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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).

Electron distributions exhibit velocity-space signatures indicative of the rapid energy released by magnetic reconnection explosions occurring in Earth’s magnetosphere and in plasmas throughout the universe. Here, the authors discover a smile-shaped signature in the electron gradient distribution associated with reconnection occurring at Earth’s dayside magnetopause boundary.

An exploratory analysis of the phase 3 ECOSPOR III trial shows that a higher dosage of the oral microbiome therapeutic VOWST led to enhanced pharmacokinetics, increased species engraftment and altered microbiome and metabolite profiles, providing mechanistic insights into how it may prevent Clostridioides difficile infection recurrence.

An expert-elicitation process identifies current methodological barriers for monitoring terrestrial biodiversity, and how technological and procedural development of robotic and autonomous systems may contribute to overcoming these challenges.

Whole-genome sequencing analysis of individuals with primary immunodeficiency identifies new candidate disease-associated genes and shows how the interplay between genetic variants can explain the variable penetrance and complexity of the disease.

Large genome-wide meta-analysis of clinically diagnosed late-onset Alzheimer’s disease (LOAD) from 94,437 individuals identifies new LOAD risk loci and implicates Aβ formation, tau protein binding, immune response and lipid metabolism.

TDP-43 dysfunction in ALS/FTD causes faulty splicing of the KCNQ2 ion channel, leading to toxic protein buildup, neuron hyperactivity and a potential new biomarker and treatment target using RNA-based therapies.

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.

Climate variability in the Southern Hemisphere is dominanted by the Southern Annular Mode, which influences temperatures and latitudinal rainfall distribution. This work reconstructs its annual variability since the year 1000. The authors find that a positive trend since the 1940s is reproduced by climate model simulations with representative greenhouse gas forcings and ozone depletion. Early trends indicate a teleconnection to tropical Pacific climate, which may need to be considered in projections under climate change.

Combined patch clamp recording, biocytin staining and single-cell RNA-sequencing of human neurocortical neurons shows an expansion of glutamatergic neuron types relative to mouse that characterizes the greater complexity of the human neocortex.

Analysing camera-trap data of 163 mammal species before and after the onset of COVID-19 lockdowns, the authors show that responses to human activity are dependent on the degree to which the landscape is modified by humans, with carnivores being especially sensitive.

Sustainable and regenerative agriculture often employs diverse systems of crop rotation to reduce environmental impacts and sequester carbon. A long-term field study, however, reveals a trade-off between soil organic carbon storage and nitrogen supply.

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.

Infrared brightening and luminosity observations from a young, solar-like star suggest a collision between two exoplanets producing a hot, highly extended post-impact remnant and transit of the debris causing the visible light eclipse of the host star.

A high-resolution kidney cellular atlas of 51 main cell types, including rare and previously undescribed cell populations, represents a comprehensive benchmark of cellular states, neighbourhoods, outcome-associated signatures and publicly available interactive visualizations.

Durable agonism of NPR1 achieved with a novel investigational monoclonal antibody could mirror the positive hemodynamic changes in blood pressure and heart failure identified in humans with lifelong exposure to NPR1 coding variants.

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

In this Stage 2 Registered Report, Buchanan et al. show evidence confirming the phenomenon of semantic priming across speakers of 19 diverse languages.

Characterization of the myotis bat morbillivirus shows that infection in human cells is restricted by innate immune responses in vitro and cross-neutralization by sera from measles, mumps and rubella vaccinees.

Sézary syndrome is a T cell malignancy that has been poorly characterized at the genome level. In this study, Kielet al. perform whole-genome analyses and identify mutations in the JAK–STAT pathway and show that primary cells are sensitive to JAK inhibitors.

Here the authors apply machine learning approaches to Alzheimer’s genetics, confirm known associations and suggest novel risk loci. These methods demonstrate predictive power comparable to traditional approaches, while also offering potential new insights beyond standard genetic analyses.

Medulloblastoma is the most common malignant brain tumour in children; having assembled over 1,000 samples the authors report that somatic copy number aberrations are common in medulloblastoma, in particular a tandem duplication of SNCAIP, a gene associated with Parkinson’s disease, which is restricted to subgroup 4α, and translocations of PVT1, which are restricted to Group 3.

Investigation of variation in three cohorts has identified multiple genetic signals associated with the pregnancy-specific liver disorder, intrahepatic cholestasis of pregnancy, giving insight into the disease which can cause preterm birth and stillbirth.

