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Large-effect variants in autism remain elusive. Here, the authors use long-read sequencing to assemble phased genomes for 189 individuals, identifying pathogenic variants in TBL1XR1, MECP2, and SYNGAP1, plus nine candidate structural variants missed by short-read methods.

Multi-omics and genetic models show that CGG repeat toxicity in GABAergic neurons drives FXTAS pathology and identify PRKCG as a critical modifier and potential therapeutic target.

Identifying jets originating from heavy quarks plays a fundamental role in hadronic collider experiments. In this work, the ATLAS Collaboration describes and tests a transformer-based neural network architecture for jet flavour tagging based on low-level input and physics-inspired constraints.

Global Burden of Disease estimates show that between 1990 and 2023, the prevalence and burden of drug use disorders, inclusive of amphetamine, cannabis, cocaine and opioid use, have been increasing in high-income countries, particularly in the USA.

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.

Confocal Airy beam integrated with single-photon oblique light-sheet tomography (CAB-OLST) is a high-throughput imaging approach for brain-wide mapping of neurons, as demonstrated in cleared mouse brains.

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.

 A transcriptomic cell-type atlas of the whole adult mouse brain with ~5,300 clusters built from single-cell and spatial transcriptomic datasets with more than eight million cells reveals remarkable cell type diversity across the brain and unique cell type characteristics of different brain regions. 

Multi-modal analysis is used to generate a 3D atlas of the upper limb area of the mouse primary motor cortex, providing a framework for future studies of motor control circuitry.

The authors developed an optimized rabies tracing system for generating brain-wide monosynaptic input connectomes, and applied it in mouse visual cortex to reveal topographically organized subnetworks co-defined by visual areas, layers and cell classes.

High-throughput mapping of neural projections at the single-cell level remains challenging. Here, the authors have developed axonal BARseq, a new technique that allows for mapping projections from thousands of neurons within a single brain.

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.

Anisotropic hybridization between conduction and unpaired f electrons is rarely observed. Now, a lanthanide-based two-dimensional compound exhibits nodal hybridization, giving rise to heavy-fermion behaviour.

Federated learning (FL) algorithms have emerged as a promising solution to train models for healthcare imaging across institutions while preserving privacy. Here, the authors describe the Federated Tumor Segmentation (FeTS) challenge for the decentralised benchmarking of FL algorithms and evaluation of Healthcare AI algorithm generalizability in real-world cancer imaging datasets.

A genome-wide association meta-analysis study of blood lipid levels in roughly 1.6 million individuals demonstrates the gain of power attained when diverse ancestries are included to improve fine-mapping and polygenic score generation, with gains in locus discovery related to sample size.

Sparse labelling and whole-brain imaging are used to reconstruct and classify brain-wide complete morphologies of 1,741 individual neurons in the mouse brain, revealing a dependence on both brain region and transcriptomic profile.

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.

The BRAIN Initiative Cell Census Network has constructed a multimodal cell census and atlas of the mammalian primary motor cortex in a landmark effort towards understanding brain cell-type diversity, neural circuit organization and brain function.

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

In this study, the authors report that post-vaccination neutralizing and binding antibody levels in the ENSEMBLE trial associate with Ad26.COV2.S vaccine efficacy (VE) against severe-critical COVID-19, with substantial VE even at unquantifiable neutralizing antibody titer.

A spatially resolved transcriptional atlas of the mid-gestational developing human brain has been created using laser-capture microdissection and microarray technology, providing a comprehensive reference resource which also enables new hypotheses about the nature of human brain evolution and the origins of neurodevelopmental disorders.

Molecular glue degraders eliminate cellular proteins by promoting their interaction with E3 ubiquitin ligases. Here, the authors identify molecular glue degraders targeting the E3 ligase TRIM21 and synthesize a heterobifunctional degrader that recruits TRIM21 to degrade an engineered protein aggregate.

The understanding of defects in bromide-based perovskites remains elusive. Electric biasing and introducing bromide in the precursor solution during crystal growth is shown to significantly reduce defects in formamidinium lead bromide.

Silicon-based photoelectrodes are attractive for solar fuel production, but suffer from vulnerability to corrosion. Using dielectric breakdown, a generic approach to improve the performance of metal-oxide semiconductor photoelectrodes is proposed.

The performance of Li-ion batteries deteriorates at elevated temperatures due to increased activity of electrode materials and parasitic reactions. Here Yi Cui and colleagues report much-improved battery cyclability at 60 °C and use cryo-electron microscopy to shed light on the origin of the phenomenon.

Here the authors analyzed 3.7 petavoxels of 3D imaging data from 204 mouse brains, aiming to comprehensively characterize diverse morphological and modular patterns conserved across six spatial scales of mouse brain anatomy, ranging from the whole-brain scale to synaptic levels.

The subcommissural organ (SCO) is a gland in the brain, and relatively little is known about its function. Zhang et al. genetically ablated SCO cells and observed severe hydrocephalus and neuronal defects. The reintroduction of SCO-derived peptides into SCO-ablated brain substantially rescued developmental defects.

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.

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.

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.

The interface between two oxide materials can play host to numerous exotic phenomenon. Here, the authors observe a four order of magnitude change in the conductance at a lanthanum-aluminate–strontium-titanate interface controlled by surface protonation, which can be reversed by exposure to light.

Using well-calibrated statistical methods the authors jointly analyze Undiagnosed Diseases Network genomes, identifying known and novel disease genes. Software is publicly available to support future cross-cohort rare disease discovery efforts.

This study uses epi-retro-seq to link single-cell epigenomes and cell types to long-distance projections for neurons dissected from different regions projecting to different targets across the whole mouse brain.

Available wheat genomes are annotated by projecting Chinese Spring gene models across the new assemblies. Here, the authors generate de novo gene annotations for the 9 wheat genomes, identify core and dispensable transcriptome, and reveal conservation and divergence of gene expression balance across homoeologous subgenomes.

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.

By comparing neural responses to diverse visual stimuli measured with a standardized two-photon imaging pipeline, the authors reveal response specializations within the mouse visual cortex.

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.

A combination of genetic strategies and tools is used to define and fate-map different subtypes of glutamatergic pyramidal neurons according to their developmental and molecular programs, providing insight into the assembly of cortical processing networks.

A study reports whole-genome sequences for 490,640 participants from the UK Biobank and combines these data with phenotypic data to provide new insights into the relationship between human variation and sequence variation.

Zhao et al. present RAPiDock, an all-atom diffusion model that predicts peptide–protein binding patterns across 92 amino acid types, enabling high-throughput virtual screening for advancing therapeutic peptide design.

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.

A high-bandwidth neuromotor interface offers performant out-of-the-box generalization across people.

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).

Synchronised neuronal activity is essential for cortical function, yet mechanistic insights into this process remain limited. Here, authors use a combination of in vivo imaging and targeted whole-cell recordings to demonstrate that Somatostatin neurons, in the superficial layers of the mouse primary visual cortex, exhibit functional heterogeneity and can be classified into two distinct subtypes characterized as either having type I uncorrelated, or type II highly correlated with network activity.

Schief and colleagues show that germline-targeting epitope scaffolds can elicit responses from rare broadly neutralizing antibody precursor B cells with predefined binding specificities and genetic features.

Genomic and phenomic screens of 827 wheat landraces from the A. E. Watkins collection provide insight into the wheat population genetic background, unlocking many agronomic traits and revealing haplotypes that could potentially be used to improve modern wheat cultivars.

Chimeric antigen receptor T cell efficacy is enhanced with an interleukin 2-recruiting molecule.

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.