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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.

Massively parallel reporter assays across five cell types identify thousands of causal, noncoding regulatory variants among 220,000 loci, revealing diverse regulatory mechanisms shaping complex traits and disease.

Robustness checks and reproduction of analyses with existing and updated data based on 110 articles in economics and political science journals with data and code-sharing requirements found high levels of robustness and reproducibility and determined that robustness was not dependent on author characteristics or data availability.

Having a rich negative emotion vocabulary is assumed to help cope with adversity. Here, the authors show that emotion vocabularies simply mirror life experiences, with richer negative emotion vocabularies reflecting lower mental health, and richer positive emotion vocabularies reflecting higher mental health.

A combination of isotopic labelling, gene silencing, single-nucleus RNA sequencing and comparative transcriptomics reveal the genes that mediate the biosynthesis of cinchona alkaloids in plants.

Results of the phase 2 POLAR trial show that biomarker-guided treatment in patients with metastatic pancreatic cancer based on homologous repair deficiency leads to encouraging clinical response rates in immune cell-infiltrated tumors.

The identification of cellular targets for natural products that potently inhibit the growth of cancer cell lines implicates oxysterol-binding proteins in the growth of cancer cells. These natural products, termed ORPphilins, also affect sphingomyelin biosynthesis.

Chen et al. present EMRAge, a biological age measure built using electronic medical records, and OMICmAge, a multi-omic signal superimposed on DNA methylation. Both measures show strong associations with disease and mortality in validation cohorts.

Saturation genome editing of a cancer mutation hotspot in CTNNB1, the gene encoding β-catenin, reveals a gradient of effects of missense mutations on Wnt signaling.

TnpB endonucleases are engineered for improved genome editing.

Neuromodulation via epidural electrical stimulation both below and above the lesion in three participants with complete spinal cord injury could enable respectively motor activation and sensory perception.

Post-transcriptional regulation of mRNA translation was explored using Ribo-STAMP and single-cell RNA sequencing to reveal cell-type-specific and isoform-specific translation patterns across hippocampal neuronal and non-neuronal cell types, highlighting functional differences between CA1 and CA3.

The role of rare pathogenic/likely pathogenic (P/LP) germline variants in pediatric central nervous system (CNS) tumour development remains poorly understood. Here, the authors investigate the prevalence and clinical significance of germline P/LP variants in cancer predisposition genes across 830 CNS tumour patients.

Here the authors combine clinical and metabolomics data to identify distinct metabotypes of pediatric metabolic dysfunction-associated steatotic liver disease (MASLD). The results provide information regarding heterogeneity of MASLD presentation, but require validation in independent cohorts.

A consensus cell type atlas for the fly brain provides both an intellectual framework and open-source toolchains for brain-scale comparative connectomics.

A method termed ac⁴C-seq is introduced for the transcriptome-wide mapping of the RNA modification N⁴-acetylcytidine, revealing widespread temperature-dependent acetylation that facilitates thermoadaptation in hyperthermophilic archaea.

Population-scale WGS reveals genetic determinants of persistent EBV DNA, linking immune regulation—especially antigen processing and MHC class II variation—to EBV persistence and heterogeneous disease associations.

The deep learning model STARLING can generate accurate ensembles of intrinsically disordered regions of proteins using only protein sequence as input.

Chronic Kidney Disease affects 1 in 10 people worldwide with prevalence continuing to rise, thus there is a need to identify novel biomarkers that can add value to existing clinical and biochemical risk predictors. Here the authors identify miR190a-5p as potential indicator of kidney health and disease progression in patients with chronic kidney disease.

The mechanisms generating the head direction cell signal in rats are not fully understood. Here, two distinct types of head direction cells in the lateral mammillary and dorsal tegmental nuclei were identified: one type is angular head velocity independent, while the second type depends on the animal’s angular head velocity.

FACED 2.0 builds on and expands the capabilities of the free-space angular-chirp-enhanced delay microscopy approach. Its high speed, large field of view and volumetric coverage enable two-photon voltage imaging of hundreds of neurons or calcium imaging of thousands of neurons in the mouse or zebrafish brain.

In young, estrogen-deprived female mice, the authors show that daily low-intensity vibration protected bone, muscle and fat metabolism. This treatment also enhanced bisphosphonate outcomes, strengthening the skeleton to counter adverse effects of cancer therapy on musculoskeletal tissue.

Inherited mitochondrial DNA mutations can result in diverse clinical phenotypes. Here, the authors characterise a heteroplasmic tRNA^Ala mutation (m.5019A>G) in mice and demonstrate that macrophages carrying this mutation display altered function and metabolism in vitro, along with increased type I IFN release following LPS challenge in vivo.

In the United States, Black patients have higher rates of cancer mortality, but the sources of such disparities remain poorly understood. Here, the authors analyze genomic data from large-scale patient cohorts and find that cancers from self-reported Black patients are significantly more likely to exhibit whole genome duplications; they also explore a potential link to environmental exposures.

