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Mutational signature analysis of blood cells isolated from 23 chemotherapy-exposed samples and 9 nonexposed controls characterizes the effects of various drugs on mutational burden, signature exposure and cell types.

Leveraging independent gains and losses of eusociality, the authors identify complementary signatures of selection in sweat bee genomes, including two proteins that bind and transport juvenile hormone.

Whole-genome sequencing of 962 clear cell renal cell carcinomas from 11 countries shows geographic variations in somatic mutation profiles, including a mutational signature of unknown cause in 70% of cases from Japan.

Analysis of genomic data from 981 colorectal cancers from participants in 11 countries reveals variations in mutational signatures of microsatellite-stable cancers that are dependent on geographical origin and age at which the cancer was diagnosed.

Neutrophils actively induce tumour necrosis, driving vascular occlusion, pleomorphic necrosis and metastasis.

Whole-genome sequencing and mutational signature analysis of 265 head and neck cancer samples collected from eight different countries provide insight into the vital contribution of tobacco smoke in disease etiology.

CD1 molecules present diverse lipid ligands to TCRs expressed by NKT cells. Rossjohn, Moody and colleagues show a unique form of autoreactivity with human CD1c molecules, whereby TCRs recognize a closed conformation of CD1c molecules, which are loaded with a diverse array of ‘headless’ glycolipids.

Here, the authors conduct a paired genome analysis of humans and Mycobacterium tuberculosis in a cohort from Lima, Peru. Their research reveals that genetic variations in both the host and pathogen significantly influence the progression to tuberculosis.

The functions of the human T cell repertoires that recognize different CD1 molecules remain unknown. Moody and co-workers show that many CD1a-autoreactive T cells home to skin, where they produce IL-22.

Fibroblasts play critical roles in tissue homeostasis, but in pathologic states they can drive fibrosis, inflammation, and tissue destruction. Here, Faust et al. find that healthy human synovial fibroblasts under the influence of adjacent adipocytes have altered lipid metabolism driven by cortisol signaling. Both adipocytes and these characteristics are lost in inflammatory arthritis.

The incidence of esophageal squamous cell carcinoma varies significantly across different geographical regions. Mutational signature analysis of tumors sampled from high- and low-incidence areas suggests that these variations may not be explained by mutagenic exposures.

Development of broadly neutralizing antibodies (bnAb) against HIV-1 in infected adults is a multi-step process unachievable by current vaccine approaches. Here the authors reconstruct the ontogeny of an infant bnAb, which develops in fewer steps, and identify its unique features that may shorten the path to HIV vaccines.

What factors explain variation in the pace and trajectory of evolutionary divergence between lineages? Here, the authors show that a proxy measure for sexual selection intensity predicts both the rate and direction of plumage colour evolution in a diverse radiation of New World passerine birds.

Moody and colleagues identify a subset of T cells with high affinity for complexes of CD1b and mycobacterial glycolipids, conserved TCRα use and biased TCRβ use. These 'GEM' T cells show interdonor conservation and proliferate after infection.

De Jong and colleagues identify staphylococcal phosphatidylglycerol lipids as antigens for human CD1a-restricted T cells, which promote type 2 immune responses and may contribute to atopic dermatitis.

Certain specific antigens have been shown to activate T cells in an MHC independent manner. Here the authors show a phycoerythrin reactive mouse TCR which recognises native protein and characterise the molecular nature of this interaction and that this specific TCR can be selected in the thymus.

T cell receptors are generally thought to contact antigens presented in an end to end configuration. Here the authors show a geometrically alternate sideways mode of recognition of the antigen-presenting molecule CD1a by a γδ T cell receptor.

Buter et al. elucidated the biological function of the terpene nucleoside 1-TbAd, which is made abundantly by virulent but not avirulent Mycobacterium tuberculosis strains, and demonstrate that 1-TbAd regulates the pH and function of host macrophage endolysosomes.

Germline-encoded mycolyl lipid-reactive (GEM) T cells recognize CD1b proteins presenting mycobacterial mycolates via their T-cell receptors (TCRs). Here, the authors present the structure of this interaction and provide a molecular basis for the co-recognition of CD1b and a mycobacterial glycolipid.

The number of single-cell RNA-seq datasets generated is increasing rapidly, making methods that map cell types to well-curated references increasingly important. Here, the authors propose an accurate method for mapping single cells onto a reference atlas in seconds.

Differences in MCT1 function among melanoma cells confer differences in oxidative stress resistance and metastatic potential.

Magnetic skyrmions are thought to possess a tube-like structure in three dimensions, but this has not been directly observed in experiment. Here, Birch et al. report real-space imaging of skyrmion tubes in a lamella of FeGe.

A single-cell Poisson model is used to analyse eQTLs in memory T cells across continuous, dynamic cell states, revealing that the cell context is critical to understanding variation in eQTLs and their association with disease.

CD1a presents a broad repertoire of lipid-based antigens. Rossjohn and colleagues show that the TCR docks over CD1a in a manner that precludes contact with permissive antigens, while nonpermissive antigens disrupt the TCR-CD1a contact.

In this study of more than 6500 emergency department patients, symptoms consistent with Long COVID are reported by 38.9% of SARS-CoV-2 test-positive and 20.7% of test-negative patients three months after their visit. A documented SARS-CoV-2 infection increased the risk fourfold of reporting Long COVID symptoms.

Phosphatidic acid and diacylglycerol are required for COPI vesicle fission. Here, the authors find that shorter forms of these lipids promote the late stage of COPI vesicle fission, further suggesting how lipid geometry contributes to membrane deformation in driving fission.

Biotin biosynthesis enables fatty acid remodelling and increased cell envelope fluidity, which counter alkaline pH in the lung and promote Mycobacterium abscessus growth during infection.

CD1 proteins present lipid antigens to T cells via the T cell receptor. Here the authors describe T cell reactivity to human membrane lipid moieties and provide structural data to define a molecular mechanism of promiscuous recognition of self-derived phospholipids.

The pathogen Mycobacterium tuberculosis uses the siderophores called mycobactins and carboxymycobactins to acquire iron from the host. Here, Zhang et al. identify a protein that is important for siderophore secretion and for the pathogen’s growth in low-iron medium.

Between 5 and 15% of latent Mycobacterium tuberculosis infections develop into active tuberculosis (TB). Here, Luo et al. report a genome-wide association study for early TB progression in a total of 4002 active TB cases and their household contacts in Peru and they identify a locus on 3q23 in which ATP1B3 is mapped as the likely causal gene.

Inter-sample variability reveals disease-associated cell subpopulations in single-cell RNA sequencing.

Primordial germ cells (PGCs) arise far from the somatic cells of the developing gonad and have to migrate across the embryo to reach their site of function. Studies of different model organisms reveal that, despite important differences, several features of PGC migration are conserved.

Hepatitis B virus (HBV) infection is known to be controlled by T and B cell responses, but the role of natural killer T (NKT) cells is less clear. Richard Blumberg and his colleagues now show that NKT cells are activated immediately after HBV infection by presentation of an HBV-altered repertoire of lysophospholipids on infected hepatocytes and are necessary for the induction of optimal T and B cell responses and rapid viral control.

Toll-like receptor 2 is activated by triacylated lipoproteins, but structural and functional studies now show that Mycobacterium tuberculosis lipoprotein LprG is a TLR2 agonist even when it is non-acylated. LprG contains a hydrophobic pocket to bind triacylated glycolipids and delivers them to TLR2, perhaps via CD14. In addition, LprG may serve as a glycolipid chaperone in cell wall assembly by Mycobacterium tuberculosis.