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Viral evolution is shaped by host factors. Here, the authors use experimental evolution to show that mouse genotype and sex alter the evolutionary trajectories of influenza A virus, with some hosts favoring mutations associated with increased virulence and others favoring defective viral genome accumulation.

Adsorption of trace transition-metal cations endows common Ca/Mg-carbonates and phyllosilicates with catalytic activity for electrochemical CO2 reduction under planetary conditions, potentially promoting prebiotic chemistry and the origin of life.

The effects of transcranial focused ultrasound (tFUS) on the human brain are poorly understood. Here, the authors elucidate the subthreshold effects of tFUS and found that integrating tFUS with electric stimulation led to suprathreshold neuromodulation in the resting-state human brain.

Three endoplasmic reticulum luminal mannosyltransferases ALG3, ALG9 and ALG12 catalyze the synthesis of the branched mannose core in N-glycans in four distinct steps. Now, cryo-electron microscopy structures and characterization of ALG3, ALG9 and ALG12 reveal the molecular logic of oligomannose core assembly.

Achieving tight Cas9 regulation without sacrificing activity remains difficult. Here, the authors design multi-level circuits combining anti-CRISPRs, splice sites, chemical induction, and degron control to enable ultra-high dynamic range and precise, on-demand genome editing across contexts.

Glacial cycles can modulate volcanism. Using models of magma transport under ice loading, this study shows that ice sheets can stall rising magma at depth, suppressing eruptions and promoting magma evolution until deglaciation resumes activity.

Dissolved Fe(II) could greatly enhance uptake of dissolved phosphorus by common phyllosilicate minerals in the Archean and Proterozoic ferruginous oceans, serving as a key mediator in early phosphorus cycling and habitability

Temporal patterns in global oil shipping reveal tankers exploring varied routes spend up to 50% more time carrying instead of seeking cargo. Tracking cargo flows uncovers annual cycles with 16% swings-insights that could optimize costs and emissions.

This study shows that mithramycin suppresses the EWS::FLI1 transcription factor in Ewing sarcoma using a hybrid CUT, Tag & GRO assay, revealing mechanism, need for continuous dosing, and supporting clinical use of next-gen analog AIT-102.

cellSTAAR advances noncoding rare variant association analysis by integrating single-cell genomics data.

Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.

Bioactivity benchmarks are key to evaluating and improving methods to predict chemicals’ specific biological activity. Here, the authors find existing benchmarks poorly suit this goal; their assays are often well-predicted simply by counting cells. They propose new guidelines and curated benchmarks.

In a phase 3 trial for Huntington’s disease, pridopidine did not meet its primary endpoints but was safe and favored in some prespecified subgroup analyses.

The J2 antibody is widely used for detecting double-stranded RNAs. Here, Bou-Nader et al. define its nucleic acid specificity and recognition mechanism by solving its co-crystal structure bound to dsRNA, establishing a framework for its reliable use in RNA detection.

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.

Scholl et al. show that PopZ forms filamentous condensates driven by its helical domain and inhibited by its disordered region. Phase-dependent conformations modulate client interactions and disruption of filamentation or condensation impairs cellular function and growth.

Rare coding variants that reduce the activity of a protein can have a beneficial impact on health. Here, researchers identify rare genetic variants in the CHRNB3 gene that associate with reduced cigarette smoking across diverse populations.

Becker et. al developed a proteomic proximity labeling platform named POCA, which makes use of a photosensitizer for singlet oxygen production and protein capture in the presence of amine, enabling profiling of interactomes of proteins and lipids in living cells.

Van den Heuvel et al. show that lesion-network mapping (LNM)-derived circuits converge across disorders and argue that this convergence reflects a fundamental methodological limitation of LNM. We evaluate ways forward for future LNM studies, including robust null models, in light of these concerns. We view recapitulation of connectome modularity and high-order network properties by LNM as clinically informative and biologically meaningful.

Viral pathogen load in cancer genomes is estimated through analysis of sequencing data from 2,656 tumors across 35 cancer types using multiple pathogen-detection pipelines, identifying viruses in 382 genomic and 68 transcriptome datasets.

Andrew Morris, Mark McCarthy, Michael Boehnke and colleagues report a meta-analysis of genome-wide association studies for type 2 diabetes, including 26,488 cases and 83,964 controls from populations of European, east Asian, south Asian and Mexican and Mexican American ancestry. They identify seven loci newly associated with type 2 diabetes and examine the genetic architecture of disease across populations.

The type VI secretion system (T6SS) and Eag chaperones deliver toxic membrane protein effectors into rival cells. However, it is unknown how Eags and their effectors dissociate. Here, the authors show Eag chaperones bind effectors tightly and may release them via a subtle conformational change.

Arp2/3 complex forms branched actin networks that drive cell and organelle motility. Here, authors show that Coro7 targets branch junctions by binding Arp2/3 complex and actin filaments, promoting debranching, and supporting ER–Golgi transport.

