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The insecticidal protein Mpf2Ba1 shows potent control against corn rootworm. Here, the authors present detailed structural analyses revealing transitions between its three main stages of pore formation. These findings uncover molecular mechanisms of bacterial pore assembly and advance both crop biotechnology and food security.

Alterations in the tumour microenvironment (TME) can contribute to prostate cancer progression, but it is unclear how tumours mediate those changes. Here, analysis of human prostate cancer tissues and key stages of prostate cancer progression in a genetically engineered mouse model using single-cell RNA-sequencing reveals the central role of MYC signalling in reprogramming the TME.

In this study, Aggarwal and colleagues perform prospective sequencing of SARS-CoV-2 isolates derived from asymptomatic student screening and symptomatic testing of students and staff at the University of Cambridge. They identify important factors that contributed to within university transmission and onward spread into the wider community.

Ex vivo engineering of antigen-specific T cells has shown therapeutic efficacy but can be costly and scarce. Here the authors show that in vitro-transcribed antigen receptor mRNA packaged in nanocarriers can directly induce, in vivo, transient their expression in circulating T cells to provide therapeutic effects in mouse models of cancer or viral infection.

Petrels are wide-ranging, highly threatened seabirds that often ingest plastic. This study used tracking data for 7,137 petrels of 77 species to map global exposure risk and compare regions, species, and populations. The results show higher exposure risk for threatened species and stress the need for international cooperation to tackle marine litter.

Lipid concentration in the serum is one of the most important risk factors for coronary artery disease and can be targeted for therapeutic intervention. A genome-wide association study in >100,000 individuals of European ancestry now finds 95 significantly associated loci that also affect lipid traits in non-European populations. Among associated loci are those involved in cholesterol metabolism, known targets of cholesterol-lowering drugs and those that contribute to normal variation in lipid traits and to extreme lipid phenotypes.

Androgen receptor (AR) is the critical driver of nearly all prostate cancer. The authors show that AR activation causes specific pre-existing chromatin loops to increase contact frequency with target promoters and drive transcription.

Happ et al. uncover an unusual regulatory mechanism in the Hedgehog signaling pathway, which enables a G protein-coupled receptor to physically block the enzymatic activity of a major cellular kinase.

Nelson Freimer and colleagues report the first genome-wide association study of a longitudinal birth cohort (the Northern Finland Birth Cohort 1966). The results include new associations for nine quantitative metabolic traits.

The influence of X chromosome genetic variation on blood lipids and coronary heart disease (CHD) is not well understood. Here, the authors analyse X chromosome sequencing data across 65,322 multi-ancestry individuals, identifying associations of the Xq23 locus with lipid changes and reduced risk of CHD and diabetes mellitus.

ONECUT2 is a targetable transcription factor that antagonizes androgen receptor signaling and drives androgen independence and neuroendocrine differentiation in castration-resistant prostate cancer.

Allogeneic hematopoietic stem cell transplantation restores the whole hematopoietic compartment of the recipient, but some cell types, such as Type II innate lymphoid cells (ILC2) are not reconstituted efficiently. Here authors show that ILC2s could be converted to ILC1-like cells in the mouse small intestine post-transplantation, which might contribute to the lower than physiological ILC2 numbers.

Resistance to pod shattering in crops is typically modulated by major loci each underpinned by a single gene. Here, the authors show that the transition from shattering in wild soybean to shattering resistance in cultivated soybean is underlain by selection of mutations within two neighboring genes.

A global dataset of the satellite-tracked movements of pelagic sharks and fishing fleets show that sharks—and, in particular, commercially important species—have limited spatial refuge from fishing effort.

Microbes structure biogeochemical cycles and food webs in the marine environment. Here, the authors sample coral reef-associated microbes across a 24-hour period, showing clear day–night patterns of microbial populations and thus calling for more studies to consider temporal variation in microbiomes at this scale.

An analysis of the impact of logging intensity on biodiversity in tropical forests in Sabah, Malaysia, identifies a threshold of tree biomass removal below which logged forests still have conservation value.

Metals such as calcium and potassium have long been known to regulate the diameter of arteries that control blood flow. Here, we report that zinc causes relaxation of blood vessels and reduces blood pressure by its coordinated action in sensory nerves, endothelium and smooth muscle cells.

To mature, dendritic cells collect and synthesize cholesterol to construct lipid nanodomains on their membranes. Obstructing this process impairs their ability to prime T cells.

By leveraging microcavity-integrated photonics and Kerr-induced optical frequency division, an integrated photonic millimetre-wave oscillator with low phase noise is demonstrated, achieving –77 dBc Hz^–1 and –121 dBc Hz^–1, respectively, at 100-Hz and 10-kHz offset frequencies, corresponding to –98 dBc Hz^–1 and –142 dBc Hz^–1 when scaled to a 10-GHz carrier.

Stratified medicine promises to tailor treatment for individual patients, however it remains a major challenge to leverage genetic risk data to aid patient stratification. Here the authors introduce an approach to stratify individuals based on the aggregated impact of their genetic risk factor profiles on tissue-specific gene expression levels, and highlight its ability to identify biologically meaningful and clinically actionable patient subgroups, supporting the notion of different patient ‘biotypes’ characterized by partially distinct disease mechanisms.

The integrator complex is required for the synthesis of protein coding and non-coding RNA and contains the protein INTS13. Here, the authors find germline mutations in INTS13 in two families with oral facial digital syndrome and show that the mutation affects the c-terminal domain of the protein and disrupts cilliogenesis.

