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Visceral adiposity is a risk factor for severe COVID-19, and infection of adipose tissue by SARS-CoV-2 has been reported. Here the authors confirm that human adipose tissue is a possible site for SARS-CoV-2 infection, but the degree of adipose tissue infection and the way adipocytes respond to the virus depend on the adipose tissue depot and the viral strain.

SUMOylation is a post-translational modification that has been shown to be altered in cancer. Here, the authors show that loss of the SUMO isopeptidase SENP6 leads to unrestricted SUMOylation and genomic instability promoting lymphomagenesis and generating vulnerability to PARP inhibition.

The authors show that rare genetic variants contribute to large gene expression changes across diverse human tissues and provide an integrative method for interpretation of rare variants in individual genomes.

A plurality of epidemiological models are analyzed using physics-informed neural networks to identify time-dependent parameters and data-driven fractional models. The results are reported for different geographical locations by inferring unknown parameters and unobserved dynamics.

Dynamic nuclear polarization (DNP) greatly improves the NMR sensitivity, but its implementation in aqueous solutions is challenging. Here the authors demonstrate carbon polarization enhancement via in situ Overhauser DNP in small biomolecules in water at room temperature and high magnetic field.

The ligand-activated transcription factor farnesoid X receptor (FXR) acts as a cellular sensor for bile acids and is of interest as a drug target. Here the authors employ X-ray crystallography and NMR to characterize the molecular determinants of FXR agonists, antagonists and a partial agonist that drive FXR activation and antagonism.

Cyclic di-GMP signalling leads to lipopolysaccharide modification and reduced inflammatory response during Pseudomonas aeruginosa infection.

Cholesterol is important for axonal myelination during development. Here the authors show that cholesterol levels are reduced in a cuprizone mouse model of multiple sclerosis and that dietary cholesterol supplementation enhances remyelination and recovery.

Sestrins are conserved stress-inducible metabolic regulators implicated in the prevention of agerelated diseases. Here, Kim et al.report the crystal structure of human Sestrin2 and propose a molecular mechanism for how Sestrin2 functions to prevent ROS accumulation and inhibit mTORC1 activity.

Tyrosine sulfation strongly enhances the inhibition of thrombin by the tick-derived anticoagulants madanin-1 and chimadanin. Protein chemical synthesis and structural studies have revealed a mode of inhibition that is unprecedented among cysteine-free anticoagulant proteins. This inhibition occurs through the recognition of the highly basic exosite II of thrombin.

Polo-like kinase 1 is a key regulator of mitosis and is a candidate for drug development to treat cancer. Here, reduced expression of polo-like kinase 1 in adult mice has a minor impact on animal physiology, suggesting that polo-like kinase 1 inhibitors may be useful in the killing of tumour cells while sparing normal cells.

Antimicrobial peptides are considered promising alternatives to antibiotics. Here the authors developed a computational algorithm that starts with peptides naturally occurring in plants and optimizes this starting material to yield new variants which are highly distinct from the parent peptide.

A global dataset of the satellite-tracked movements of pelagic sharks and fishing fleets show that sharks—and, in particular, commercially important species—have limited spatial refuge from fishing effort.

Phenotypic variation and diseases are influenced by factors such as genetic variants and gene expression. Here, Barbeira et al. develop S-PrediXcan to compute PrediXcan results using summary data, and investigate the effects of gene expression variation on human phenotypes in 44 GTEx tissues and >100 phenotypes.

Inventory data from 90 lowland Amazonian forest plots and a phylogeny of 526 angiosperm genera were used to show that taxonomic and phylogenetic diversity are both predictive of wood productivity but not of biomass variation.

This study presents a model-agnostic framework that pairs deep neural operators and Bayesian experimental design for the accurate prediction of extreme events, such as rogue waves, pandemic spikes and structural ship failures.

The H-latch is a well-defined structural change occurring in PrP^C bound to the neurotoxic antibody POM1, and its presence shows a positive correlation with neurotoxicity. Inhibition of the H-latch prolongs the lifespan of prion-diseased mice.

Insect biodiversity in tropical forests is poorly understood but is probably facing declines, with serious consequences for ecosystem functions and services. This Review describes the major threats to insect biodiversity, which include the effects of a burgeoning human population and of climate change. The authors further highlight the urgent need for greater efforts to measure and monitor insect biodiversity in the tropics and discuss emerging approaches to facilitate such studies.

Reactive oxygen species (ROS) are generated by cells during viral infection. Pichlmair and colleagues demonstrate a ROS-dependent form of cell death, ‘oxeiptosis’, that resembles apoptosis but uses a pathway distinct from all previously described death pathways.

RNA editing by the adenosine deaminase ADAR1 controls cathepsin S expression in endothelial cells, a mechanism that is implicated in determining cathepsin S levels in patients with atherosclerotic vascular diseases.

Voltage-gated K⁺ channels (K_V) are involved in diverse physiological processes and offer important drug development opportunities for cancer and autoimmune diseases, as well as metabolic, neurological and cardiovascular disorders. Here, Wulff and colleagues discuss strategies to pharmacologically modulate K_V channels and highlight recent progress in developing drugs that target specific K_Vsubfamilies.

Systemic lupus erythematosus (SLE) is an autoimmune disease with a strong ethnic and gender bias. In a transancestral genetic association study, Langefeldet al. identify 24 novel regions associated with risk to lupus and propose a cumulative hits hypothesis for loci conferring risk to SLE.

The mechanism behind Trim-Away, a protein-depletion approach using E3 ligase, TRIM21 and an antibody against the target, is now clarified, allowing expansion of the toolbox.

There is an urgent need of cleaner and energy-efficient technologies for future sustainable chemicals and fuels. Here the authors report the gas phase synthesis of long hydrocarbon chains from atomic carbon and molecular hydrogen precursors in an inert carrier gas, avoiding the use of metal catalysts.

In the parathyroid gland, in thyroid C-cells and in many other tissues, the calcium-sensing receptor (CaR) plays a crucial role in calcium homeostasis. The molecular basis of several diseases resulting from abnormalities in the CaR has been characterized; this has provided the framework for the development of pharmacologic CaR activators for clinical use.

A study mapping the tree species richness in Amazonian forests shows that soil type exerts a strong effect on species richness, probably caused by the areas of these forest types. Cumulative water deficit, tree density and temperature seasonality affect species richness at a regional scale.