Genetic mapping in mice identified Homer1a as a key modifier of attention. Developmental downregulation in the prefrontal cortex enhances inhibitory tone, neural signal to noise and adult attentional performance, revealing a new control mechanism and target.

Many perennial plants reproduce in irregular pulses, known as masting, triggered by weather cues. This global study finds temperature is the key driver, with climate change expected to cause divergent reproductive impacts in tropical versus temperate regions.

As Nature Aging celebrates its fifth anniversary, the journal asks some of the researchers who contributed to the journal early on to reflect on the past and the future of aging and age-related disease research, the impact of the field on human health now and in the future, and what challenges need to be addressed to ensure sustained progress.

Genome-wide analyses identify common variants associated with 11 distinct neuropathology endophenotypes, providing insights into the mechanisms underlying the genetic risk of Alzheimer’s disease and related dementias.

Otopetrins form proton channels in animals ranging from nematodes to humans. Here, authors identify small molecule inhibitors and characterize their binding in the intrasubunit interface region, thus highlighting the area for pharmacological targeting for channel modulation.

Little millet is an orphan crop offering a promising yet underutilized option in the pursuit of food and nutritional security. Here, the authors report its genome assembly, and elucidate its recent tetraploid structure, sub-genome dominance, and the genetic basis for micronutrient content.

In a post-hoc analysis of circulating tumor DNA (ctDNA) features from patients with metastatic prostate cancer treated with [¹⁷⁷Lu]Lu–PSMA-617 or cabazitaxel in the randomized phase 2 TheraP trial, low ctDNA levels at baseline were predictive of clinical benefit from [¹⁷⁷Lu]Lu–PSMA-617, and PTEN or ATM alterations were identified as potential biomarkers of response.

Hydrogen exchange–mass spectrometry (HX–MS) is used to qualitatively assess how perturbations such as mutations and ligand binding impact protein ensembles. However, in theory, HX–MS data contain the information necessary to derive residue-level energies of local unfolding (ΔG_op). Now, a method called PIGEON-FEATHER has been developed, which can unambiguously determine residue-level ΔG_op from conventional HX–MS datasets.

The authors analyze 162 primary mismatch-repair-deficient gliomas and identify three subgroups underpinned by distinct somatic mutations in replicative DNA polymerases and IDH1.

Here, the authors present an update to a widely used curatedMetagenomicData (cMD) database and use it to create a catalog of microbiome-phenotype associations (age, sex, body mass index), and develop an oral enrichment score in the gut microbiome independently of age.

Combining 32 genome-wide association studies with high-density imputation provides a comprehensive view of the genetic contribution to type 2 diabetes in individuals of European ancestry with respect to locus discovery, causal-variant resolution, and mechanistic insight.

In this study, the authors assess the global response to the toxic aldehyde glyoxal (GO) in Pseudomonas aeruginosa, suggesting that GO controls quorum sensing during infection through a mechanism involving a novel protein, ArqI.

Experimental demonstration of quantum speedup that scales with the system size is the goal of near-term quantum computing. Here, the authors demonstrate such scaling advantage for a D-Wave quantum annealer over analogous classical algorithms in simulations of frustrated quantum magnets.

The authors present an integrated acousto-optic modulator fabricated in a wafer-scale process that realizes efficient, high-speed modulation of visible light with high optical power handling.

nELISA miniaturizes the sandwich immunoassay and transforms it into a massively scalable platform for quantitative proteomics.

Here the authors show that MRAP2 tunes the melanocortin-4 receptor by boosting its G-protein signaling while limiting β-arrestin2 interaction and destabilizing receptor oligomers, shaping appetite regulation.

Intracellular redox state orchestrates a self-reinforcing circuit connecting hypoxia inducible factor 1α-dependent signalling with post-translational regulation of the metabolic enzyme isocitrate dehydrogenase 1 to govern intestinal stem cell fate.

Reduced fitness of the tumor microenvironment is mediated by a long non-coding RNA expressed in tumors.

Radical Fe^II/α-ketoglutarate-dependent halogenases are powerful biocatalysts for C–H functionalization. Here, the authors reveal the mechanistic basis for chemoselectivity in a lysine halogenase.

The authors revise the classical view that homeostasis of neuronal activity is achieved by negative firing rate feedback: during sensory deprivation, homeostasis occurs via the sliding threshold, which acts via firing patterns rather than rates.

How do humans learn complex rules from small available data? Rule et al introduce metaprogram learning as a model that fits human behaviour in complex learning situations. Unlike previous approaches, this model is based on programs revising programs, making it more efficient.

This study highlights that IFITM3 deficiency lowers the minimum infectious dose of influenza virus, enhances adaptation of influenza viruses to a new host species, and broadly increases infection of human cells by avian and swine influenza viruses.