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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.

Typically, quantitative trait loci studies find genetic variants associated with the total quantity of a quantitative trait, but other measures, such as variance, can detect different biology. Here, the authors map variance quantitative trait loci for blood cell traits, finding associations with gene-by-environment interactions and genetically-predicted alcohol use.

Green hydrogen production via water electrolysis requires a low-cost solution to provide efficient catalysts. Here, the authors report an industrially scalable method for synthesizing NiFe layered double hydroxide at room temperature and atmospheric pressure, enhancing alkaline electrolysis.

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).

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.

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.

Seawater is the most abundant water source for hydrogen fuel production. Here the authors report a binary photoelectrode of Pt catalyst-GaN semiconductor with promising efficiency, productivity, and stability for seawater hydrogen evolution.

Biohybrid microrobots consisting of nanoparticle-modified microalgae are constructed for active drug delivery in the lungs. In an acute bacterial pneumonia model, the microrobots effectively reduce bacterial burden and lessen animal mortality.

Type 2 inflammation drives the formation of pathologic mucus in patients with asthma. Here, authors reveal a role for intelectin-1 in IL-13-induced mucus properties, and that an ITLN1 eQTL is associated with protection from the formation of mucus plugs in T2-high asthma.

Mucin glycoproteins are biologically relevant but are challenging to study. Here, the authors characterized the SmE enzyme and used it to glycoproteomic ally map immune checkpoint proteins. This information then drove MD simulations and binding assays to understand how glycosylation controls structure and function.

Blood plasma protein data was combined with machine learning models for a simple method to determine differences in organ-specific aging; the study provides a basis for the prediction of diseases and aging effects using plasma proteomics.

A screening approach finds VH-domain antibodies that bind the SARS-CoV-2 Spike protein receptor-binding domain at its interface with host ACE2. Bi-paratopic and multivalent binders have high affinity and potency.

The understanding of altered lipid metabolism by isocitrate dehydrogenase 1 (IDH1) mutations in gliomas at a compartment-specific level is limited. Here, the authors use Raman spectroscopy to monitor organelle-specific metabolic changes and report that IDH1 mutations induce phospholipid imbalances which lead to ER and Golgi dilation.

The antibody response to COVID-19 vaccines varies among individuals. Here the authors find that older age, male sex, smoking, higher BMI, vaccine type, and certain comorbidities are associated with lower anti-S1 antibody levels after COVID-19 vaccinations, indicating that certain groups might benefit from higher frequency or doses of vaccination.

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.

Cell free DNA fragmentation is a promising biomarker for disease, but its epigenetic regulation is incompletely understood. Here, the authors investigated the effects of DNA methylation in the production of cfDNA fragmentation, and corelate these changes with gene expression in human cancer.

Protein S1, a subunit of the Qß phage RNA-directed RNA polymerase, was thought to only initiate copying of the phage RNA plus strand. Here, the authors show that S1 stimulates replication of any cognate template by promoting release of the newly synthesized product strand.

Circulating cell-free DNA (cfDNA) assays for monitoring individuals with cancer typically use tumor-specific mutations that may not be detected in many patients. Here, the authors develop a tumor-independent and mutation-independent approach (DELFI-TF) to estimate tumor burden in cfDNA for treatment response monitoring and clinical outcome prediction.

Fetal development plays an important role in defining adult diabetes risk. Here, authors identified a genetic link between fetal pancreatic gene expression, obesity, and diabetes risk through eQTL mapping of iPSC-derived pancreatic progenitor cells.

Restoration of coronary blood flow after a heart attack may lead to reperfusion injury and pathologic iron deposition. Here, the authors perform magnetic susceptibility imaging showing its association with iron in a large animal model of myocardial infarction during wound healing, and showing feasibility in acute myocardial infarction patients undergoing percutaneous coronary intervention.

In a C. elegans model of defective leucine catabolism, Lee et al. analyse how the complex interplay between host and bacteria rewires metabolism to enable host survival.

Nasally delivered live attenuated influenza vaccines (LAIV) have been shown to be effective in vaccine trials yet immune responses are mostly measured in blood. Here the authors report a clinical trial in young adults and measure immune responses in the mucosa and blood to identify compartmentalised responses.

A cross-ancestry meta-analysis of genome-wide association studies identifies association signals for stroke and its subtypes at 89 (61 new) independent loci, reveals putative causal genes, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as potential drug targets, and provides cross-ancestry integrative risk prediction.

Programmed death-ligand 1 (PD-L1) is involved in the inhibition of antigen specific T cells via ligation of programmed death 1 (PD-1). Here, the authors show checkpoint inhibition by use of small molecule inhibition of PD-L1 which in a humanised mouse model was shown to restore T cell responses and reduced tumour burden.

Somatic mutations are identified from circulating cell-free DNA using a single-molecule-based lowpass whole-genome sequencing method. The regional distribution of mutations can identify a tumor-specific mutational profile in patients with cancer and can be used to monitor patients through treatment.

Proprioception: is the sensory system that supports body posture and movement also the root of our understanding of physical laws?

The streptococcal M1 protein can cause vascular leakage and tissue injury and these pathologies are dependent on its interaction with host fibrinogen and subsequent activation of neutrophils. This study presents the structural basis for this process.

Global metal ore extraction has increased almost fourfold since 1970. This Review explores the drivers, patterns and environmental consequences of the growth of metal ore extraction and discusses interventions to reduce negative impacts across metal supply chains.

Severe sepsis has a high mortality rate. Here, the authors provide genomic, transcriptomic, proteomic and metabolomic data across four sepsis-causing pathogens and identify a signature of global increase in fatty acid and lipid biosynthesis as well as cholesterol acquisition.

Coupling cure interventions with ART during early HIV infection may accelerate virus clearance and enhance T cell responses, supporting tailoring of monoclonal antibodies to sensitive viruses to improve their effects.

Studies in the chick, mouse, zebrafish and other vertebrate model systems are beginning to uncover the complexities of skeletal muscle development. Distinct sets of precursor cells and various different gene regulatory networks are responsible for the spatial and temporal heterogeneity of the process.

Sponges are early-diverging marine organisms that establish complex symbioses with microorganisms. Here, Thomas et al.analyse the microbial communities associated with 81 species of sponges from around the world, shedding light on the ecological and evolutionary drivers of these host-microbe associations.

Here, the authors show that SARS-CoV-2 infection causes gut microbiome dysbiosis and gut epithelial cell alterations in a mouse model, and correlate dysbiosis observed in COVID-19 patients with blood stream infections, matching reads of bacterial sequences from stool samples to organisms found in the blood.

Early stellarator designs suffered from high particle losses, an issue that can be addressed by optimization of the coils. Here the authors measure the magnetic field lines in the Wendelstein 7-X stellarator, confirming that the complicated design of the superconducting coils has been realized successfully.

The burden of mosaic chromosomal alterations in blood-derived DNA, a type of clonal hematopoiesis, is associated with an increased risk for diverse types of infections, including sepsis and pneumonia.

The BRAIN Initiative Cell Census Network has constructed a multimodal cell census and atlas of the mammalian primary motor cortex in a landmark effort towards understanding brain cell-type diversity, neural circuit organization and brain function.