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Siew et al. using multi-omic, physiological & imaging approaches have demonstrated that spaceflight causes kidney remodelling, suggesting a contribution to kidney stone formation, & that space radiation causes kidney damage & early signs of dysfunction.

Multi-omic single-cell and spatial analyses of lung cancer brain metastases from multiple cohorts identify high levels of chromosomal instability and a neural-like profile in brain metastases compared with primary tumors.

The ATR inhibitor ceralasertib has shown clinical activity in combination with immune-checkpoint inhibitors in several cancer types. Here the authors report the anti-tumor activity and the immunomodulatory changes, dependent on up-regulation of type I interferon pathway, following intermittent ATR inhibition in preclinical cancer models.

Centromere fragility can drive tumourigenesis, so protective mechanisms are important. Here, the authors suggest that the PBAF chromatin remodelling complex, which is frequently misregulated in cancer, helps to maintain the integrity of centromeres.

Salmonella employ a range of strategies to counter host defences during infection. Here, Aulicino et al. use single-cell RNA-sequencing to examine the effects of invasive and non-invasive strains of Salmonella, revealing discrete and divergent immune evasion strategies in infected and bystander dendritic cells.

Lenardo and colleagues identify a new human genetic disease, GISELL, whereby ceramide lipid homeostasis is disrupted, thereby altering T cell longevity. Deficiency of GTPase of the immunity-associated protein 5 (GIMAP5) in patients leads to cellular senescence, immunodeficiency and early mortality.

Exploring the diversity of the wild progenitor of the wheat D subgenome allows for rapid trait discovery.

Scientists have travelled the ancient Silk Road to understand how genes shape people's love for foods.

Cox and colleagues develop PXS-5505, a first-in-class selective pan-lysyl oxidase inhibitor and show that it reduces chemotherapy-induced desmoplasia and stiffness, thereby improving chemotherapy response and survival in pancreatic cancer models.

Paneth cell metaplasia (PCM) typically arises in diseases intrinsic to the gastrointestinal tract; however, whether extra intestinal diseases can trigger PCM and the mechanistic pathway by which PCM develops is unknown. Herein, the authors show in an inducible murine model of chronic myelogenous leukaemia that a systemic inflammatory state can trigger IL-33- mediated IL-9 production that leads to small intestinal remodelling and PCM.

Lineage tracing of human stem cells is achieved by measuring fluctuating DNA methylation.

Cancer metabolism adapts the metabolic network of its cell of origin. Mahendralingam et al. find that lineage-rooted metabolic identities of normal mammary cells reflect breast cancer subtype metabolism.

Ageing reshapes immune composition, function and regenerative capacity, with profound effects on tumour immunity, cancer progression and treatment outcomes. In this Review, Dolan and colleagues examine how age-resolved immunoprofiling, insights from ageing haematopoiesis and preclinical modelling are uncovering immune ageing dynamics and therapeutic challenges — revealing new opportunities to optimize cancer therapy across diverse age groups.

Genome-wide analyses of vaccine antibody responses in 2,499 infants from Uganda, South Africa and Burkina Faso identify associations between specific HLA genes and response to eight vaccines, providing insights that could be considered for population-adjusted vaccine design strategies.

Chemical, genetic and proteomic approaches were used to elucidate the mode of action of orpinolide, a withanolide-inspired OSBP inhibitor, revealing sterol transport as a druggable metabolic dependency in leukemia.

Where is it best to hunt for genes that underlie cancer and heart disease? Isolated populations such as Iceland's, or ethnic melting pots like the United States? And what are the technological challenges, asks Alison Abbott.

The vesicles that transport proteins between intracellular organelles are small, short-lived, and elusive. Here, the authors show that capture of these vesicles through relocalizing tethers to mitochondria allows their contents to be characterised by organelle proteomics.

Montserrat Garcia-Closas and colleagues report a genome-wide association study for bladder cancer. They identify three new susceptibility loci on chromosomes 22q13.1, 19q12 and 2q37.1.

The ability to maintain blood stem cells (HSCs) in vitro would allow us to provide better therapies for blood diseases. Here, the authors report that polymer-organised extracellular proteins, coupled to soft environments mimicking bone marrow stiffness, allow stromal cells to maintain HSCs in vitro.

Oxybipins were identified as potent selective inhibitors of oxysterol-binding protein, promoting Golgi fragmentation, inhibiting retrograde trafficking and attenuating Shiga toxin toxicity.

Signaling of IL-33 via its receptor, ST2, has been implicated in macrophage function in tissue repair. Here the authors show, using genetic mouse models and single-cell transcriptomic data, that the IL-33/ST2 axis regulates both ILC2-derived IL-13 and macrophage differentiation/reparative function required for club cell regeneration.

