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Pol ι forms Hoogsteen base pairs with the incoming nucleotide. Here, the authors use time-lapse X-ray crystallography to show that Hoogsten base pairing is maintained within the pol ι active site throughout the nucleotide incorporation reaction.

While immune dysregulation is acknowledged as causal for multiple sclerosis (MS), how monocytes contribute to MS etiology is still unclear. Here the authors analyze peripheral blood and cerebrospinal fluid samples as well as brain MRI image data from MS patients to implicate FABP7 in alteration of monocyte glycolysis, and as a potential marker for MS progression.

Intense squeezed light with focusable intensities of 0.1 TW cm⁻² is created by propagating a classical, intense and noisy input beam through an optical fibre. The noise 4 dB below the shot-noise level is achieved by selecting a set of wavelengths whose intensity fluctuations are maximally anticorrelated.

Untrustworthy sources or detectors mean that quantum entanglement cannot always be ensured, but quantum steering inequalities can verify its presence. Using a highly efficient system, Smithet al. are able to close the detection loophole and clearly demonstrate steering between two parties.

Observations from the Lucy spacecraft of the small main-belt asteroid (152830) Dinkinesh reveals unexpected complexity, with a longitudinal trough and equatorial ridge, as well as the discovery of the first contact binary satellite.

Proximity ferroelectricity is reported in wurtzite heterostructures, which enables polarization reversal in wurtzites without the chemical or structural disorder that accompanies elemental substitution.

The most parsimonious network of routes taken by the first people navigating Sahul emerge from landscape-based rules, which can also be applied to other peopling events, to quantify the likely patterns of the peopling of Earth.

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.

Ecological transitions, like shifts between habitats, can shape genomic variation. By analyzing genomes from 66 sea catfish species, this study finds that younger freshwater lineages show more positive selection and body shape disparity, with prolactin gene adaptations likely aiding their colonization and radiation.

An integrated device that combines optical parametric oscillation and electro-optic modulation in lithium niobate creates a flat-top frequency-comb-like output with low power requirements.

Targeted proteomics enables robust hypothesis-driven research. Here, Yu et al. present a multiplexed approach for targeted pathway proteomics and apply it to quantify protein families across 480 fully genotyped Diversity Outbred mice, revealing impacts of genetic variation on protein expression and lipid metabolism.

The authors build recombination maps of marine, freshwater and hybrid sticklebacks at a scale of 3.8 kb, examining differences in recombination rates and evolutionary implications in populations undergoing adaptive divergence. They find evidence of recombination suppression in hybrids and reduced fitness of recombinants in a natural hybrid zone.

Here the authors provide evidence that 3D chromatin structure in the mouse brain differs between males and females and undergoes dynamic remodelling during the female ovarian cycle. They show female-specific 3D genome dynamics affects neuronal gene expression and brain disorder-relevant genes, and could play a role in reproductive hormone-induced brain plasticity and female-specific risk for brain disorders.

Wu, Harrison and colleagues visualize lactate production at subcellular resolution in migrating endothelial cells and identify hotspots of glycolytic activity, mediated by RhoA and the glucose transporter SLC2A3, that couple cellular energy metabolism with cytoskeleton remodelling and cell motility.

Myosin-binding protein C (MyBP-C) resides and interacts with the myosin filaments in striated muscle and regulates contraction via an unclear mechanism. Here, the authors demonstrate that MyBP-C regulates the performance of myosin heads.

Timothy Frayling, Joel Hirschhorn, Peter Visscher and colleagues report a meta-analysis of genome-wide association studies for adult height in 253,288 individuals. They identify 697 variants in 423 loci significantly associated with adult height and find that these variants cluster in pathways involved in growth and together explain one-fifth of the heritability for this trait.

The clinical detection of fluorescent protoporphyrin IX during glioma-resection surgery can be improved via a microscope that pairs stimulated Raman histology and two-photon excitation fluorescence microscopy.

Hicks et al. report that human regenerating myofibres expressing ACTC1 substantially contribute to supporting PAX7⁺ skeletal muscle progenitor cells.

Integrating functional data with GWAS loci can help interpret the function of genetic variants associated with disease. Here the authors map cis and trans methylation QTL in CD4 + T cells from patients and colocalize with GWAS loci in order to interpret genetic variants associated with multiple sclerosis.

A citywide experiment tested the effects of three high-pay-off, geo-targeted lotteries to motivate adults to get a COVID-19 vaccine. Zip-code-targeted lotteries in which residents were given 50–100× boosts in their chances of a win did not result in higher vaccine uptake.

Schief and colleagues show that germline-targeting epitope scaffolds can elicit responses from rare broadly neutralizing antibody precursor B cells with predefined binding specificities and genetic features.

Here, in a follow-up of a clinical study, the authors show that protein pacing and intermittent fasting improves gut symptomatology and microbial diversity, as well as reduces visceral fat compared to a heart-healthy, calorie-restricted diet matched for overall energy intake and expenditure in free-living humans.

SIVmac239 infection of macaques is a favored model of human HIV infection, but antibody-mediated protection for SIVmac239 is insufficiently understood. Here, Zhao and Berndsen et al isolated nAbs and confirmed protection against SIVmac239 infection in passive transfer studies in macaques. The nAb was used to provide the first high-resolution structure of a rhesus SIV trimer by CryoEM. Analysis of the glycosylation pattern of this SIV trimer suggests a denser glycan shield on Env for rhesus SIV compared to chimpanzee SIV or HIV-1, which partially explains the poor nAb response of rhesus macaques to SIVmac239 infection.

