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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.

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.

Lapique, Kim, and colleagues present an open-source approach together with an online probe design platform for in situ RNA and protein analysis. This is an easy-to-use approach that enables vast feature detection, with cycling times under 20 minutes per feature.

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

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.

The dorsal peduncular area of the mouse brain functions as a network hub that integrates diverse cortical and thalamic inputs to regulate neuroendocrine and autonomic responses.

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.

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare cancer. Here, the authors develop a NLPHL specific model to identify 34 distinct cell states across 14 cell types that co-occur within 3 lymphocyte predominant ecotypes (LPEs) for 171 cases.

Analyses of ancient human DNA show that cultural and political transformations in Central Europe during the second half of the first millennium ce were associated with movements of Slavic populations into Germany, Poland and Croatia.

Reliable measuring the voltage dynamics of individual neurons in the intact brain is significantly challenging. Here authors developed an all-optical method combining two-photon voltage imaging and optogenetics to measure and induce synaptic plasticity in vivo, revealing LTP of inhibition in cerebellar circuits and providing a blueprint to link synaptic changes to learning.

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.

Cross-modality mapping extends to 3D with image-varifold based technologies for partial matching, spatial resampling, and feature selection to efficiently represent and integrate high-dimensional spatial-omics data with tissue-scale imaging.

Hippocampal neurons adapt to experience through changes in gene expression and chromatin accessibility. Here, authors show that novel environment exposure induces region- and cell-type specific transcriptional changes coordinated by FOS/AP-1.

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.

A pangenome of the Cannabis genus including 193 genomes demonstrates high variability in most of the genome but low diversity in cannabinoid synthesis genes and provides a resource for future genetic studies and crop optimization.

An approach combining bioorthogonal chemistry with genetically encoded fluorogen-activating proteins enables subcellular imaging of phospholipids and glycans, as well as the visualization of lipid transport between organelles and lipid asymmetry across membrane leaflets.

A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants.

In the canonical model of auditory processing, thalamocortical inputs to the primary auditory cortex initiate a hierarchical transmission to higher-order cortices. Here, authors reveal alternative auditory pathways that bypass the primary auditory cortex and directly activate higher-order cortex within <10 ms in mice, enabling parallel and distributed processing of fast sensory information across cortical areas.

 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. 

Multiancestry fine-mapping of brain protein quantitative trait loci coupled with Mendelian randomization analyses identifies protein–trait pairs consistent with causal effects across neurological and psychiatric conditions.

Joint profiling of chromatin and splicing in the brain uncovers shared and distinct patterns.

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

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.

The number of individuals in a given space influences animal interactions and network dynamics. Here the authors identify general rules underlying density dependence in animal networks and reveal some fundamental differences between spatial and social dynamics.

Navigating the complex structure of the brain poses a challenge to neuroscientists. Here, the authors have trained an AI (DeepSlice) that can automatically register brain images with speed and accuracy, thus simplifying this process.

In this phase 3 trial, a two-dose Ebola vaccine regimen in healthy pregnant women in Rwanda was found to be safe and immunogenic in women and offspring through passive transfer.

Sydnor et al. developed a new tractography atlas of thalamocortical structural connections and applied it to three youth samples. They uncovered coordinated development between thalamic connectivity and hierarchical cortical plasticity in humans.

A comprehensive single-cell RNA sequencing study delineates cell-type-specific transcriptomic changes in the brain associated with normal ageing that will inform the investigation into functional changes and the interaction of ageing and disease.

EchoNext, a deep learning model for electrocardiograms trained and validated in diverse health systems, successfully detects many forms of structural heart disease, supporting the potential of artificial intelligence to expand access to heart disease screening at scale.

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.

This study presents an analytic framework to link imaging-derived brain phenotypes to gene expression. In the future, this approach may facilitate in vivo pharmacotranscriptomics and the development of personalized (pharmacological) interventions.

The affected cellular populations during Alzheimer’s disease progression remain understudied. Here the authors use a cohort of 84 donors, quantitative neuropathology and multimodal datasets from the BRAIN Initiative. Their pseudoprogression analysis revealed two disease phases.

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).

The impact of α-synuclein aggregates on neurons has been unclear. Here, the authors identify a Lewy Associated Molecular Dysfunction from Aggregates (LAMDA) signature in inclusion bearing neurons in human brain and a mouse model of α-synucleinopathy.

Many approaches exist to process data from individual imaging modalities, but integrating them is challenging. The authors develop an automated resource that enables co-registered network- and tract-level analysis of macroscopic in-vivo imaging and microscopic imaging of cleared tissue.

This study shows that aboveground plant diversity is only weakly related to belowground mycorrhizal fungal diversity, although these relationships can be stronger at regional scales. Therefore, conservation efforts centered only on plant diversity may overlook critical fungal diversity hotspots.

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.

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.

How various factors dynamically influence neuronal variability is a longstanding question. Here, the authors build an encoding model to partition variability, revealing heterogeneous source contributions to individual units and state-dependent changes of variability across the visual hierarchy.

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.

Inflammatory monocytes in the brain meninges promote stress-induced fear behaviour, and the pathways involved can be modulated using psychedelic compounds.

Whole-brain anatomical and activity surveys identify the lateral hypothalamus as a key driver of recovery from spinal cord injury, leading to a deep brain stimulation therapy that augments the recovery of walking in humans.

Targeting CD8⁺ T cell exhaustion is a strategy to enhance immune checkpoint inhibition and to fight cancer. Here the authors show a NRF2-dependent role for the prostaglandin I₂ receptor PTGIR in controlling T cell exhaustion.

The BIN1 SNP rs744373 is associated with higher CSF tau and phosphorylated tau levels. Here the authors show, using PET imaging, that this SNP is associated with tau accumulation in the brain as well as impaired memory in older individuals without dementia.

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.

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.

Multiplexed error-robust fluorescence in situ hybridization (MERFISH) together with deep-learning-based nucleus segmentation enabled the construction of a highly detailed and informative spatially resolved single-cell atlas of human fetal cortical development.