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During ageing, S-adenosylmethionine (SAM) is depleted from muscle stem cells (MuSCs) because of increased synthesis of the polyamine spermidine, leading to loss of heterochromatin and dysfunction of MuSCs. SAM restoration rescues the mouse MuSC defects.

Here the authors use single cell profiling of T cells across the human lifespan to show that a suboptimal TCR shift in T cells as we enter older age results in a molecular signature that resembles that of T cells from newborns and children.

Seismic imaging of subducted plates offers a way to improve plate tectonic reconstructions. Here, Braszus et al. use new ocean-bottom seismometer data from the Lesser Antilles to locate subducted spreading centres and faults thus providing a new understanding of the evolution of the Caribbean plate.

Obesity has been reported to promote tumourigenesis and chemoresistance but the underlying mechanisms are not completely understood. Here, the authors show that adipocytes induce Galectin-9 (GAL-9) expression in B-acute lymphoblastic leukaemia (B-ALL) cells which leads to chemoresistance and antibody-mediated blockade of GAL-9 increases survival in preclinical B-ALL murine models.

Multi-ancestry genome-wide analyses identify new risk loci for age-related macular degeneration. Ancestry-specific analyses identify distinct effects at major risk loci, including smaller effect sizes for CFH risk alleles in haplotypes of African ancestry.

DNA methylation loss has been observed in aging tissues and cancers for decades. Researchers from Van Andel Institute have now provided experimental evidence that this process is directly driven by cell division.

In a single-arm, non-randomized trial, neoadjuvant atezolizumab therapy in a large cohort of patients with resectable non-small cell lung cancer was safe and the study met its primary end point of major pathological response ≥15%.

The potential use of circulating tumour DNA in classic Hodgkin lymphoma detection, classification and monitoring is defined.

Bacteriophage repressor proteins downregulate viral lytic gene expression. Herein, the authors present the X-ray crystal structure of a monomeric repressor that binds an asymmetric DNA sequence using two independent domains.

The structure of the major histocompatibility complex (MHC)-class-I-like molecule MR1 in complex with a vitamin B9 derivative is determined; metabolites of vitamin B2 are shown to activate MR1-restricted mucosal-associated invariant T cells, implicating them in microbial immunosurveillance.

HLA-C expression levels correlate with immune responses to pathogens and autoimmunity, and vary in an allele-specific manner across individuals. Here the authors identify factors that drive differential expression of HLA-C allomorphs at the cell surface, and influence the structure of the peptide-binding cleft and diversity of peptides bound by HLA-C molecules.

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.

Oldupai Gorge, Tanzania is a key site for understanding early human evolution. Here, the authors report a multiproxy dataset from the Western basin of Oldupai Gorge dating to 2 million years ago, enabling the in situ comparison of lithic assemblages, paleoenvironments and hominin behavioral adaptability.

Mucosal-associated invariant T cells recognize vitamin-B-derived ligands presented via the major-histocompatibility-complex-like molecule MR1. Rossjohn and colleagues demonstrate that these cells recognize a wide variety of ligands, some derived from common drugs, in an agonist or antagonist manner.

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.

MR1 molecules present bacterial metabolites to MAIT innate lymphocytes, but the processing and presentation pathway of these ligands are unclear. McCluskey, Rossjohn, Villadangos and colleagues demonstrate that MR1 ligands bind in the ER, which initiates trafficking to the plasma membrane and subsequent presentation.

A survey of the fitness effects conferred by mosaic chromosomal alterations (mCAs) in UK Biobank shows that most mCAs—despite being relatively infrequent—are associated with increased fitness. Mosaic loss of the sex chromosomes was more common but these events afforded only small fitness gains.

The neural mechanisms underlying transcranial ultrasound stimulation (TUS) in humans are not well understood. Here, the authors show that theta-burst stimulation reduces gamma-aminobutyric acid (GABA) levels in the posterior cingulate cortex, as well as increasing functional connectivity in the anterior and posterior cingulate cortex.

A hybrid analogue–digital quantum simulator is used to demonstrate beyond-classical performance in benchmarking experiments and to study thermalization phenomena in an XY quantum magnet, including the breakdown of Kibble–Zurek scaling predictions and signatures of the Kosterlitz–Thouless phase transition.

The effects of climate on vector-borne disease systems are highly context-dependent. Here, the authors incorporate laboratory-measured physiological traits of the mosquito Aedes aegypti into climate-driven mechanistic models to predict number, timing, and duration of outbreaks in Ecuador and Kenya.

To ensure correct cell division Staphylococci must remember which plane they previously divided along, but the mechanism by which this is achieved is unclear. In this article, using atomic force microscopy, peptidoglycan ribs are reported to mark previous planes of division.

Crystal engineering is a powerful process for assembling complex materials but tends to require organic building blocks, which can limit stability. Here, the authors use inorganic polyoxometalates to assemble an all-inorganic metamorphic framework that can be switched between eight distinct states.

