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NEDD4-binding protein 1 (N4BP1) is identified as a suppressor of cytokine production that is inactivated by caspase-8, which provides insight into the mechanisms underlying the immunodeficiency caused by mutations in FADD and caspase-8.

An interim report from the GAIN/iCat2 study shows that molecular profiling of pediatric solid malignancies clarifies diagnostic classifications and provides opportunities for matched targeted therapy.

Here, the authors show that CD8⁺ T cells egress from tumors via lymphatic vessels in a CXCL12/CXCR4-dependent manner. High-affinity antigen encounter inhibits CXCR4 and increases retention, while no encounter or weak affinity directs T cell exit to limit local tumor control.

FlyWire presents a neuronal wiring diagram of the whole fly brain with annotations for cell types, classes, nerves, hemilineages and predicted neurotransmitters, with data products and an open ecosystem to facilitate exploration and browsing.

Vasek et al. demonstrate that distal processes of microglia locally translate specific mRNAs including those related to immunity and phagocytosis. They then show that local protein synthesis is necessary for microglial process-initiated phagocytosis.

STAARpipeline is a comprehensive framework for flexible and scalable rare-variant association analysis using whole-genome sequencing data and annotation information.

A paradoxical case of a well-defined diradicaloid that has an unusually large singlet–triplet energy gap (ΔE_S-T) imparted by the thiophene sulfur atom is reported. Quantum chemistry, organic synthesis, molecular spectroscopies, X-ray crystal analysis and high-temperature magnetic measurements help account for the dichotomy between the large diradical character and large ΔE_ST.

A risk score based on a 34-gene signature for outcome prediction in meningioma was developed and validated in large multi-institutional cohorts and showed better performance in discriminating postoperative menignioma outcomes compared with existing meningioma classification systems.

A new Burden of Proof meta-analytic method that accounts for between-study heterogeneity and corrects for bias between different study designs is used to interpret the strength of evidence between different pairs of risk factors and health outcomes.

A study shows that clonal haematopoiesis of indeterminate potential is associated with an increased risk of chronic liver disease specifically through the promotion of liver inflammation and injury.

The goals, resources and design of the NHLBI Trans-Omics for Precision Medicine (TOPMed) programme are described, and analyses of rare variants detected in the first 53,831 samples provide insights into mutational processes and recent human evolutionary history.

A sprayable dynamically crosslinked supramolecular polymer–nanoparticle hydrogel that robustly adheres to tissue reduces the severity of cardiac adhesions in rats and sheep.

Goel and colleagues show that CDK4/6 inhibition induces global chromatin changes mediated by AP-1 factors, which mediate key biological and clinical effects in breast cancer.

Chloroquine resistance in Plasmodium falciparum is characterized using population genomics, genetic crosses and gene editing.

COVID-19 is often characterized by a hyperinflammatory syndrome. Wang and colleagues show that low levels of IgG fucosylation enhance interactions with activating Fcγ receptors, boosting the inflammatory cytokines associated with severe COVID-19.

The ATLAS Collaboration reports the observation of the electroweak production of two jets and a Z-boson pair. This process is related to vector-boson scattering and allows the nature of electroweak symmetry breaking to be probed.

Gold-standard evidence for correlates of protection is provided by analysis of a randomized phase 3 trial of Ad26.COV2.S for protection against moderate to severe-critical COVID-19 disease.

SARS-CoV-2 variants with mutations in spike have emerged during the pandemic. Magaret et al. show that in Latin America, efficacy of the Ad26.COV2.S vaccine against moderate to severe–critical COVID-19 varied by sequence features, antibody escape scores, and neutralization impacting features of the SARS-CoV-2 variant.

Perinatal infection with Group B Streptococcus (GBS) is associated with preterm birth, neonatal sepsis, and stillbirth. Here, Korir et al. show that gene cadD, encoding a putative metal efflux transporter, is important for metal detoxification, immune evasion and bacterial proliferation in the pregnant host.

