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Here the authors develop a genetic priority score to predict side effects by integrating multiple lines of genetic evidence. By applying this score, they provide evidence of known side effects and suggest ones with no clinical trial evidence.

Examination of the viral E1 hexameric helicase structure finds that a loop of each subunit becomes attached to a nucleotide and remains associated with it during the next six steps of translocation, thereby escorting a single nucleotide through the channel.

Polygenic scores for body mass index and obesity constructed using data from 5 million people with different ancestries were associated with distinct weight gain trajectories from early childhood to adulthood.

This paper quantified carbon flux between two major plant metabolisms—photorespiration and C₁ metabolism—using ¹³CO₂ labelling and isotopically non-stationary metabolic flux analysis.

The loading of the replicative helicase MCM2-7 is vital for replication fork assembly. Here, the authors reconstituted human MCM2-7 loading and identified the roles of Cdc6 in complex resolution and cancer-associated mutations in Mcm3 recruitment.

Falling raindrops play an essential but as-yet unquantified role in planetary climate change. Here the authors use the concept of precipitation efficiency to establish that raindrops play a critical role in predicting future tropical atmospheric circulation and extreme precipitation.

The bacterial defense system McrBC is a two-component motor-driven nuclease complex that cleaves foreign DNA. Here, the authors present the structures of the GTP-specific AAA + motor protein McrB and two McrBC complexes and discuss the molecular mechanism of how McrC binding stimulates McrB GTP hydrolysis.

A long-period radio transient with coincident radio and X-ray emission and observational properties unlike any known Galactic object has been observed by the Australian Square Kilometre Array Pathfinder.

Cortex morphology varies with age, cognitive function, and in neurological and psychiatric diseases. Here the authors report 160 genome-wide significant associations with thickness, surface area and volume of the total cortex and 34 cortical regions from a GWAS meta-analysis in 22,824 adults.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

MultiSTAAR provides a general and flexible statistical framework for functionally informed multi-trait rare variant analysis of biobank-scale sequencing studies by jointly analyzing multiple traits and incorporating annotation information.

Data collected from more than 2,000 taxa provide an unparalleled opportunity to quantify how extreme wildfires affect biodiversity, revealing that the largest effects on plants and animals were in areas with frequent or recent past fires and within extensively burnt areas.

Using data from a single time point, passenger-approximated clonal expansion rate (PACER) estimates the fitness of common driver mutations that lead to clonal haematopoiesis and identifies TCL1A activation as a mediator of clonal expansion.

Analyses of genome and exome sequencing data identify rare coding and structural variants associated with atrial fibrillation and highlight genetic links between atrial fibrillation and cardiomyopathies.

Wastewater surveillance could provide a means of monitoring SARS-CoV-2 prevalence that does not rely on testing individuals. Here, the authors report results from England’s national wastewater surveillance program, use it to estimate prevalence, and compare estimates with those from population-based prevalence surveys.

Streptococcus pyogenes is a deadly bacteria without a vaccine. Here, researchers measured antibodies in serum and saliva from a strep throat human challenge trial. Baseline antibodies led to variable responses and affected susceptibility to strep throat.

This study provides a nuanced understanding of the trade-offs and synergies between carbon sequestration goals and water security, and offers a data–model integrated framework to guide ecosystem restoration strategies under water resource constraints.

The influence of tectonics, continental weathering, and seafloor weathering in the geological carbon cycle remain unclear. Here, the authors develop a new carbon cycle model and, through comparison with proxy data, critically evaluate the influence of these components on carbon fluxes since 100 Ma.

How regional anatomy shapes function is not well understood. Here, the authors evaluate the performance of 40 communication models in predicting functional connectivity, and find regional heterogeneity in terms of fit and optimal model, and that regional coupling varies over the human lifespan.

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.

With the generation of large pan-cancer whole-exome and whole-genome sequencing projects, a question remains about how comparable these datasets are. Here, using The Cancer Genome Atlas samples analysed as part of the Pan-Cancer Analysis of Whole Genomes project, the authors explore the concordance of mutations called by whole exome sequencing and whole genome sequencing techniques.

Examination of the sulfur and copper contents of global cratonic peridotites combined with new high-pressure experiments shows that the migration of carbonated melts towards cratonic margins explains the co-location of magmatic metal deposits with carbonatites.

Our social lives involve interactions in many different domains, including networks of family members, friends, colleagues and online contacts. Su et al. show that networks with multiple domains of interaction tend to promote cooperative behaviour.

PELO–HBS1L and SKI complexes in the human mRNA quality control pathway exhibit a synthetic lethal interaction and may represent novel targets for the development of cancer therapies.

N-terminal acetylation dysregulation in the heart causes severe arrhythmia and cardiomyopathy. The authors show that stem cell models demonstrate ion channel trafficking defects and sarcomeric disarray as the underlying mechanisms, with gene therapy reversing both phenotypes

We have developed an automated and high-throughput, three-dimensional, vision-controlled inkjet deposition process that enables the high-resolution, contactless printing of a range of materials with varying elastic moduli to create complex structures and robots.

A genome-wide association meta-analysis study of blood lipid levels in roughly 1.6 million individuals demonstrates the gain of power attained when diverse ancestries are included to improve fine-mapping and polygenic score generation, with gains in locus discovery related to sample size.

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

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.

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

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

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.

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.

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 large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants.

Platelet aggregation is associated with myocardial infarction and stroke. Here, the authors have conducted a whole genome sequencing association study on platelet aggregation, discovering a locus in RGS18, where enhancer assays suggest an effect on activity of haematopoeitic lineage transcription factors.

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.

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.

Hyperbolic metamaterials exhibit interesting optical phenomena that could provide useful functionalities, if the losses can be reduced. Here Caldwell et al.show that hexagonal boron nitride supports hyperbolic polaritons, presenting a natural alternative to metamaterial systems.

Analysis of whole-genome sequences of 25,465 individuals of European ancestry shows that rare variants contribute substantially to the heritability of height and body mass index.

Observations of TOI-849b reveal a radius smaller than Neptune’s but a large mass of about 40 Earth masses, indicating that the planet is the remnant core of a gas giant.

Approximately 25 percent of animal feeding operations in the US are located in thirty counties, and the location of these operations is associated with heightened concentrations of fine particulate matter, according to an analysis that utilizes data on animal operations and emissions.

Using single-molecule visualization and manipulation, Chang et al. show that the eukaryotic Smc5/6 complex preferentially binds to and stabilizes ssDNA-dsDNA junctions, which could serve as the molecular basis for its diverse roles in genome maintenance.

Hurricanes and typhoons are tracking further poleward due to the effects of climate change, according to a synthesis of numerical modelling results, observations and palaeoclimate records.