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Monoclonal antibodies and ligands targeting CD40 exhibit diverse agonistic and antitumor activities that are influenced by their design. Here, the authors identify mechanistic differences between clinically relevant anti-CD40 subclasses and CD40L, focusing on the dynamics and strengths of multi-bond formation at the single-molecule level.

The Tweety homologue TTYH2 is identified as the lipid transfer mediator for APOE-containing lipoproteins.

It’s poorly understood how renal manifestations develop in HEV infection in patients. Here, the authors observe glomerular accumulation of the viral protein ORF2 in complex with host IgG in immunocompromised patients with chronic or acute HEV infection who developed glomerulonephritis.

Spin-crossover compounds are molecular switches with functional high- and low-spin states. Here, the authors present an iron(III) complex that additionally also allows for continuous population of both states at low temperatures.

Multisystem inflammatory syndrome following SARS-CoV-2 infection results from increased serum levels of TGFβ, which impairs the reactivation of virus-specific T cells.

The advantage of living in cities compared with rural areas with respect to height and BMI in children and adolescents has generally become smaller globally from 1990 to 2020, except in sub-Saharan Africa.

Analyses of genomes from 914 children, adolescents, and young adults provide a comprehensive resource of genomic alterations across a spectrum of common childhood cancers.

The third variable (V3) loop on the HIV-1 Env glycoprotein is required for viral entry. Here, the authors applied DARPin technology to produce broadly neutralizing inhibitors targeting a region of V3 that becomes accessible after binding to the CD4 receptor.

This systematic review and meta-analysis examines the evidence for transdiagnostic cognitive behavioural psychotherapy for the treatment of emotional disorders.

This Resource describes data, code and tools developed for the Human Reference Atlas and the Human BioMolecular Atlas Program for building and navigating a multiscale human atlas.

Plants immune responses are triggered upon perception of volatile monoterpenes. Here, Wenig et al. show that a feed-forward loop featuring LEGUME LECTIN-LIKE PROTEIN1 propagates monoterpene-associated cues both within and between plants, illustrating how systemic immunity could act at a population level.

Lifespan can be affected by both physiological ageing and specific sets of pathologies associated with old age. Here the authors report a resource of large-scale cross-sectional phenotyping of aging male mice at different time points to analyse a large set of phenotypes and molecular markers, including during genetic and diet interventions affecting lifespan.

Steve Brown and colleagues report an analysis of 20 phenotyping tests, including 413 data parameters, across 449 mutant mouse alleles. They identify widespread pleiotropy and assign putative functions to genes that lacked previous phenotypic annotation.

Large oil spills have negative effects on marine ecosystems, but the effects of chronic smallscale spills are less well understood. Here, Brussaard et al. detect high bioavailability and toxicity of small-scale crude oil spills within 24 hours after release, which are associated with localised declines in marine plankton.

The 2S–2P transitions in muonic helium-4 ions are measured using laser spectroscopy and used to obtain an α-particle charge-radius value five times more precise than that from electron scattering.

A candidate vaccine against SARS-CoV-2 that uses the yellow fever 17D live-virus vector is highly efficacious and displays a favourable safety profile in Syrian hamster, mouse and cynomolgus macaque models.

The genetic basis of metabolic diseases is incompletely understood. Here, by high-throughput phenotyping of 2,016 knockout mouse strains, Rozman and colleagues identify candidate metabolic genes, many of which are associated with unexplored regulatory gene networks and metabolic traits in human GWAS.

Dietary restriction can extend the life of various model organisms. Here, Xie et al. show that intermittent periods of fasting achieved through every-other-day feeding protect mice against neoplastic disease but do not broadly delay organismal aging in animals.

The nasal commensal bacterium Staphylococcus lugdunensis produces a novel cyclic peptide antibiotic, lugdunin, that inhibits colonization by S. aureus in animal models and is associated with a significantly reduced S. aureus carriage rate in humans, suggesting that human commensal bacteria could be a valuable resource for the discovery of new antibiotics.

Lipid nanoparticles, viruses, exosomes and liposomes are characterized by analysis of fluorescence fluctuations.

Systemic dissection of sexually dimorphic phenotypes in mice is lacking. Here, Karp and the International Mouse Phenotype Consortium show that approximately 10% of qualitative traits and 56% of quantitative traits in mice as measured in laboratory setting are sexually dimorphic.

The full extent of the genetic basis for hearing impairment is unknown. Here, as part of the International Mouse Phenotyping Consortium, the authors perform a hearing loss screen in 3006 mouse knockout strains and identify 52 new candidate genes for genetic hearing loss.

Tharyan et al. identify NFYB-1 as a regulator of mitochondrial function that represses lysosomal prosaposin. The NFYB-1–prosaposin signalling axis coordinates lysosomal-to-mitochondria signalling via cardiolipin to enhance cellular mitochondrial function and longevity in C. elegans.

Sarah von Spiczak, Holger Lerche and colleagues identify mutations in GRIN2A that cause idiopathic focal epilepsy with rolandic spikes.

The chemokines CCL5 and CXCL4 promote monocyte recruitment to atherosclerotic plaques. Recent findings in vitro have shown that heteromerization of CCL5 and CXCL4 increases their potency in stimulating monocyte adhesion and chemotaxis. Koenen et al. now show that this heteromerization has functional consequences in vivo. Treatment of atherosclerotic mice with a cyclic peptide that specifically disrupts the CCL5-CXCL4 interaction inhibited monocyte recruitment to atherosclerotic plaques. Moreover, selective inhibition of heteromer formation may offer therapeutic advantages compared to complete blockade of chemokine function.

An overview of the nature and timescales of stratospheric ozone recovery and the extent to which it can currently be detected.