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In this Stage 2 Registered Report, Buchanan et al. show evidence confirming the phenomenon of semantic priming across speakers of 19 diverse languages.

A survey across 90 societies reveals that variation and change in everyday norms are explained by a single value dimension: the priority societies place on individualizing versus binding moral concerns.

By using a combined computational and experimental approach, peptide exchange of 12 abundant MHC-II allotypes is shown to maintain responsiveness to HLA-DM catalysis. HLA-DM susceptibility is postulated to contribute to disease association.

Truncated version of adenylyl cyclase 3 acts as a cold-induced rheostat during long-term brown adipose tissue activation.

Analyses of genome and exome sequencing data identify rare coding and structural variants associated with atrial fibrillation and highlight genetic links between atrial fibrillation and cardiomyopathies.

A genome-wide study by the Long COVID Host Genetics Initiative identifies an association between the FOXP4 locus and long COVID, implicating altered lung function in its pathophysiology.

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.

MultiSTAAR provides a general and flexible statistical framework for functionally informed multi-trait rare variant analysis of biobank-scale sequencing studies by jointly analyzing multiple traits and incorporating annotation information.

Using data from a single time point, passenger-approximated clonal expansion rate (PACER) estimates the fitness of common driver mutations that lead to clonal haematopoiesis and identifies TCL1A activation as a mediator of clonal expansion.

SPNS2 exports S1P and FTY720-P to control immune cell migration. Here, the authors use cryo-EM, immunofluorescence, in vitro binding and in vivo S1P export, and MD simulations to uncover the mechanisms of SPNS2’s transport and inhibition.

This cross-sectional study in two independent middle-aged and aged cohorts investigates whether psychological characteristics associated with varying dementia risk aggregate into psychological profiles and relate to aging brain health.

An integrated single-cell multiomic analysis of complex karyotype acute myeloid leukemia characterizes intratumoral heterogeneity and highlights links to therapeutic sensitivities.

In the observational ZERO Childhood Cancer Precision Medicine Program PRecISion Medicine for Children with Cancer (PRISM) trial, children with high-risk cancer were treated with molecular tumor board-recommended therapies, resulting in overall clinical response rates that translated into survival benefit after long-term follow-up.

Genome editing of three SWEET gene promoters endows rice with resistance to all Xanthomonas bacterial blight strains tested.

Current approaches for live imaging of cellular actin dynamics have several drawbacks. Now the use of Lifeact, a 17-aa actin-binding peptide from yeast that is not present in higher eukaryotes, allows imaging of actin dynamics in live mammalian cells without disruption of function and without competition with endogenous binding proteins.

Members of the CHD chromatin remodeler family are implicated in human pathologies, however CHD6 remained poorly studied. Here, the authors show that CHD6 binds to and regulates autophagy and stress response genes across cell types. They identify a clinical mutation that affects its ability to recruit cofactors, leading to impaired autophagy induction and DNA repair.

Understanding the emergence, evolution, and transmission of antibiotic resistance genes (ARGs) is essential to combat antimicrobial resistance. Here, Munk et al. analyse ARGs in hundreds of sewage samples from 101 countries and describe regional patterns, diverse genetic environments of common ARGs, and ARG-specific transmission patterns.

Infant gliomas behave differently to their childhood or adult counterparts. Here, the authors perform a large-scale genetic analysis of these tumours, revealing genetic alterations which may offer therapeutic opportunities.

The Zero Childhood Cancer pediatric precision medicine program informs treatment recommendations for children with high-risk cancers through comprehensive molecular profiling

MHCII proteins bind and present both foreign and self-antigens to potentially activate CD4+ T cells via cognate T cell receptors (TCRs) during the adaptive immune response. Here, the authors combine NMR-detected H/D exchange with Markov modelling analysis to shed light on the dynamics of MHCII peptide exchange.

Local delivery of mRNA-based immunotherapy represents an option for cancer therapy. Here the authors report that intratumoral delivery of lipid nanoparticle-formulated mRNA encoding IL-21, IL-7, and 4-1BBL induces systemic anti-tumor immunity in preclinical cancer models.

Therapeutic stress induces phenotypic plasticity in glioma stem cells although the mechanisms underlying this remain poorly understood. Here, the authors show that P300 mediates the radiation-induced vascular-like conversion of glioma stem cells to promote tumor recurrence.

