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FXR regulates the levels of ACE2 in tissues of the respiratory and gastrointestinal systems that are affected by COVID-19, and inhibiting FXR with ursodeoxycholic acid downregulates ACE2 and reduces susceptibility to SARS-CoV-2 infection.

Erik Ingelsson and colleagues report a large-scale genome-wide meta-analysis for associations to the extremes of anthropometric traits, including body mass index, height, waist-to-hip ratio and clinical obesity. They identify four loci newly associated with height and seven loci newly associated with clinical obesity and find overlap in the genetic structure and distribution of variants identified for these extremes of the trait distributions and for the general population.

Ruth Loos and colleagues report results of a large genome-wide association study for body mass index. They identify 18 new loci associated with this trait, some of which map near key hypothalamic regulators of energy balance.

Despite the importance of difluoromethyl (CF₂H)-bearing centres for pharmaceuticals, there is currently no general strategy for the stereoselective introduction of a CF₂H group at chiral centres. Here the authors describe an enantioconvergent difluoromethylation method for racemic alkyl halides to construct such stereocentres.

Multi-instrument detection of a nearby type 1a supernova shows that the exploding star was probably a carbon–oxygen white dwarf star in a binary system with a main-sequence companion.

In twisted 2D materials, spontaneous lattice reconstructions mean that twist angle alone provides an incomplete description. Here, using electron diffraction, the authors show that the displacement field in twisted bilayer graphene can be described as a superposition of three periodic lattice distortion (PLD) waves with wavevectors oriented at 120° from each other, forming a “torsional" PLD.

Tissue damage and turnover lead to the release of DNA in the blood and can be used to monitor changes in tissue state. Here, the authors developed a tool to accurately estimate the proportion of cell types contributing to cell-free DNA in the blood, with an application to pregnant women and ALS patients.

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.

Observations of the super-massive Neptune-sized transiting planet TOI-1853 b show a mass almost twice that of any other Neptune-sized planet known so far and a bulk density implying that heavy elements dominate its mass.

Current single cell protein expression profiling approaches come with substantial measurement noise. Here the authors discover the sources of this noise and develop a denoising algorithm that improves data quality and downstream applications.

Genome-wide association studies (GWAS) have become a key tool to discover genetic markers for complex traits; however, environmental factors that interact with genes are rarely considered. Here, the authors conduct a GWAS of obesity traits, and find that smoking may alter genetic susceptibilities.

Past genome-wide associate studies have identified hundreds of genetic loci that influence body size and shape when examined one trait at a time. Here, Jeff and colleagues develop an aggregate score of various body traits, and use meta-analysis to find new loci linked to body shape.

Cecilia Lindgren and colleagues report results of a large-scale genome-wide association study for waist-to-hip ratio, a measure of body fat distribution. They identify 13 new loci associated with this trait, several of which show stronger effects in women than in men.

Vyas et al. show that epicardial adipose tissue is a reservoir for a subpopulation of tissue-resident memory T cells that can increase the vulnerability of the heart to atrial fibrillation.

Interpretation of lipid-like densities in cryo-EM structures of membrane proteins is challenging. Here authors present LipIDens, enabling molecular dynamics analysis of protein-lipid interactions.

Davidson et al. visualize ferroptosis-like cell death using three-colour live imaging in vivo and demonstrate its role in triggering macrophage recruitment but delaying resolution of inflammation during wounding in the Drosophila embryo.

A genetic method to block immune rejection of allogeneic cells is validated in monkeys.

It is certainly possible to define the reliable prediction of individual earthquakes so narrowly that success is impossible. For instance, in Main's level 4 he refers to predictions with such precision and accuracy that a planned evacuation can take place. None of the contributors have yet to suggest that this is a possibility and I agree with Wyss that using this straw man as the standard will not lead to a useful debate. However, Main's levels 2 and 3 may lead to socially useful tools regardless of whether we call them predictions or probabilistic forecasts.

Alkylsulfonic acids represent an alternative source of sulfur for the origins of life. Here the authors demonstrate, via laboratory simulation experiments, the formation of these compounds in interstellar analog ices with implications for their incorporation into asteroids such as Ryugu.

Radio pulses from a rare, radio-loud magnetar, XTE J1810−197, are seen to have undergone a conversion in their polarization state. This change can be linked to the magnetar’s magnetic field geometry, and has commonalities with an effect also seen in fast radio bursts.

A near-field imaging approach based on nonlinear wave mixing that can provide a detailed picture of evanescent waves in real time and with a single shot is demonstrated. Using only standard optical components, this approach will make near-field imaging much more affordable and accessible.

Other routes of infection are not the dominant contributor to the African epidemic.

We integrate approximately one million aerial site measurements into regional emissions inventories for six regions in the USA, finding methane emission intensities that vary by more than a factor of ten.

Suppressed Dexter transfer is needed to achieve efficient and stable hyperfluorescence, but complex matrices must be involved. A molecular design strategy has been proposed where Dexter transfer can be substantially reduced by an encapsulated terminal emitter, leading to ‘matrix-free’ hyperfluorescence.