Malaria can persist at levels that escape detection by standard microscopy, but can be detected by PCR. Okell et al.now show that rates of submicroscopic infection can be predicted using more widely available microscopy data, and are most epidemiologically significant in areas with low malaria transmission.

Bacterial cell wall peptidoglycan is essential for viability and shape determination. Using high-resolution microscopy, Foster and colleagues elucidate the peptidoglycan architecture and insertion pattern in Escherichia coliand other Gram-negative bacteria, and propose a new model for cell wall elongation.

Marine turbidite deposition is confirmed to relate to earthquake ground motions by an analysis of turbidite deposits and simulations of ground motions from the 2016 Kaikōura earthquake.

Chronic lung diseases are characterized by molecular and cellular composition changes. Here the authors use single-cell RNA sequencing to map cell type-specific changes in human tracheal epithelium related to smoking, and to provide evidence for a tuft-like progenitor for pulmonary neuroendocrine cells and ionocytes.

Motile and non-motile cilia have distinct functions and protein complexes associated with them. Here, the authors show the conserved protein CFAP20 is important for both motile and non-motile cilia and is distinct from other ciliopathy-associated domains or macromolecular complexes.

Primary ciliary dyskinesia (PCD) is a genetically heterogeneous disease resulting in reduced mucus clearance and impaired lung function. Here, the authors show that mutations in PIH1D3 are responsible for an X-linked form of PCD, affecting assembly of a subset of inner arm dyneins.

Mobile genetic elements can confer antibiotic resistance on their bacterial hosts. However, they are often costly leading to conflict with the host chromosome, which can drive intragenomic coevolution and consequent modulation of resistance.

We present the complete 62,460,029-base-pair sequence of a human Y chromosome from the HG002 genome (T2T-Y) that corrects multiple errors in GRCh38-Y and adds over 30 million base pairs of sequence to the reference.

HERG channel inactivation is critical for normal heart rhythm. Authors determine structures of open and non-conducting states of HERG and identify a key role for S620 on the pore helix in coordinating transitions between open and inactivated states.

The authors show that fruit flies briefly silence visual processing during voluntary flight turns, which likely helps flies to ignore the image of the world sweeping over the retina during such turns.

Authors show that a common SNP upregulates endometrial Wnt4 expression and proimplantation genes in mouse proestrus and estrus. They suggest that this increases uterine permissiveness to embryo invasion, while decreasing resistance to invasion in reproductive cancers and endometriosis.

During apoptosis, mitochondrial outer membrane permeabilization results in cytosolic mitochondrial RNA (mtRNA). Here, the authors demonstrate that caspase-3/7 inhibition promotes a cytosolic mtRNA-driven Type I interferon response via MDA5/MAVS/IRF3, increasing the immunogenicity of chemotherapy-induced apoptosis.

Ancestry and socioeconomic factors influence predictable changes in the vaginal microbiome that occur early in pregnancy in women who experience normal term birth.

As part of the second phase of Human Microbiome Project, the Multi-Omic Microbiome Study: Pregnancy Initiative presents a community resource to help better understand how microbiome and host profiles change throughout pregnancy as well as to identify new opportunities for assessment of the risk of preterm birth.

The dominant mechanism of nanoparticle entry into solid tumours has now been shown to be an active trans-endothelial pathway rather than the currently established passive transport via inter-endothelial gaps.

Reconstructing Holocene range and extinction dynamics of moa (order Dinornithiformes), the authors determine that despite interspecifically different dynamics, spatial patterns of collapse were probably similar. They also find that the likely final refugia for moa were in the same areas and ecological conditions where New Zealand’s remaining flightless birds persist today.

Understanding mutational processes and evolution in acral melanoma remains critical. Here, the authors sequence different progression stages of acral melanomas, finding early, punctuated emerging clusters of copy number alterations as well as inverted order in which telomerase and MAP-kinase pathway mutations arise, compared to other melanoma subtypes.

In this study, the authors delineate a global biogeographic map for ants based on their distributions and phylogenetic relationships. They show that current biogeographic maps based on tetrapod groups fail to capture important regions for biodiversity shared by insects and plants, which are both known to possess strong ecological and evolutionary ties.

It has been reported that inhibition of the epigenetic regulator DNA methyltransferase 1 (DNMT1) is associated with improved response to immune checkpoint blockade (ICB). Here the authors show that conditional deletion of Dnmt1 in endothelial cells is sufficient to promote T cell infiltration, reduce tumor growth and enhance ICB response in preclinical models.

A high-resolution kidney cellular atlas of 51 main cell types, including rare and previously undescribed cell populations, represents a comprehensive benchmark of cellular states, neighbourhoods, outcome-associated signatures and publicly available interactive visualizations.

The identification of patient-specific disease mechanisms and druggable targets is crucial for precision medicine in glioblastoma. Here, the authors show that comparing patients-matched glioma-initiating cells with neural stem cells enables the discovery of patient-specific mechanisms of disease and the identification of effective drugs

Robots that can change their shape offer flexible functionality. A modular robotic platform is shown that implements physical polygon meshing, by combining triangles with sides of adjustable lengths, allowing flexible three-dimensional shape configurations.