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Population-level analyses and in vitro experiments show that a specific genetic variant of cyclin D3 inhibits the growth of the malaria-causing parasite Plasmodium falciparum in erythrocytes, and suggest that its high frequency in Sardinia was driven by past endemic malaria.

From 2014–2017, marine heatwaves caused global mass coral bleaching, where the corals lose their symbiotic algae. The authors find, this event exceeded the severity of all prior global bleaching events in recorded history, with approximately half the world’s reefs bleaching and 15% experiencing substantial mortality.

It is unclear whether the harsh abiotic conditions of drylands hinder biological invasions. This global analysis shows that drylands are vulnerable to non-native plants and are likely to become more so as native plant diversity declines and grazing pressure intensifies.

The lowest-frequency gravitational wave background may be shaped by supermassive black hole binaries that scatter nearby stars or dark matter. In this case, the NANOGrav 15-year dataset favours dense galactic centres with 10⁶ solar masses per cubic parsec.

HIV-1 integrase forms an RNA-binding module on the luminal side of the mature capsid lattice.

In a phase 1b/2 trial, an off-the-shelf vaccine using gorilla adenoviral and modified vaccinia Ankara vectors with over 200 mutated peptides known to be present in persons with mismatch-repair-deficient tumors is safe and elicits neoantigen-specific T cells in individuals with Lynch syndrome.

Constraining projections using best-performing climate models, uncertainties in future temperature variability can be narrowed, yet remain large over poorly modelled regions, highlighting the need for multiple model ensembles to assess future risks.

De novo and inherited dominant variants in genes encoding U4 and U6 small nuclear RNAs are identified in individuals with retinitis pigmentosa. The variants cluster at nucleotide positions distinct from those implicated in neurodevelopmental disorders.

Contact matrices are used to describe social mixing patterns and inform mathematical models of disease transmission. Here, the authors evaluate the accuracy of synthetic contact matrices generated using mobility data compared to those derived empirically through surveys.

Behaviour changes, rather than vaccination or postinfection immunity, best explained the sudden decline of mpox cases among men who have sex with men during an outbreak in the Paris region in 2022, according to a network model and survey data.

The authors describe the discovery of a series of potent non-competitive allosteric inhibitors of the ZIKV NS2B-NS3 protease, which exhibit antiviral activity in vitro and robust oral efficacy against ZIKV infections in a mouse model.

This study reveals diverse soil nematode community patterns across Atacama habitats, including dunes, high elevation mountains and fog oases. Latitude, rainfall and elevation were found to be associated with diversity and reproductive modes.

Including data from 1,047 patients across 19 inflammatory diseases, a new atlas presents a comprehensive model of inflammation in circulating immune cells.

Kinematic measurements of the Perseus galaxy cluster reveal two drivers of gas motions: a small-scale driver in the inner core associated with black-hole feedback and a large-scale driver in the outer core powered by mergers.

Spatiotemporal insight into photoactivation of the prototypical B₁₂ photoreceptor CarH is revealed across nine orders of magnitude in time, identifying a transient adduct that distinguishes it from thermally activated B₁₂ enzymes.

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.

Grazing affects plant diversity, but plant diversity in turn may modulate the effect of grazing on the plant community. This global analysis explores the association between plant species richness and plant cover resistance to grazing intensity in drylands.

Alström syndrome (AöS) is a rare genetic disorder characterized by metabolic problems. Here, the authors show that in AöS models, defects in cilia and autophagy lead to ACBP accumulation, which drives obesity. An anti-ACBP antibody reduces weight gain and metabolic dysfunction, highlighting ACBP as a therapeutic target for this ciliopathy.

In this study, the authors show that microbial rhodopsins, proteins that drive the ocean’s most widespread light-driven microbial metabolism, display overlapping distributions with algal blooms in nutrient-rich waters, expanding rhodopsins’ known role of supporting bacterioplankton beyond oligotrophic regions.

A large sulfur-bearing carbon ring molecule has been detected in space, 2,5-cyclohexadien-1-thione, using laboratory spectroscopy and a radio telescope. Found near the Galactic Centre, it opens the door to a new family of interstellar molecules.

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).

Annunziato, Quan and Donckele et al. identify G3BP2 (Ras–GAP SH3 domain-binding protein 2) as a molecular glue-induced neosubstrate of the CRL4^CRBN E3 ubiquitin ligase. The CRBN–glue neosurface uses a molecular surface mimicry mechanism to recruit and degrade G3BP2 in a compound-dependent manner.

Affinity-proteomics platforms often yield poorly correlated measurements. Here, the authors show that protein-altering variants drive a portion of inter-platform inconsistency and that accounting for genetic variants can improve concordance of protein measures and phenotypic associations across ancestries.

