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Recovery of neurotransmitter involves the endocytic retrieval of vesicles from the plasma membrane. Jonas and colleagues show that in hippocampal synapses, the anti-apoptotic protein Bcl-x_L enhances the recovery of a vesicle pool. It does this independently of its mitochondrial function, through its calmodulin-stimulated translocation to clathrin-coated pits and recruitment of the dynamin-related protein Drp1.

Genotype and exome sequencing of 150,000 participants and whole-genome sequencing of 9,950 selected individuals recruited into the Mexico City Prospective Study constitute a valuable, publicly available resource of non-European sequencing data.

Melanocytic nevus count is associated with melanoma risk. In this study, a meta-analysis of 11 nevus GWAS studies identifies novel SNPs in KITLG and 9q32, and bivariate analysis with melanoma GWAS meta-analysis reveals that most nevus genes affect melanoma risk, while melanoma risk loci do not alter the nevus count.

A multi-ancestry transcriptome-wide association study using an optimal linear combination of association statistics provides insights into tobacco use biology and suggests opportunities for drug repurposing.

Paul Pharoah and colleagues report the results of a large genome-wide association study of ovarian cancer. They identify new susceptibility loci for different epithelial ovarian cancer histotypes and use integrated analyses of genes and regulatory features at each locus to predict candidate susceptibility genes, including OBFC1.

An exciting genome-wide association study in the British population for seven common diseases. This analysis confirms previously identified loci and provides strong evidence for many novel disease susceptibility loci.

Chromosome 8q24 is known to be a major susceptibility region for prostate cancer risk. Here the authors analyze genetic data across the 8q24 region from 71,535 prostate cancer patients identifying 12 risk loci, three previously unreported, highlighting the contribution of germline variation at this locus.

Progressive tubule cell damage results in defects in mitochondrial metabolism and exercise seems to be beneficial during chronic kidney disease. Here Peng et al. show that irisin, an exercise-induced myokine, improves kidney energy metabolism by inhibiting TGF-β type 1 receptors and ameliorates fibrosis.

Christopher Newton-Cheh and colleagues report genome-wide association analyses for QT interval, an electrocardiographic measure reflecting myocardial repolarization, in 100,000 individuals. They identify 35 loci associated with QT interval and highlight a role for calcium regulation in myocardial repolarization.

Based on a consensus conference of experts in the evolution and ecology of cancer, this article proposes a framework for classifying tumours that includes four evolutionary and ecological processes: neoplastic cell diversity and changes over time in that diversity, hazards to cell survival and available resources.

Reconstructions of ocean and land temperatures since ad 1500 indicate that sustained, industrial-era warming of land areas in the Northern Hemisphere and tropical oceans began earlier than previously thought, around the mid-nineteenth century.

There is emerging evidence that mice with a history of microbial exposures can better model the human immune system than laboratory mice maintained in pathogen-free conditions. In this Perspective, Rehermann and colleagues summarize different approaches that have been used to incorporate microbiota and pathogen exposures into laboratory mouse models. They suggest that the term ‘mice with natural microbiota’ should be used instead of ‘dirty mice’ to describe these systems in the future.

An engineered patch of retinal pigment epithelium generated from human embryonic stem cells is transplanted into the eyes of two patients.

A microfluidic CRISPR-based platform enables multiplexed and high-throughput identification of a wide range of respiratory viruses, including the ability to identify specific SARS-CoV-2 variants such as Delta and Omicron.

ZTF J1406+1222 is a wide hierarchical triple system that hosts a low-metallicity subdwarf star and a ‘black widow’ millisecond pulsar that has a highly varying optical flux and a 62-minute period.

Primary biliary cirrhosis is an autoimmune liver disease with poor therapeutic options. Here Cordell et al. a perform meta-analysis of European genome-wide association studies identifying six novel risk loci and a number of potential therapeutic pathways.

Prostate cancer (PrCa) involves a large heritable genetic component. Here, the authors perform multivariate fine-mapping of known PrCa GWAS loci, identifying variants enriched for biological function, explaining more familial relative risk, and with potential application in clinical risk profiling.

MetaSTAAR enables functionally informed rare variant association analysis in biobank-scale cohorts using an efficient, sparse matrix approach for summary statistic storage.

Genome sequence data from colorectal tumours show how adenomas progress to carcinomas on the fitness landscape.

Luis Pérez-Jurado, Stephen Chanock and colleagues detect clonal chromosomal abnormalities in peripheral blood or buccal samples from individuals in the general population. They show that the frequency of such events increases with age and is associated with elevated risk of developing subsequent hematological cancers.