Irisin is shown to mediate beneficial effects on cognitive function associated with exercise and to improve cognitive function in mouse models of Alzheimer’s disease, probably through its direct action in the brain.

Most cases of craniofacial microsomia are sporadic but familial cases have been reported. Here the authors report that variants in FOXI3 can cause a small fraction of cases with different modes of inheritance including autosomal dominant with reduced penetrance.

Kinesins regulate intracellular transport and microtubule dynamics. Here, the authors show that KIF21B variants in humans associate with corpus callosum agenesis and microcephaly. Using mice and zebrafish, they showed the cellular mechanisms altered by the missense KIF21B variants.

A distinct class of broadly neutralizing antibodies to the influenza virus target a membrane-proximal anchor epitope of the haemagglutinin stalk domain.

Most studies of the genetics of the metabolome have been done in individuals of European descent. Here, the authors integrate genomics and metabolomics in Black individuals, highlighting the value of whole genome sequencing in diverse populations and linking circulating metabolites to human disease.

The ATLAS Collaboration reports a measurement of the ratio of the decay rates of W bosons to τ leptons and muons, in agreement with universal lepton couplings as postulated in the standard model of particle physics.

Identification of a hyperstable boronate enables automated lego-like synthesis to access a wider range of three-dimensionally complex small organic molecules rich in Csp³–C bonds. 

Pooling participant-level genetic data into a single analysis can result in variance stratification, reducing statistical performance. Here, the authors develop variant-specific inflation factors to assess variance stratification and apply this to pooled individual-level data from whole genome sequencing.

Useful materials must satisfy multiple objectives. The Pareto front expresses the trade-offs of competing objectives. This work uses a self-driving laboratory to map out the Pareto front for making highly conductive coatings at low temperatures.

DNA methylation quantitative trait locus (mQTL) analyses on 32,851 participants identify genetic variants associated with DNA methylation at 420,509 sites in blood, resulting in a database of >270,000 independent mQTLs.

Analysis of 97,691 high-coverage human blood DNA-derived whole-genome sequences enabled simultaneous identification of germline and somatic mutations that predispose individuals to clonal expansion of haematopoietic stem cells, indicating that both inherited and acquired mutations are linked to age-related cancers and coronary heart disease.

Phosphonates, compounds with a carbon–phosphorus bond, are a key component of the marine-dissolved organic phosphorus pool. Nuclear magnetic resonance spectroscopy measurements suggest that the cyanobacteria Trichodesmium is a significant source of phosphonates in nutrient-poor regions of the ocean.

Although the common genetic variants contributing to blood lipid levels have been studied, the contribution of rare variants is less understood. Here, the authors perform a rare coding and noncoding variant association study of blood lipid levels using whole genome sequencing data.

A study comparing the pattern of single-nucleotide variation between unique and duplicated regions of the human genome shows that mutation rate and interlocus gene conversion are elevated in duplicated regions.

The ATLAS experiment at the Large Hadron Collider reports a search for charged-lepton-flavour violation in decays of Z bosons into a τ lepton and an electron or muon of opposite charge.

An experiment reports the unexpected behaviour of an object in uniform motion in superfluid helium-3 above the Landau critical velocity — the limit above which it can generate excitations at no energy cost.

The influence of X chromosome genetic variation on blood lipids and coronary heart disease (CHD) is not well understood. Here, the authors analyse X chromosome sequencing data across 65,322 multi-ancestry individuals, identifying associations of the Xq23 locus with lipid changes and reduced risk of CHD and diabetes mellitus.

The researchers showcase all-crystalline and hybrid mid-infrared supermirrors with the lowest optical losses ever demonstrated in this wavelength range, representing an unprecedented improvement over any existing mirrors made with any production technology.

Scientists study the coupling, guiding and polarizing of electromagnetic waves in graphene and demonstrate a graphene-based fibre polarizer that exhibits a transverse-electric-pass polarization at an extinction ratio of up to ∼27 dB in the telecommunications band.

The in vivo efficacy of antibody-drug conjugates is enhanced by decreasing their hydrophobicity.