Deep transcriptome profiling reveals limited conservation of A-to-I RNA editing in Xenopus.

BACKGROUND: Xenopus has served as a valuable model system for biomedical research over the past decades. Notably, ADAR was first detected in frog oocytes and embryos as an activity that unwinds RNA duplexes. However, the scope of A-to-I RNA editing by the ADAR enzymes in Xenopus remains underexplored. RESULTS: Here, we identify millions of editing events in Xenopus with high accuracy and systematically map the editome across developmental stages, adult organs, and species. We report diverse spatiotemporal patterns of editing with deamination activity highest in early embryogenesis before zygotic genome activation and in the ovary. Strikingly, editing events are poorly conserved across different Xenopus species. Even sites that are detected in both X. laevis and X. tropicalis show largely divergent editing levels or developmental profiles. In protein-coding regions, only a small subset of sites that are found mostly in the brain are well conserved between frogs and mammals. CONCLUSIONS: Collectively, our work provides fresh insights into ADAR activity in vertebrates and suggest that species-specific editing may play a role in each animal's unique physiology or environmental adaptation.

MED13 and glycolysis are conserved modifiers of α-synuclein-associated neurodegeneration.

α-Synuclein (α-syn) is important in synucleinopathies such as Parkinson's disease (PD). While genome-wide association studies (GWASs) of synucleinopathies have identified many risk loci, the underlying genes have not been shown for most loci. Using Drosophila, we screened 3,471 mutant chromosomes for genetic modifiers of α-synuclein and identified 12 genes. Eleven modifiers have human orthologs associated with diseases, including MED13 and CDC27, which lie within PD GWAS loci. Drosophila Skd/Med13 and glycolytic enzymes are co-upregulated by α-syn-associated neurodegeneration. While elevated α-syn compromises mitochondrial function, co-expressing skd/Med13 RNAi and α-syn synergistically increase the ratio of oxidized-to-reduced glutathione. The resulting neurodegeneration can be suppressed by overexpressing a glycolytic enzyme or treatment with deferoxamine, suggesting that compensatory glycolysis is neuroprotective. In addition, the functional relationship between α-synuclein, MED13, and glycolytic enzymes is conserved between flies and mice. We propose that hypoxia-inducible factor and MED13 are part of a druggable pathway for PD.

Effectiveness of educational interventions on evidence-based practice for nurses in clinical settings: A systematic review and meta-analysis.

OBJECTIVES: This study aimed to synthesise the best available evidence on the effectiveness of education interventions to teach evidence-based practice (EBP) on nurse-related and patient-related outcomes. DESIGN: This is a systematic review and meta-analytic paper. DATA SOURCES: Published and unpublished studies in English were searched from 10 databases from 2005 to 2021. REVIEW METHODS: Randomised controlled trials (RCTs) and clinical controlled trials (CCTs) describing education interventions to improve EBP knowledge, skills, attitude, confidence and behaviours among nurses were eligible. Two reviewers independently screened, appraised and extracted data. Meta-analysis was conducted using a random-effect model to synthesise data using review manager software. Standardised mean difference (SMD) represented an effect measure. Heterogeneity was assessed using Cochran-Q square test and I square statistics. Subgroup and narrative synthesis were also conducted. RESULTS: Ten studies (6 RCTs and 4 CCTs) were selected for this review. Results from a CCT suggested that education interventions improved EBP knowledge with a large effect size (SMD = 2.01). Education interventions also enhanced EBP skills (n = 1), combined knowledge/skills (SMD = 0.48, N = 5), attitude toward EBP (SMD = 0.39, N = 4), confidence to conduct EBP (SMD = 0.43, n = 1) and EBP behaviour (SMD = 0.26, n = 5). None of the studies used patient-related outcomes. CONCLUSION: Overall, education interventions improved nurses' EBP knowledge, skills, attitude, confidence and behaviour. EBP education interventions should be part of nurses' professional development in clinical settings. The interventions may be delivered through combined lectures, group discussions, hands-on practice via face-to-face and/or online learning. Future research should test education interventions using RCTs, large sample size, and in-depth qualitative data.