The clinical efficacy of standard therapy in lung cancer is limited by high level of heterogeneity. Here, the authors report patient-derived lung cancer organoids from different histological subtypes and show them to faithfully recapitulate the histology, genomics, and drug responses of the primary lung tumours.

Data from over 700,000 individuals reveal the identity of 83 sequence variants that affect human height, implicating new candidate genes and pathways as being involved in growth.

Luis Pérez-Jurado, Stephen Chanock and colleagues detect clonal chromosomal abnormalities in peripheral blood or buccal samples from individuals in the general population. They show that the frequency of such events increases with age and is associated with elevated risk of developing subsequent hematological cancers.

Plasmids carry antimicrobial resistance genes and contribute to the rapid dissemination of resistance. Here, the authors sequence 1,880 complete plasmids from 738 isolates from bloodstream infections, shedding light on the links between plasmid types, bacterial hosts and antimicrobial resistance.

Spatial profiling and single-cell RNA sequencing are used to map the spatial distribution of the microbiota within human tumours, revealing how intratumoral microbial communities contribute to tumour heterogeneity and cancer progression.

Leng et al. establish CRISPRi screens in astrocytes to dissect pathways controlling inflammatory reactivity. They uncover two distinct inflammatory reactive signatures that are inversely regulated by STAT3 and validate that these exist in human disease.

Infection with Omicron after vaccination produces cross-neutralizing antibodies to other variants of concern, whereas this induces a limited response to non-Omicron variants in unvaccinated individuals.

Manju Kurian and colleagues report heterozygous variants in KMT2B in 27 unrelated individuals with a complex progressive childhood-onset dystonia, often associated with a typical facial appearance. Their findings highlight a clinically recognizable form of dystonia and demonstrate a crucial role for KMT2B in the physiological control of voluntary movement.

Adaptation of wheat to environments where growth is limited by boron toxicity has resulted from multiple genomic changes and selection for functionally diverse alleles.

Single-cell transcriptomics and protein expression analyses of salivary glands and gingiva, along with the detection of infectious virus and virus-specific antibodies in saliva from SARS-CoV-2-infected individuals, support a potential role for the oral cavity in COVID-19 pathogenesis.

PetaKit5D offers versatile processing workflows for light sheet microscopy data including performant image input/output, geometric transformations, deconvolution and stitching. The software is efficient and scalable to petabyte-size datasets.

The inability of tyrosine kinase inhibitors to eliminate quiescent leukaemic stem cells (LSC) in chromic myeloid leukaemia (CML) results in recurrence. Here, the authors identify a reliance of CML LSCs on low P53 expression for self-renewal and therapeutically target this by combining an MDM2 inhibitor with TKI in preclinical models of CML.

In the second case in which a genetically modified pig heart was transplanted into a living person, the xenografted heart functioned well initially, but antibody-mediated rejection occurred thereafter, pointing to the need for improved strategies to avoid this complication.

A framework for metagenomic variation analysis to explore variation in the human microbiome is developed; the study describes SNPs, short indels and structural variants in 252 faecal metagenomes of 207 individuals from Europe and North America.

Pathologically altered stromas are a common contributing factor to cancer progression and fibrogenesis. This report uncovers the role of LOXL2 in the creation and maintenance of the pathological microenvironment of human cancers and fibrotic diseases and presents the development of a LOXL2-specific antibody that shows therapeutic activity in tumor as well as lung and liver fibrosis models.

How neurons and neuronal activity regulate astrocyte functions is poorly understood. Haselet al. identify two large groups of astrocytic genes that are regulated by neuronal contact and synaptic activity respectively, with distinct roles in astrocytic function; interestingly, many of these genes are dysregulated in neurodegeneration.

Advances in automation and genome sequence data will allow new protein structures to be produced faster than ever before. As the era of structural genomics unfolds, it could revolutionize drug discovery, says Alison Abbott.

The authors report data from a Phase IIa randomised, double-blind trial in patients with NASH showing that BI 1467335 strongly and dose-dependently inhibited AOC3 activity (involved in hepatic inflammation) and was well tolerated at all tested doses.

How does a fission yeast know where its ends are, so that the two poles can grow directly away from one another? New work indicates that a protein called tea1 acts as a marker, to direct the cellular growth machinery to the poles. Moreover, tea1 is localized to, and maintained at, the poles by the microtubular cytoskeleton.

The people who brought you Dolly the cloned sheep now present the sequel — Polly. Using the same technique that they used to create Dolly, scientists have produced lambs designed to produce a human protein, factor IX, in their milk. People with haemophilia B require factor IX, and the new method should allow for the production of large amounts at a low cost, and without the risks associated with purification from blood plasma.

Rps genes are used to manage the major soybean pathogen Phytophthora sojae, which causes Phytophthora stem and root rot (PRR). Here, the authors show that widely used Rps genes are no longer effective for managing PRR in the United States, Canada and Argentina.