One bond makes all the difference: Three suitably positioned amino acid side chains (see picture) and a hydrophobic environment are all that is required for an amidation reaction with remarkable consequences. An emerging central building block of bacterial surface proteins owes its stability to a spontaneously formed isopeptide bond. The impact of this bond on protein structure and dynamics and the mechanism of its formation are scrutinized in detail.

ObjectivesTo systematically reivew the observational evidence of the effect of school closures and school reopenings on SARS-CoV-2 community transmission.SettingSchools (including early years settings, primary schools and secondary schools).InterventionSchool closures and reopenings.Outcome measureCommunity transmission of SARS-CoV-2 (including any measure of community infections rate, hospital admissions or mortality attributed to COVID-19).MethodsOn 7 January 2021, we searched PubMed, Web of Science, Scopus, CINAHL, the WHO Global COVID-19 Research Database, ERIC, the British Education Index, the Australian Education Index and Google, searching title and abstracts for terms related to SARS-CoV-2 AND terms related to schools or non-pharmaceutical interventions (NPIs). We used the Cochrane Risk of Bias In Non-randomised Studies of Interventions tool to evaluate bias.ResultsWe identified 7474 articles, of which 40 were included, with data from 150 countries. Of these, 32 studies assessed school closures and 11 examined reopenings. There was substantial heterogeneity between school closure studies, with half of the studies at lower risk of bias reporting reduced community transmission by up to 60% and half reporting null findings. The majority (n=3 out of 4) of school reopening studies at lower risk of bias reported no associated increases in transmission.ConclusionsSchool closure studies were at risk of confounding and collinearity from other non-pharmacological interventions implemented around the same time as school closures, and the effectiveness of closures remains uncertain. School reopenings, in areas of low transmission and with appropriate mitigation measures, were generally not accompanied by increasing community transmission. With such varied evidence on effectiveness, and the harmful effects, policymakers should take a measured approach before implementing school closures; and should look to reopen schools in times of low transmission, with appropriate mitigation measures.

Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency, MAF > 0.05). In a meta-analysis of up to >1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (MAF ≤ 0.01) variant BP associations ( P < 5 × 10 -8 ), of which 32 were in new BP-associated loci and 55 were independent BP-associated SNVs within known BP-associated regions. Average effects of rare variants (44% coding) were ~8 times larger than common variant effects and indicate potential candidate causal genes at new and known loci ( e.g. GATA5 , PLCB3 ). BP-associated variants (including rare and common) were enriched in regions of active chromatin in fetal tissues, potentially linking fetal development with BP regulation in later life. Multivariable Mendelian randomization suggested possible inverse effects of elevated systolic and diastolic BP on large artery stroke. Our study demonstrates the utility of rare variant analyses for identifying candidate genes and the results highlight potential therapeutic targets.