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This work introduces a pedigree-derived benchmark for single-nucleotide variants, indels, structural variants and tandem repeats, offering a variant map to validate sequencing workflows or to support the development and evaluation of new variant callers.

The nucleoporin RanBP2 functions in cellular transport, mitosis and SUMO conjugation. Here, the authors determine cryo-EM structures of RanBP2 complexed with SUMO1-RanGAP1, Ubc9, Crm1, Ran and use cell and biochemical assays to probe its functions.

Genome-wide association analysis in over one million individuals of European ancestry identifies 2,103 independent genetic signals (including 113 new loci) associated with blood pressure traits.

Using pancreatic organoids and genetic mouse models, Antonucci et al. show that cellular stress activates an NRF2–EZH2 epigenetic axis leading to metabolic reprogramming and subsequent malignant transformation of KRAS-mutant benign lesions.

When learning new tasks, both humans and artificial neural networks face a trade-off between reusing prior knowledge to learn faster and avoiding the disruption of earlier learning. This study shows that people and artificial neural networks have similar patterns of transfer and interference and vary in how they balance this trade-off.

The human Polycomb-like protein PHF1 has been implicated in transcription-regulatory and DNA damage repair pathways. A new study demonstrates that the Tudor domain of PHF1 binds histone H3K36me3 with high specificity and affinity, that Tudor-H3K36me3 interaction inhibits Polycomb repressive complex 2-mediated H3K27 methylation and that PHF1 accumulates at DNA damage sites in a Tudor-dependent manner.

The low-density lipoprotein receptor family members LRP1, LRP4 and VLDLR are entry receptors for yellow fever virus.

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.

Openshaw and colleagues find myeloid inflammation and complement activation signatures in patients with long COVID who were previously hospitalized.

Global shark and ray populations have declined sharply, driven by expanding fisheries and inequitable gaps in catch, trade and distribution data. This Review assesses global status, highlights drivers of decline, and outlines the regulatory, market-based and conservation actions needed to reduce mortality and reverse shark and ray biodiversity loss.

Optical control of atomic quantum systems poses stringent requirements on modulators. Here, the authors present a piezoelectrically actuated silicon-nitride-based high-speed spatial light modulator technology meeting those needs.

Previous investigations of Floquet states in solid state samples have been mostly based on ultrafast light excitations. Here, the authors report evidence of non-equilibrium steady states in graphene under continuous-wave mid-infrared irradiation, consistent with a long-lived Floquet phase physical picture.

Efficient, large-scale genomic analysis is facilitated on the cloud by a computational tool with error-diagnosing and self-healing capabilities.

Exome sequencing and copy number analysis are used to define genomic aberrations in early sporadic pancreatic ductal adenocarcinoma; among the findings are mutations in genes involved in chromatin modification and DNA damage repair, and frequent and diverse somatic aberrations in genes known as embryonic regulators of axon guidance.

The regulatory landscape controlling Hoxd gene expression in tetrapod digit development was probably co-opted from a pre-existing cloacal regulatory mechanism, as evidenced by the effects of genetic deletion experiments in zebrafish fin, cloaca and mouse urogenital development.

The Eridania region of Mars bears various topographic and geomorphologic signatures of extensive volcanotectonic episodes and diverse volcanism that happened 3.5–4 billion years ago, indicative of vertical crustal recycling similar to Archaean Earth.

High-resolution imaging of organic 2D materials using transmission electron microscopes is challenging. Here, the authors find the optimal electron acceleration voltage, and demonstrate 1.9 Å resolution, enabling detection of interstitial defects and functional groups in 2D polymer thin films.

The authors use developmental changes in chromatin accessibility to identify thousands of enhancer elements that are active at different postnatal developmental stages in granule neurons of the cerebellum. Zic transcription factors were found to promote gene expression patterns key for neuronal maturation by binding to late-acting enhancer elements.

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.

Azacitidine (AZA) response in myelodysplastic neoplasms is unpredictable. Here, the authors show in a phase 2 trial that while global methylation changes did not differ by response, baseline and initial CpG methylation differences in HSPCs predicted AZA response.

Rydberg atoms have the potential to serve as broadband receivers but require lasers with  > 100 GHz scan ranges to observe multiple states. We bridge this major gap with an optical frequency comb for rapid preparation of over 7 Rydberg states.

Information has been encoded into the quantum wavefunctions of a two-dimensional electron gas using electronic holograms constructed from single molecules. The information is stored in two spatial dimensions and one energy dimension and is read with a scanning tunnelling microscope, to enable information densities exceeding 20 bits nm⁻².

The archaeological site Shinfa-Metema 1 in the lowlands of northwest Ethiopia provides early evidence of intensive riverine-based foraging aided by the likely adoption of the bow and arrow.

