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Neighborhood social determinants of health influence cardiovascular risk, but early-life exposure effects remain unclear. Here the authors show that higher early adulthood neighborhood social determinants of health indices are associated with higher middle-aged coronary artery calcification.

Atmospheric river (AR) characteristics, particularly AR shape associated with large-scale circulation, as well as interactions with other weather systems, significantly influence surface warming over Antarctic ice shelves and their future stability.

Coronary artery disease has several genetic risk factors. Here, the authors develop a model that combines germline and somatic genetic drivers to predict coronary artery disease risk, identifying high-risk individuals not detected by polygenic risk scores alone.

Atopic dermatitis is an immune disease driven by cytokines including IL-4/IL-13. This study shows that a topical ITK/TRK inhibitor blocks an array of T cell cytokines, inhibits NGF-induced basophil activation, and reduces inflammation in human skin explants and dermatitis models, indicating therapeutic potential.

Biallelic inactivation of the VHL tumour suppressor gene is a hallmark of Clear cell renal cell carcinoma (ccRCC). Here the authors perform genome-wide CRISPR/Cas9 screening to identify that loss of Core Binding Factor β (CBF-β), a component of RUNX transcription factor complexes, is synthetically lethal in VHL-deficient ccRCC tumour models.

Divergent white matter metabolic patterns reveal a mechanistic basis for cognitive resilience and enhance prediction of future cognitive decline beyond established aging and dementia biomarkers.

Tracking oceanic microbial populations in situ over time is challenging. Here, the authors use autonomous underwater vehicles to show how microbes at the deep chlorophyll maximum respond to diel cycles and isopycnal uplift by a cyclonic eddy.

A large-scale study on the replicability of claims from social and behavioural science journals reports that about half of the results replicate in the same patterns as the original study.

Young, cognitively normal APOE4 mice display hippocampal network hyperactivity that predicts later memory decline. This phenotype is driven by neuronal APOE4 expression, which causes hyperexcitability of hippocampal neurons and can be reversed by targeting Nell2.

The authors have applied an eight-tissue rat multi-omic dataset to analyze the gene regulatory landscape of endurance exercise training, identifying tissue-specific regulatory patterns involved in muscle function, metabolism and immune response.

Analysis combining multiple global tree databases reveals that whether a location is invaded by non-native tree species depends on anthropogenic factors, but the severity of the invasion depends on the native species diversity.

Humanity’s Last Exam, a multi-modal benchmark at the frontier of human knowledge, is designed to be an expert-level closed-ended academic benchmark with broad subject coverage.

A study of reproducibility in a stratified random sample of 600 papers published from 2009 to 2018 in 62 journals spanning the social and behavioural sciences finds higher reproducibility among more recent papers and papers from journals that require data sharing.

Operando birefringence microscopy measurements of the stresses around growing dendrites in solid electrolytes show that stresses decrease as current densities increase, revealing a linkage between electrochemical and mechanical stability that informs the design of solid-state batteries.

The flagship paper of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium describes the generation of the integrative analyses of 2,658 cancer whole genomes and their matching normal tissues across 38 tumour types, the structures for international data sharing and standardized analyses, and the main scientific findings from across the consortium studies.

cellSTAAR advances noncoding rare variant association analysis by integrating single-cell genomics data.

The APOE-ε4 allele is the strongest genetic risk factor for late-onset Alzheimer’s disease, but it is not deterministic. Here, the authors show that common genetic variation changes how APOE-ε4 influences cognition.

A new platform making use of hexagonal boron nitride interfaced with the molecular superconductor κ-(BEDT-TTF)₂Cu[N(CN)₂]Br is demonstrated for realizing cavity-altered materials, confirmed by magnetic force microscopy and nano-optical measurements.

Sargassum biomass in the north Sargasso Sea declined drastically since 2015, co-occurring with related reductions in the northwest Gulf of Mexico and an expansion of the Great Atlantic Sargassum Belt, according to in situ and satellite observations.

Smyth et al. demonstrate that a cellular inhibitor of apoptosis, cIAP2, exacerbates inflammation and cardiac injury after myocardial infarction and that its inhibition, either genetically or via Smac mimetics, offers a promising immunotherapeutic strategy to reduce post-MI damage and progression to heart failure.

Evo 2 is an artificial intelligence-based biological foundation model trained on 9 trillion DNA base pairs spanning all domains of life that predicts functional properties from genomic sequences and provides a rich generative model for researchers in biology.

In this study, long-read RNA sequencing achieves accurate single-nucleotide polymorphism calling, haplotype phasing and allele-specific expression analysis.

Conventional and time-resolved cryo-electron microscopy reveal how NTSR1 dynamically engages and releases different G proteins, capturing over 20 intermediates and uncovering key mechanistic steps in GDP- and GTP-driven activation, subtype selectivity and distinct dissociation pathways.

