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Archive - Oct 25, 2015

Human Gene for Key Sepsis Protein (Gasdermin-D) Identified; Cleavage of GSDMD Triggers Cell Daath by Pyroptosis; Discovery May Lead to More Effective Treatments of Often-Lethal Whole-Body Infection Condition, and Also of Other Inflammatory Disorders

Scientists have identified a gene that could potentially open the door for the development of new treatments of the lethal disease sepsis. Researchers from The Australian National University (ANU) and the Garvan Institute of Medical Research worked with Genentech, a leading United States biotechnology company, to identify a gene that triggers the inflammatory condition that can lead to the full-body infection sepsis. "Isolating the gene so quickly was a triumph for the team," said Professor Simon Foote, Director of The John Curtin School of Medical Research (JCSMR) at ANU. Sepsis is a severe whole-body infection that kills an estimated one million people in the United States alone each year. It occurs as a complication to an existing infection, and, if not treated quickly, can lead to septic shock and multiple organ failure, with death rates as high as 50 per cent. Professor Foote acknowledged the vital support of the Australian Government's National Collaborative Research Infrastructure Strategy in setting up the Australian Phenomics Facility at JCSMR, where the gene was identified. Researchers were aware that sepsis occurs when molecules known as lipopolysaccharides (LPS) on the surface of gram-negative bacteria infiltrate cells, triggering an immune response that causes the cells to self-destruct. But exactly how the self-destruct button was pressed had remained a mystery, until now. The team found that the protein gasdermin-D (image) plays a critical role in the pathway to sepsis. Scientists at Genentech showed that gasdermin-D usually exists in cells in an inactive form.

DNA from Bronze Age Human Teeth Suggests Pneumonic Plague Was Spread from Human-to-Human without Flea Vector Almost 6,000 Years Ago; Evolved 3,000 Years Later to Permit Flea-Borne Pandemic Transmission of Deadlier Bubonic Plague

New research analyzing ancient DNA has revealed that plague has been endemic in human populations for more than twice as long as previously thought, and that the ancestral plague would have been predominantly spread by human-to-human contact -- until genetic mutations allowed Yersinia pestis (Y. pestis), the bacteria that causes plague, to survive in the guts of fleas. These mutations, which may have occurred near the turn of the 1st millennium BC, gave rise to the bubonic form of plague that spreads at terrifying speed through flea – and, consequently, rat -- carriers. The bubonic plague caused the pandemics that decimated global populations, including the Black Death, which wiped out half the population of Europe in the 14th century. Before its flea-borne evolution, however, researchers say that plague was in fact endemic in the human populations of Eurasia at least 3,000 years before the first plague pandemic in historical records (the Plague of Justinian in 541 AD). The scientists say the new evidence that Y. pestis bacterial infection in humans actually emerged around the beginning of the Bronze Age (~4,000 BC) suggests that plague may have been responsible for major population declines believed to have occurred in the late 4th and early 3rd millennium BC. The new findings were published as the open-access cover article of the October 22, 2015 issue of Cell.