Septins are the key component of the cytoskeleton. Here, the authors show that Septin5 is assembled in microtubule-plasma membrane contact sites and mediates insulin secretion in pancreatic islet β-cells through cortical microtubule remodeling.

Velocimetry diagnostics such as photon Doppler velocimetry (PDV) are essential to the field of shock and high energy density physics. Here, the authors demonstrate a system that dramatically extends the velocity dynamic range of PDV into the regime of fusion experiments by harnessing a time lens.

Spatially resolved transcriptomic, metabolomic and proteomic analyses of human liver samples highlight the role of lipid-associated macrophages in metabolic dysfunction-associated steatotic liver disease.

Eusociality evolved independently in Hymenoptera and in termites. Here, the authors sequence genomes of the German cockroach and a drywood termite and provide insights into the evolutionary signatures of termite eusociality.

Sera from vaccinated individuals and some monoclonal antibodies show a modest reduction in neutralizing activity against the B.1.1.7 variant of SARS-CoV-2; but the E484K substitution leads to a considerable loss of neutralizing activity.

The neural processes involved in memory formation for realistic experiences remain poorly understood. Here, the authors found that ripple-like activity in the human hippocampus and neocortex tracks key moments during movie watching and predicts which events are later remembered.

Promising clinical activity of Claudin (CLDN) 18.2-directed CAR-T cell therapy in patients with gastric cancer has been recently reported, however gastrointestinal toxicities have also been described. Here the authors recapitulate the on-target off-tumor toxicity of CLDN18.2-directed CAR-T cells due to gastric mucosa damage in preclinical models, suggesting an AND-gate strategy targeting CLDN18.2 and mesothelin to overcome CAR-T cell toxicity

An automation tool has been designed that enables partitioning of an algorithm into subcircuits split across cells for biological computing. The tool was applied to a hashing algorithm requiring 110 logic gates across 66 cells.

Lipid concentration in the serum is one of the most important risk factors for coronary artery disease and can be targeted for therapeutic intervention. A genome-wide association study in >100,000 individuals of European ancestry now finds 95 significantly associated loci that also affect lipid traits in non-European populations. Among associated loci are those involved in cholesterol metabolism, known targets of cholesterol-lowering drugs and those that contribute to normal variation in lipid traits and to extreme lipid phenotypes.

The authors propose a nomenclature of SARS-CoV-2 lineages to assist research on epidemiology and decision-making during the COVID-19 pandemic. This nomenclature is based on the SARS-CoV-2 phylogeny and designed to provide a real-time bird’s-eye view of the diversity of the hundreds of thousands of genome sequences collected worldwide. The authors develop a set of rules to produce a hierarchical four-level nomenclature of labels that is flexible and dynamic.

A fresh approach to protein design that incorporates excited intermediate states enables precise control over the lifetime of protein interactions, with potential applications in cell-signalling modulation and in biosensors and synthetic circuits.

The Nr4a family of nuclear receptors has been implicated in thymocyte central tolerance via clonal deletion and regulatory T cell induction. Here the authors show, using mouse bone marrow chimeras, that Nr4a1 and Nr4a3 are also redundantly required for Bcl211/BIM induction and contribute to an anergy-like transcriptome in auto-reactive thymocytes.

PD-L2 can bind the immune checkpoint PD-1. However, its potential as a therapeutic target for immune checkpoint blockade in cancer has not been extensively explored. Here, the authors demonstrate that αPD-L2 is effective in aged, but not young, melanoma murine models.

Interlocked molecules offer a platform to control the relative motion between different molecular components with precision which is a cornerstone of synthetic nanotechnology. Here, the authors utilize a molecular dual pump to achieve the assembly of translational isomers with high efficiency and accuracy.

Early drivers of T2D include ectopic fat accumulation that impairs insulin sensitivity. Here, the authors show that GLP1/GCGR dual agonism provides multimodal benefits in obese male mice by reducing liver fat and improving insulin sensitivity resulting in endogenous β-cell recovery.

Biological nitrogen fixation may impose stronger constraints on the carbon sink in natural terrestrial biomes and represent a larger source of agricultural nitrogen than is generally considered in analyses of the global nitrogen cycle.

Genome-wide analyses identify 30 independent loci associated with obsessive–compulsive disorder, highlighting genetic overlap with other psychiatric disorders and implicating putative effector genes and cell types contributing to its etiology.

A single component built from sputtered niobium dioxide, a Mott insulator–metal transition material, can simultaneously exhibit both visible light emission and electrical threshold switching with neuron-like oscillations.

Genome-wide association analyses of prostate cancer in men from sub-Saharan Africa identify population-specific risk variants and regional differences in effect sizes. Founder effects contribute to continental differences in the genetic architecture of prostate cancer.