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Shigella sonnei is divided into five lineages and most infections are caused by Lineage 3. Here, the authors investigate factors contributing to the epidemiological success of Lineage 3 through comparative genomics and virulence analyses in a zebrafish infection model.

A study of several longitudinal birth cohorts and cross-sectional cohorts finds only moderate overlap in genetic variants between autism that is diagnosed earlier and that diagnosed later, so they may represent aetiologically different conditions.

Understanding the mechanisms behind clinical immunity to malaria is crucial for developing effective interventions. Here, the authors demonstrate that clinical immunity to Plasmodium vivax develops rapidly after a single controlled human malaria infection, reducing inflammatory responses and protecting against symptoms, while not significantly affecting parasite load.

Women of reproductive age may have specific concerns relating to perceived impacts on fertility and menstrual cycles that make them hesitant to receive COVID-19 vaccination. In this study, the authors explore COVID-19 vaccine uptake rates in women of reproductive age using linked data for ~13 million women in England.

A proteotoxic stress response specific to exhausted T cells, governed by AKT signaling and accompanied by increased protein translation, represents a mechanistic vulnerability and a new therapeutic target to improve cancer immunotherapies.

A lung-on-a-chip device containing immune cells and stromal cells mimics the small airways, recapitulating human immune response to severe H1N1 infection.

Analysis of soundscape data from 139 globally distributed sites reveals that sounds of biological origin exhibit predictable rhythms depending on location and season, whereas sounds of anthropogenic origin are less predictable. Comparisons between paired urban–rural sites show that urban green spaces are noisier and dominated by sounds of technological origin.

Mepolizumab (anti-IL-5 therapy) has been shown to reduce type 2 inflammation in asthma. Here the authors use bulk transcriptomics from nasal samples before and after mepolizumab treatment to assess the changes and associations with treatment outcomes.

Phenotype variation is higher in mutants than wild types. Examining a range of mutant severities, this study unexpectedly found that variation decreases in severe conditions. A quadratic trend best fits the relationship between severity and variation.

A study presents ALPACA, a computational method for inferring clone- and allele-specific copy numbers of individual clones from multi-sample bulk DNA-sequencing data, and demonstrates its use to study metastasis trajectories.

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).

Cell state plasticity of neuroblastoma cells is linked to therapy resistance. Here, the authors develop a transcriptomic and epigenetic map of indisulam (RBM39 degrader) resistant neuroblastoma, demonstrating bidirectional cell state switching accompanied by increased NK cell activity, which they therapeutically enhance by the addition of an anti-GD2 antibody.

Beading combines soft, compliant threads with discrete, rigid elements to make architected materials. Here, authors show how geometry, tension, and friction together enable programmable shape and tunable mechanical behavior.

Integrated multi-omic analyses using samples from the TRACERx study highlight cross-talk between DNA hypermethylation and genomic lesions in non-small cell lung cancer.

The reconstruction of phospholipase Ce in complex with a Fab identifies two of its N-terminal regulatory domains and helps define the basal state of the enzyme.

Soft electronic probes for measuring neural activity can be made scalably in an initially planar form and turned into various three-dimensional geometries through a controlled rolling method.

In a phase 1/2a umbrella trial in patients with glioblastoma matching targeted therapies according to tumor molecular profiling, temsirolimus plus radiotherapy improved PFS compared to standard of care in patients with phospho-mTOR activation.

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.

The scope of Lewis acid catalysis mediated by enzymes is low compared with the range of reactions it drives in organic synthesis. Now the substitution of the iron centre with copper, and the subsequent directed evolution, enabled a non-haem iron hydroxylase to efficiently catalyse asymmetric abiotic Conia-ene cyclizations.

The DNA-dependent protease SPRTN cleaves toxic DNA-protein crosslinks (DPCs). Here, the authors show that SPRTN is activated by DPC-ubiquitylation through an allosteric ubiquitin binding interface. This regulatory mechanism enables precise control of SPRTN activity during DNA repair.

Protein sequences from fossil tooth enamel of a rhinocerotid from Canada’s High Arctic are used to develop phylogenetic frameworks from a specimen too old to preserve ancient DNA.

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.

Using genome-wide meta-analyses of clinical measures of depression and biobank data, the authors investigate symptom-specific genetic associations between depression and subsequent risk for Alzheimer’s disease, finding an absence of a putative genetic overlap between disorders.

