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Grankvist et al. combine global isotopic tracing and metabolic flux modelling to characterize metabolic networks in human intact liver tissue.

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).

Amino acids possess a new and broad colloidal property: they stabilize patchy nanoscale colloids, such as proteins, by adsorbing onto their surfaces through weak interactions.

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.

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.

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.

A transancestral exome-wide association study for body-fat distribution identifies protein-coding variants that are significantly associated with waist-to-hip ratio adjusted for body mass index.

In this study, the authors describe SANA, a nitroalkene derivative of salicylate, as a potential activator of creatine-dependent energy expenditure and thermogenesis in adipose tissue. Preclinical and clinical data from this paper also suggest that SANA improves glucose homeostasis and promotes weight loss in mice and humans.

RH5, which is part of the trimeric RCR-complex essential for invasion, is a vaccine candidate for malaria. Here, Williams et al. show that monoclonal antibodies targeting each of the three proteins in the RCR-complex can work together to more effectively block the invasion of red blood cells by Plasmodium falciparum and design a combination vaccine candidate.

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.

Genome-wide association analyses identify new risk loci for heart failure and its subtypes, extending understanding of the underlying biological pathways and disease mechanisms.

Proinflammatory activation of liver macrophages and their secretion of proinflammatory cytokines have been linked to obesity. Here Morgantini et al. report a mechanism through which liver macrophages can impair liver metabolism and promote insulin resistance in obesity in the absence of an overt proinflammatory phenotype, through secretion of non-inflammatory factors such as IGFBP7.

Time-resolved serial femtosecond crystallography is used to reveal the structural changes that stabilize the charge-separation steps of electron-transfer reactions in the photosynthetic reaction centre of Blastochloris viridis on a timescale of picoseconds.

A large body of work into the role of oestrogen receptor b (ERb) in breast cancer is contradictory, hindering future progress. Here the authors conduct extensive validation of anti-ERb antibodies , and show that normal and cancerous breast tissue do not express ERb, consistent with RNA-seq data.

Polygenic risk scores for Alzheimer’s disease derived from individuals of European ancestry can show improved performance in multiancestry settings after incorporating genome-wide association summary statistics from diverse populations.

Single-cell and spatial transcriptomic profiling of the human endometrium highlights pathways governing the proliferative and secretory phases of the menstrual cycle. Analyses of endometrial organoids show that WNT and NOTCH signaling modulate differentiation into the secretory and ciliated epithelial lineages, respectively.

Large genome-wide meta-analysis of clinically diagnosed late-onset Alzheimer’s disease (LOAD) from 94,437 individuals identifies new LOAD risk loci and implicates Aβ formation, tau protein binding, immune response and lipid metabolism.

Combining field data from 83 sites on five continents, together with microcosm experiments, the authors show that nutrient cycling, decomposition, plant production and other ecosystem functions are positively associated with a higher diversity of a wide range of soil organisms.

Here authors show that machine learning derives the degree of background retinal pigmentation with more nuance than self-described ethnicity. Retinal pigment scores are associated with genes linked to melanin and may improve algorithmic fairness.

A region on chromosome 19p13 is associated with the risk of developing ovarian and breast cancer. Here, the authors genotyped SNPs in this region in thousands of breast and ovarian cancer patients and identified SNPs associated with three genes, which were analysed with functional studies.

Species-rich plant communities often have higher productivity than monocultures. Here, the authors analyse biodiversity-ecosystem functioning experiments in grasslands and forests and find that the biodiversity effects on community productivity strengthen over time thanks to shifts in contributions of species with different resource acquisition traits.

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.

Poorly performing antibodies contribute to the reproducibility crisis in biomedical research. The market offers millions of antibodies and validating them is a cumbersome process. Now, the non-profit Antibody Characterization through Open Science (YCharOS) organization shares a step-by-step protocol for rigorous antibody validation using genetic (knockout) cell line controls.

Investigation of variation in three cohorts has identified multiple genetic signals associated with the pregnancy-specific liver disorder, intrahepatic cholestasis of pregnancy, giving insight into the disease which can cause preterm birth and stillbirth.

The genome of the model fern species Ceratopteris richardii reveals a history of remarkably dynamic genome evolution, including rapid changes in genome content and structure following the most recent whole-genome duplication approximately 60 million years ago.

Radiocarbon dating of mud wasp nests in the Kimberley region of Western Australia has established ages of up to 17,000 years for rock art from the earliest known, naturalistic, period of Australian Aboriginal figurative paintings.

Soil age is thought to be an important driver of ecosystem development. Here, the authors perform a global survey of soil chronosequences and meta-analysis to show that, contrary to expectations, soil age is a relatively minor ecosystem driver at the biome scale once other drivers such as parent material, climate, and vegetation type are accounted for.

The global ecological predictors of soil priming remain unclear. Here the authors conducted a global survey of soils from 86 global locations using an isotopic approach and find that in more mesic sites with high SOC concentrations, soil priming effects are more likely to be negative.

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.

The MAGIC investigators report results of a large genome-wide association study meta-analysis to identify common variants influencing fasting glucose homeostasis. They further show that several of the newly discovered loci influencing glycemic traits are also associated with risk of type 2 diabetes.

Lean body mass is a highly heritable trait and is associated with various health conditions. Here, Kiel and colleagues perform a meta-analysis of genome-wide association studies for whole body lean body mass and find five novel genetic loci to be significantly associated.

Serial femtosecond crystallography is an X-ray free-electron-laser-based method that uses X-ray bursts to determine protein structures. Here the authors present the structure of a photosynthetic reaction centre, an integral membrane protein, achieved with no sign of X-ray-induced radiation damage.

Known genetic loci account for only a fraction of the genetic contribution to Alzheimer’s disease. Here, the authors have performed a large genome-wide meta-analysis comprising 409,435 individuals to discover 6 new loci and demonstrate the efficacy of an Alzheimer’s disease polygenic risk score.

The mechanism underlying vegetative desiccation tolerance (DT) of plants remains elusive. A study now sequences the genome and transcriptome for the resurrection plant, Xerophyta viscosa, and supports that vegetative DT arose by redirection of the seed DT pathway.

Comprehensive integration of gene expression with epigenetic features is needed to understand the transition of kidney cells from health to injury. Here, the authors integrate dual single nucleus RNA expression and chromatin accessibility, DNA methylation, and histone modifications to decipher the chromatin landscape of the kidney in reference and adaptive injury cell states, identifying a transcription factor network of ELF3, KLF6, and KLF10 which regulates adaptive repair and maladaptive failed repair.

Cox and colleagues develop PXS-5505, a first-in-class selective pan-lysyl oxidase inhibitor and show that it reduces chemotherapy-induced desmoplasia and stiffness, thereby improving chemotherapy response and survival in pancreatic cancer models.

Sven van der Lee, Julie Williams, Gerard Schellenberg and colleagues identify rare coding variants in PLCG2, ABI3 and TREM2 associated with Alzheimer's disease. These genes are highly expressed in microglia and provide additional evidence that the microglia-mediated immune response contributes to the development of Alzheimer's disease.

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.

The role of T cells in modulating the course of influenza infection in humans is not clear. Wilkinson et al. now report that, in the absence of strain-specific humoral immunity, preexisting cytotoxic CD4⁺ T cells limit the severity and duration of symptoms in humans challenged with influenza virus and suggest these CD4⁺ T cell responses might be harnessed in vaccine development.

This study provides a comprehensive spatiotemporal map of human and mouse gonadal differentiation, using a combination of single-cell and spatial transcriptomics, chromatin accessibility assays and fluorescent microscopy, which can guide in vitro gonadogenesis.