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A dataset of 3D images from more than 200,000 human induced pluripotent stem cells is used to develop a framework to analyse cell shape and the location and organization of major intracellular structures.

Seagrass genomes of the deep-water Zostera pacifica and shallow-water Z. marina from the Eastern Pacific Ocean provide evidence for low-light adaptation exemplified in the wild hybrid Z. marina × pacifica subjected to low-light stress in aquaria.

A large, open dataset containing parallel recordings from six visual cortical and two thalamic areas of the mouse brain is presented, from which the relative timing of activity in response to visual stimuli and behaviour is used to construct a hierarchy scheme that corresponds to anatomical connectivity data.

The authors report a computational framework for determining the meiotic/mitotic origin of nondisjunction (NDJ) in trisomies without parental data. Applying this to Down syndrome, they uncover links between NDJ error stage and leukemia genomics.

The authors describe an integrated atlas of the diverse cell types in the mouse primary motor cortex.

Nakada, Titus et al. show that p22^phox, a heterodimeric partner of NADPH oxidases, prevents sarcoplasmic/endoplasmic reticulum Ca²⁺ ATPase 2a (SERCA2a) oxidation at Cys498 and its downregulation. This study suggests that therapeutic interventions to protect this residue may sustain SERCA2a expression in heart failure.

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.

Meta-analysis of genome-wide association studies on Alzheimer’s disease and related dementias identifies new loci and enables generation of a new genetic risk score associated with the risk of future Alzheimer’s disease and dementia.

An examination of motor cortex in humans, marmosets and mice reveals a generally conserved cellular makeup that is likely to extend to many mammalian species, but also differences in gene expression, DNA methylation and chromatin state that lead to species-dependent specializations.

Antimicrobial resistance poses a significant global health threat, necessitating swift and precise diagnostic solutions. Here, the authors introduce a culture-free diagnostic platform integrating microfluidic cell enrichment, single-cell Raman spectroscopy, and deep learning, that identifies bacterial and fungal infections directly from clinical samples within 20 minutes.

Noel et al. show aberrant updating of expectations in three distinct mouse models of autism spectrum disorder. Brain-wide neurophysiology data suggest this stems from excess units encoding deviations from prior mean and a lack of sensory prediction errors in frontal areas.

The response to immune checkpoint blockade in head and neck cancer has been heterogenous. Here, the authors utilise longitudinal sampling of a head and neck squamous cell carcinoma model to identify biomarkers of response.

Improved vaccines and antivirals are needed for many enveloped viruses. Here, the authors identify sulfur-based small molecules that disrupt viral membrane properties, inhibiting fusion and entry, and safely inactivate influenza virus. The resulting inactivated influenza vaccine is protective in mice.

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.

Acute lymphoblastic leukemias (ALL) with an ETV6::RUNX1 fusion comprise the largest subtype of this cancer, and their optimal treatment strategy remains unclear. Here, the authors perform genomic profiling of 194 ETV6::RUNX1-rearranged pediatric ALL cases, finding two molecular subtypes associated with distinct drug sensitivities.

Cell type epigenetic and topographic information of primate brain is lacking. Here, authors identified transcriptional regulatory network, gradient expression pattern and disease vulnerability at cell type level in PFC, M1 and V1 of monkey brain by snRNAseq, snATAC-seq and Stereo-seq.

Despite often being poorly immunogenic, some subsets of patients with hormone receptor-positive, HER2-negative (HR + /HER2-) breast cancer benefit from immunotherapy. Here, the authors present a randomised pilot clinical trial comparing a neoadjuvant run-in of either nab-paclitaxel or pembrolizumab (anti-PD-1) monotherapy, followed by the combination, in patients with stage II-III HR + /HER2- breast cancer.

FACED 2.0 builds on and expands the capabilities of the free-space angular-chirp-enhanced delay microscopy approach. Its high speed, large field of view and volumetric coverage enable two-photon voltage imaging of hundreds of neurons or calcium imaging of thousands of neurons in the mouse or zebrafish brain.

Entanglement was observed in top–antitop quark events by the ATLAS experiment produced at the Large Hadron Collider at CERN using a proton–proton collision dataset with a centre-of-mass energy of √s  = 13 TeV and an integrated luminosity of 140 fb⁻¹.

Immune receptors regulate immune responses and are key cancer immunotherapy targets. Here, the authors designed helical concave scaffolds to bind convex sites in immune receptors, creating high-affinity protein binders for TGFβRII, CTLA-4, and PD-L1. Co-crystal structures confirmed their therapeutic potential.

Methylome-based clustering and cross-modality integration with companion datasets from the BRAIN Initiative Cell Census Network enabled the construction of a 3D multi-omic genome atlas of the adult mouse brain featuring thousands of cell-type-specific profiles.

