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Jason Carroll and colleagues report that the forkhead protein FOXA1 is an important determinant of estrogen receptor binding and show that expression of FOXA1 in non–breast cancer cells is sufficient to confer estrogen receptor binding and response to endocrine treatment.

In neurons, the microtubule cytoskeleton provides support and directionality of axons. Here, the authors report that microtubule dynamics in axons may be regulated by the autophagy proteins (ATGs) independently of their known role in autophagy.

Here, the authors discover small molecules that inhibit glycosylation processes that occur in the Golgi apparatus of cells. The molecules reversibly inhibit formation of elaborate glycan structures without affecting secretion of glycoproteins.

A dataset of 16 plant traits sampled from 2,461 individual trees from 74 tropical forest sites around the world is used to show a strong link between climate and plant functional diversity and redundancy, with drier tropical forests likely being less able to respond to declines in water availability.

Gain-of-function mutations in NLRP3 result in Cryopyrin-Associated Periodic Syndrome in human patients. Here authors show that although these NLRP3 variants are constitutively active, they preserve their responsiveness to external pro-inflammatory stimuli, and they interfere with the immune-metabolic inflammatory pathways in monocytes.

NGTs glycosylate asparagine residues in proteins, crucial for bacterial adhesion and pathogenicity. Here, the authors provide insights via crystallography and simulations, showing acceptor asparagine uses imidic form for catalysis and UDP-glucose phosphate group acts as general base.

In metastatic urothelial carcinoma, it has not been established whether circulating tumor DNA (ctDNA) can replace archival primary tissue to assess mutations and biomarkers. Here, the authors show high mutation concordance between ctDNA and tumour tissue, with high consistency in serial samples.

Lipid membrane fusion is an essential function in many biological processes but little is known about membrane fusion in prokaryotes. The authors here study how haloarchaeal pleomorphic viruses (HRPVs) infect archaeal hosts. The structure-function analysis of the spike proteins shed light on prokaryotic membrane fusion.

This study reveals that population aging intensifies heat- and cold-related deaths, more so than climate change, in 50 countries. At 1.53 °C global warming, aging contributes to rising heat-related deaths, offsetting declines in cold related death.

Iron is shown to have a central role in senescence, both by triggering senescence and through its accumulation in senescent cells, which is driving the senescence-associated secretory phenotype and, in turn, promotes fibrogenesis.

Current and future climate change is expected to impact human health, both indirectly and directly, through increasing temperatures. Climate change has already had an impact and is responsible for 37% of warm-season heat-related deaths between 1991 and 2018, with increases in mortality observed globally.

Although patients with chronic kidney disease (CKD) are at high risk of developing cardiovascular disease, therapies proven to protect both the cardiovascular and renal systems are used only at low doses or not at all. Ruiz-Hurtado et al. describe available and emerging treatments that can provide adequate cardiorenal protection without adverse effects in patients with CKD.

The shape of the pinna varies widely in the general human population but the genetic basis of this variation is unknown. Here Adhikari et al. conduct a genome-wide association study in Latin Americans and discover seven gene regions influencing pinna morphology, including EDAR and TBX15.

The type III secretion system effectors NleB and SseK are glycosyltransferases (GT) that specifically glycosylate arginine residues. Here the authors provide insights into their mechanism by combining X-ray crystallography, NMR, enzyme kinetics measurements, molecular dynamics simulations and in vivo experiments and show that SseK/NleB enzymes are retaining GTs.

By examining Latin American individuals of mixed European, Native American and African ancestry, Adhikari et al. identify novel loci influencing various features of facial and scalp hair. The study also provides experimental evidence that one of the implicated genes (PRSS53) is expressed in the hair follicle and that the top associated variant alters processing of this enzyme.

The most up-to-date combination of results on the properties of the Higgs boson is reported, which indicate that its properties are consistent with the standard model predictions, within the precision achieved to date.

The CMS Collaboration reports evidence for off-shell Higgs boson contributions in the production of Z boson pairs, and measures the width of the Higgs boson, which is inversely related to its lifetime.

The CMS Collaboration reports the study of three simultaneous hard interactions between quarks and gluons in proton–proton collisions. This manifests through the concurrent production of three J/ψ mesons, which consist of a charm-quark–antiquark pair.

AM0627 is a bis-O-glycan mucinase that might work in the final steps of mucus degradation, thereby providing a carbon and nitrogen source for Akkermansia muciniphila. Here, the authors provide molecular insights into AM0627 function from X-ray crystallography and computer simulations.

Pericytes are essential for the development, maintenance and function of vascular networks. Here, Eilken and colleagues show that expression of the decoy receptor VEGFR1 by pericytes spatially restricts VEGF signalling, thus regulating VEGF-induced endothelial cell sprouting in developing tissues.

APJ is shown to be a bifunctional receptor for both mechanical stretch and the endogenous peptide apelin, a finding that is important for the development of APJ agonists to treat heart failure.

Varicocele is the most common correctable cause of male infertility, but some men with varicoceles are able to father children, even without intervention, and so the link between varicoceles and male infertility remains a matter of debate. Oxidative stress seems to be a central mechanism of testicular damage; however, no single theory to explain the differential effect of varicoceles on infertility has been suggested. In this Review, a panel of expert authors discuss the epidemiology and pathophysiology of varicocele-related infertility, and consider the optimal treatment for men with varicocele.

