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Here the authors provide an explanation for 95% of examined predicted loss of function variants found in disease-associated haploinsufficient genes in the Genome Aggregation Database (gnomAD), underscoring the power of the presented analysis to minimize false assignments of disease risk.

Research on sustainable diets has primarily focused on human and planetary health, neglecting workers in food value chains. This study quantifies the risk of forced labour embedded in five different diets in the USA, underscoring the need to integrate such risk in sustainable diet transition efforts.

Context counts, and not just for social and economic aspects of urban life. This study finds that, for 16 cities in the United Kingdom, the landcover of the rural surroundings is a better predictor of ticks and environmental Lyme disease hazard than the landcover within the cities themselves.

CNS toxicity was unexpectedly observed for anti-miR-17 RGLS4326 in nonclinical studies. Here, authors identify AMPA receptor inhibition as the likely culprit. Replacement of 3’-terminus guanine to adenine leads to discovery of farabursen (RGLS8429) that is devoid of CNS toxicity.

Here Jaster et al., show a single psilocybin dose produce sex-specific post-acute changes in opioid reward and withdrawal via 5-HT2A receptors in frontal cortex-to–nucleus accumbens circuits, with epigenetic and synaptic changes shaping therapeutic potential.

Here, the authors perform metagenomic analysis of Ecuadorian mothers and children showing that improved WASH and reduced animal exposure can lower antimicrobial resistance in the gut but may reduce gut microbial diversity, with the strongest effects observed in mothers.

The P2X4 receptor, an ATP-activated ion channel, plays a role in chronic pain, inflammation, and cancer. Authors in this work discover an extracellular allosteric binding site that interacts with anthraquinone derivatives, and is narrowed by ionic lock formation.

Chromatin heterogeneity in the cell nucleus modulates the size, mobility, and formation of biomolecular condensates; decreasing chromatin heterogeneity correlates with decreased mobility of both endogenous and engineered condensates, revealing a key role for nuclear organization in cellular function.

Pilcher et al. present a single-cell transcriptomics-based immune atlas of participants with newly diagnosed multiple myeloma, reporting on the association of cell types, gene expression and intercellular interactions with disease progression phenotypes.

The GroEL/ES chaperonin can act during protein synthesis to promote folding. Here, Roeselová et al. show how GroEL captures, remodels and sequesters nascent proteins in its central chamber, while they remain tethered to the ribosome.

Here, the authors report recent updates to the ENCODE data portal including a redesigned home page, an improved search interface, custom-designed pages highlighting biologically related datasets and an enhanced cart interface for data visualisation plus user-friendly data download options.

Telomerase reverse-trancriptase promoter mutations have been recently found in human melanomas. Here, Nault et al.identify telomerase reverse-trancriptase promoter mutations as the most frequent somatic genetic alterations in hepatocellular carcinomas and as the first mutation identified in cirrhotic preneoplastic lesions.

Mitochondrial diseases lead to chronic health impairment, aggravated by infections and other environmental exposures. Here authors show, in a mouse model of polymerase gamma (Polg)-related mitochondrial disease, that Pseudomonas aeruginosa infection prompts innate immune hyperreactivity via interferon-mediated upregulation of caspase11 and guanylate-binding proteins, leading to lung inflammation.

An empty room can be intimidating. But with some thoughtful planning, you can create a thriving scientific community.

Chronic care manages long-term, progressive conditions, while acute care handles short-term ones. Here, authors show chronic conditions account for most of the global health burden, with 68% of DALYs and 93% of YLDs attributed to chronic care needs.

This Perspective considers the addition of ACKR1 genetic testing for identifying ACKR1/DARC-associated neutropenia in patients receiving clozapine, recommending eligibility criteria and testing strategies while estimating substantial cost savings for the UK healthcare system and enhancing equitable treatment access.

K11/K48 branched ubiquitin chains regulate protein degradation and cell cycle progression. Here, the authors report the structural basis of how such a branched ubiquitin chain is recognized by the human 26S proteasome, revealing a multivalent binding mode that underlies selective recognition.

Electrical tuning of the recombination zone in circularly polarized (CP) OLEDs enables switching the CP generation mechanism between normal and anomalous CP electroluminescence. This is exploited to electrically control the handedness of emitted CP light from the same device with the same enantiomer material.

Political ecology aims to understand how politics and power influence both social and ecological dynamics. Conservation biologists and political ecologists tackle many of the same pressing environmental problems, but from quite different perspectives. In this Viewpoint, five political ecologists discuss their views on how the field can understand and tackle the biodiversity crisis.

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.

Promising clinical activity of Claudin (CLDN) 18.2-directed CAR-T cell therapy in patients with gastric cancer has been recently reported, however gastrointestinal toxicities have also been described. Here the authors recapitulate the on-target off-tumor toxicity of CLDN18.2-directed CAR-T cells due to gastric mucosa damage in preclinical models, suggesting an AND-gate strategy targeting CLDN18.2 and mesothelin to overcome CAR-T cell toxicity

Transcriptomic screening identifies pairs of cell-surface proteins that mediate repulsive interactions between axons and dendrites of non-cognate partner neurons, thereby contributing to correct synaptic partner matching.