Here, using longitudinal pre- and post-infection samples from the RV217 Early Capture HIV Cohort Study, the authors show that mucosa-associated invariant T (MAIT) cells become activated and expand during the early acute phase of HIV infection, with subsequent reprogramming towards innate-like functionality.

Genome-wide association analyses identify new risk loci for heart failure and its subtypes, extending understanding of the underlying biological pathways and disease mechanisms.

COVID-19 can be associated with neurological complications. Here the authors show that markers of brain injury, but not immune markers, are elevated in the blood of patients with COVID-19 both early and months after SARS-CoV-2 infection, particularly in those with brain dysfunction or neurological diagnoses.

The overlap of different crystal lattices can give rise to a Moire structure with long range periodicity. While this feature has been heavily exploited in twisted van der Waals heterostructures, here, Yao et al find the telltale signatures of Moire magnetism in CrBr3 multilayers induced by differential strain, in the absence of twisting.

Ruth Loos and colleagues report results of a large genome-wide association study for body mass index. They identify 18 new loci associated with this trait, some of which map near key hypothalamic regulators of energy balance.

Early adversity may sensitize people to the effects of later stress, amplifying psychopathology risk. Here, the authors show this stress sensitization effect for adolescents who experienced prolonged institutional deprivation in childhood, but not those assigned to foster care intervention.

SARS-CoV-2 infection can lead to progressive pathology in patients with COVID-19, but information for this disease progression is sparse. Here the authors use multi-omics approach to profile the immune responses of patients, assessing immune repertoire and effects of tocilizumab treatments, to find a dyssynchrony between innate and adaptive immunity in progressive COVID-19.

Anti-disialoganglioside (GD2) antibody therapy has proven beneficial to neuroblastoma patients and intra-tumoral copper levels have been associated with immune evasion. Here the authors show that copper chelation potentiates anti-GD2 immunotherapy through improved infiltration and function of Fc receptor bearing neutrophils.

Sexual dimorphism in genetic vulnerability to schizophrenia, systemic lupus erythematosus and Sjögren’s syndrome is linked to differential protein abundance from alleles of complement component 4.

The inter- and intra-tumor heterogeneity of metastatic prostate cancer (mPC) is underexplored. Here the authors use Digital Spatial Profiling to study gene and protein expression heterogeneity in 27 mPC patients, finding variation in associated pathways and potential immunotherapy targets.

The Structural Variation Analysis Group of The 1000 Genomes Project reports an integrated structural variation map based on discovery and genotyping of eight major structural variation classes in 2,504 unrelated individuals from across 26 populations; structural variation is compared within and between populations and its functional impact is quantified.

The radial-velocity technique could detect a small gas giant orbiting a binary star and determine its mass: 65.2 ± 11.8 Earth masses. The system also hosts a smaller inner planet, making it one of the few known multiplanetary circumbinary systems.

Fluorescence imaging of the spinal cord poses challenges, including depth of imaging. Here the authors describe a custom microscope and chronically implanted microprism that enables multicolor translaminar imaging of sensory and motor evoked activity in behaving mice, and show that spinal astrocytes show sensorimotor program-dependent calcium excitation.

Leading thinkers choose past works illuminating crucial issues today.

Genome-wide association analyses of 41,917 bipolar disorder cases and 371,549 controls of European ancestry provide new insights into the etiology of this disorder and identify novel therapeutic leads and potential opportunities for drug repurposing.

Meta-analysis of genome-wide association studies on Alzheimer’s disease and related dementias identifies new loci and enables generation of a new genetic risk score associated with the risk of future Alzheimer’s disease and dementia.

RNA-sequencing analysis of cells in the human cortex enabled identification of diverse cell types, revealing well-conserved architecture and homologous cell types as well as extensive differences when compared with datasets covering the analogous region of the mouse brain.

Data from over 700,000 individuals reveal the identity of 83 sequence variants that affect human height, implicating new candidate genes and pathways as being involved in growth.

Cecilia Lindgren and colleagues report results of a large-scale genome-wide association study for waist-to-hip ratio, a measure of body fat distribution. They identify 13 new loci associated with this trait, several of which show stronger effects in women than in men.

Most studies of the genetics of the metabolome have been done in individuals of European descent. Here, the authors integrate genomics and metabolomics in Black individuals, highlighting the value of whole genome sequencing in diverse populations and linking circulating metabolites to human disease.

Individuals with severe motor impairments use gaze to type and communicate. This paper presents a large language model-based user interface that enables gaze typing in highly abbreviated forms, achieving significant motor saving and speed gain.

A genome-wide association study in ~3 million individuals identifies 3,952 independent variants associated with educational attainment. A polygenic index explains 12–16% of variance for this trait and contributes to risk prediction for ten diseases.

Calcium/calmodulin-dependent kinase kinase 2 (CaMKK2) is highly expressed in several cancers. Here the authors investigate the role of CaMKK2 expression in the tumour microenvironment and show that CaMKK2 expression in tumour-associated macrophages promotes tumour growth by suppressing T cell anti-tumour activity.

Genomic analysis of Plasmodium DNA from 36 ancient individuals provides insight into the global distribution and spread of malaria-causing species during around 5,500 years of human history.

JWST observations of a massive galaxy at a redshift of 2.45 show a powerful outflow of neutral gas, with a mass outflow rate that is sufficient to shut down star formation.