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Glutamine can feed into the TCA cycle as a fuel for oxidative phosphorylation and thereby can affect metabolic pathways in lymphocytes. Yet here the authors show that glutamine serves predominantly as a signalling molecule that sustains cMyc expression to control NK cell metabolism and effector function.

In Arabidopsis, lateral root emergence requires the penetration of overlying tissues by stem cells deep within the root. Voß et al. reveal that changes in auxin signalling required for this process are mediated by local rephasing of the circadian clock.

Hydroxychloroquine and chloroquine have been investigated as a potential treatment for Covid-19 in several clinical trials. Here the authors report a meta-analysis of published and unpublished trials, and show that treatment with hydroxychloroquine for patients with Covid-19 was associated with increased mortality, and there was no benefit from chloroquine.

Genetic and phenotypic analysis reveals expression quantitative trait loci in human induced pluripotent stem cell lines associated with cancer and disease.

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.

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.

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.

By integrating healthcare and exome-sequencing data from parent–offspring trios of patients with developmental disorders, 28 genes that had not previously been associated with developmental disorders were identified.

Over one hundred loci have been identified to be associated with the familial risk of prostate cancer but the functional effects are poorly understood. Here the authors use single-nucleotide variant and epigentic data to show an underlying genetic architecture marked by histone modification.

Chromodomain Helicase DNA-binding (CHD) proteins have been implicated in neurodevelopmental processes. Here, the authors identify missense variants in CHD3 that disturb its chromatin remodeling activities and cause a neurodevelopmental disorder with macrocephaly and speech and language impairment.

Whole-exome analysis of individuals with developmental disorders shows that de novo mutations can equally cause loss or altered protein function, but that most mutations causing altered protein function have not yet been described.

This Brain Somatic Mosaicism Network analysis of 283 cases of malformations of cortical development identifies 69 candidate and known genes in 76 patients. Single-nucleus RNA sequencing and mouse modeling implicate radial glia and daughter excitatory neurons.

Three-dimensional ptychographic imaging with electrons has remained a challenge because, unlike X-rays, electrons are easily scattered by atoms. Here, Gao et al. extend multi-slice methods to electrons in the multiple scattering regime, paving the way to nanometer-scale 3D structure determination with electrons.

Many RNA viruses that replicate in the cytoplasm express proteins that localize to nucleoli, but the nucleolar functions remain largely unknown. Here, the authors show that the Henipavirus matrix protein mimics an endogenous Treacle partner of the DNA-damage response, resulting in suppression of rRNA biogenesis.

The concerted action of the hormones cytokinin and auxin is an important regulator of plant development. Here Šimášková et al. propose a mechanistic basis by which cytokinin-responsive transcription factors regulate transport of auxin in Arabidopsisroots.

Repeat expansion mutation in C9ORF72 is the most common cause of familial ALS. Here, the authors generate motor neurons from cells of patients with C9ORF72 mutations, and characterize changes in gene expression in these motor neurons compared to genetically corrected lines, which suggest that glutamate receptor subunit GluA1 is dysregulated in this form of ALS.

A systematic review of evidence, across the key pillars of prevention, diagnosis, treatment and prognosis, outlines milestones that need to be met to enable the broad clinical implementation of precision medicine in diabetes care.

The levels of 1,251 metabolites are measured in 475 phenotyped individuals, and machine-learning algorithms reveal that diet and the microbiome are the determinants with the strongest predictive power for the levels of these metabolites.

Lateral roots grow at specific angles with respect to gravity. Two auxin transporters, PIN3 and PIN7, in gravi-sensing cells establish hormone gradients that balance downward and upward growth to generate stable, non-vertical roots.

The European Lead Factory combines assets and experience from major pharma with innovation and agility of academia and SMEs in a collaborative platform to expand access to high-throughput screening. With many successes heading towards the clinic, the organization is broadening its approach to screening and partnering.

The cellular heterogeneity in brain obscures the identification of robust cellular regulatory networks. Here the authors integrate genome-wide chromosome conformation data from sorted neurons and glia, with transcriptomic and enhancer profiles, to characterize cell-type-specific gene regulatory landscapes in the human brain, and provide insights into cell-type-specific gene regulatory networks in brain disorders.

Genome-wide and multitrait analyses identify novel loci associated with hypertrophic cardiomyopathy and relevant left ventricular traits. Gene-level burden analyses show that rare truncating SVIL variants are associated with high risk of hypertrophic cardiomyopathy.

Studying the genetic effects on early stages of human development is challenging due to a scarcity of biological material. Here, the authors utilise induced pluripotent stem cells from 125 donors to track gene expression changes and expression quantitative trait loci at single cell resolution during in vitro endoderm differentiation.

Cardelino leverages variant information from single-cell RNA-seq data for inferring clonal tree configuration and mapping cells to their clone of origin.

Grieger, Takele, Vesco, et al. perform a systematic review and meta-analysis of gestational weight gain interventions. Findings indicate lifestyle interventions that reduce excessive gestational weight gain provide greater benefits for women with a normal BMI and higher HDL cholesterol levels at the initiation of interventions.

Although the CRISPR–Cas system of prokaryotes has an established role in defence, recent studies suggest that this system has other functional roles. Here, Westra and colleagues explore the more unconventional roles of CRISPR–Cas, such as endogenous gene regulation and genome remodelling, and consider their evolutionary implications.

A single dose of the ChAdOx1 nCoV-19 vaccine elicits antibodies and cytokine-producing T cells that might help control or prevent SARS-CoV-2 infection.

This Review discusses the mechanisms via which changes in the gut can influence the development and progression of NAFLD. Understanding of such mechanisms is hoped to pave the way for new treatments for what has become the most common form of liver disease.

Young, McInnes, Massey et al. systematically review published studies evaluating features associated with heterogenous treatment effects for SGLT2-inhibitor and GLP1-receptor agonist therapies in people with type 2 diabetes. They find limited current evidence on treatment effect heterogeneity, for glycaemic, cardiovascular and renal outcomes.