Trees come in all shapes and size, but what drives this incredible variation in tree form remains poorly understood. Using a global dataset, the authors show that a combination of climate, competition, disturbance and evolutionary history shape the crown architecture of the world’s trees and thereby constrain the 3D structure of woody ecosystems.

The structure of a neutralizing human monoclonal antibody isolated from an individual immunized in a Plasmodium vivax Duffy binding protein vaccine clinical trial, in complex with its target, elucidates the mechanism by which parasite invasion of immature red blood cells is inhibited.

Circulating tumour DNA profiling in early-stage non-small-cell lung cancer can be used to track single-nucleotide variants in plasma to predict lung cancer relapse and identify tumour subclones involved in the metastatic process.

Known genetic loci account for only a fraction of the genetic contribution to Alzheimer’s disease. Here, the authors have performed a large genome-wide meta-analysis comprising 409,435 individuals to discover 6 new loci and demonstrate the efficacy of an Alzheimer’s disease polygenic risk score.

The Vertebrate Genome Project has used an optimized pipeline to generate high-quality genome assemblies for sixteen species (representing all major vertebrate classes), which have led to new biological insights.

Reengineering polyketide synthase encoding genes to produce analogues of natural products can be slow and low-yielding. Here the authors use accelerated evolution to recombine the gene cluster for rapid production of rapamycin-related products.

The International Barley Genome Sequencing Consortium reports sequencing and assembly of a reference genome for barley, Hordeum vulgare.

Sven van der Lee, Julie Williams, Gerard Schellenberg and colleagues identify rare coding variants in PLCG2, ABI3 and TREM2 associated with Alzheimer's disease. These genes are highly expressed in microglia and provide additional evidence that the microglia-mediated immune response contributes to the development of Alzheimer's disease.

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.

Comprehensive integration of gene expression with epigenetic features is needed to understand the transition of kidney cells from health to injury. Here, the authors integrate dual single nucleus RNA expression and chromatin accessibility, DNA methylation, and histone modifications to decipher the chromatin landscape of the kidney in reference and adaptive injury cell states, identifying a transcription factor network of ELF3, KLF6, and KLF10 which regulates adaptive repair and maladaptive failed repair.

Jones et al. examine the generalizability of the valence–dominance model of social judgements of faces in 41 countries across 11 world regions. They find evidence of both generalizability and variation, depending on the analytical method.

Domain walls play an important role in the switching of ferroelectrics. Here, mapping out electric fields within ferroelectric thin films, the authors uncover electronic band bending as the origin of head-to-head domain walls that are difficult to switch and may hamper ferroelectric device performance.

Whole-exome sequencing in a large autism study identifies over 100 autosomal genes that are likely to affect risk for the disorder; these genes, which show unusual evolutionary constraint against mutations, carry de novo loss-of-function mutations in over 5% of autistic subjects and many function in synaptic, transcriptional and chromatin-remodelling pathways.

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.

Fishing has had a profound impact on global reef shark populations, and the absence or presence of sharks is strongly correlated with national socio-economic conditions and reef governance.

Here, the genomes of a malignant melanoma and a lymphoblastoid cell line from the same person are sequenced, providing the first comprehensive catalogue of somatic mutations from an individual cancer. The data provide insight into the causes of tumour formation and the development of the cancer genome, with the dominant mutational signature reflecting DNA damage due to ultraviolet light exposure.

The magnetic field measured by the InSight lander on Mars varies daily and is ten times stronger than expected. The field is inferred to originate from components of basement rocks magnetized by an ancient dynamo of Earth-like strength.

Polygenic risk scores for Alzheimer’s disease derived from individuals of European ancestry can show improved performance in multiancestry settings after incorporating genome-wide association summary statistics from diverse populations.

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.

The CNV analysis group of the Psychiatric Genomic Consortium analyzes a large schizophrenia cohort to examine genomic copy number variants (CNVs) and disease risk. They find an enrichment of CNV burden in cases versus controls and identify 8 genome-wide significant loci as well as novel suggestive loci conferring either risk or protection to schizophrenia.

Parkinson’s disease brain neurons exhibit a widespread epigenetic dysregulation of enhancers that is linked to an upregulation of TET2. Inactivation of TET2 protects against nigral dopaminergic neuronal loss and neuroinflammation.