Helper T cell subsets are characterized functionally by the cytokines they produce. Benoist and colleagues demonstrate that in vivo helper T cells do not manifest as discrete helper subsets but rather form a continuum shaped by microbial exposure.

Current food production systems are heavily dependent on synthetic inputs that threaten the environment and human wellbeing. Results from multi-site field experiments in Thailand, China and Vietnam reveal that surrounding rice fields with nectar-producing plants significantly reduces pest numbers and the need for insecticide applications, while increasing yields.

Understanding the factors determining pathogen host range is critical for human health. Here, the authors show that bacteria use cooperative secretions to modify their environment and to infect multiple host species, which suggests that cooperative secretions are key determinants of host range in bacteria.

The cellular heterogeneity in brain obscures the identification of robust cellular regulatory networks. Here the authors integrate genome-wide chromosome conformation data from sorted neurons and glia, with transcriptomic and enhancer profiles, to characterize cell-type-specific gene regulatory landscapes in the human brain, and provide insights into cell-type-specific gene regulatory networks in brain disorders.

Circoviruses are the simplest viruses known to autonomously replicate in vertebrates. Here the authors present three structures for distinct macromolecular assemblies of the capsid protein from the beak and feather disease virus that provides insights into the regulation of viral capsid assembly.

Whole-genome sequencing and phenotype data sharing are introduced in a national health system to streamline diagnosis and to discover coding and non-coding variants that cause rare diseases.

Wave energy offers vital diversification for Net-Zero goals, though further cost reductions are needed. Emma Edwards and colleagues optimise device geometry to minimise reaction moments while preserving high-power output, advancing economic viability.

Ma and colleagues show that when the EMT-associated transcription factor ZEB1 is stabilized by the ATM kinase, it interacts with the ubiquitin protease USP7 to counteract CHK1 degradation and promote DNA repair in breast cancer cells.

This paper describes molecular subtypes of cervical cancers, including squamous cell carcinoma and adenocarcinoma clusters defined by HPV status and molecular features, and distinct molecular pathways that are activated in cervical carcinomas caused by different somatic alterations and HPV types.

Statins are effectively used to prevent and manage cardiovascular disease, but patient response to these drugs is highly variable. Here, the authors identify two new genes associated with the response of LDL cholesterol to statins and advance our understanding of the genetic basis of drug response.

An exome-wide association study of six smoking phenotypes in up to 749,459 individuals identifies associations of rare coding variants in CHRNB2 that may reduce the likelihood of smoking.

Analysis of antibody responses to COVID-19 vaccines encoding variant-specific spike, with or without ancestral spike, suggests no loss of neutralization of the ancestral virus with variant-only vaccines, which may simplify future vaccine updates.

Using the attosecond streak camera method, researchers measure the temporal characteristics of coherent, spatially separated attosecond pulses generated from the attosecond lighthouse.

Robert Graham and colleagues report results of a large-scale replication study for systemic lupus erythematosus (SLE) in individuals of European ancestry. Their findings expand the number of confirmed SLE susceptibility loci and implicate several key immunologic pathways in SLE pathogenesis.

Michael Talkowski and colleagues analyze balanced chromosomal abnormalities in 273 individuals by whole-genome sequencing. Their findings suggest that sequence-level resolution improves prediction of clinical outcomes for balanced rearrangements and provides insight into pathogenic mechanisms such as altered gene regulation due to changes in chromosome topology.

REVOLVER uses transfer learning on multi-region tumor sequencing data to jointly infer tumor evolution models in multiple individuals and to detect repeated evolutionary trajectories. Repeated evolution can be used to stratify the cohort.

Here, the authors present a fully automatic computational approach for reconstructing and virtually unfolding volumetric scans of locked letters with complex internal folding, producing legible images of the letter’s contents and crease pattern while preserving letterlocking evidence.

β-Diguetoxin-Dc1a, a component of desert bush spider venom, targets insect voltage-gated sodium channels, but not those of humans. Bende et al. find that American, but not German cockroaches are sensitive to the toxin, and identify two residues in the voltage-sensor domain that underlie this difference.

A common immune signature in the blood of patients with COVID-19, who are otherwise clinically heterogeneous, sheds light into the pathogenesis and clinical progression of the disease.

Changes in the electronic states of two-dimensional semiconductor devices resulting from electrical gating can be monitored directly using micrometre-scale angle-resolved photoemission spectroscopy.