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Most studies of the genetics of the metabolome have been done in individuals of European descent. Here, the authors integrate genomics and metabolomics in Black individuals, highlighting the value of whole genome sequencing in diverse populations and linking circulating metabolites to human disease.

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.

Restoring mitochondrial function has emerged as a promising therapeutic strategy for diabetic retinopathy. Here, the authors show that mitochondrial hyperfusion blunts mitophagy during the disease process, and that rescuing this process pharmacologically confers retinal neuroprotection independent of an improved glycaemic status in type-1 diabetic mice.

A combination of the level and rate of human-induced warming allows estimation of remaining emission budgets to peak warming across a broad range of scenarios, suggests an analysis of emissions budgets expressed in terms of CO₂-forcing-equivalent emissions.

An investigation using various methods reports an association between adeno-associated virus 2 and paediatric hepatitis of unknown aetiology.

Conventional theories for interfacial thermal transport are derived from bulk phonon properties. Here, the authors report experimental observation of interfacial phonon modes localized at interfaces, changing how interfacial thermal transport should be understood.

Associations between of omega-3 fatty acids and mortality are not clear. Here the authors report that, based on a pooled analysis of 17 prospective cohort studies, higher blood omega-3 fatty acid levels correlate with lower risk of all-cause mortality.

In a zebrafish model of human cutaneous and acral melanomas, CRKL amplification causes tumours to favour a fin location, indicating that tumour location is determined by both the driver oncogenes and the pre-existing positional identity gene program.

Exercise has beneficial effects on metabolism and overall physiologic fitness in aged organisms. Here the authors show that MOTS-c is a mitochondrial-encoded exercise-induced peptide that regulates skeletal muscle metabolism and improves healthspan of older mice.

Thousands of recombinant antibodies enriched for specificity against defined targets are assembled in multivalent mixtures with enhanced therapeutic activity.

Low read depth sequencing of whole genomes and high read depth exomes of nearly 10,000 extensively phenotyped individuals are combined to help characterize novel sequence variants, generate a highly accurate imputation reference panel and identify novel alleles associated with lipid-related traits; in addition to describing population structure and providing functional annotation of rare and low-frequency variants the authors use the data to estimate the benefits of sequencing for association studies.

Examining drivers of the latitudinal biodiversity gradient in a global database of local tree species richness, the authors show that co-limitation by multiple environmental and anthropogenic factors causes steeper increases in richness with latitude in tropical versus temperate and boreal zones.

Due to fundamental anatomical and biochemical differences, C₃ and C₄ plant species tend to differ in their biogeography and response to climate change. Here, the authors use global observations and optimality theory to map patterns and temporal trends in C₄ species distribution and the contribution of C₄ plants to global photosynthesis.

Dimethyl fumarate (DMF) is an anti-inflammatory drug proposed as a treatment for COVID19. Here the results are reported from a randomised trial testing DMF treatment in 713 patients hospitalised with COVID-19. DMF was not associated with any improvement in day 5 outcomes.

Recent evidence has suggested that blood type may be associated with severe COVID-19. Here, the authors use data from ~14,000 individuals tested for SARS-CoV-2 at a New York City hospital, and find that certain ABO and Rh blood types are associated with infection, intubation, and death.

Age at voice-breaking is used to determine puberty timing in men, recall of which is considered less accurate than age at first menarche in women. Here, the authors perform multi-trait GWAS for male puberty timing by including both age at voice breaking and age of first facial hair for improved phenotype definition and power.

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 authors use fisheries databases and predictive models to understand past and future changes in the availability of iron, calcium omega-3 and protein from seafood. They show disproportional loss of nutrients in tropical low-income countries, which will be exacerbated by higher levels of global warming.

David van Heel and colleagues report results of a large genome-wide association study of celiac disease. Most of the associated loci contain genes with immune functions, and over half harbor risk variants that are correlated with variation in cis gene expression.

Statins are effectively used to prevent and manage cardiovascular disease, but patient response to these drugs is highly variable. Here, the authors identify two new genes associated with the response of LDL cholesterol to statins and advance our understanding of the genetic basis of drug response.

Analysis of data on species co-occurrence in the Paleobiology Database using a new machine learning algorithm reveals that mass extinctions and mass radiations are not coupled in evolutionary history.