The goals, resources and design of the NHLBI Trans-Omics for Precision Medicine (TOPMed) programme are described, and analyses of rare variants detected in the first 53,831 samples provide insights into mutational processes and recent human evolutionary history.

The species threat abatement and restoration (STAR) metric quantifies the contributions that abating threats and restoring habitats offer towards reducing species’ extinction risk in specific places.

Reversible mitochondrial stress leading to improved mitochondrial function (mitohormesis) has been reported as an anti-aging mechanism. Here the authors report that harmol (a beta-carboline compound) induces mitohormesis in peripheral organs, alleviates aging-related phenotypes in mice, and extends lifespan in invertebrate models.

Analysis of whole-genome sequences of 25,465 individuals of European ancestry shows that rare variants contribute substantially to the heritability of height and body mass index.

Ruth Loos and colleagues report a meta-analysis of genome-wide association studies in 181,171 individuals identifying 14 new loci associated with heart rate and test these for association with cardiac conduction, rhythm disorders and cardiovascular disease. Their experimental studies in Drosophila melanogaster and zebrafish models provide support for a role for 20 candidate genes at 11 of these loci in regulation of heart rate.

Hydrous conditions extend across the 660 km discontinuity between Earth’s mantle transition zone and lower mantle, according to analysis of a polyphase mineral inclusion in a gem diamond from the Karowe mine, Botswana

A study shows that clonal haematopoiesis of indeterminate potential is associated with an increased risk of chronic liver disease specifically through the promotion of liver inflammation and injury.

STAARpipeline is a comprehensive framework for flexible and scalable rare-variant association analysis using whole-genome sequencing data and annotation information.

Most studies of the genetics of the metabolome have been done in individuals of European descent. Here, the authors integrate genomics and metabolomics in Black individuals, highlighting the value of whole genome sequencing in diverse populations and linking circulating metabolites to human disease.

Although the common genetic variants contributing to blood lipid levels have been studied, the contribution of rare variants is less understood. Here, the authors perform a rare coding and noncoding variant association study of blood lipid levels using whole genome sequencing data.

Platelet aggregation is associated with myocardial infarction and stroke. Here, the authors have conducted a whole genome sequencing association study on platelet aggregation, discovering a locus in RGS18, where enhancer assays suggest an effect on activity of haematopoeitic lineage transcription factors.

Analysis of 97,691 high-coverage human blood DNA-derived whole-genome sequences enabled simultaneous identification of germline and somatic mutations that predispose individuals to clonal expansion of haematopoietic stem cells, indicating that both inherited and acquired mutations are linked to age-related cancers and coronary heart disease.

Pooling participant-level genetic data into a single analysis can result in variance stratification, reducing statistical performance. Here, the authors develop variant-specific inflation factors to assess variance stratification and apply this to pooled individual-level data from whole genome sequencing.

The influence of X chromosome genetic variation on blood lipids and coronary heart disease (CHD) is not well understood. Here, the authors analyse X chromosome sequencing data across 65,322 multi-ancestry individuals, identifying associations of the Xq23 locus with lipid changes and reduced risk of CHD and diabetes mellitus.

The authors summarize the data produced by phase III of the Encyclopedia of DNA Elements (ENCODE) project, a resource for better understanding of the human and mouse genomes.

Early stellarator designs suffered from high particle losses, an issue that can be addressed by optimization of the coils. Here the authors measure the magnetic field lines in the Wendelstein 7-X stellarator, confirming that the complicated design of the superconducting coils has been realized successfully.

Common genetic variants associated with plasma lipids have been extensively studied for a better understanding of common diseases. Here, the authors use whole-genome sequencing of 16,324 individuals to analyze rare variant associations and to determine their monogenic and polygenic contribution to lipid traits.

Circulating lipoprotein(a) is an important risk factor for cardiovascular disease and shows variability between different ethnic groups. Here, Zekavat et al. perform whole-genome sequencing in individuals of European and African ancestries and find ancestry-specific genetic determinants for lipoprotein(a) levels.

A nanopore DNA sequencer is used for real-time genomic surveillance of the Ebola virus epidemic in the field in Guinea; the authors demonstrate that it is possible to pack a genomic surveillance laboratory in a suitcase and transport it to the field for on-site virus sequencing, generating results within 24 hours of sample collection.

MetaSTAAR enables functionally informed rare variant association analysis in biobank-scale cohorts using an efficient, sparse matrix approach for summary statistic storage.