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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.

Defining the spatial organization of tissues and organs like the brain from large datasets is a major challenge. Here, authors introduce CellTransformer, an AI tool that defines spatial domains in the mouse brain based on spatial transcriptomics, a technology that measures which genes are active in different parts of tissue.

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.

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.

Root-knot nematodes locate host plants by sensing microbial volatiles shaped by plant defence metabolites, revealing a surprising ecological link between plant chemistry, soil microbes and parasite behaviour in the rhizosphere.

Specific pain-sensing nociceptors and chemosensory tuft cells form a circuit to promote type 2 immune responses in the intestine.

In vitro propagation of the pathogenic bacterium Coxiella burnetii, the causative agent of Q fever, leads to attenuated virulence and lipopolysaccharide (LPS) truncation. Here, Long et al. show that a strain considered to be avirulent (NMII) can be recovered from infected animals, and these isolates display increased virulence and an elongated LPS due to reversion of a 3-bp mutation in a gene.

iGluSnFR4f and iGluSnFR4s are the latest generation of genetically encoded glutamate sensors. They are advantageous for detecting rapid dynamics and large population activity, respectively, as demonstrated in a variety of applications in the mouse brain.

Linking prior epigenetic status to future outcomes remains a challenge. Here, authors show recording neuronal enhancer activity across postnatal development in mice reveals loci that predict and can be manipulated to modify acute seizure response.

There are limited vaccines available for Ebola virus and none for broad protection from filoviruses. Here, the authors rationally design vaccines using nanoparticles and stabilized Ebola virus and other filovirus glycoproteins, characterize antibody epitopes and profile lymph node and antibody responses in mice.

Reframing of arousal as a latent dynamical system can reconstruct multidimensional measurements of large-scale spatiotemporal brain dynamics on the timescale of seconds in mice.

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.

The authors previously pinpointed OLAH (oleoyl-ACP-hydrolase) as a driver of life-threatening viral diseases. Here, the authors identify increased IL-18Rα expression on CD8⁺ T cells, which acquire a reduced cytotoxic signature, correlates with severe respiratory viral infection of influenza A virus, RSV and COVID-19.

This study maps the connections of layer 5 pyramidal neurons in the mouse cortex, revealing distinct local and intercortical wiring patterns, and provides an open framework for exploring the connectivity of cell types.

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.

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.

A comprehensive cell atlas of the whole mouse brain with high molecular and spatial resolution is generated.

In this study, the authors develop a comprehensive taxonomy of brain-wide SPNs, identifying several novel subsets via their transcriptional signatures.

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.

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.

Bacterial resistance to polymyxin antibiotics is conferred by enzymes such as phosphoethanolamine transferases, which add positively charged phosphoethanolamine to lipid A. Here, the authors present the structure of one such enzyme in its liganded form, and propose an enzymatic mechanism that may be generally applicable to other phosphoform transferases.

Dense calcium imaging combined with co-registered high-resolution electron microscopy reconstruction of the brain of the same mouse provide a functional connectomics map of tens of thousands of neurons of a region of the primary cortex and higher visual areas.

Brain-wide recordings in mice reveal that prior expectations are distributed through recurrent loops across all levels of cortical and subcortical processing.

3D brain atlases enable spatial data integration across studies. Here, the authors present the Developmental Mouse Brain Common Coordinate Framework, a 3D multimodal atlas from embryonic to adult ages for cell type mapping through brain development.

 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. 

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.

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.

Mutual paracrine regulation of the cytokines GREM1 and SPP1 mediate mesenchymal and epithelial cell fate in pancreatic cancer.

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.

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.

Artis and colleagues show that enteric neurons produce CGRP-related ADM2 to promote intestinal tissue-protective functions in ILC2s.

Systematic studies are needed to discover molecular determinants of blood brain barrier dysfunction in Alzheimer’s disease. This study identifies perturbed pericytic SMAD3-astrocytic VEGFA interactions as a potential driver of this dysfunction.

To address the phase instability issue of perovskites, ammonium propionic acid is introduced to enhance the phase stability of both perovskite layers in perovskite/perovskite/silicon triple-junction solar cells, resulting in improved efficiency and reproducibility.

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.

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.

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.

BARseq interrogates the expression of 104 cell-type marker genes in 10.3 million cells over nine mouse forebrain hemispheres to reveal the role of peripheral inputs on cortical area development.

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.

The collapse of tropical forests during the Permian–Triassic Mass Extinction weakened carbon sequestration, sustaining high CO2 and extreme global warmth for millions of years: an example of a runaway feedback in Earth’s climate-carbon system.

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.

Gene selection for spatial transcriptomics is currently not optimal. Here the authors report PERSIST, a flexible deep learning framework that uses existing scRNA-seq data to identify gene targets for spatial transcriptomics; they show this allows you to capture more information with fewer genes.

Little is known about von Economo neurons, which have been described in a subset of mammals and appear to be selectively lost in several human neurological diseases. Here, authors reveal the gene expression profile of these cells and show that they are likely long-distance projection neurons.

ONIX is a data acquisition system for recording freely behaving mice. It can accommodate a variety of recording technologies, while maintaining minimal impact on animal behavior.

Collaborative augmented reconstruction (CAR) is a platform for large-scale reconstruction of neurons and other cells from multi-dimensional imaging datasets. It can be accessed from a variety of devices simultaneously for efficient and accurate reconstruction.

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.

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.

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.

Activity in a set of parabranchial neurons in the mouse brain is increased during chronic pain, predicts coping behaviour, and can be modulated by circuits activated by survival threats.