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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.

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 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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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

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 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.

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.

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.

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.

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.

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.

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 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.

Experimental measurements of high-order out-of-time-order correlators on a superconducting quantum processor show that these correlators remain highly sensitive to the quantum many-body dynamics in quantum computers at long timescales.

Mosquitoes are major vectors for the transmission of many serious pathogens. This study uses genome-wide CRISPR screens in the mosquito, Anopheles gambiae, to reveal new insights into mosquito fitness and the function of clodronate-liposome mediated immune cell ablation.

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.

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

A flexible micro-electrocorticography brain–computer interface that integrates a 256 × 256 array of electrodes, signal processing, data telemetry and wireless powering on a single complementary metal–oxide–semiconductor substrate can provide stable, chronic in vivo recordings.

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.

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.

Genomic analyses applied to 14 childhood- and adult-onset psychiatric disorders identifies five underlying genomic factors that explain the majority of the genetic variance of the individual disorders.

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.

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.

EGF-induced recruitment of UPF1 adjacent to HNRNPC induces splicing surveillance of cell proliferation mRNAs.

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.

Ipecac alkaloids are plant-derived compounds historically used to induce vomiting. Here the authors elucidate how two evolutionary distant plant species have evolved to produce the same ipecac alkaloid.

Chou et al. generate transdifferentiated human neurons from fibroblasts from young or aged individuals and patients with Alzheimer’s disease. Studies of endolysosomes and proteostasis suggest a role for lysosomal quality control in Alzheimer’s disease pathology.

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).

Discovery of a near-complete colchicine biosynthetic pathway enables the engineered production of the tropolone-containing alkaloid N-formyldemecolcine from amino acid precursors in Nicotiana benthamiana.

The genomic profiling of tumours has not been widely adopted in the clinic due to technical and practical hurdles. Here, the authors develop PGDx elio tissue complete, a scalable, standardised and FDA-cleared test comprising a targeted gene panel and automated machine-learning analysis, which detects clinically relevant sequence biomarkers in cancer samples.

Using avian trait data and genomic data, the authors infer whether changes in net effective population size over time in response to climate change are correlated with multiple morphological and life history traits; they find that larger-bodied, slower-reproducing species with limited dispersal capacity are most sensitive to changes in warming and cooling climates.

A dataset of 3D images from more than 200,000 human induced pluripotent stem cells is used to develop a framework to analyse cell shape and the location and organization of major intracellular structures.

The pilot phase of PigGTEx, re-analyzing 5,457 published RNA-seq samples, presents a pan-tissue catalog of molecular quantitative trait loci. Cross-species comparisons identify traits with shared genetic regulation in humans.

Single-cell proteomics is an emerging technology but protein coverage, throughput and quantitation accuracy are often still insufficient. Here, the authors develop a nested nanowell chip that improves protein recovery, throughput and robustness of isobaric labeling-based quantitative single-cell proteomics.

End-of-life nonhuman primates can be used to screen pools of lipid nanoparticles for clinical safety studies.

The Zika viral protease NS2B-NS3 is a crucial target for antiviral drug development due to its role in processing viral polyproteins. Here, the authors utilize crystallographic fragment screening and deep mutational scanning to identify binding sites for resistance-resilient inhibitors.

Analysis of colorectal cancer bulk gene expression data at the pathway level identifies a poor-prognosis subtype associated with cell differentiation. The subtypes are reproducible in single-cell data and offer biological insights beyond existing stratification strategies.

Resistance to first line treatment is a major hurdle in cancer treatment, that can be overcome with drug combinations. Here, the authors provide a large drug combination screen across cancer cell lines to benchmark crowdsourced methods and to computationally predict drug synergies.