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Angiogenesis plays a vital role for postnatal development and tissue repair following ischemia. Reactive oxygen species (ROS) generated by NADPH oxidases (NOXes) and mitochondria act as signaling molecules that promote angiogenesis in endothelial cells (ECs) which mainly relies on aerobic glycolysis for ATP production. However, the connections linking redox signaling with glycolysis are not well understood. The GTPase Drp1 is a member of the dynamin superfamily that moves from cytosol to mitochondria through posttranslational modifications to induce mitochondrial fission. The role of Drp1 in ROS-dependent VEGF signaling and angiogenesis in ECs has not been previously described. Here, we identify an unexpected function of endothelial Drp1 as a redox sensor, transmitting VEGF-induced H 2 O 2 signals to enhance glycolysis and angiogenesis. Loss of Drp1 expression in ECs inhibited VEGF-induced angiogenic responses. Mechanistically, VEGF rapidly induced the NOX4-dependent sulfenylation (CysOH) of Drp1 on Cys 644 , promoting disulfide bond formation with the metabolic kinase AMPK and subsequent sulfenylation of AMPK at Cys 299 / 304 via the mitochondrial fission-mitoROS axis. This cysteine oxidation of AMPK, in turn, enhanced glycolysis and angiogenesis. In vivo , mice with EC-specific Drp1 deficiency or CRISPR/Cas9-engineered "redox-dead" (Cys to Ala) Drp1 knock-in mutations exhibited impaired retinal angiogenesis and post-ischemic neovascularization. Our findings uncover a novel role for endothelial Drp1 in linking VEGF-induced mitochondrial redox signaling to glycolysis through a cysteine oxidation-mediated Drp1-AMPK redox relay, driving both developmental and reparative angiogenesis.

This study examines employee perceptions on the effective adoption of artificial intelligence (AI) principles in their organizations. 49 interviews were conducted with employees of 24 organizations across 11 countries. Participants worked directly with AI across a range of positions, from junior data scientist to Chief Analytics Officer. The study found that there are eleven components that could impact the effective adoption of AI principles in organizations: communication, management support, training, an ethics office(r), a reporting mechanism, enforcement, measurement, accompanying technical processes, a sufficient technical infrastructure, organizational structure, and an interdisciplinary approach. The components are discussed in the context of business code adoption theory. The findings offer a first step in understanding potential methods for the effective adoption of AI principles in organizations., Competing Interests: Conflict of interestThe author declares that she has no conflict of interest., (© The Author(s), under exclusive licence to Springer Nature B.V. 2022.)

Context: Disparities in the prevalence, morbidity, and mortality of multiple mental health conditions have been described between rural and urban populations. However, there is limited information regarding differences in exposure to trauma and trauma-related mental health conditions in these populations. Given the number of veterans who are returning to rural communities after serving in Operation Enduring Freedom and Operation Iraqi Freedom, differences in trauma exposure are of particular relevance. Trauma exposure is related to a variety of mental health disorders including substance use disorders (SUD)., Purpose: The objectives of this preliminary study were to describe lifetime military and nonmilitary trauma and to compare trauma history between rural and urban veterans in SUD treatment., Methods: Sixty adults in SUD treatment were enrolled at 3 Veterans Health Administration sites in Nebraska over a 3-month period in 2008. Subjects completed an interview with study staff, which assessed SUD diagnoses and childhood, lifetime, and military trauma. Rural or urban status was determined by self-report of childhood residence. Childhood trauma, lifetime trauma, and response to military trauma were compared between rural and urban veterans., Findings: Although there were no significant differences in trauma exposure between rural and urban groups, there was an association between specific types of trauma and measures typically associated with increased substance abuse severity and poorer SUD treatment outcome., Conclusion: This is the first study, to our knowledge, which compared trauma exposure between rural and urban veterans and identified an association between childhood trauma exposure and multiple SUD treatment attempts., (No claim to original US government works.)