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Membrane ion channels can be responsive to a variety of stimuli such as pressure, temperature, or pH. Here, the authors show that simply shining 365 nm light activates a native potassium channel in rodent pain-sensing neurons, delivering powerful analgesia without drugs or genetic manipulations.

Variants in the PSMC5 gene impair proteasome function and cellular homeostasis, altering brain development in children. This study reveals underlying molecular mechanisms contributing to this neurodevelopmental phenotype, and suggests therapeutic leads for neurodevelopmental proteasomopathies.

In this Review, the authors address considerations for enteral antithrombotic therapy in patients with cardiovascular disease and gastrointestinal comorbidities, who often have an increased risk of gastrointestinal bleeding. Approaches include tailoring of antithrombotic regimens and gastrointestinal-protection strategies.

Panos Deloukas, Nilesh Samani and colleagues report a large-scale association analysis using the Metabochip array in 63,746 coronary artery disease cases and 130,681 controls. They identify 15 susceptibility loci, refine previous associations and use network analysis to highlight biological pathways.

Multi-omic time course experiments reveal intricate biology of salt stress response mechanisms of the historically and industrially relevant algae, Scenedesmus obliquus UTEX393.

Currently, systematic care for adults and adolescents with oesophageal atresia–tracheoesophageal fistula (EA-TEF) as they transition into adulthood is lacking. A multidisciplinary group of experts structured this Consensus Statement offering guidelines for the care of adolescents and adults with EA-TEF during transition.

Relevance of indirect protection of household members of vaccinees is unclear. Here, Tsang et al. quantify the direct and indirect protection of vaccination in a randomized controlled trial and show that benefits of individual vaccination remain important even when other household members are vaccinated.

Photoaffinity analogs of a family of glycosylated macrolides, apoptolidins, revealed the F₁ subcomplex of mitochondrial ATP synthase as the target. Cryo-EM analysis of the apoptolidin–ATP synthase complex enabled identification of resistance mutations.

Acquired mutations of the gene UBA1 occurring in myeloid cells that result in the expression of impaired isoforms of the enzyme E1 have been described in patients with a severe adult onset auto-inflammatory syndrome called VEXAS. Here the authors profile patients with UBA1 mutations presenting with or without VEXAS disease and show VEXAS disease is characterized by inflammasome activation and monocyte dysregulation.

Heribert Schunkert and colleagues report a meta-analysis of 14 genome-wide association studies of coronary disease (CAD) followed by replication in additional cohorts. They confirm 10 previously associated loci and identify 13 loci newly associated with CAD.

Classification of archaeal and bacterial viruses can be automated with an algorithm that identifies relationships on the basis of shared gene content.

An atomic model for a type 2 secretion system pseudopilus from Klebsiella oxytoca reveals a comprehensive network of inter-subunit contacts while mutational and functional analyses highlight the role of calcium in PulG folding and stability.

The authors use an agent-based model to investigate the potential of reactive vaccination strategies for COVID-19 outbreak mitigation. They find that distributing vaccines in schools and workplaces where cases are detected is more impactful than non-reactive strategies in a wide range of epidemic scenarios.

A study shows that, although the number of incarcerated people in the USA decreased during the first year of the COVID-19 pandemic, the fraction of incarcerated Black and Latino individuals increased.

Polygenic scores (PGS) have high potential for clinical use but are currently underpowered for many applications. Here, the authors develop an approach that leverages an agnostic library of hundreds of PGS to increase prediction of complex diseases and other traits. This multi-PGS framework is ideal for emerging biobank data.

In contrast to dsDNA phages where multiple genes are involved in programmed host lysis, ssRNA Fiersviridae phages require only a single gene. Here, genome-wide host suppressors of diverse single-gene lysis systems are identified using a high-throughput genetic screen.

The assembly, architecture and role of the bacterial type VI secretion system (T6SS) membrane core complex is presented.

The interferon response has been shown to be linked to severity of SARS-CoV-2 infection and is an essential component of the immune response to COVID-19. Here the authors stratify patients according to COVID-19 severity and asses the interferon response showing defective responses in severe infection and highlight the importance of assay variables and confounding factors that impact the detection of interferon.