The early postnatal roles of dendrite-targeting interneurons in primary visual cortex (V1) remain elusive. Here, the authors find that somatostatin interneurons in mouse V1 exhibit a uniquely delayed developmental trajectory for innervation and sensory responses, highlighting a window for the emergence of a key mechanism for normalization in cortical circuits.

Using a mouse model enabling an inducible ‘switch’, Golden et al. show that an astrocyte-specific replacement of the Alzheimer’s risk gene APOE4 with protective APOE2 alters metabolism and gene expression, reducing amyloid pathology and gliosis.

When learning new tasks, both humans and artificial neural networks face a trade-off between reusing prior knowledge to learn faster and avoiding the disruption of earlier learning. This study shows that people and artificial neural networks have similar patterns of transfer and interference and vary in how they balance this trade-off.

This study reports a modular-cloning-based platform for high-throughput chloroplast engineering in Chlamydomonas reinhardtii that allows large-scale characterization of genetic parts and prototyping of new traits, as demonstrated for the photorespiration pathway.

This multi-omic longitudinal analysis of the healthy human peripheral immune system constructs the Human Immune Health Atlas and assembles data on immune cell composition and state changes with age, including responses to cytomegalovirus infection and influenza vaccination.

Long-distance migration and dispersion is a common characteristic of nearly all classes of telencephalic GABAergic neurons, which diversify extensively after birth in the cortex and striatum, but show limited postnatal changes in the septum, preoptic area and pallidum.

Digital archivists are already experts at tackling the complex challenges of making research data open and accessible. We can help to smooth the transition.

The ability to perform operations in an indefinite causal order allows advantages for various quantum information-processing tasks, yet it’s still unclear to what extent such exotic sequences could be simulated using standard quantum circuits. Here, the authors prove that such simulations - even if approximate or probabilistic - would incur an exponential quantum query complexity overhead.

A previously uncharacterized microbial enzyme is responsible for the production of molecular hydrogen in the gut, which drives the growth of other bacteria and has implications for human health.

This study shows that future exposures to moist-heat increase more rapidly than those to dry-heat, and irrigation can further amplify moist-heat-related health risks. Improving irrigation efficiency and cutting emissions are key to reducing water stress and climate impacts.

How age affect the immune response to malaria is not fully understood. Here, the authors characterise the transcriptome and serum inflammatory cytokines in children and adults in response to malaria, showing that there is an increase of inflammatory chemokine and cellular responses in adults compared to children.

This global meta-analysis of freshwater stressor–response relationships reveals that the biodiversity loss of five riverine organism groups reflects elevated salinity, oxygen depletion and fine sediment accumulation, while the relationship with nutrient enrichment and warming varies among groups.

Finding ways to connect with the public — as part of my work to get people to take action on climate change — took me to an interesting place, says Jessica Eise.

This study incorporates local ancestry into the Genome Aggregation Database (gnomAD) to improve allele frequency estimates for admixed populations, enhancing variant interpretation and enabling more accurate and equitable genomic research and clinical care.

Cellular senescence is an underlying mechanism of aging. Among older Americans, higher expression of genes linked to cellular senescence is seen in women and those with class II obesity, and is associated with worse health outcomes.

The gut microbiota-derived metabolite indole-3-propionic acid (IPA) is found to enhance mitochondrial fatty acid and amino acid oxidation in CD4⁺ T cells. In mice, IPA-mediated metabolic reprogramming of CD4⁺ T cells exerts anti-inflammatory effects and protects against colitis.

Walmsley and colleagues report that systemic hypoxia induces persistent loss of histone H3K4me3 marks and epigenetic reprogramming in neutrophil progenitors, resulting in long-term impairment of subsequent neutrophil effector functions.

A pangenome of oat, assembled from 33 wild and domesticated oat lines, sheds light on the evolution and genetic diversity of this cereal crop and will aid genomics-assisted breeding to improve productivity and sustainability.

The authors show that regenerating liver requires de novo pyrimidine synthesis and it uses ammonia as precursors differentially as it traverses the liver zones. Tracing studies and spatial metabolomics reveal that assimilation periportally is via the urea cycle, and pericentrally through conversion into glutamine.

In this work, authors show that Salmonella uses its SPI-1 injectisome to infect macrophages, triggering rapid translational upregulation of transcription factors, such as EGR1 which suppresses the inflammatory response, aiding the bacteria in establishing systemic infection

Results of an early-phase breast cancer prevention trial demonstrate the potential for breast cancer prevention in premenopausal women with anti-progestin therapy by inducing epithelial–stromal remodelling and suppression of luminal progenitors.

SpaceBar is a cellular barcoding strategy for simultaneous analysis of cell clonal and spatial identities.

The BabyScreen+ study offered genomic screening to 1,000 newborns in Australia, and showed that the approach is feasible and positively received by families, leading to molecular diagnoses in 1.6% of babies.