KREH2 helicase represses ND7 mRNA editing in procyclic-stage Trypanosoma brucei by opposite modulation of canonical and ‘moonlighting’ gRNA utilization creating a proposed mRNA structure

Unknown factors regulate mitochondrial U-insertion/deletion (U-indel) RNA editing in procyclic-form (PCF) and bloodstream-form (BSF) T. brucei. This editing, directed by anti-sense gRNAs, creates canonical protein-encoding mRNAs and may developmentally control respiration. Canonical editing by gRNAs that specify protein-encoding mRNA sequences occurs amid massive non-canonical editing of unclear sources and biological significance. We found PCF-specific repression at a major early checkpoint in mRNA ND7, involving helicase KREH2-dependent opposite modulation of canonical and non-canonical ‘terminator’ gRNA utilization. Terminator-programmed editing derails canonical editing and installs proposed repressive structure in 30% of the ND7 transcriptome. BSF-to-PCF differentiation in vitro recreated this negative control. Remarkably, KREH2-RNAi knockdown relieved repression and increased editing progression by reverting canonical/terminator gRNA utilization. ND7 transcripts lacking early terminator-directed editing in PCF exhibited similar negative editing control along the mRNA sequence, suggesting global modulation of gRNA utilization fidelity. The terminator is a ‘moonlighting’ gRNA also associated with mRNA COX3 canonical editing, so the gRNA transcriptome seems multifunctional. Thus, KREH2 is the first identified repressor in developmental editing control. This and our prior work support a model whereby KREH2 activates or represses editing in a stage and substrate-specific manner. KREH2’s novel dual role tunes mitochondrial gene expression in either direction during development

Mercury isotopic composition of hydrothermal systems in the Yellowstone Plateau volcanic field and Guaymas Basin sea-floor rift

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155680/1/Sherman_et_al_2009_Mercury_isotope.pd

Economic evaluation of quality improvement interventions to prevent catheter-associated urinary tract infections in the hospital setting: a systematic review.

BACKGROUND: Hospitals have implemented diverse quality improvement (QI) interventions to reduce rates of catheter-associated urinary tract infections (CAUTIs). The economic value of these QI interventions is uncertain. OBJECTIVE: To systematically review economic evaluations of QI interventions designed to prevent CAUTI in acute care hospitals. METHODS: A search of Ovid MEDLINE, Econlit, Centre for Reviews & Dissemination, New York Academy of Medicines Grey Literature Report, WorldCat, IDWeek conference abstracts and prior systematic reviews was conducted from January 2000 to October 2020.We included English-language studies of any design that evaluated organisational or structural changes to prevent CAUTI in acute care hospitals, and reported programme and infection-related costs.Dual reviewers assessed study design, effectiveness, costs and study quality. For each eligible study, we performed a cost-consequences analysis from the hospital perspective, estimating the incidence rate ratio (IRR) and incremental net cost/savings per hospital over 3 years. Unadjusted weighted regression analyses tested predictors of these measures, weighted by catheter days per study. RESULTS: Fifteen unique economic evaluations were eligible, encompassing 74 hospitals. Across 12 studies amenable to standardisation, QI interventions were associated with a 43% decline in infections (mean IRR 0.57, 95% CI 0.44 to 0.70) and wide ranges of net costs (mean US$52 000, 95$288 000 to $392 000), relative to usual care. CONCLUSIONS: QI interventions were associated with large declines in infection rates and net costs to hospitals that varied greatly but that, on average, were not significantly different from zero over 3 years. Future research should examine specific practices associated with cost-savings and clinical effectiveness, and examine whether or not more comprehensive interventions offer hospitals and patients the best value