Standard of care in patients with unresectable stage III non-small cell lung cancer (NSCLC) is concurrent chemo-radiotherapy followed by immunotherapy. Here, the authors report a phase II trial investigating induction chemo-immunotherapy (atezolizumab, carboplatin and paclitaxel) followed by concurrent chemoradiotherapy and immunotherapy maintenance in patients with stage III NSCLC.

A narrow ‘Goldilocks zone’ of oxidation levels during exoplanetary core formation allows both nitrogen and phosphorus to remain in the mantle. Earth lies within this zone, but more oxidized or reduced exoplanets may lock these elements in their cores, limiting habitability.

Polygenic scores for body mass index and obesity constructed using data from 5 million people with different ancestries were associated with distinct weight gain trajectories from early childhood to adulthood.

Anti-tumor functions of low-avidity T cells are often suboptimal. Here the authors show that genetic disruption of TIGIT in TCR-engineered T cells enhances their anti-tumor activity against pancreatic and other gastrointestinal cancers by increasing TCR signal strength.

Here the authors perturb genes linked to schizophrenia risk in human neurons. They find that single perturbations share common downstream effects on gene networks, while joint perturbations result in downstream effects being saturated.

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.

Pender et al. evaluated depression and anxiety symptom trajectories in autistic adults receiving routine therapy in UK primary care.

Oat consumption, particularly a short-term, high-dose oat diet, improves metabolic health in individuals with metabolic syndrome by increasing microbially produced phenolic metabolites, leading to lower blood cholesterol levels.

This study identifies key neurocognitive domains that distinguish patients with schizophrenia from healthy individuals using machine learning. Analyzing data from 1,304 participants, it demonstrates that verbal learning and emotion identification effectively classify conditions, promoting efficient neurocognitive profiling strategies.

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.

MAGPIE is a computational framework for co-registering spatially-resolved transcriptomics, metabolomics and tissue morphology for integrated downstream analysis. Case studies across lung, brain and breast reveal coordinated cross-modality molecular changes.

Patin and colleagues present a mineable Resource database for identifying demographic and genetic factors that impact antiviral antibody repertoires in humans.

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.

The discovery of a vast reservoir of primordial neutral hydrogen gas surrounding a young galaxy cluster just one billion years after the Big Bang offers new insight into how the first large cosmic structures assembled.

Our annual survey highlights startups taking on gene therapy, adoptive immune cell therapy, gene editing, and drugs targeting RNA modifications and the unfolded protein response. Ken Garber, Esther Landhuis, Melanie Senior, Cormac Sheridan and Laura DeFrancesco report.

In the phase 1/2 CASTLE basket trial, autologous CD19 CAR-T cell therapy in patients with treatment-refractory systemic lupus erythematosus, systemic sclerosis or idiopathic inflammatory myopathy was safe, with improved disease activity and patient-reported global health in most patients.

Nature Biotechnology’s annual survey highlights university startups that are, among other things, rethinking how to deliver gene-editing therapy and tackling various metabolic conditions, immune disorders and cancer with microbiome treatments or immunotherapy. Michael Eisenstein, Ken Garber, Esther Landhuis, Caroline Seydel and Laura DeFrancesco report.

Our annual survey highlights startups tackling intractable viruses with new vaccine design, engineering a reliable source of platelets, universalizing cell therapies, improving cancer screening, developing RNA-editing platforms and targeting protein–RNA interactions. Michael Eisenstein, Ken Garber, Caroline Seydel and Laura DeFrancesco report.

This Perspective offers a roadmap for tackling the challenges of the facsimile problem, moral multidimensionality and moral pluralism in large language models.

The cool sub-Neptune LP 791-18 c, with an equilibrium temperature of 355 K, was found to host a hazy atmosphere, distinct from any other temperate sub-Neptune studied so far. The discovery demonstrates the intrinsic diversity of these worlds.

The fetal globin gene repressors BCL11A and ZBTB7A directly bind γ-globin gene promoter regions. Repressor binding is disrupted by naturally occurring point mutations located upstream of the transcriptional start site that are associated with hereditary persistence of fetal hemoglobin.

The authors propose a Generalized Latent Equilibrium framework for fully local credit assignment in physical, dynamical neuronal networks such as the brain. By exploiting dendritic structure and prospective coding in cortical neurons, it enables an online approximation of backpropagation through space and time.

Polygenic risk scores can help identify individuals at higher risk of type 2 diabetes. Here, the authors characterise a multi-ancestry score across nearly 900,000 people, showing that its predictive value depends on demographic and clinical context and extends to related traits and complications.

The authors identify a Cys→Ser transformation (C19S) in insulin leading to neoepitope presentation and CD4⁺ T cell autoreactivity in type 1 diabetes. Inflammation and oxidative stress enhanced C19S transformation in β cells and antigen-presenting cells, resulting in C19S-specific CD4⁺ T cells with an activated memory phenotype linked to disease progression.