Defaunation is linked to the decline of tree species that depend on large animals for seed dispersal, but it is unclear if this affects carbon storage. Here the authors show that defaunation effects on carbon storage vary across continents, driven by relationships between seed dispersal strategies and adult tree size.

A consensus definition for urinary intrinsic sphincter deficiency (ISD) is lacking. As a result, studies evaluating the success of any treatment for ISD are difficult to interpret. In this Review, Shah and Gaunay examine surgical and nonsurgical treatments, and the outcomes, for type III stress urinary incontinence caused by ISD.

The glycosyltransferase C1GalT1 directs a key step in protein O-glycosylation important for the expression of the cancer-associated Tn and T antigens. Here, the authors provide molecular insights into the function of C1GalT1 by solving the crystal structure of the Drosophila enzyme-substrate complex.

Pigmentation variation in humans is influenced by complex genetic architecture in different populations. Here, the authors perform a genome-wide association analysis involving > 6,000 Latin Americans for pigmentation of skin and eyes, and identify known and novel genetic associations.

As companies compete for talent, a candidate’s attitude can matter more than their credentials.

Polypeptide GalNAc-transferase T3 catalyzes the specific glycosylation of threonine-178 of fibroblast growth factor 23, and structural insights reveal a unique lectin-based mechanism of substrate recognition.

Tamoxifen is commonly used for breast cancer therapy. This paper shows that the transcriptional repression of the ERBB2 oncogene by tamoxifen in breast cancer cells is affected by an antagonistic interaction between the transcriptional regulators PAX2 and AIB-1. This affects the ability of tamoxifen to inhibit cancer cell proliferation. The relative levels of PAX2 and AIP1 in breast cancer patients treated with tamoxifen correlates with relapse-free survival.

Humans show great diversity in facial appearance and this variation is highly heritable. Here, Andres Ruiz-Linares and colleagues examined facial features in admixed Latin Americans and identify genome-wide associations for 14 facial traits, including four gene loci (RUNX2, GLI3, DCHS2 and PAX1) influencing nose morphology.

The semiconducting ABC configuration of trilayer graphene is more challenging to grow on large scales than its semimetallic ABA counterpart. Here, an approach to trilayer growth via chemical vapor deposition is presented that utilizes substrate curvature to yield enhanced fraction and size of ABC domains.

Chronic graft versus host disease (cGvHD) is a major cause of morbidity and mortality in allogeneic bone marrow transplantation. Here the authors identify a recurrent activating mTOR mutation in expanded donor T-cell clones of 3 cGvHD patients, which suggests somatic mutations may contribute to GvHD pathogenesis and opens avenues to targeted therapies.

Promoter capture Hi-C maps in human pancreatic islets identify more than 1,300 three-dimensional regulatory hubs, linking diabetes-associated enhancers to their target genes. Genetic variation in hubs impacts insulin secretion heritability.

Kumar and colleagues report cryo-EM structures of Arabidopsis O-fucosyltransferase SPINDLY in its apo and GDP-fucose bound states, revealing distinct active-site features enabling GDP-fucose recognition and surprisingly dynamic conformations that regulate its enzymatic activity.

Polypeptide GalNAc-transferases decorate proteins with dense arrays of O-glycans, which in the case of mucins are essential for their barrier functions. Here the authors present comprehensive structural studies that shed light on the molecular attributes that allow GalNAc-T2 to efficiently carry out dense O-glycosylation.

Here, using human cells and mouse models, the authors show that Zika virus can infect preimplantation trophectoderm. Pre-implantation infection can affect nervous system development and survival of neural progenitors, and can result in miscarriage or spontaneous abortion.

Macroautophagy involves remodelling of intracellular membranes, but the role of lipids and lipid enzymes in this process is poorly understood. Here, the authors demonstrate that phospholipase D1, an enzyme that catalyses the production of phosphatidic acid, has a modulatory role in the autophagy process in mammalian cells.

In this Perspectives article, Ruilope and colleagues discuss the relevance and caveats of the SPRINT trial, with particular focus on patient cohort characteristics, the method used to measure blood-pressure levels, and applicability of the SPRINT blood-pressure targets in real-world clinical practice and future hypertension management guidelines.

Jorge Ferrer and colleagues have mapped regulatory SNP variants associated in GWAS with type 2 diabetes risk and glycemic traits to large clusters of enhancer elements regulating the transcriptional identity of pancreatic β cells via a highly connected transcription factor network.

Nanoparticle-based fluorescence imaging does not usually allow cell membrane-bound particles and intracellular particles to be distinguished from each other. Now, using functionalized silver nanoparticles as plasmonic probes, this distinction can be made following a rapid, non-toxic etching process that selectively removes the extracellular nanoparticles but leaves the intracellular nanoparticles unharmed.

Possible effects of weather conditions on COVID-19 transmission are debated. Here, the authors analyse data from early in the pandemic and show that although temperature and humidity had small effects on transmission, they were far out-weighed by the effects of non-pharmaceutical interventions.