Amado et al. develop a gene therapy for sporadic ALS using motor neuron-targeting AAVs to deliver RNAi targeting ataxin-2. In a mouse model, survival, strength, and disease-related pathology are improved; and human motor neurons are strongly transduced.

A genome-wide study by the Long COVID Host Genetics Initiative identifies an association between the FOXP4 locus and long COVID, implicating altered lung function in its pathophysiology.

_{Household survey data is vital to health and development. The study describes and maps data quality in 35 African countries, finding that data quality varies and worsens with distance from towns, indicating a need for investment in data collection.}

By affecting which form of a gene is expressed, alternative splicing is a major source of diversity in the nervous system. Here, the authors present an atlas of splice variants across neurons, and explore its impacts and mechanisms in the nematode nervous system.

This work identified immune signatures of COVID-19 including broad Interferon signatures that are unique to infants. Compared with infected adults, infants display similar Interferon signatures in monocytes but enhanced signatures in T and B cells.

Complete sequences of chromosomes telomere-to-telomere from chimpanzee, bonobo, gorilla, Bornean orangutan, Sumatran orangutan and siamang provide a comprehensive and valuable resource for future evolutionary comparisons.

Acquiring biomarkers from blood or sweat is limited by invasiveness or biofouling. Skin gas emissions bypass these issues, offering rich biosignals. Authors present passive sensing strategies capturing water vapor (Sweat rate), CO2, and VOCs, enabling real-time tracking of physiological changes.

Over the last 15 years, the content of Nature Physics has covered an enormous breadth of subjects at the forefront of physics. The journal’s past and present editors recount their favourite papers and what made chaperoning them to publication special.

Andrejek et al. evaluate the barriers and facilitators of leveraging telemedicine and task-sharing to improve access to psychotherapy for perinatal patients with symptoms of depression and anxiety in the SUMMIT trial. The qualitative implementation assessment demonstrates that both solutions are feasible, patient-centered approaches.

Fibrosis arises from pathological fibroblast activation into myofibroblasts, causing tissue stiffening. Fibroblast phenotyping is largely subjective, yet crucial for drug screening. Here, authors develop mathematical descriptors of cell morphology and structures to consistently grade fibroblasts.

Genome-wide analyses identify variants associated with infertility and reproductive hormone levels but find limited polygenic overlap between reproductive hormone levels and infertility at the population level.

Study shows PTSD predisposition shares distinct genes and genomic regions with several cardiovascular conditions. Here the findings reveal neuronal, immune, and metabolic pathways, and repurposed drug targets that further the understanding of the comorbidity.

Leydig cells are essential for male sexual development, but their developmental origins are not fully established. Here, authors map early developmental stages of fetal Leydig cells in mice, revealing critical genetic factors that guide their maturation and function.

Analyses of multiregional tumour samples from 421 patients with non-small cell lung cancer prospectively enrolled to the TRACERx study reveal determinants of tumour evolution and relationships between intratumour heterogeneity and clinical outcome.

Genetic mechanisms of blood pressure regulation remain poorly defined. Here, the authors perform a kidney multi-omics study to identify 399 kidney effector genes, 11 miRNAs and 97 proteins for blood pressure and hypertension.

A two-species eco-evolutionary model based on consumer–resource interactions and quantitative genetic inheritance shows how evolution among competitors changes the components of stable coexistence.

A scheme for watermarking the text generated by large language models shows high text quality preservation and detection accuracy and low latency, and is feasible in large-scale-production settings.

Here the authors show that lab mice have retained ancient gut bacterial symbionts that diversified in parallel with rodent species, but the genomes of these gut bugs have accumulated mutational burdens over the past ~ 120 years of inbreeding in captivity.

A longitudinal evolutionary analysis of 126 lung cancer patients with metastatic disease reveals the timing of metastatic divergence, modes of dissemination and the genomic events subject to selection during the metastatic transition.

Parvalbumin-positive interneurons in the hippocampal CA3 substantially reduce firing on approach to and at goal locations while food-deprived mice learn to find food.

TERT promoter mutations are the most common noncoding alterations in cancers, although some remain to be characterised. Here, the authors identify TERT promoter duplications across seven cancer types that are functionally equivalent to well-known hotspot TERT mutations and are clonal in a multifocal glioblastoma patient.

By engaging a group of 27 certified radiologists in the United States and India, the accuracy and quality of radiology reports generated by a vision–language model is evaluated, exploring synergistic combinations with clinicians.