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The physiology and behavioral function of proprioceptors that detect joint limits are not fully understood. In this study, the authors used calcium imaging, optogenetics, behavioral genetics, and the connectome to demonstrate that hair plate proprioceptors on the fly leg detect joint limits and engage circuits to drive the leg away from those limits.

Global patterns in animal size and shape have been long observed, but their underlying drivers are not well understood. Here the authors suggest latitudinal patterns in shorebird size and shape are best explained by thermal adaptation to warm climates.

The APOE-ε4 allele is the strongest genetic risk factor for late-onset Alzheimer’s disease, but it is not deterministic. Here, the authors show that common genetic variation changes how APOE-ε4 influences cognition.

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.

Carbonate production and accretion is negatively affected by ocean warming and acidification, threatening coral reef persistence. This Review synthesizes understanding of environmental impacts on reefs, highlighting the dominant role of heatwaves in reef decline and the importance of thermal adaption for future reef persistence.

Childhood mortality is a global health problem. Plasma lipopolysaccharide levels, inflammatory stool biomarkers and proteomics were used in a nested case-cohort in sub-Saharan Africa and South Asia to predict mortality and decode immune mechanisms.

The neural mechanisms driving seizure development in peritumoral brain regions remain incompletely defined. Here, using patient tissue, glioma mouse model, and computational simulation, the authors identify early pathological activities that are predictive of tumor-associated seizures.

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.

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.

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.

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.

Chris Sherwell on Professor Geoffrey Allen

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.

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

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).

This Pediatric Cell Atlas study analyzes temporal cortex single-nucleus RNA sequencing datasets from eight diverse donors from 4 to 50 years of age, describing gene expression dynamics over the course of brain maturation.

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.

Aarrestad et al. show that, in contrast to psychedelics, the nonhallucinogenic psychoplastogen tabernanthalog promotes neuroplasticity through 5-HT_2AR activation without immediately increasing extracellular glutamate levels or immediate early gene expression.

Using human cerebrospinal fluid proteomics, the authors found that proteins associated with Aβ pathology in Alzheimer disease were mainly expressed in glial cells, whereas those associated with tau tangle were linked to metabolism and mainly expressed in neurons.

In mouse, an axonal connectivity map showing the wiring patterns across the entire brain has been created using an EGFP-expressing adeno-associated virus tracing technique, providing the first such whole-brain map for a vertebrate species.

Using volumetric electron microscopy, the authors map and analyze the structure of cortical inhibition with synaptic resolution across a column of visual cortex.

Stroke affects the brain in complex, highly individual ways. Here, the authors show that applying generative and causal AI methods to routinely collected brain scans may enable more closely personalized treatment recommendations.

Although live birth evolved repeatedly in other clades, it has not been found in archosauromorphs, the group including modern birds and crocodilians. Here, the authors describe a fossilized pregnantDinocephalosaurusfrom ∼245 million years ago, providing evidence of live birth in archosauromorphs.

Altering cellular responses to double-strand breaks in DNA could rebalance CRISPRediting outcomes. Here, the authors use a pooled CRISPR screen to identify inhibition of CDC7 as a strategy to improve HDR outcomes.

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.

Plasma wakefield accelerators produce gradients that are orders of magnitude larger than in conventional particle accelerator, but beams tend to be disrupted by transverse forces. Here the authors create an extended hollow plasma channel, which accelerates positrons without generating transverse forces.

This study reveals that brain aberrations after preterm birth are highly individual yet shaped by early injury and social environment, influencing long-term cognitive outcomes.

Data collected from more than 2,000 taxa provide an unparalleled opportunity to quantify how extreme wildfires affect biodiversity, revealing that the largest effects on plants and animals were in areas with frequent or recent past fires and within extensively burnt areas.

Genome-wide ancient DNA data from individuals from the Middle Bronze Age to Iron Age documents large-scale movement of people from the European continent between 1300 and 800 bc that was probably responsible for spreading early Celtic languages to Britain.

Accurate spectral libraries are essential for analyzing data-independent acquisition (DIA) proteomics data. Here, the authors present Carafe, which trains on DIA data to build experiment-specific spectral libraries, boosting peptide detection across diverse datasets.

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.

Automated reconstruction of dense neural networks in the ventral nerve cord of the fruit fly provides a resource for investigating the neural control of movement.

Trudel et al. investigate the relationship between tau pathology and reactive astrogliosis in Alzheimer’s disease using PET imaging and CSF biomarkers. Their findings suggest that APOE ε4 amplifies tau-associated glial inflammation, offering insights into genotype-specific mechanisms driving AD-associated neuroinflammation.

Astrocytes are a major cell type in the central nervous system. Using single cell transcriptome sequencing, the authors identify multiple astrocyte subtypes in the adult mouse CNS, which map to distinct spatial locations and show correlations to cell morphology and physiology.

Naked mole rat (NMR) is an exceptionally long-lived rodent species that on the phenotypic level seems to evade aging. Here the authors show that NMRs age epigenetically, while epigenetic clocks detect that NMR queens age more slowly than nonbreeding females.

The authors use Patch-seq and electron microscopy datasets to relate synaptic connectivity to the transcriptomic cell type of different types of inhibitory neuron.

Understanding the growth dynamics of GBMs can help expand therapeutic options. Here, authors use a cross-species computational approach to compare GBM cells to healthy neural stem cells, identifying predictors and modulators of tumour growth, including the Wnt antagonist, SFRP1, which stalls growth in preclinical xenograft models.

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

Paul Davies's latest book argues that the search for intelligent life beyond Earth should be expanded. Chris McKay considers why we should look closer to home — perhaps even in our DNA.

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.

To construct a comprehensive atlas of cell types in each brain structure, we paired high-throughput single-nucleus RNA sequencing with Slide-seq, a recently developed spatial transcriptomics method with near-cellular resolution, across the entire mouse brain.

Chronic infection with SARS-CoV-2 leads to the emergence of viral variants that show reduced susceptibility to neutralizing antibodies in an immunosuppressed individual treated with convalescent plasma.