COVID-19-related travel restrictions were imposed in China around the same time as major annual holiday migrations, with unknown combined impacts on mobility patterns. Here, the authors show that restructuring of the travel network in response to restrictions was temporary, whilst holiday-related travel increased pressure on healthcare services with lower capacity.

The relationships between people can have important consequences for the systems they depend on. Here the authors show that when coral reef fishers face commons dilemmas, the formation of cooperative communication with competitors can lead to positive gains in reef fish biomass and functional richness.

Multilevel network modelling shows that social network exposure promotes both adaptive and transformative responses to climate change among Papua New Guinean islanders. Different social–ecological network structures are associated with adaptation versus transformation.

Non-saturating relationships of biodiversity with biomass and productivity are shown in remote assemblages of coral reef fishes. These positive relationships were robust to both an extreme heatwave and invasive rats.

In 355 coastal coral reef fish species, body size changed with warming, but the direction of a species’ body size response to warming through time was generally consistent with its response to temperature changes through space, rather than generally negative.

Navigating the complex structure of the brain poses a challenge to neuroscientists. Here, the authors have trained an AI (DeepSlice) that can automatically register brain images with speed and accuracy, thus simplifying this process.

Inherent limitations on continuously measured quantum systems calls into question whether they could even in principle be used for online learning. Here, the authors experimentally demonstrate a quantum machine learning framework for inference on streaming data of arbitrary length, and provide a theory with criteria for the utility of their algorithm for inference on streaming data.

Meta-analysis of genome-wide association studies on Alzheimer’s disease and related dementias identifies new loci and enables generation of a new genetic risk score associated with the risk of future Alzheimer’s disease and dementia.

The Toll receptor superfamily has a role in innate immunity that arose early in evolution. Here the authors show that in fruit flies, Toll-6 and Toll-7 function in the CNS as receptors for the fly neurotrophins DNT1 and DNT2.

Neutrophils are increased in response to injury and infection but how they form from a common granulocyte-macrophage progenitor is unclear. Here, the authors identify a role for the transcriptional repressor ZBTB11 in zebrafish, which is regulated by master myeloid regulators and repressesTP53.

Levels of circulating thyrotropin and free thyroxine reflect thyroid function, however, their genetic underpinnings remain poorly understood. Taylor et al. take advantage of whole-genome sequence data from cohorts within the UK10K project to identify novel variants associated with these traits.

Methods that analyze intra-tumor genetic heterogeneity often do not preserve the spatial context of tumor subclones. Here, the authors present BaseScope, a mutation-specific RNA in situ hybridization assay and spatially map colorectal cancer and adenoma KRAS, BRAF and PIK3CA driver gene mutant subclones.

Population-based genome sequencing provides an increasingly rich resource for the identification of low-frequency, large effect variants associated with clinically important phenotypes. Timpson et al. use UK10K data to identify a variant of the APOC3gene strongly associated with plasma triglyceride levels.

Long-term experiments show that corals acquire dissolved inorganic nitrogen and phosphorus by feeding on symbiont cells, which provide essential nutrients enabling their success in nutrient-poor waters.

Bacterial cell shape is dependent on the formation of the extracellular sugar polymer called peptidoglycan. Here the authors describe RodA-PBP2, the enzymatic core of the elongasome, which is the complex responsible peptidoglycan synthesis, and utilize an integrated approach to investigate the mechanism of peptidoglycan biosynthesis.

A genome-wide association study of critically ill patients with COVID-19 identifies genetic signals that relate to important host antiviral defence mechanisms and mediators of inflammatory organ damage that may be targeted by repurposing drug treatments.

The X-ray crystal structure of BluB is solved. Blub is an enzyme that uses molecular oxygen to cleave a flavin mononucleotide cofactor to form 5,6-dimethylbenzimidazole, which is incorporated into vitamin B₁₂. The enzymatic destruction of one cofactor to synthesis another is quite unusual and this biochemical reaction represents the last unknown step in the biosynthesis of this vitamin.

Yardena Samuels and colleagues report the analysis of 501 melanoma exomes and the identification of RASA2 as a tumor-suppressor gene mutated in 5% of melanomas. RASA2 mutations led to increased RAS activation, and RASA2 loss was associated with shorter patient survival times.

Deeper ocean waters were anoxic during the Neoproterozoic. Geochemical data suggest a transition from sulphidic to iron-rich mid-depth waters about one billion years ago, coincident with increased iron influx from the supercontinent Rodinia.