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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.

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).

Acyclic cucurbituril-type molecular containers have been found to increase the solubility of insoluble pharmaceutical agents in water by up to 2,750-fold. In vitro and in vivo toxicology studies suggest that the containers are well tolerated, and paclitaxel solubilized in this manner efficiently kills HeLa and SK-OV-3 cancer 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.

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 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.

Soil respiration (R_S) is the flux of microbial- and plant-respired carbon dioxide from the soil surface to the atmosphere, and constitutes the second-largest terrestrial carbon flux. It has been suggested that R_S should change with climate, but this has been difficult to confirm observationally. It is shown here, however, that the air temperature anomaly (the deviation from the 1961–1990 mean) correlates significantly and positively with changes in R_S.

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.

In a large-scale analysis of ambulatory electrocardiographic recordings, a deep learning algorithm had a substantially higher sensitivity for the detection of critical arrhythmias as compared to technicians, opening a path toward artificial intelligence-assisted direct-to-physician reporting of ambulatory electrocardiography results.

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.

In this study, Aggarwal and colleagues perform prospective sequencing of SARS-CoV-2 isolates derived from asymptomatic student screening and symptomatic testing of students and staff at the University of Cambridge. They identify important factors that contributed to within university transmission and onward spread into the wider community.

The Omicron variant evades vaccine-induced neutralization but also fails to form syncytia, shows reduced replication in human lung cells and preferentially uses a TMPRSS2-independent cell entry pathway, which may contribute to enhanced replication in cells of the upper airway. Altered fusion and cell entry characteristics are linked to distinct regions of the Omicron spike protein.

Genetic and testing data from England show that the SARS-CoV-2 variant of concern B.1.1.7 has a transmission advantage over other lineages.

Analysis of HbA1c and FPG levels across 117 population-based studies demonstrates regional variation in prevalence of previously undiagnosed screen-detected diabetes using one or both measures and suggests that use of elevated FPG alone could underestimate diabetes prevalence in low- and middle-income countries.

Macrophages are pleiotropic and can have different functions and phenotypes. Here the authors show that a population of macrophages, previously described as pro-fibrotic, can be induced through Notch2 blockade and that in a mouse lung injury and fibrosis model this macrophage population does not promote inflammation or fibrosis.

Post-international travel quarantine has been widely implemented to mitigate SARS-CoV-2 transmission, but the impacts of such policies are unclear. Here, the authors used linked genomic and contact tracing data to assess the impacts of a 14-day quarantine on return to England in summer 2020.

In this study, Omry Koren, Samuli Rautava and colleagues report a sex-specific association between neonatal antibiotic exposure and weight and height gain during the first six years of life and showing that boys but not girls exposed to neonatal antibiotics exhibit impaired weight and height development.

Topoisomerases are required to release topological stress on DNA during replication and transcription. Here, Broderick et al. report genetic variants in TOP2B that cause a syndromic B cell immunodeficiency associated with reduced TOP2B function, defects in B cell development and B cell activation.

A new spatial transcriptomic approach reveals astrocyte heterogeneity across layers of the mammalian cerebral cortex. Astrocytes diversify into superficial-, mid- and deep-layer subtypes distinct from neuronal laminae, yet instructed by neuronal cues.

A study of the evolution of the SARS-CoV-2 virus in England between September 2020 and June 2021 finds that interventions capable of containing previous variants were insufficient to stop the more transmissible Alpha and Delta variants.

Genome-wide association meta-analyses identify more than 350 loci associated with atrial fibrillation. A polygenic score derived from these results improves atrial fibrillation risk prediction compared to published clinical and polygenic scores.

A study of SARS-CoV-2 variants examining their transmission, infectivity, and potential resistance to therapies provides insights into the biology of the Delta variant and its role in the global pandemic.

Examining the molecular mechanism behind neuronal genomic stability, Dobbin et al. show that the histone lysine deacetylases HDAC1 and SIRT1 are recruited to the sites of DNA double-strand breaks in neurons and demonstrate the importance of HDAC1-SIRT1 functional interactions in DNA double strand–break repairs. The authors also show that pharmacological activation of SIRT1 can stimulate HDAC1 activity and confer neuroprotection after DNA damage in cultured neurons and in two mouse models of neurodegeneration.

The spike protein of the Omicron variant of SARS-CoV-2 has a higher affinity for ACE2 than Delta, and a marked change in its antigenicity increases Omicron’s evasion of therapeutic and vaccine-elicited neutralizing antibodies.

Individuals over eighty years of age are less likely to mount a good immune response against SARS-CoV-2 (measured by neutralization titres) after the first dose of the BNT162b2 mRNA vaccine, but achieve good neutralization after the second dose.

Mfsd2a is a key regulator of blood–brain barrier (BBB) formation and function in mice: Mfsd2a is selectively expressed in BBB-containing blood vessels in the CNS; Mfsd2a^−/− mice have a leaky BBB and increased vesicular transcytosis in CNS endothelial cells; and Mfsd2a endothelial expression is regulated by pericytes to facilitate BBB integrity.

Although observations of volcanic deposits on Mars are more accessible than ever, constraining Martian eruption styles remains a challenge. Here, the authors show that volcanic eruption style can be characterized through X-ray diffraction analysis of groundmass crystallinity in basaltic volcanic deposits.

The α-oxoamine synthases (AOSes) are a class of pyridoxal 5’-phosphate-dependent enzymes that catalyse Claisen-like condensation of amino acids with an acyl-CoA thioester to generate α-aminoketones, however, their application in chemoenzymatic synthesis remains limited due to the substrate specificity. Here, the authors report the structure-guided engineering of thermostable AOS from Thermus thermophilus to expand the range of amino acids and simplify N-acetylcysteamine acyl-thioester substrates.

Transcriptomic and proteomic profiling of blood samples from individuals with COVID-19 reveals immune cell and hematopoietic progenitor cell alterations that are differentially associated with disease severity.

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

Global soil respiration is rising, probably in response to environmental changes, suggesting that climate-driven losses of soil carbon are occurring worldwide.

1000 Genomes imputation can increase the power of genome-wide association studies to detect genetic variants associated with human traits and diseases. Here, the authors develop a method to integrate and analyse low-coverage sequence data and SNP array data, and show that it improves imputation performance.

This report from the 1000 Genomes Project describes the genomes of 1,092 individuals from 14 human populations, providing a resource for common and low-frequency variant analysis in individuals from diverse populations; hundreds of rare non-coding variants at conserved sites, such as motif-disrupting changes in transcription-factor-binding sites, can be found in each individual.