A genome-wide association study including over 76,000 individuals with schizophrenia and over 243,000 control individuals identifies common variant associations at 287 genomic loci, and further fine-mapping analyses highlight the importance of genes involved in synaptic processes.

Laser microdissection and microarrays are used to assess 900 precise subdivisions of the brains from three healthy men with 60,000 gene expression probes; the resulting atlas allows comparisons between humans and other animals, and will facilitate studies of human neurological and psychiatric diseases.

The authors present DNA-Diffusion, a generative AI framework that designs synthetic regulatory elements with tunable cell-type specificity. Experimental validation demonstrates their ability to reactivate AXIN2 expression, a leukemia-protective gene, in its native genomic context.

A genome-wide association study of critically ill patients with COVID-19 identifies genetic signals that relate to important host antiviral defence mechanisms and mediators of inflammatory organ damage that may be targeted by repurposing drug treatments.

A large language model designed for health monitoring provides personalized sleep and fitness predictions, insights and advice.

A fresh approach to protein design that incorporates excited intermediate states enables precise control over the lifetime of protein interactions, with potential applications in cell-signalling modulation and in biosensors and synthetic circuits.

Enhanced polyamine depletion in neuroblastoma models decreases translation of mRNA codons with adenosine in the third position, reprogramming the tumour proteome away from cell cycle progression and towards differentiation.

A consensus cell type atlas for the fly brain provides both an intellectual framework and open-source toolchains for brain-scale comparative connectomics.

Together with a companion paper, the generation of a transcriptomic atlas for the mouse lemur and analyses of example cell types establish this animal as a molecularly tractable primate model organism.

B-cell acute lymphoblastic leukaemia (B-ALL) is a common childhood cancer. Here, the authors conducted a meta-analysis with four genome-wide association studies, totalling 5,321 cases and 16,666 controls of European descent, identifying B-ALL risk loci, whose integration with epigenomic profiling indicates cell-cycle and B-cell development deregulation as central mechanisms in B-ALL susceptibility, often in a subtype-specific fashion.

Therapeutic T cells engineered to recognize tumour antigens are frequently short-lived and acquire unfavourable phenotypes in tumours. Here authors show that a tandem approach using autologous T cells targeted against the tumour antigen NY-ESO-1, followed by transfer of hematopoietic stem cells with the same specificity in the clinical trial NCT03240861, provides a safe and promising therapeutic option.

Together with an accompanying paper presenting a transcriptomic atlas of the mouse lemur, interrogation of the atlas provides a rich body of data to support the use of the organism as a model for primate biology and health.

FlyWire presents a neuronal wiring diagram of the whole fly brain with annotations for cell types, classes, nerves, hemilineages and predicted neurotransmitters, with data products and an open ecosystem to facilitate exploration and browsing.

Different molecular subtypes defined by specific gene rearrangements have been described for acute lymphoblastic leukaemia (ALL). Here, the authors show that ZNF384 fusion activates FLT3 expression conferring a therapeutic vulnerability for ZNF384- rearranged ALL subtype.

TIRTL-seq is a high-throughput method for paired T cell receptor sequencing at the cohort scale.

Electron microscopy (EM) is the gold standard for biological ultrastructure but acquisition speed is slow, making it unsuitable for large volumes. Here the authors present a parallel imaging pipeline for continuous autonomous imaging with six transmission EMs to image 1 mm³ of mouse cortex in less than 6 months.

The ATLAS experiment at the Large Hadron Collider reports a search for charged-lepton-flavour violation in decays of Z bosons into a τ lepton and an electron or muon of opposite charge.

Here, the authors characterize the epigenetic status of hybrid ecDNA in HPVOPC, identifying HPV oncogenes E6/E7 in hybrid ecDNA are flanked by somatic DNA enhancers with strong cis-interaction. It can be targeted with ecDNA disrupting therapeutics.

Siew et al. using multi-omic, physiological & imaging approaches have demonstrated that spaceflight causes kidney remodelling, suggesting a contribution to kidney stone formation, & that space radiation causes kidney damage & early signs of dysfunction.

Diamond, a statistically rigorous method, is capable of finding meaningful feature interactions within machine learning models, making black-box models more interpretable for science and medicine.

With increasing reliance on public data sources, researchers are concerned whether low-quality or even adversarial data could have detrimental effects on medical models. Yang et al. developed Scorpius, a malicious text generator, to investigate whether large language models can mislead medical knowledge graphs. They show that a single generated paper abstract can mislead a medical reasoning system that has read millions of papers.

The ATLAS Collaboration reports the observation of the electroweak production of two jets and a Z-boson pair. This process is related to vector-boson scattering and allows the nature of electroweak symmetry breaking to be probed.

This resource describes a collection of neurons from a variety of light microscopy-based datasets, which can serve as a gold standard for testing automated tracing algorithms, as shown by comparison of the performance of 35 algorithms.