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A cross-ancestry meta-analysis of genome-wide association studies identifies association signals for stroke and its subtypes at 89 (61 new) independent loci, reveals putative causal genes, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as potential drug targets, and provides cross-ancestry integrative risk prediction.

De novo design, combined with a high-throughput receptor-diversion microscopy-based screen, complementary display methods and functional assays, enabled the development of G-protein-coupled receptor-binding miniprotein agonists and antagonists targeting receptors implicated in itch, pain, cancer, metabolic disease and migraine.

Quantitative phosphoproteomics has become a standard method in molecular and cell biology. Here, the authors compare performance and parameters of phosphoproteome quantification by LFQ, SILAC, and MS²-/MS³-based TMT and introduce a TMT-adapted algorithm for calculating phosphorylation site stoichiometry.

TaxVAMB combines sequence features with taxonomic information for improved metagenome binning.

Mineralized plaque, or dental calculus, is a valuable reservoir of the ancient oral microbiome. Here, the authors use quantitative metaproteomics to analyze the dental calculus of 21 individuals from a medieval cemetery, identifying human and microbial proteins that shed light on their oral health status.

The crystal structure of a PNA duplex reveals both a right- and a left-handed helix in the unit cell. The helices are wide (28 Å), large pitched (18 bp) with the base pairs perpendicular to the helix axis, thereby demonstrating that PNA besides adapting to oligonucleotide partners also has a unique structure by itself.

Gluten-free diets are increasingly common in the general population. Here, the authors report the results of a randomised cross-over trial involving middle-aged, healthy Danish adults, showing evidence that a low-gluten diet leads to gut microbiome changes, possibly due to variations in dietary fibres.

Integrated data, including 100 human genomes from the Mesolithic, Neolithic and Early Bronze Age periods show that two major population turnovers occurred over just 1,000 years in Neolithic Denmark, resulting in dramatic changes in the genes, diet and physical appearance of the local people, as well as the landscape in which they lived.

A genome-wide association meta-analysis of individuals with clinically assessed or self-reported depression identifies 44 independent risk loci. Comparisons with other psychiatric disorders and candidate gene analyses provide new insights into major depressive disorder.

Two human JmjC-domain-containing enzymes are shown to catalyse demethylation of histone H3K27me3, a histone modification mediated by polycomb proteins and associated with stem cell maintenance and differentiation

A genome-wide-association meta-analysis of 18,381 austim spectrum disorder (ASD) cases and 27,969 controls identifies five risk loci. The authors find quantitative and qualitative polygenic heterogeneity across ASD subtypes.

FOXO transcription factors are known to promote longevity via effects on transcriptional targets. In this study, the authors identify OSER1 as an evolutionarily conserved target of FOXO. OSER1 expression improves resistance to oxidative stress, supports mitochondrial function, and extends lifespan across multiple species.

Chiral communication can propagate in secondary structures within the effective intermolecular force (IMF) range but it is not known whether long-range chiral communication exists between tertiary peptide structures. Here, the authors use single-molecule force spectroscopy to investigate chiral interaction between DNA duplexes/triplexes and peptide coiled-coils and demonstrate chiral communication beyond the IMF distance.

Ancient DNA analyses reveal that Viking Age migrations from Scandinavia resulted in differential influxes of ancestry to different parts of Europe, and the increased presence of non-local ancestry within Scandinavia.

Analyses of the proteomes of dental enamel from Homo antecessor and Homo erectus demonstrate that the Early Pleistocene H. antecessor is a close sister lineage of later Homo sapiens, Neanderthal and Denisovan populations in Eurasia.

Oxaliplatin resistance in colorectal cancers is a major clinical problem, and predictive markers are urgently needed. Here, the authors show that miR-625-3pexpression reduces the sensitivity of colorectal cancer cells to oxaliplatin by targeting the kinase MAP2K6, an activator of the MAPK14 pathway.

One of two papers in this issue that identifies enzymes capable of demethylating a tri-methyl group from Lys 9 of histone H3 — a mark required for the establishment of heterochromatin and previously considered to be stable. GASC1, a member of the JMJD2 enzyme family, can disrupt heterochromatin structure when overexpressed and may contribute to tumour development.

Peptide and oligonucleotide systems are known to self-assemble both in nature and artificial systems. Here, the authors combine both forms of self-assembly through the synthesis of peptideoligonucleotide conjugates and show formation of a three-helix structure that dimerises at higher concentrations.

Detection of circulating tumor DNA using MRD-EDGE, a machine-learning-guided single-nucleotide variant and copy-number variant detection platform for signal enrichment, enables monitoring of minimal residual disease and immunotherapy response in settings of low tumor burden.

Palaeoproteomic analysis of dental enamel from an Early Pleistocene Stephanorhinus resolves the phylogeny of Eurasian Rhinocerotidae, by enabling the reconstruction of molecular evolution beyond the limits of ancient DNA preservation.

Ancient diets have been reconstructed from archaeological pottery based on lipid remains, but these can lack specificity. Here, Hendy and colleagues analyze ancient proteins from ceramic vessels up to 8000 years old to produce a more nuanced understanding of ancient food processing and diet.

Environmental influences during prenatal development may have implications for health and disease later in life. Here, Czamara et al. assess DNA methylation in cord blood from new-born under various models including environmental and genetic effects individually and their additive or interaction effects.

Using UbiSite, an antibody-based approach that specifically detects protein lysine and N-terminal ubiquitination, Blagoev and colleagues uncover lack of correlation between changes in protein ubiquitination and abundance upon proteasome inhibition.

Analysis of a six-year time series of SDO/HMI images of the solar photosphere reveals the existence of global-scale equatorial Rossby waves in the Sun, which contain a large fraction of the radial vorticity at these scales.

A combined ancient genomic, metagenomic, and paleoproteomic analysis reveals lifestyle and dietary information of Upper Palaeolithic huntergatherers from San Teodoro cave in Sicily, Italy.

Mercury is emitted by anthropogenic activities and accumulates in the Arctic. This Review presents a mercury budget for the Arctic, describing fluxes and cycling.

Reduction in key air pollutants, especially particulate carbon, can help mitigate Arctic warming with associated benefits for global climate and human health, according to Earth system model simulations under future emissions scenarios.