A genomic analysis of ductal carcinoma in situ (DCIS) samples with matched ipsilateral invasive breast cancer recurring later shows that around 18% of tumors were unrelated to the DCIS, and had distinct clonal origins.

Activating mutations of BRAF alone are inadequate to drive melanoma formation. Here the authors show that activation of Hippo signalling by oncogenic BRAF represents an additional safeguard to limit BRAF-dependent human melanocyte growth and melanoma formation.

The relative importance of the mechanisms underlying species radiation remains unclear. Here, the authors combine reference genome assembly and population genetics analyses to show that neutral forces have contributed to the radiation of the most species-rich tree genus Syzygium.

One hundred and ten Zika virus genomes from ten countries and territories involved in the Zika virus epidemic reveal rapid expansion of the epidemic within Brazil and multiple introductions to other regions.

Sequencing data from two large-scale studies show that most of the genetic variation influencing the risk of type 2 diabetes involves common alleles and is found in regions previously identified by genome-wide association studies, clarifying the genetic architecture of this disease.

To consider the impact of sex on adaptation to space, the European Space Agency initiated VIVALDI dry immersion microgravity simulation in female subjects. Here, the authors show marked deconditioning with 5-day exposure, and propose comprehensive multi-system physiological assessment in 18 healthy women.

Patricia Munroe, Joanna Howson and colleagues genotype ∼350,000 individuals and identify 30 new blood pressure– or hypertension-associated risk loci. Their analyses provide insights into the pathophysiology of hypertension and highlight new potential targets for clinical intervention.

In a 15-year whole-ecosystem, single-factor experiment, stopping experimental mercury loading results in rapid decreases in methylmercury contamination of fish populations and almost complete recovery within the timeframe of the study.

Cellular models are needed to study disease in vitro and to screen drugs for toxicity and efficacy. Here the authors develop a bioprinting approach to transfer spheroids into self-healing support hydrogels at high resolution, which enables their patterning and fusion into high-cell density microtissues of prescribed spatial organization.

Large-scale Mendelian randomization and colocalization analyses using gene expression and soluble protein data for 1,263 actionable druggable genes, which encode protein targets for approved drugs or drugs in clinical development, identify IFNAR2 and ACE2 as the most promising therapeutic targets for early management of COVID-19.

Electron-capture supernovae are thought to come from progenitors with a narrow range of masses, and thus they are rare. Here the authors present six indicators of an electron-capture supernova origin, and find that supernova 2018zd fulfils all six criteria.

The gut microbiome is causally linked to body weight in preclinical models. Here, in a controlled feeding study, the authors show that greater delivery of gut-microbiome fermentable dietary substrates to the colon leads to a net negative energy balance that is accompanied by robust microbial and host responses.

Two high-quality nanopore genome assemblies of Brassica nigra are reported, one of which has particularly high contiguity with a contig N50 of 17.1 Mb, allowing localization of active centromeres and reconstruction of the ancestral Brassica genome.

Observations of ZTF SLRN-2020, a short-lived optical outburst in the Galactic disk accompanied by bright, long-lived infrared emission, show that the resulting light curve and spectra are consistent with the signatures of a planet being engulfed by its host star.

Reduced glomerular filtration rate (eGFR) is a hallmark of chronic kidney disease. Here, Pattaro et al. conduct a meta-analysis to discover several new loci associated with variation in eGFR and find that genes associated with eGFR loci often encode proteins potentially related to kidney development.

Assembly of phased human genomes is achieved by combining long reads and long-range conformational data.

HIV infection results in the depletion of CD4⁺ T cells overtime and the loss of coordinated cellular immunity, but how this corresponds to the SIV infected African Green Monkey (AGM) model of non-progressive disease is not known. Here the authors assess the impact of experimental CD4⁺ T cell depletion in AGM and show that lack of disease progression and resistance to AIDS in this model are independent of CD4⁺ T cell loss.

Focusing on the serial differentiation of the presacral column across 1,136 extant mammal species, the authors find evidence of high within-group variation and an evolutionary trend towards increasing complexity.

A new method to quantify three masting components from individual tree-years has revealed that globally, masting is uncommon in tree species that depend on mutualist dispersers, with its distribution further mediated by climate and nutrient availability.

The functions of many putative membrane transport proteins of malaria parasites are unknown. Here, Kenthirapalan et al. use mutant strains carrying targeted gene deletions to study the functions of 35 such proteins during the life cycle of Plasmodium bergheiin mosquito and mouse hosts.

Feedback between biological and economic systems may lead to persistent poverty traps. Coupling dynamic population ecology and economic growth models reveals how to build for resilience in human health and subsistence.

A study using a mouse solid tumour model suggests that adjusting the dosing frequency of the PI3Kδ inhibitor AMG319 in the treatment of human cancers could decrease tumour growth with fewer adverse effects.