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T cells contribute to protection and pathogenesis in tuberculosis. Here the authors sequence T cell receptor repertoires in human skin biopsies from the site of the tuberculin skin test and show enrichment of clonotypes reactive to Mycobacterium tuberculosis using a computational pipeline metaclonotypist to identify distinct TCRs predicted to share peptide-MHC reactivity across participants, as an approach to explore T cell correlates of tuberculosis disease-risk stratification and vaccine efficacy.

A hand stencil painted on a cave wall on a small island off the coast of Sulawesi more than 67,800 years ago suggests a very early occupation of Wallacea.

Understanding collective behaviour is an important aspect of managing the pandemic response. Here the authors show in a large global study that participants that reported identifying more strongly with their nation reported greater engagement in public health behaviours and support for public health policies in the context of the pandemic.

Neutrophils infiltrate glioblastomas with the capacity to engage pro/anti tumoural responses. Here the authors developed proteomic workflows to stratify neutrophil heterogeneity by function. This work provides a platform to study neutrophil proteomes with single cell resolution in glioblastoma.

The advantage of living in cities compared with rural areas with respect to height and BMI in children and adolescents has generally become smaller globally from 1990 to 2020, except in sub-Saharan Africa.

Integrated multi-omic analyses using samples from the TRACERx study highlight cross-talk between DNA hypermethylation and genomic lesions in non-small cell lung cancer.

A CRISPR knock-in strategy that uses endogenous gene regulatory mechanisms can engineer ‘armoured’ CAR T cells that secrete proinflammatory cytokines directly within a tumour without causing toxicity, leading to prolonged survival in mice.

McGeachan et al. observe oligomeric tau in synapses from individuals with progressive supranuclear palsy and provide evidence that tau pathology may spread through the brain via synapses.

Axonal injury, induced in the white matter by expansion of early tumour cells, is a key driver of glioblastoma progression.

The authors show that mitochondria can chronically hyperpolarize under normal or disease conditions and be induced by environmental exposures. This triggers phospholipid remodeling, which in turn affects the epigenome to regulate transcription.

Vaccination provides protection from COVID-19, but optimization in design and route is an ever-ongoing process. Here the authors pursue an open-label, multi-arm phase I clinical trial to report the safety of a multi-valent, aerosol vaccine administered via inhalation, as well as superior mucosal immunity induced by ChAd over HuAd vectors.

This study shows that the total energy loss of gravity currents has a non-linear dependence on the work required to keep sediment in suspension, highlighting the importance of large-scale mixing for the particulate transport of gravity currents.

A connectome of the right optic lobe from a male fruitfly is presented together with an extensive collection of genetic drivers matched to a comprehensive neuron-type catalogue.

This study finds that CRISPR-knockout phenotypes from genome-wide screens systematically show increased similarity to knockouts of unrelated genomically proximal genes located on the same chromosome arm. Multiple lines of evidence suggest that this proximity bias is caused by telomeric truncations of chromosome arms and is consistent across cell types, labs and Cas9 delivery methods.

Understanding synapse loss in Alzheimer’s disease has been hampered by a lack of human model systems. Here, the authors show that manipulation of physiological or pathological Aβ has differing effects on synapses in live human brain slice cultures.

Embryonal tumour with multilayered rosettes (ETMR) is a rare and aggressive paediatric brain tumour. Here, the authors analyse intratumour heterogeneity and the tumour microenvironment in ETMR using single-cell and spatial transcriptomics, in vitro cultures, and a 3D forebrain organoid model, finding important aspects – such as the communication with pericytes – for ETMR development and response to therapy.

GABAB receptors contribute to complex inhibition that regulates cortical neurons in a translationally relevant manner over adult life. Here, authors show stronger presynaptic inhibition in humans than rats, and a role for GABAB receptors in the anti-seizure profile of levetiracetam.

Activation of the adenosine receptor A2AR is associated with suppression of T cell function in the tumor microenvironment. To overcome immunosuppression, here the authors show that CRISPR/Cas9 mediated deletion of A2AR enhances CAR T cell effector functions without altering memory or persistence properties, improving CAR-T mediated tumor control in pre-clinical models.

The authors show that anxiety-like behavior in mice varies based on striatal D1/D2 receptor ratios. Elevated D1/D2 ratios enhanced alcohol relief, risk-avoidance, and persistent drinking, suggesting anxiety may predispose individuals to alcohol use disorder (AUD).

We show the evolution of a case of EGFR mutant lung cancer treated with a combination of erlotinib, osimertinib, radiotherapy and a personalized neopeptide vaccine targeting somatic mutations, including EGFR exon 19 deletion.

Analytical gaps limit the utility of scATAC-seq for studying gene regulatory programs in human disease. Here, authors describe MOCHA, a robust analytical tool with advanced statistical modelling that enables functional genomic inference in large cross-sectional and longitudinal human studies.

Fine-scale geospatial mapping of overweight and wasting (two components of the double burden of malnutrition) in 105 LMICs shows that overweight has increased from 5.2% in 2000 to 6.0% in children under 5 in 2017. Although overall wasting decreased over the same period, most countries are not on track to meet the World Health Organization’s Global Nutrition Target of <5% in over half of LMICs by 2025.

A cave art scene at Leang Karampuang, Indonesia, dated to at least 51,200 years ago using laser-ablation uranium-series imaging, depicts human-like figures interacting with a pig.

This international Consensus Statement provides guidelines on the management of pituitary incidentalomas.

By leveraging paired microbiome and human gene expression data from pediatric patients who underwent hematopoietic cell transplantation, distinct lung–immune system–microorganism interactions were identified as important drivers of fatal lung injury.

Analysis of HbA1c and FPG levels across 117 population-based studies demonstrates regional variation in prevalence of previously undiagnosed screen-detected diabetes using one or both measures and suggests that use of elevated FPG alone could underestimate diabetes prevalence in low- and middle-income countries.

Immune lymphocyte estimation from nucleotide sequencing (ImmuneLENS) infers B cell and T cell fractions from whole-genome sequencing data. Applied to the 100,000 Genomes Project datasets, circulating T cell fraction provides sex-dependent and prognostic insights in patients.

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

Bacterial products in the gut–liver axis and tissue stromal factors can tune liver immunity by driving myeloid instruction of CD8⁺ T cells with immunomodulatory ability.