treatment or prevention of any of the rhino- or enteroviruses. To replicate, viruses must interact with host cells, and in doing so, often need to change shape; stabilizing the virus particle is therefore thought to be a promising strategy for preventing replication. In a search for potential antiviral candidates, the authors found a compound that stabilized a model picornavirus. The scientists performed cryo-electron microscopy (cryo-EM) of the drug-virus complex to determine how the drug exerted its effect. Cryo-EM involves combining thousands of two-dimensional images to develop a highly detailed three-dimensional image of the target. Although picornaviruses have been studied for decades, the authors discovered a previously unknown pocket, or indentation, on the surface of the virus, in which the compound had lodged, thereby stabilizing the virus against the kind of shape change that would allow interaction with host cells.