Macrophages stimulated by lipopolysaccharide (LPS) generate mitochondria-derived reactive oxygen species (mtROS) that act as antimicrobial agents and redox signals; however, the mechanism of LPS-induced mitochondrial superoxide generation is unknown. Here we show that LPS-stimulated bone-marrow-derived macrophages produce superoxide by reverse electron transport (RET) at complex I of the electron transport chain. Using chemical biology and genetic approaches, we demonstrate that superoxide production is driven by LPS-induced metabolic reprogramming, which increases the proton motive force (∆p), primarily as elevated mitochondrial membrane potential (Δψ) and maintains a reduced CoQ pool.
View Article and Find Full Text PDFThe Calgary Kids' Hand Rule (CKHR) is a clinical prediction rule intended to guide referral decisions for pediatric hand fractures presenting to the emergency department, identifying "complex" fractures that require surgical referral and optimizing care through better matching of patients' needs to provider expertise. The objective of this study was to externally validate the CKHR in two different tertiary pediatric hospitals in Canada. We partnered with British Columbia Children's Hospital (BCCH) and the Children's Hospital of Eastern Ontario (CHEO) to externally validate the CKHR using data from retrospective cohorts of pediatric hand fractures (via electronic medical record and x-ray review).
View Article and Find Full Text PDFMitochondria are major sites of reactive oxygen species (ROS) production within cells. ROS are important signalling molecules, but excessive production can cause cellular damage and dysfunction. It is therefore crucial to accurately determine when, how and where ROS are produced within mitochondria.
View Article and Find Full Text PDFDuring recent decades, changes in lifestyle have led to widespread nutritional obesity and its related complications. Remodelling adipose tissue as a therapeutic goal for obesity and its complications has attracted much attention and continues to be actively explored. The endothelium lines all blood vessels and is close to all cells, including adipocytes.
View Article and Find Full Text PDFRothera is a British Antarctic Survey research station located on Adelaide Island adjacent, to the Antarctic Peninsula. Diving is vital to support a long-standing marine science programme but poses challenges due to the extreme and remote environment in which it is undertaken. We summarise the diving undertaken and describe the medical measures in place to mitigate the risk to divers.
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