Analysis of copy number alterations in 1,451 patient-derived xenografts (PDXs) and matched patient tumor samples shows strong conservation from patient tumors through late-passage PDXs and a lack of systematic copy number evolution driven by the mouse host.

Shared inter-brain neural dynamics, reflecting aspects of social interaction including self and other’s behaviours, arise in GABAergic neurons of the dorsomedial prefrontal cortex of socially interacting mice, as well as in the neurons of socially interacting artificial intelligence agents.

The authors develop and characterise a selective Greatwall inhibitor, C-604, and show that its cytotoxicity stems from PP2A-B55α hyperactivation. They identify B55α and Greatwall levels as biomarkers of responses to Greatwall-targeted therapy.

A generalizable framework to prospectively engineer cis-regulatory elements from massively parallel reporter assay models can be used to write fit-for-purpose regulatory code.

This manuscript from Choquette and colleagues finds that sclerostin gene expression is up-regulated in bone by β3-adrenergic signaling via an adipose to bone relay and acts as an endocrine factor to inhibit adipose tissue beiging in mice.

Available wheat genomes are annotated by projecting Chinese Spring gene models across the new assemblies. Here, the authors generate de novo gene annotations for the 9 wheat genomes, identify core and dispensable transcriptome, and reveal conservation and divergence of gene expression balance across homoeologous subgenomes.

Perineural invasion and cancer-induced nerve injury of tumour-associated nerves are associated with poor response to anti-PD-1 therapy, which can be reversed by combining anti-PD-1 therapy with anti-inflammatory interventions.

Cold-sensitive engrams contribute to learned thermoregulation in mice that are returned to an environment in which they previously experienced a cold challenge, through a network formed between the hippocampus and hypothalamus that enables the recall of cold-related memories.

This study characterizes the three-dimensional (3D) genome architecture of 15 primary human cancer types from The Cancer Genome Atlas. The analyses identify different archetypes of enhancer usage and enhancer rewiring events due to different classes of mutations and structural variants.

The authors developed an LXR inverse agonist, TLC-2716, and show it is effective in reducing triglycerides and cholesterol in dysmetabolic preclinical models. Additionally, a phase 1 trial in healthy participants shows that TLC-2716 is well tolerated and reduces plasma triglycerides and postprandial remnant cholesterol, highlighting its potential for managing cardiovascular risk.

Here, the authors examine the mechanisms behind cheatgrass’s successful invasion of North American ecosystems. Their genetic analyses and common garden experiments demonstrate that multiple introductions and migrations facilitated cheatgrass local adaptation.

GWAS in difficult-to-recruit populations identifies variants associated with Lassa fever outcome and susceptibility at loci proximal to LIF, GRM7 and LARGE1.

A multiancestry phenome-wide analysis of copy number variants in the UK Biobank genomes increases power to detect genetic associations with complex traits across human populations.

Over 20 species of geographically and phylogenetically diverse bird species produce convergent whining vocalizations towards their respective brood parasites. Model presentation and playback experiments across multiple continents suggest that these learned calls provoke an innate response even among allopatric species.

The authors previously pinpointed OLAH (oleoyl-ACP-hydrolase) as a driver of life-threatening viral diseases. Here, the authors identify increased IL-18Rα expression on CD8⁺ T cells, which acquire a reduced cytotoxic signature, correlates with severe respiratory viral infection of influenza A virus, RSV and COVID-19.

Turley and colleagues find that Gremlin1-expressing lymph node fibroblastic reticular cells support dendritic cell homeostasis via provision of FLT3L.

Brain-wide recordings in mice show that learning leads to sensory evidence integration in many brain areas simultaneously, allowing sensory input to drive global movement preparatory dynamics, which collapse upon movement onset.

Polycystic ovary syndrome (PCOS) is a common disorder, the causes of which remain incompletely understood. Here the authors report the discovery of gene regulatory mechanisms that help to explain genetic associations with PCOS in the GATA4, FSHB and DENND1A loci.

Age is a risk factor for many diseases, but the impact of aging on molecular phenotypes is not fully understood. Here, the authors quantify the relative contributions of genetics and aging to gene expression patterns across 27 tissues in humans, showing that age and genetics each play distinct roles in shaping expression phenotypes.

Improved imaging methods are crucial to map pancreatic ductal adenocarcinoma (PDAC). Here, the authors analyse PDAC samples using spatial transcriptomics and proteomics, identify claudin-4 as a potential theranostic target, and develop an imaging agent to track claudin-4 in primary and metastatic PDAC tumours.

Here the authors show that expanding global ancestry diversity in genomic datasets improves detection of genomic regions intolerant to variation, identifying areas more likely to harbor disease-causing mutations.

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).

Using high-resolution stable isotope and microstructure analyses of otoliths, this study reveals that sardine populations in the western and eastern North Pacific have different early life metabolic and growth rates that respond contrastingly to temperature variations. These findings could explain observations of different responses in these populations to decadal-scale temperature anomalies.

MILTON uses phenotype information in the UK Biobank to identify clinical biomarkers and other quantitative traits that characterize diseases. It then constructs augmented cohorts by predicting undiagnosed individuals, improving power to discover gene–disease relationships.