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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.

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 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.

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.

Genome-wide sequencing of 180 ancient individuals shows a continuous gradient of ancestry in Early-to-Mid-Holocene hunter-gatherers from the Baltic to the Transbaikal region and distinct contemporaneous groups in Northeast Siberia, and provides insights into the origins of modern Uralic and Yeniseian speakers.

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.

A hybrid epoxy–acrylate resin is reported for the digital light processing 3D printing of bioinspired metamaterial structures with precisely patterned hard and soft domains.

Cascadia is a mass spectrometry-based de novo sequencing model that uses a transformer architecture to handle data-independent acquisition data and achieves substantially improved performance across a range of instruments and experimental protocols.

Ryan et al. report a highly conserved mechanism by which arginine induces changes in hypervirulent Klebsiella pneumoniae bacterial cell surface capsule. K. pneumoniae arginine sensing is critical for full virulence potential.

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.

A theoretical foundation for entrapment methods is presented, along with a method that enables more accurate evaluation of false discovery rate (FDR) control in proteomics mass spectrometry analysis pipelines. Evaluation of popular data-dependent acquisition tools indicates that these generally seem to control the FDR, but data-independent acquisition tools exhibit inconsistent control of the FDR at both the peptide and protein levels.

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.

Sinonasal squamous cell carcinoma (SNSCC) is an uncommon tumor, which has been associated with the human papillomavirus (HPV). Here the authors perform comprehensive genome-wide characterization of HPV-associated and HPV-independent SNSCC patient samples to reveal molecular patterns of tumorigenesis and identify HPV-driven mutational profiles.

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

How different cell types in primary motor cortex contribute to movement during learning and/or execution is not fully understood. Here authors show that corticothalamic neurons of the primary motor cortex are silent during movement and that this activity signature is critical for proficient movement generation.

The choroid plexus (ChP) provides molecular cues for brain development. However, the underlying mechanisms are unclear. This study identifies an apocrine secretion mechanism in the ChP that modulates the CSF protein composition and instructs cortical development.

Reducing the stigma and discrimination that people living with liver conditions experience requires rethinking how diagnoses, diseases, etiologies and circumstances are perceived — a shift that begins with the language used to name and describe them.

 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. 

Early expression of intraneuronal amyloid-β (not phospho-tau) and inflammatory and glycosylation pathway transcripts distinguish neocortical RORB⁺ and GAD1⁺ neurons selectively vulnerable to neurodegeneration in Alzheimer’s disease.

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.

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.

This work shows that receptor use in merbecovirus is clade-specific by clustering them into clades based on the receptor-binding ___domain (RBD) of their spike proteins. While MERS-CoV and its close relatives use the DPP4 receptor, several other clades—including all HKU5 bat coronaviruses—rely on ACE2, the same receptor used by SARS-CoV and SARS-CoV-2.

Malaria chemoprevention is used for young children, but resistance mutations raise concerns on efficacy. In this analysis of trials across Africa, the authors show that prevention treatment protects >42 days against susceptible parasites but <12 days against highly resistant strains highlighting the importance of genomic surveillance for chemoprevention strategies.

Multimodal results (iEEG, fMRI and MEG) of predictions from integrated information theory and global neuronal workspace theory align with some predictions of both theories on visual consciousness, but also critically challenge key tenets of both theories.

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.

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.

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.

Nitroxoline is a bacteriostatic quinoline antibiotic, known to form complexes with metals, with few clinical applications. Here, Cacace et al. show that the compound displays a broad activity spectrum, with species-specific bactericidal activity, and acts as a metallophore inducing copper and zinc intoxication in bacterial cells.

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.

Genomic studies often lack representation from diverse populations, limiting equitable insights. Here, the authors show that the BIG Initiative captures extensive genetic diversity and reveals ancestry-linked health disparities in a community-based Mid-South cohort.

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.

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).

Citizen science taps the efforts of non-experts. Here, authors describe Drugit, an extension of the crowdsourcing game Foldit, and its use in designing a non-peptide binder of Von Hippel Lindau E3 ligase for use with proteolysis targeting chimeras.

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.

Neurodegenerative diseases are linked to changes in the immune system and inflammation. Here, the authors studied immune cells from healthy individuals and neurodegenerative diseases and identified sex-specific disease-associated changes.

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.

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.

The taurine–taurine transporter axis is a critical dependency of aggressive myeloid leukaemias.

Navigation relies on detecting left versus right body asymmetries for gaze and course stability. A central three-layer optic flow-sensitive network with competitive lateral disinhibition extracts asymmetries from complex motion patterns.

Omics data’s diversity and high-dimensionality challenge integration across technologies and with imaging. Here, authors introduce mapping method xIV-LDDMM that estimates geometric and feature transformations to integrate tissue-scale atlases with molecular and cellular-scale data.

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.

A multi-cohort genome-wide association study of tau PET, a brain imaging-based marker of Alzheimer’s disease, identifies a CYP1B1-RMDN2 locus as associated with higher tau and faster cognitive decline. These results suggest a new genetic contribution to cerebral tau and target for Alzheimer’s disease research.

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.

Spatial transcriptomics (ST) enables gene expression characterisation within tissue sections, but comparing across sections and technologies remains challenging. Here, authors develop STalign to spatially align ST data and demonstrate applications including aligning to common coordinate frameworks.

Here the authors measure how the absence of certain DNA repair genes change the frequencies of unique mutational outcomes generated by Cas9 DSBs at synthetic target sequences in mouse embryonic stem cells: they use this to build predictive models of the mutagenic outcomes of Cas9 scission.

Observations of the Phoenix cluster using the James Webb Space Telescope reveal rapid cooling in galaxy cluster cores, driven by black hole jets, with gas temperatures mapped between 10⁵ K and 10⁶ K and cooling rates of 5,000–23,000 M_⊙ yr⁻¹.