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A new optical imaging study demonstrates that norepinephrine and the state of arousal influence hemodynamic correlations across cerebral cortex, calling for a conceptual shift in interpreting functional magnetic resonance imaging data.

Prime editing is improved with engineered RNA-stabilizing motifs.

Here, by integrating host gene expression and airway microbiome data, the authors distinguish true lower respiratory infection from incidental pathogen carriage, and identify biologically distinct patterns that improve diagnostic precision beyond pathogen detection alone

A computational redesign strategy improves evolved prime editors.

High-throughput barcoded neuroanatomy of two closely related rodent species with divergent vocalizations reveals differences in long-range projection motifs in the brain that may support these differences in vocal complexity.

Young, cognitively normal APOE4 mice display hippocampal network hyperactivity that predicts later memory decline. This phenotype is driven by neuronal APOE4 expression, which causes hyperexcitability of hippocampal neurons and can be reversed by targeting Nell2.

Mice with higher levels of parenting show more prosocial allogrooming towards stressed adults, and both behaviours share neural substrates in the medial preoptic area, suggesting that parenting circuitry may form an evolutionary foundation for adult-directed prosocial helping behaviour.

RNA velocity is a widely used method to predict the fate of single cells. Here the authors show that the concept can be adapted to predict the fate of individual human subjects, using RNA velocity of whole blood at a single point in time to predict future clinical outcomes and treatment responses.

Neurons in medial entorhinal cortex collectively represent discrete nonlocal positions during immobility. During this nonlocal coding, CA1 is uncoupled from entorhinal cortex. These representations are of task-relevant locations.

NextBrain is an open source, probabilistic atlas of the entire human brain, assembled using artificial-intelligence-enabled registration and segmentation methods to reconstruct the multimodal serial histology of five human half brains, and which can be used to automatically segment brain MRI scans into 333 regions.

When 100 social and behavioural science claims were examined, 34% of reanalyses closely matched the original results, with 74% reaching the same conclusion, revealing limited robustness of single-path analyses and the need to address analytical uncertainty.

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).

Most advanced triple-negative breast cancers remain resistant to immunotherapy. Here, the authors discover that RIPK1-driven necroptosis in both tumor and stromal compartments is essential for effective immunogenic cell death-based therapy and immune checkpoint blockade.

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.

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.

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.

Hodgson, Huang, Lang et al. show that TDP-43 limits ribonucleoprotein particle condensation into paraspeckles in a concentration- and polymerization-dependent manner. They also link paraspeckle condensation to stress response and neuroprotection.

How the pulvinar represents complex visual information, its functional topography, and its relationship to cortical processing of visually presented objects remains unclear. Here authors show that responses to natural scenes in the human pulvinar reveal organized spatial maps for both low-level visual features, such as local contrast, as well as high-level visual features, such as bodies and faces.

Here authors show that the function of prefrontal cortex, an area that controls executive function and cognition, is impaired on a cellular and network level in mice born preterm.

The anterior cingulate cortex encodes affective pain behaviours modulated by opioids; targeting opioid-sensitive neurons through a new chemogenetic gene therapy replicates the analgesic effects of morphine, providing precise chronic pain relief without affecting sensory detection.

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.

CaBLAM is a bioluminescent genetically encoded calcium indicator that delivers high-contrast signals as shown in cell culture, in the in vivo mouse brain and in zebrafish larvae.

Germline and somatic interactions define actionable genomic patterns driving acquired therapy resistance in breast cancer.

A large, open dataset containing parallel recordings from six visual cortical and two thalamic areas of the mouse brain is presented, from which the relative timing of activity in response to visual stimuli and behaviour is used to construct a hierarchy scheme that corresponds to anatomical connectivity data.

An exploratory analysis of the phase 3 ECOSPOR III trial shows that a higher dosage of the oral microbiome therapeutic VOWST led to enhanced pharmacokinetics, increased species engraftment and altered microbiome and metabolite profiles, providing mechanistic insights into how it may prevent Clostridioides difficile infection recurrence.

Aerobic exercise influences physiology and generally reduces cancer risk, yet the mechanisms connecting these effects remain incompletely understood. In this Perspective, Zhuang and colleagues outline a model in which exercise-induced physiological adaptation regulates adult stem cell behaviour in ways that limit transformation and tumour initiation.

Whole-genome sequencing analysis of individuals with primary immunodeficiency identifies new candidate disease-associated genes and shows how the interplay between genetic variants can explain the variable penetrance and complexity of the disease.

Sleep deprivation impacts molecular changes across brain regions. Here, the authors utilize a spatial. transcriptomics approach to elucidate acute sleep deprivation-induced gene expression signature. across regions and subregions of the brain.

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.

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.

Sandhoff disease (SD) is a lysosomal storage disorder caused by deficiency in the β subunit of the β-hexosaminidase enzyme. Here, the authors show via bone marrow-based microglial replacement in a SD mouse model that myeloid-derived β-hexosaminidase is necessary for maintaining neuronal health.

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.

A study of the evolution of the SARS-CoV-2 virus in England between September 2020 and June 2021 finds that interventions capable of containing previous variants were insufficient to stop the more transmissible Alpha and Delta variants.

RNA sequencing reveals widespread transcriptomic changes across the cerebral cortex in autism spectrum disorder, including primary sensory regions, in addition to association regions, as well as an attenuation of regional identity.

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.

An analysis of cell-type diversity in brain samples from a variety of mammalian species, both during development and in adult animals, reveals that the TAC3 initial class of striatal interneurons is conserved across placental mammals and is homologous to Th striatal interneurons in rodents.

Brain region-specific oligodendrocyte population dynamics are unclear. Here the authors implement long-term in vivo three-photon imaging to determine those dynamics in the cortical and subcortical areas in the living intact and demyelinated adult mouse brain.

Whether or not deep neural networks require hierarchical representations to predict brain activity is not known. Here, the authors show that a multi-branch deep neural network can predict neural activity independently in visual areas in the absence of hierarchical representations.

Walmsley and colleagues report that systemic hypoxia induces persistent loss of histone H3K4me3 marks and epigenetic reprogramming in neutrophil progenitors, resulting in long-term impairment of subsequent neutrophil effector functions.

CellSAM uses an object detector, CellFinder, to detect cells and prompt the Segment Anything Model (SAM) to generate segmentations. This universal model achieves human-level performance across a range of bioimaging data encompassing mammalian cells, yeast and bacteria.

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.

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.

The genetic prehistory of central America has not been well explored. Here, the authors find evidence from ancient DNA from twenty individuals who lived in Belize 9,600 to 3,700 years ago of a migration from the south that coincided with the first evidence for forest clearing and the spread of maize horticulture.

A generative artificial intelligence-powered method enables de novo design of highly active enzymes based on information about the geometry of residues in the active site, without requiring protein backbone or sequence information.

COVID-19 can be associated with neurological complications. Here the authors show that markers of brain injury, but not immune markers, are elevated in the blood of patients with COVID-19 both early and months after SARS-CoV-2 infection, particularly in those with brain dysfunction or neurological diagnoses.

Shared inter-brain neural dynamics, reflecting aspects of social interaction including self and other’s behaviours, arise in GABAergic neurons of the dorsomedial prefrontal cortex of socially interacting mice, as well as in the neurons of socially interacting artificial intelligence agents.