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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.

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.

Humanity’s Last Exam, a multi-modal benchmark at the frontier of human knowledge, is designed to be an expert-level closed-ended academic benchmark with broad subject coverage.

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.

The International Brain Laboratory presents a brain-wide electrophysiological map obtained from pooling data from 12 laboratories that performed the same standardized perceptual decision-making task in mice.

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 rat prefrontal cortex has been implicated in cued food-seeking behaviour. Here, the authors identify two parallel prefrontal pathways: one that suppresses food seeking during potential threats, and another that drives pleasure-based eating even when animals are satiated.

Neural networks fundamentally dictate function. Here, the authors show thirteen uniquely connected neuron populations within the anterior thalamic nuclei, suggesting multiple parallel subnetworks support its emotional and cognitive functions.

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.

mBrainAligner is a cross-modal registration platform for whole mouse brains imaged with different modalities. In addition, a fluorescence micro-optical sectioning tomography-based mouse brain atlas has been generated.

Reducing critical materials such as indium and silver is of high importance for photovoltaics. Yu et al. demonstrate a certified 25.94% efficiency silicon heterojunction solar cell replacing part of indium-based electrodes with undoped tin oxide and using copper for contacts.

As part of the BICCN consortium, the authors used a single-cell transcriptomic imaging method to produce a highly defined atlas of cell types across the mouse primary motor cortex.

The expression of each of the roughly 22,000 genes of the mouse genome has been mapped, at cellular resolution, across all major structures of the mouse brain, revealing that 80% of all genes appear to be expressed in the brain.

Miniaturization of devices and machines requires advanced lithographic techniques, whilst the high cost and complexity are the bottlenecks. Li et al.now show an approach for direct, arbitrary nano-patterning using self-propelled nanomotors acting as mobile nanomasks and near-field lenses.

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.

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.

This Resource presents a method to define connectivity types of neurons based on a spatially registered large database containing more than 20,000 neuronal reconstructions. A brain connectivity map is also generated using such connectivity features.

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.

Chen et al. show that in mice, extracellular matrix remodeling drives early migration of the anterior signaling center, establishing the body axis sooner than expected—a mechanism potentially conserved in humans.

Aurora, a new large-scale foundation model trained on more than one million hours of diverse geophysical data, outperforms operational forecasts in predicting air quality, ocean wave dynamics, tropical cyclone tracks and high-resolution weather.

Synthetic mouse embryos assembled from embryonic stem cells, trophoblast stem cells and induced extraembryonic endoderm stem cells closely recapitulate the development of wild-type and mutant natural mouse embryos up to embryonic day 8.5.

This Consensus Statement clarifies the existing subset-based nomenclature for T cells. Furthermore, it proposes an alternative modular nomenclature that is designed to be brief and flexible and to avoid ambiguity and unwanted implications. The authors also provide guidance on how T cell nomenclature should be described in research papers.

This resource article describes a bioinformatical tool that, accessing an extensive gene expression database, allows the definition and identification of new brain structures based on gene expression patterns.

By tuning the plasma frequency, Yu, Gao et al. develop an industrial-scale chemical vapour deposition system for uniform nanocrystalline silicon oxide coatings, enabling 26.41% efficiency in silicon heterojunction solar cells with copper electrodes.

How the circadian clock generates rhythms of arousal remains unclear. Here, authors show that a clock-output molecule reduces excitability of an arousal circuit during the active phase. These results suggest a multifaceted role for the clock in arousal.

A deep-learning method designs lipid nanoparticles that deliver mRNA to the ferret lung.

TP63 is a master regulator transcription factor in squamous cell carcinomas (SCCs). Here the authors report that TP63 suppresses IFNγ signaling in SCC tumors and that its inhibition is associated with enhanced anti-tumor immunity and response to anti-PD1.

Lightning Pose is an efficient pose estimation approach that requires few labeled training data owing to its semi-supervised learning strategy and ensembling.

Multi-ancestry genome-wide analyses identify new risk loci for age-related macular degeneration. Ancestry-specific analyses identify distinct effects at major risk loci, including smaller effect sizes for CFH risk alleles in haplotypes of African ancestry.

An intelligent headset system that uses real-time neural networks run on an embedded central processing unit can create sound bubbles that selectively isolate groups of users from outside sounds.

In this study, the authors report that target-derived NGF signaling induces the expression of Coronin-1, which consequently gets recruited to the NGF-TrkA–carrying signaling endosome, where it regulates endosomal fusion with lysosomes, trafficking and recycling. In addition, Coronin-1 appears to be necessary for NGF-dependent signaling events such as CREB phosphorylation, Ca²⁺ release and activation of calcineurin.

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.

A single-cell multiomics analysis of over 200,000 cells of the primary motor cortex of human, macaque, marmoset and mouse shows that divergence of transcription factor expression corresponds to species-specific epigenome landscapes, and conserved and divergent gene regulatory features are reflected in the evolution of the three-dimensional genome.

Non-human primates are important animal models for studying SARS-CoV-2 infection. Here, Salguero et al. directly compare rhesus and cynomolgus macaques and show that both species represent COVID-19 disease of mild clinical cases, and provide a lung histopathology scoring system.

This overview of the ENCODE project outlines the data accumulated so far, revealing that 80% of the human genome now has at least one biochemical function assigned to it; the newly identified functional elements should aid the interpretation of results of genome-wide association studies, as many correspond to sites of association with human disease.

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.

Synthetic polymer wires, which contain short oligonucleotides extending from each repeat, can assemble into predesigned routings on two- and three-dimensional DNA origami templates.

As vesicles fuse to the plasma membrane, they form intermediate Ω-shaped structures followed by either closure of the pore or full merging with the plasma membrane. Here Wen et al. show that dynamic actin assembly provides membrane tension to promote Ω merging in neuroendocrine cells and synapses.

BiomedParse is a foundation model for image analysis that uses a joint learning approach to jointly conduct segmentation, detection and recognition and offer state-of-the-art performance across a wide range of datasets and nine modalities.

Influenza B viruses are linked to significant morbidity and mortality, and yet their immunobiology is comparatively poorly understood. Here Menon et al identify influenza B virus-specific CD8⁺ T cell epitopes and characterise these in adults, children and the elderly.

The DANIO-CODE consortium leverages a large-scale multiomic dataset to improve zebrafish genome annotation. They identify ~140,000 cis-regulatory elements throughout development and perform a comparison with the mouse regulatory landscape.

Two doses of the coronavirus disease 2019 vaccine ChAdOx1 nCoV-19 boost antibody responses and functions in phase 1/2 trial participants.

A technique for threading long protein strands through a nanopore by electrophoresis and back using a protein unfoldase motor, ClpX, enables single protein molecules to be analyzed multiple times with single-amino-acid sensitivity.

Ependymoma is a type of neural tumour that arises throughout the central nervous system. Using comparative transcriptomics in mouse and human tumours, these authors home in on mutations that are specific to individual tumour subgroups. In doing so, they generate the first mouse model of ependymoma and demonstrate the power of interspecific genomic comparisons to interrogate cancer subgroups.

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.