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Acetyl-CoA synthetases have been proposed as targets for development of new antimicrobial drugs. Here, Jezewski et al. identify isoxazole-based compounds with activity against the pathogenic fungus Cryptococcus neoformans, and describe their mechanism of action as inhibitors of fungal acetyl-CoA synthetases.

A new version of nanorate DNA sequencing, with an error rate lower than five errors per billion base pairs and compatible with whole-exome and targeted capture, enables epidemiological-scale studies of somatic mutation and selection and the generation of high-resolution selection maps across coding and non-coding sites for many genes.

Neural processing speed slows with age, but the relationship between this slowing and brain atrophy is unknown. Here, authors show that age-related functional brain differences in auditory and visual processing are partly due to structural differences in the distinct brain regions underlying these processes.

Stabilization of continental crust requires temperatures of over 900 °C, establishing a link between ultrahigh-temperature metamorphism and craton formation, according to a study of U and Th concentrations in metasedimentary and metaigneous rocks.

Understanding collective behaviour is an important aspect of managing the pandemic response. Here the authors show in a large global study that participants that reported identifying more strongly with their nation reported greater engagement in public health behaviours and support for public health policies in the context of the pandemic.

A study in Drosophila has identified a neural circuit that selectively suppress movement-encoding proprioceptors during self-generated movements such as walking and grooming.

BindCraft, an open-source, automated pipeline for de novo protein binder design with experimental success rates of 10–100%, leverages AlphaFold2 weights to generate binders with nanomolar affinity without the need for high-throughput screening.

Head and neck squamous cell carcinoma (HNSCC) frequency and risk factors vary considerably across regions and ancestries. Here, the authors conduct a multi-ancestry genome-wide association study and fine mapping study of HNSCC subsites in cohorts from multiple continents, finding susceptibility and protective loci, gene-environment interactions, and gene variants related to immune response.

A combined sequencing technique assesses 18 patients with high-grade serous ovarian cancer over a multi-year period from diagnosis to recurrence and shows drug resistance typically arises from selective expansion of one or a few clones present at diagnosis.

Using SCN2A haploinsufficiency as a proof-of-concept, upregulation of the existing functional gene copy through CRISPR activation was able to rescue neurological-associated phenotypes in Scn2a haploinsufficient mice and human neurons.

GTPase-activating proteins (GAPs) often contain regulatory PH domains. In this work, Soubias et al, using an integrated structure-function approach, discovered a mechanism where a GAP PH domain binds directly to a GTPase to induce allosteric changes facilitating GTP hydrolysis.

McCreery, Stubb et al. show that mechano-osmotic changes in the nucleus induce general transcriptional repression and prime chromatin for cell fate transitions by relieving repression of specific differentiation genes.

PBK is a mitotic kinase implicated in cancer. This study reveals how PBK evicts key C2H2-zinc finger transcription factors such as Ikaros, Aiolos and CTCF from DNA as cells divide, regulating mitotic chromatin accessibility and chromosome compaction.

Here, the authors present fossilized neural traits from the lower Cambrian euarthropod Jianfengia multisegmentalis, including structured eyestalks and compound eyes, that resolve multiple phylogenetic relationships within Euarthropoda.

A study of millions of couples shows spouses often share psychiatric disorders. This pattern is consistent across cultures (Taiwan and Nordic countries) and has persisted for generations, impacting how these disorders are inherited.

High-resolution 3D printing technology making use of two-photon polymerization instead of traditional machining is described, allowing low-cost and scalable production of large arrays of high-quality 3D Paul traps.

The flagship paper of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium describes the generation of the integrative analyses of 2,658 cancer whole genomes and their matching normal tissues across 38 tumour types, the structures for international data sharing and standardized analyses, and the main scientific findings from across the consortium studies.

An atlas study of adipose tissue in people with obesity undergoing weight loss and their lean counterparts reveals that weight loss reduces cell senescence but cannot reverse all the metabolic problems caused by obesity.

By carefully dispersing small amounts of Ir into the RuO₂ lattice, a Ru₆IrOₓ catalyst reduces Ir usage by 80% while still running stably for over 1,500 h at 2 A cm⁻² in both laboratory- and industrial-scale proton-exchange membrane water electrolysers.

It has been proposed that phonons propagating through a material can be used for quantum computing, in a similar manner to photons. Now, several of the quantum gates and measurements needed for this approach have been demonstrated.

The results from a state-of-the-art suite of hydrodynamical cosmological zoom-in simulations show how globular clusters naturally emerge in the Standard Cosmology and also reveal the existence of a new class of object called globular-cluster-like dwarfs.

Structural analyses of antibody-virus complexes offer critical insights into immune recognition mechanisms. In this report, we present how a patient-derived IgG recognizes a quaternary epitope on EEEV particles through strictly bivalent interactions.

This work reveals how a regulatory domain in O-GlcNAc hydrolase (OGA) shapes enzyme flexibility and activity, uncovering mechanisms that help maintain O-GlcNAc balance in cells.

