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Endometrial cancer is the most common invasive gynaecological cancer in developed countries. Here a meta-analysis identifies an additional nine novel endometrial cancer risk loci and eQTL analysis reveals risk variants associate with reduced expression of negative regulators of oncogenic signal transduction proteins.

A comparison of alpha diversity (number of plant species) and dark diversity (species that are currently absent from a site despite being ecologically suitable) demonstrates the negative effects of regional-scale anthropogenic activity on plant diversity.

In vivo and in silico analyses suggest that bradyzoite-directed immunity contributes to control of cyst numbers, tissue damage and mortality in mice.

The Kemp elimination has been catalysed in the cavity of a coordination cage with a rate enhancement (k_cat/k_uncat) of 200,000 at pD 8.5. The catalysis requires two orthogonal interactions to bring together the components: hydrophobic binding of benzisoxazole, and accumulation of hydroxide ions at the cationic cage surface by ion-pairing.

The transmission of chemical information across lipid bilayer membranes is crucial in biological systems. Now, an artificial chemical system able to both transduce and amplify chemical signals across a membrane has been developed. The system works by exploiting the controlled translocation of a synthetic molecule that is embedded within a vesicle membrane.

The synthesis of interlocked compounds such as catenanes and rotaxanes has undergone much development in recent years, but molecular knots are still relatively hard to make. It has now been shown that a linear bipyridine oligomer can fold around a single zinc-ion template to form a complex that can be cyclized to give a molecular trefoil knot.

Singlet molecular oxygen, produced by indoleamine 2,3-dioxygenase 1 activity, gives rise to a signalling molecule that regulates arterial relaxation under inflammatory conditions.

IL-35 is an immunomodulatory cytokine, but the molecular details of its effects have remained obscure. Vignali and colleagues determine the IL-35 receptor and how its signaling pathway leads to its suppressive action.

Multiancestry genome-wide association analyses identify new risk loci for stroke and stroke subtypes. Fine mapping and bioinformatics analyses of these risk loci point to mechanisms not previously implicated in stroke pathophysiology.

A multi-ancestry genome-wide association study for age at menarche followed by fine mapping and downstream analysis implicates 665 pubertal timing genes, such as the G-protein-coupled receptor 83 (GPR83) and other genes expressed in the ovaries involved in the DNA damage response.

Reduced glomerular filtration rate (eGFR) is a hallmark of chronic kidney disease. Here, Pattaro et al. conduct a meta-analysis to discover several new loci associated with variation in eGFR and find that genes associated with eGFR loci often encode proteins potentially related to kidney development.

Giardia intestinalis is a protozoan parasite that can cause severe enteric disease. The immune response to this organism provides unexpected benefits to limit gut inflammation.

A multi-ancestry genome-wide association study meta-analysis, combined with transcriptome- and methylome-wide association analyses, identifies risk loci associated with colorectal cancer. Credible effector genes and their target tissues are also highlighted, showing that over a third probably act outside the colonic mucosa.

Production of reactive oxygen species is an ancient antimicrobial mechanism, but its role in antiviral defense in mammals is unclear. Here, To et al. show that virus infection activates endosomal NOX2 oxidase and restricts TLR7 signaling, and that an endosomal NOX2 inhibitor decreases viral pathogenicity.

Repeat expansion disorders are found in all major global populations, and their frequency is up to three times higher than typically quoted, suggesting underdiagnosis or incomplete penetrance.

A transcriptome-wide association study identifies associations of genetically predicted gene expression with breast cancer risk. This analysis finds 48 candidate genes implicated in breast cancer susceptibility, including 14 at novel loci.

Chronic infection with SARS-CoV-2 leads to the emergence of viral variants that show reduced susceptibility to neutralizing antibodies in an immunosuppressed individual treated with convalescent plasma.

Whole-genome sequencing and phenotype data sharing are introduced in a national health system to streamline diagnosis and to discover coding and non-coding variants that cause rare diseases.

The Last Glacial Maximum (LGM) represents the most severe climatic event since modern humans arrived in Europe and it is likely that it has changed their morphology. Here, Brewster et al. examine human cranial morphology from before and after the LGM and show significant differences across periods.

Highly pathogenic avian influenza viruses from H5 clade 2.3.4.4b are circulating widely in birds and have recently caused large outbreaks in mammals. Here, Furey et al. develop a clade 2.3.4.4b HA-expressing mRNA-LNP vaccine and show that it elicits strong protective immune responses in mice and ferrets.

Global megafaunal extinctions took place in the late Quaternary, yet the relative impact of climate and humans in the faunal collapse is unclear. Here, the authors show that megafaunal extinctions in Australia were independent of climate variability and took place approximately 13,500 years after human arrival.

Encoding recognition units into sequence-defined synthetic oligomers enables hybridization into unique assemblies in non-aqueous solutions. In this Review Article, we explore the chemistries that enable production of sequence-selective, duplex-forming oligomers through noncovalent or dynamic covalent bonds.

Association analyses in over 1 million individuals identify 535 new loci influencing blood pressure traits. The results provide new insights into blood pressure regulation and highlight shared genetic architecture between blood pressure and lifestyle exposures.

Mitochondria are able to maintain two competing metabolic pathways—oxidative phosphorylation and the reductive synthesis of proline and ornithine—by generating two mitochondrial subpopulations that are enriched in either pyrroline-5-carboxylate synthase or ATP synthase.

Dimethyl fumarate (DMF) is an anti-inflammatory drug proposed as a treatment for COVID19. Here the results are reported from a randomised trial testing DMF treatment in 713 patients hospitalised with COVID-19. DMF was not associated with any improvement in day 5 outcomes.

Samples of different body regions from hundreds of human donors are used to study how genetic variation influences gene expression levels in 44 disease-relevant tissues.

The Somatic Mosaicism across Human Tissues Network aims to create a reference catalogue of somatic mosaicism across different tissues and cells within individuals.

Breast cancer risk for BRCA1/BRCA2 mutation carriers varies depending on other genetic factors. Here, the authors perform a case-only genome-wide association study and highlight novel loci associated with breast cancer risk for BRCA1/BRCA2 mutation carriers.

Previous studies have shown that both rare pathogenic mutations and common genetic variants contribute to the familial risk of developing colorectal cancer. Here, the authors carry out a two-stage genome-wide association study and identify six new loci associated with colorectal cancer.

It is unclear how often genetic mosaicism of chromosome X arises. Here, the authors examine women with cancer and cancer-free controls and show that X chromosome mosaicism occurs more frequently than on autosomes, especially on the inactive X chromosome, but is not linked to non-haematologic cancer risk

Herbert and colleagues show MrgprA3⁺ neurons activate myeloid cells to promote cutaneous IL-17-dependent immunity against Schistosoma mansoni.

Analysis of snRNA genes in individuals with rare disorders identifies de novo and recurrent variants in RNU5B-1 and RNU5A-1, in addition to previously unreported cases with pathogenic or likely pathogenic variants in RNU4-2.

Waste production is a basic output of human society, and its scale and logistics challenge cities and our Earth system. This study identifies universal patterns by which wastewater, municipal solid waste, and greenhouse gas waste scale across urban systems worldwide.