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Genome-wide analyses identify common variants associated with 11 distinct neuropathology endophenotypes, providing insights into the mechanisms underlying the genetic risk of Alzheimer’s disease and related dementias.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

Ataxia telangiectasia and Rad3-related kinase (ATR) is a rational radiosensitization target. This trial evaluates the combination of the ATR inhibitor, ceralasertib, with palliative radiotherapy in 27 patients with advanced solid tumors.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

Populations of many migratory taxa have been declining over recent decades. This study examines how well protected areas in Europe cover the dynamic distributions of migratory birds throughout their annual cycles and finds that many species are inadequately protected, especially farmland birds, and that higher protected area coverage correlates with more positive long-term population trends.

.Insight into the high-temperature behavior of uranium dioxide is essential for both technological applications and fundamental studies. This work examines the evolution of uranium’s oxidation state during the thermal oxidation of uranium dioxide using U M₄ edge X-ray absorption spectroscopy in high energy resolution fluorescence detection mode.

Species’ range shifts projections are usually based on climate and land cover variables. Here, the authors use long-term records for bird species to show that species distribution models accounting for climate and land cover often fail to predict observed range shifts.

GWAS analysis currently relies mostly on linear mixed models, which do not account for linkage disequilibrium (LD) between tested variants. Here, Sesia et al. propose KnockoffZoom, a non-parametric statistical method for the simultaneous discovery and fine-mapping of causal variants, assuming only that LD is described by hidden Markov models (HMMs).

Polθ has been recently identified as a therapeutic target in cancer but specific inhibitors are currently unavailable. Here, the authors identify small molecule inhibitors of Polθ’s polymerase activity which elicit BRCA1/2 synthetic lethality, enhance the effect of PARP inhibitors and target PARP inhibitor resistance caused by 53BP1/Shieldin pathway defects.

Offshore wind energy is key to the transition to renewable energies, but its development has varied effects on marine biodiversity. This Review explores how turbine structures can create new habitats while also causing ecological disturbance. The Review highlights knowledge gaps and discusses innovative methods for assessing, monitoring and mitigating environmental impacts.

Migraine headaches are a debilitating condition that affect many individuals. Now, Guy Rouleau and his colleagues link loss-of-function mutations in a potassium channel protein with a particular migraine syndrome in humans.

Traditional type 2 diabetes (T2D) screening methods often depend on age, BMI guidelines and glucose measurements. Here, authors use a deep learning model that leverages chest radiographs and electronic health record data to screen for T2D, highlighting potential for early detection and intervention.

Openshaw and colleagues find myeloid inflammation and complement activation signatures in patients with long COVID who were previously hospitalized.

The bed bug, Cimex lectularius, is a ubiquitous human ectoparasite with global distribution. Here, the authors sequence the genome of the bed bug and identify reductions in chemosensory genes, expansion of genes associated with blood digestion and genes linked to pesticide resistance.

Rapid diagnosis and implementation of treatments is crucial in many genetic conditions. Here the authors describe Genome-to-Treatment, a virtual disease management system that can achieve a rapid diagnosis by expedited whole genome sequencing in 13.5 hours and provide guidance to clinicians for possible therapies.

This Registered Report presents evidence from 87 countries and regions showing that brief emotion-regulation interventions consistently reduced negative emotions and increased positive emotions during the COVID-19 pandemic.

Analysis of changes in functional groups of species and potential drivers of environmental change for protected areas across the world’s major tropical regions reveals large variation between reserves that have been effective and those experiencing an erosion of biodiversity, and shows that environmental changes immediately outside reserves are nearly as important as those inside in determining their ecological fate.

DNA-dependent protein kinase (DNA-PK) plays a major role in the DNA damage response upon double-strand break formation. Here, the authors show that the DNA-PK inhibitor AZD7648, enhances the activity of radiotherapy, chemotherapy and the PARP inhibitor olaparib in multiple mouse tumour models.

Most work on phenological mismatch has focused on temporal trends only. Here, the authors analyse trends in spatial and temporal mismatch between trees, caterpillars and birds in the UK, and find delayed phenology of all species with increasing latitude and little spatial variation in the magnitude of mismatch between caterpillars and birds.

A consortium reports the tripling of the number of genetic markers in Phase II of the International HapMap Project. This map of human genetic variation will continue to revolutionize discovery of susceptibility loci in common genetic diseases, and study of genes under selection in humans.

A genome-wide association study of critically ill patients with COVID-19 identifies genetic signals that relate to important host antiviral defence mechanisms and mediators of inflammatory organ damage that may be targeted by repurposing drug treatments.

Cancer cells rely on glutamine to replenish the TCA cycle. Here, the authors show that oncogenic PIK3CAmutations drive this metabolic rewiring in colorectal cancer cells by up-regulating glutamate pyruvate transaminase expression, thus increasing sensitivity to glutamine starvation.

Notch1 signalling and the dosage of the Notch1 ligand, Dll4, are critical for vascular development. Here the authors show that the transcriptional repressor, Snail1, is expressed in endothelial cells, where it regulates vascular development by downregulating Dll4 levels and Notch1 signalling during mouse embryogenesis.

Factors inducing epithelial to mesenchymal transition, such as the transcriptional repressor Snail1, have been implicated in cancer stem cell development and function. Here Lin et al.report that endogenous Snail1 is not required for embryonic stem cell pluripotency and self-renewal, but rather regulates Wnt-induced epiblast differentiation.

Orthogonal aminoacyl-tRNA synthetase–tRNA pairs are discovered by analyzing millions of sequences.

Active enhancers are defined by the presence of post-translational modifications of histones. Here, the authors use these marks to identify enhancers recurrently activated in colorectal cancer and find that these enhancers turn on oncogenes and are associated with known risk loci for developing the disease.

Chromosomal inversions can promote speciation. Here, the authors identify a young inversion that has captured ecologically important genetic variants in a hybrid zone of the plant Boechera stricta, promoting local adaptation and incipient speciation.

An approach called chemo-optical modulation of epigenetically regulated transcription (COMET) combines azobenzene-based photochromic HDAC inhibitors with microprocessor-controlled LED plates to regulate gene expression profiles in a light-dependent manner.

The Cancer Genome Atlas reports on molecular evaluation of 295 primary gastric adenocarcinomas and proposes a new classification of gastric cancers into 4 subtypes, which should help with clinical assessment and trials of targeted therapies.

The Cancer Genome Atlas Research Network report integrated genomic and molecular analyses of 164 squamous cell carcinomas and adenocarcinomas of the oesophagus; they find genomic and molecular features that differentiate squamous and adenocarcinomas of the oesophagus, and strong similarities between oesophageal adenocarcinomas and the chromosomally unstable variant of gastric adenocarcinoma, suggesting that gastroesophageal adenocarcinoma is a single disease entity.

Stroke is the second leading cause of death worldwide, and ischaemic stroke accounts for 71% of cases. This Primer by Campbell and colleagues discusses the epidemiology, mechanisms, diagnosis, prevention and treatment of ischaemic stroke.