New findings from articulated head and trunk material of Megamastax amblyodus yield previously unseen morphological details of a Silurian stem osteichthyan.

Metallic materials are generally efficient sound conductors. Yuqi Jin and colleagues introduce an approach utilizing laser powder bed fusion printed CrMnFeCoNi high entropy alloy samples with optimized intrinsic internal voids during manufacturing to achieve broadband acoustic insulation.

CRISPR–Cas9 screening identifies CLCC1 as a factor that increases neutral lipid flux to prevent hepatic steatosis and promotes nuclear pore complex assembly by promoting membrane bending and fusion.

Enhanced weathering in agriculture shows promise as a carbon dioxide removal strategy, but experts disagree on how large its impact could be, and the greatest uncertainties lie in soil and water processes, highlighting the need for targeted research, according to an expert elicitation method.

This Review discusses the promises and pitfalls of biological AI algorithms and presents a vision for generalist biological artificial intelligence, in which models can perform diverse tasks across biological domains.

Rare coding variants that reduce the activity of a protein can have a beneficial impact on health. Here, researchers identify rare genetic variants in the CHRNB3 gene that associate with reduced cigarette smoking across diverse populations.

Stable adipocytes resist lipolysis in healthy states but are highly susceptible to a catecholamine-independent, neurosystemic pathway-driven catabolic state.

Integrative analyses of transcriptome and whole-genome sequencing data for 1,188 tumours across 27 types of cancer are used to provide a comprehensive catalogue of RNA-level alterations in cancer.

In this study the authors consider the structural variants (SVs) present within cancer cases of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. They report hundreds of genes, including known cancer-associated genes for which the nearby presence of a SV breakpoint is associated with altered expression.

Here researchers reveal a microexon in the Ank3 gene encoding Ankyrin G allows cortical interneurons to fine-tune calcium signaling and firing, revealing the contribution of alternative splicing to the functional diversity among different types of neurons.

Genome-wide association analyses using data from 19 biobanks identify variants influencing risk of thyroid diseases and yield polygenic risk scores associated with features of aggressive thyroid cancer.

KRAS is an oncogene that switches between a GDP-bound inactive state and a GTP-bound active state. Recently developed KRAS G12C inhibitors are specific to the GDP-bound inactive state. Here, the authors develop a class of covalent KRAS G12C inhibitors capable of targeting both states for the treatment of KRAS-driven cancer.

Analyses of 2,658 whole genomes across 38 types of cancer identify the contribution of non-coding point mutations and structural variants to driving cancer.

Typical quantum error correcting codes assign fixed roles to the underlying physical qubits. Now the performance benefits of alternative, dynamic error correction schemes have been demonstrated on a superconducting quantum processor.

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.

Antscan is a publicly accessible database of synchrotron X-ray CT images of ants. The database covers almost 800 species from more than 200 genera and is coordinated with genome sequencing projects that will enable integrative analyses.

The variability in clinical outcomes of SARS-CoV-2 infection is partly due to deficiencies in production or response to type I interferons (IFN). Here, the authors describe a FIP200-dependent lysosomal degradation pathway, independent of canonical autophagy and type I IFN, that restricts SARS-CoV-2 replication, offering insights into critical COVID-19 pneumonia mechanisms.

Understanding deregulation of biological pathways in cancer can provide insight into disease etiology and potential therapies. Here, as part of the PanCancer Analysis of Whole Genomes (PCAWG) consortium, the authors present pathway and network analysis of 2583 whole cancer genomes from 27 tumour types.

Analysis of cancer genome sequencing data has enabled the discovery of driver mutations. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium the authors present DriverPower, a software package that identifies coding and non-coding driver mutations within cancer whole genomes via consideration of mutational burden and functional impact evidence.

A pan-cancer genomic analysis reports the effects of structural variations on chromatin domains (TADs). Most TAD disruptions do not result in appreciable changes in expression of nearby genes.

Multi-omics datasets pose major challenges to data interpretation and hypothesis generation owing to their high-dimensional molecular profiles. Here, the authors develop ActivePathways method, which uses data fusion techniques for integrative pathway analysis of multi-omics data and candidate gene discovery.

Large-effect variants in autism remain elusive. Here, the authors use long-read sequencing to assemble phased genomes for 189 individuals, identifying pathogenic variants in TBL1XR1, MECP2, and SYNGAP1, plus nine candidate structural variants missed by short-read methods.

Federated learning (FL) algorithms have emerged as a promising solution to train models for healthcare imaging across institutions while preserving privacy. Here, the authors describe the Federated Tumor Segmentation (FeTS) challenge for the decentralised benchmarking of FL algorithms and evaluation of Healthcare AI algorithm generalizability in real-world cancer imaging datasets.

Species’ traits and environmental conditions determine the abundance of tree species across the globe. Here, the authors find that dominant tree species are taller and have softer wood compared to rare species and that these trait differences are more strongly associated with temperature than water availability.