Al-Hilal, Chrysovergi et al. identify a role for durotaxis in lung fibrosis and metastatic pancreatic cancer, mediated by the FAK–paxillin mechanosensor complex, and demonstrate therapeutic targeting of this pathway using the small molecule JP-153.

Phaeocystales are ecologically significant nanoplankton whose evolutionary history and functional diversity remain incompletely characterized. Here, the authors integrate genomic and transcriptomic data to reveal their lineage diversification, metabolic plasticity, and adaptation to polar and temperate regimes.

Analyses of 2,658 whole genomes across 38 types of cancer identify the contribution of non-coding point mutations and structural variants to driving cancer.

Bats harbor diverse coronaviruses but temporal dynamics are less well studied. Here, the authors analyzed coronaviruses in Australian flying foxes over 3 years showing peak shedding and co-infections in juveniles and subadults and providing evidence of historical and contemporary recombination between viral clades.

The combination of electricity and light can provide a sustainable route to drive challenging synthetic transformations, but current catalysts are plagued by poor stability and mechanistic ambiguity. Now it has been shown that recyclable, polymer-based electrophotocatalysts mediate electron transfer to chloroarenes to enable their conversion into valuable products.

A combination of whole-genome NanoSeq with deep whole-exome and targeted NanoSeq is used to accurately characterize mutation rates and genes under positive selection in sperm cells.

Using experimental and modelling evidence, this study reveals that small coral populations face fertilization failure due to Allee effects. The findings identify critical population thresholds needed to maintain reproductive success.

The cause of abnormal alveolar regeneration in idiopathic pulmonary fibrosis is unknown. Here, the authors generated a temporo-spatial cellular map of the regenerating niche and, using unbiased mathematical methods, identified a spatial interaction between a subset of macrophages and aberrant alveolar epithelial cells across all stages of the disease.

Designing materials for CO₂ capture under humid conditions is challenging due to the preferential binding of water in most porous adsorbents. Now it has been shown that shape-selective organic macrocycles, identified via bottom-up computational screening, can preferentially bind CO₂ through multiple weak interactions, even in the presence of water.

Customizing the output from a laser is typically done by appropriate optical elements. Here Ngcobo et al.show that a digitally controlled holographic mirror placed within the laser cavity can be used to dynamically select the desired laser output modes.

In an integrated analysis of transcriptomic data from the SUBSPACE consortium and public datasets of patients with sepsis, acute respiratory distress syndrome, trauma and burns, dysregulation within four consensus molecular clusters related to myeloid and lymphoid cells is associated with mortality and illness severity.

2023 CX1 is the only L-chondrite-like asteroid analysed from space to ground. It catastrophically fragmented in the atmosphere, depositing 98% of its energy in one burst—an unusual, high-risk fragmentation mode with implications for planetary defence.

The XRISM Resolve spectrum of the galactic neutron star X-ray binary, GX 13+1, reveals one of the densest winds ever seen in absorption lines.

The authors study the widespread transcriptomic response of macrophages to a variety of environmental stimuli. They show that genetic determinants of this response are overrepresented among those linked to immune-mediated diseases.

The authors show that alternative splicing is an important layer of macrophage response to environmental stimuli. Genetic determinants of this response, often targeting low-usage splicing events, are linked to several immune-mediated diseases.

Deep learning-based generative tools are used to design protein building blocks with well-defined directional bonding interactions, allowing the generation of a variety of scalable protein assemblies from a small set of reusable subunits.

A pulse of ocean acidification is reconstructed from the boron isotope composition of fossilized oysters at the Triassic-Jurassic boundary, implicating ocean acidification from volcanic outgassing as a kill mechanism during the extinction event.

Simulating molecular adsorption on surfaces presents considerable challenges, as computational methods typically suffer from either insufficient accuracy or prohibitive computational costs. Now, with an open-source multilevel embedding approach, adsorption processes on the surfaces of ionic materials can be modelled routinely with an accuracy comparable to that of experiments.

The composition of Earth’s inner core can be constrained by the supercooling required for its formation. Based on molecular dynamic simulations this work shows that inner core nucleation from an iron-carbon composition fits geophysical constraints.

This study provides evidence that agricultural irrigation artificially recharges the groundwater in the Po Plain, highlighting the importance of irrigation inefficiencies for groundwater recharge.

Dire wolves split from living canids around 5.7 million years ago and originated in the New World isolated from the ancestors of grey wolves and coyotes, which evolved in Eurasia and colonized North America only relatively recently.

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.

Strontium analysis of Paranthropus robustus teeth from two South African sites reveals that the Pleistocene hominin probably exploited both savanna and riparian woodland habitats, had a home-range size compatible with that of present-day hunter-gatherers and had periodic ranging patterns. While some individuals lived their lives in the same place, others dispersed during their lifetime.

In schistosomiasis-endemic regions, the cyclical nature of infection and treatment complicates understanding of host immune responses. Repeated controlled human Schistosoma mansoni infection, designed to reflect the reinfection cycles common in endemic areas, shows that repeated exposure induces mixed worm-specific CD4⁺ T cell responses similar to those seen in endemic infection.