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Mesothelioma is a highly lethal cancer that remains challenging to diagnose. Here, the authors curate a histomorphological atlas of resected mesothelioma and map it using self-supervised AI endorsed by human pathological assessment, revealing patterns that generate highly interpretable predictions.

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).

Genome-wide and targeted perturbation of DNA methylation at centromeres affects CENP-A positioning and centromere structure, resulting in aneuploidy and reduced cell viability.

An analysis of the EPIC study demonstrates that dietary plant biodiversity presents benefits for human and planetary health, but adverse environmental impacts are associated with dietary animal species richness.

Analysis of snRNA genes in individuals with rare disorders identifies de novo and recurrent variants in RNU5B-1 and RNU5A-1, in addition to previously unreported cases with pathogenic or likely pathogenic variants in RNU4-2.

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.

Blood flow through a vessel deforms vessel walls. Cells lining these walls sense the changes in pressure as blood flows and reorient their actin fibres in the direction of largest tension.

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.

Prion-like proteins in Escherichia coli trigger an abortive infection mechanism in response to phage infection—a process similar to amyloid-mediated immune signalling in fungi and animals.

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

Drugs of abuse exert both motivational and emotional effects. Here, the authors show that nicotine and ethanol activate a VTA–NAc loop that inhibits dopamine neurons projecting to the amygdala, thereby inducing anxiety-like behavior and linking the reward and emotional circuits.

Targeting the integrin VLA-4 with natalizumab has shown efficacy in treating multiple sclerosis, but relapse still occurs in some patients. Here the authors use a high-content cell imaging (HCI) pipeline and machine learning to assess the morphology of T cells from MS patients prior to natalizumab regime for defining features associated with treatment responses.

It has been proposed that phylogenetic diversity can be used as a proxy to estimate functional diversity and to predict ecosystem functioning. Here, the rapid evolutionary response of marine bacteria is used to study the positive effects of evolutionary history and species diversity on ecosystem productivity.

Sepsis induces a period of immunosuppression which can be problematic in the face of subsequent infectious challenge. Here the authors show the presence of PD-L1 expressing regulatory plasma cells that can inhibit T cells in a murine model and in patients with sepsis.

Here, the authors show that Intracortical recordings in human motor cortex during attempted multi-finger movements reveal a largely linear code with two violations: magnitude normalization and greater shifts in tuning direction for weakly represented fingers.

A geospatial levelized cost model shows that green hydrogen imports from Africa to Europe remain uncompetitive without major policy support. De-risking policies and strategic site selection are key, but major risks remain.

Preventing axon breakdown is key to treating neurodegeneration. Here, the authors show that after axotomy, DLK kinase drives apoptotic mitochondrial fission in axons. Blocking this reduces axon degeneration and neuron death in both human and mouse models.

Metabolites in the tumor microenvironment, including adenosine, have been shown to suppress anti-tumor immune responses. Here, the authors show that T cell expression of the adenosine transporter ENT1 is involved in this immunosuppression and can be targeted to boost T cell function, tumor killing and immune checkpoint blockade.

Computer models of mantle convection with plate-like behaviour are used to demonstrate that the size–frequency distribution of tectonic plates on Earth is controlled by subduction geometry—the spacing between subducting slabs controls the layout of large plates, and the stresses caused by the bending of trenches break plates into smaller fragments.

How nicotine impacts the adolescent development of neural circuitry is not fully understood. Here authors show that early adolescent nicotine exposure in male mice blocked the maturation of nicotine-evoked dopamine signaling, causing an immature, vulnerable behavioral response in adult mice. Restoring their adult-like nicotine-evoked signaling unmasks a mature behavioral response in male mice.

An investigation using various methods reports an association between adeno-associated virus 2 and paediatric hepatitis of unknown aetiology.

Arsenic incorporation into pyrite nuclei reveals that the 2.1-billion-year-old Francevillian biota actively detoxified arsenic by sequestration in specialized body compartments.

Single-unit ensemble activity recorded in unilateral human precentral gyrus reveals a wide range of gesture-related signals across both hands, providing an intuitive and diverse set of potential command signals for intracortical BCI use.

A region on chromosome 19p13 is associated with the risk of developing ovarian and breast cancer. Here, the authors genotyped SNPs in this region in thousands of breast and ovarian cancer patients and identified SNPs associated with three genes, which were analysed with functional studies.

Pluripotent epiblast cells segregate from primitive endoderm in the blastocyst inner cell mass (ICM). Here the authors show that mosaic epiblast differentiation during mouse and human preimplantation development initiates stochastically in ICM progenitors, independently of the FGF pathway, and requires NANOG activity

Netrin-1, via precise Neo1/Unc5B stoichiometry, promotes naive pluripotency, embryonic stem cell self-renewal in combination with leukaemia inhibitory factor, and the formation of the mouse epiblast in vivo.

In birds, the hand-wing index is a morphological trait that can be used as a proxy for flight efficiency. Here the authors examine variation of hand-wing index in over 10,000 bird species, finding that it is higher in migratory and non-territorial species, and lower in the tropics.

In this immunological ancillary study of the PREVAC trial, the authors show that approved Ebola virus vaccines induce memory T-cell responses that persist during the five year follow-up after initial vaccination.

Clinically significant genetic variation in Asian populations is under-characterized. Here, the authors show the diversity in prevalence and spectrum of human disease and pharmacogenetic variants in a multi-ethnic Asian population.

In a mouse model of prostate cancer, neural progenitors from the central nervous system that express doublecortin infiltrate tumours and metastases, and can generate new adrenergic neurons in tumours.

Statins and aminobisphosphonates inhibit post-translational modifications and membrane accumulation of progerin, the protein that causes Hutchinson-Gilford progeria syndrome, pointing to a potential combination therapy for this disease.

CD8⁺ T cell activation involves cooperation between the T cell receptor and the integrin LFA-1. Here authors show how LFA-1 nanoclusters participate in the calibration of TCR stimulation strength and activation of cytotoxic function in CD8⁺ T cells.

The iron-sulfur cluster (ISC) assembly complex is activated by frataxin (FXN) and Friedreich’s ataxia is caused by FXN deficiency. Here the authors present the 3.2 Å resolution cryo-EM structure of the human frataxin bound ISC complex and discuss how FXN activates enzymatic activity.