Deconvolution algorithms facilitate studying cell type-specific changes using bulk data from complex tissues. Here, the authors present a deconvolution method that predicts DNA methylation levels in 12 leukocyte subtypes using human microarray data and apply it to various examples.

Streptomyces are discovered to produce antibacterial protein complexes that selectively inhibit the hyphal growth of related species, a function distinct from that of the small-molecule antibiotics they are known for.

Antibody based biologics are a rapidly growing class of therapeutics with interest to enhance their performance, distribution, longevity and effectivity. Here, authors report the engineering of human IgG Fc to enhance plasma half-life, mucosal distribution and killing of cancer cells and bacteria.

Disambiguating abbreviations is important for automated clinical note processing; however, deploying machine learning for this task is restricted by lack of good training data. Here, the authors show novel data augmentation methods that use biomedical ontologies to improve abbreviation disambiguation in many datasets.

This overview of the ENCODE project outlines the data accumulated so far, revealing that 80% of the human genome now has at least one biochemical function assigned to it; the newly identified functional elements should aid the interpretation of results of genome-wide association studies, as many correspond to sites of association with human disease.

Diet affects the human gut microbiome, but studies linking crop genetics to seed traits that influence the human gut microbiome are lacking. Here, the authors develop an in vitro microbiome screening method and reveal the association between sorghum genes regulating condensed tannin biosynthesis and human gut microbiome.

HIV-1 vaccine design aims to induce broadly neutralizing antibodies such as IOMA, the only described antibody in its class. Here, the authors present the isolation, characterisation and structure of three additional antibodies within the IOMA class

Proton migration in the acetylene cation is commonly used as a model to study isomerisation dynamics. Here, the authors use X-ray pump-probe experiments to study this process, and show that isomerization occurs significantly faster than expected—within the first 12 femtoseconds following core ionization.

An analysis of human chromosome 15 — which is altered in Prader-Willi and Angelman syndromes — reveals that it resembles a hall of mirrors, as it contains a number of sequence duplications throughout its length. The evolutionary events that may have led to the high number of duplications was also reconstructed.

A database and viewer is described, resulting from the assessment of the carbon stock of over 9 billion individual trees in semi-arid sub-Saharan Africa using field data, machine learning, satellite data and high-performance computing.

The Galactic Centre is orbited by two objects that look like gas and dust clouds but behave more like stars, and now four additional similar objects are reported.

Advances in omics provide a tool to understand mechanisms for plant–microbial interactions under stress. Here the authors apply genome-resolved metagenomics to investigate sorghum and its microbiome responses to drought, identifying an unexpected role of iron metabolism.

The Gaia spacecraft will soon launch on a mission to chart the heavens in unprecedented detail.

Squeezed light allows for quantum-enhanced, sub-shot-noise sensing, but its generation and use on a chip has so far remained elusive. Here, the authors fill this gap by demonstrating a thin-film lithium-niobate-based integrated quantum optical sensor, which beats shot-noise-limited SNR by ~ 4%.

A human–SARS-CoV-2 protein interaction map highlights cellular processes that are hijacked by the virus and that can be targeted by existing drugs, including inhibitors of mRNA translation and predicted regulators of the sigma receptors.

Mammalian oocytes divide asymmetrically during meiotic maturation. Here, the authors show that spindle movement away from oocyte center depends on actin filaments nucleated from the spindle periphery pushing against surrounding mitochondria, which polarizes spontaneously to produce directional spindle motion.

The molecular mechanisms underlying the dynamic nature of the female brain structure and function remain poorly understood. Here the authors characterise chromatin organization in the mouse female ventral hippocampus, finding it fluctuates with the oestrous cycle, and identify changes in chromatin organization associated with the transcription of genes important for neuronal function and behaviour.

Glucocorticoids, such as dexamethasone, are used as anti-inflammatory and immunosuppressive drugs, however patients may exhibit resistance or side effects. Here the authors propose that a dexamethasone related neutrophil-specific DNA methylation index can be used as a marker of glucocorticoid exposure and response and as a prognostic factor in brain tumor survival.

The development of native-like envelope trimers has been a major focus in the efforts to produce HIV vaccines. Here the authors demonstrate the production and characterization of virus-like nanoparticles displaying trimeric HIV-1 antigens with the potential to elicit broadly neutralizing antibodies.

A major goal of HIV-1 vaccine development is to produce antigens that can induce broadly neutralizing antibodies. Here the authors examine the underlying causes of HIV-1 envelope metastability and design uncleaved, prefusion-optimized gp140 trimers with potential for use as HIV-1 vaccine antigens.

Little is known about the recent evolution of the Y chromosome because only the human Y chromosome has been fully sequenced. The sequencing of the male-specific region of the Y chromosome (MSY) in the chimpanzee and comparison between the MSYs of the two species now reveals that they differ radically in sequence structure and gene content, indicating rapid evolution over the past 6 million years.

A proposal for a simple, unified model in which a single mechanism — passive gene loss — enabled whole-genome duplication and led to the rapid emergence of new yeast species.

Niarchou et al. identify 69 genomic loci associated with people’s synchronization to a musical beat. The genetic architecture of beat synchronization was enriched for genes involved in early brain development and lifelong brain function.