Serratus, an open-source cloud-computing infrastructure, can be used to screen millions of nucleic acid sequencing libraries at the petabase scale, and has enabled many new RNA viruses to be identified efficiently.

The gastrointestinal tract is an important source of endocrine signals. Gut hormones such as glucagon-like peptide 1, peptide YY, and islet amyloid polypeptide act in an integrated fashion to modulate appetite and energy expenditure. This Review addresses the physiological roles of gut hormones and discusses their potential as targets for the development of novel treatments for obesity, on the basis of pharmacological mimicry of the hormonal milieu after bariatric surgery.

Classical light is as good as quantum light to characterize a quantum channel. This unexpected result has practical consequences that make an experimentalist’s life easier in some situations.

The BRAIN Initiative Cell Census Network has constructed a multimodal cell census and atlas of the mammalian primary motor cortex in a landmark effort towards understanding brain cell-type diversity, neural circuit organization and brain function.

The recovery of viral populations from peatland soils across a permafrost thaw gradient provides insights into soil viral diversity, their hosts and the potential impacts on carbon cycling in this environment.

Entomopathogenic bacteria used for pest control secrete potent Tc toxins. Here, the authors combine biochemistry, solution and solid-state NMR spectroscopy and cryo-EM to show in atomic detail how the toxin disrupts the host cell cytoskeleton and kills the target cell.

Pacific oyster mortality syndrome is a poorly understood cause of mortality in commercially important oyster species. Here, the authors use multiple infection experiments to show that the syndrome is caused by sequential infection by herpesvirus and opportunistic bacteria.

RNase III from all three domains of life elicits RNA-targeting antiviral activity that is independent of, and possibly predates, other known eukaryotic antiviral systems.

Ageing-associated decline in intestinal stem cell function is mediated by increased Notum, a protein inhibitor of stemness-maintaining Wnt signalling, which is secreted by Paneth cells.

Mucosal surfaces of the respiratory tract are the first sites of entry and defense against SARS-CoV-2. Di Santo and colleagues perform paired analysis of the nasopharyngeal and systemic immune responses of SARS-CoV-2-infected patients and demonstrate distinct compartmentalization of immunity and shifts in the microbiome.

Ca²⁺ is an intracellular messenger that has a critical role in zebrafish development. Here Prudent et al. show that during gastrulation, the newly identified Bcl-2 homologue, Bcl-wav and the mitochondrial calcium uniporter regulate cell migration by controlling mitochondrial Ca²⁺storage.

Cytokinesis relies on central spindle organization and provides a spatial landmark for lumen formation. Here, the authors show that intraflagellar transport proteins are required for the localization of the cytokinetic regulator Aurora B and subsequent cleavage furrow ingression and lumen positioning.

Spiropyrans are ideal molecular photoswitches, as they change nuclear configuration upon exposure to light, although the quantum yield of this process is low. Based on simulations, the authors identify time-resolved X-ray absorption spectroscopy as potential technique to test the mechanism leading to the inherently low quantum yield of the process.

High-density lipoproteins (HDLs) have various antiatherosclerotic effects; however, inflammation can cause HDL to become dysfunctional, which impairs its protective properties. In this Review, Rosenson and colleagues discuss the mechanisms by which HDL and apolipoprotein A-I protect against atherosclerosis, and how diagnostic and therapeutic approaches might target these proteins when they become dysfunctional.

Cataloging microbial genomes from Earth’s environments expands the known phylogenetic diversity of bacteria and archaea.

The sequencing and analysis of the banana genome is reported; these results inform plant phylogenetic relationships and genome evolution, and provide a resource for future genetic improvement of this important crop species.

Here, large-scale genome-wide association studies were carried out with the naturally occurring inbred lines of Arabidopsis thaliana, which can be genotyped once and phenotyped repeatedly. The results range from significant associations, usually corresponding to single genes, to findings that are more difficult to interpret, because confounding by complex genetics and population structure makes it hard to distinguish true associations from false.