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In this work, authors show that the nucleoside prodrug obeldesivir has potent antiviral activity across respiratory syncytial virus (RSV) clinical isolates with a high resistance barrier. Once-daily obeldesivir treatment was efficacious against RSV in a non-human primate model.

An analysis of rare genetic variants identifies three genes—MAP1A, ANO8 and ANK2—that have a role in attention deficit hyperactivity disorder (ADHD) and investigates the potential underlying biological mechanisms.

Leveraging RNA-targeting dCas13d enables selective interference with phage protein translation and facilitates measurement of phage gene fitness at a transcriptome-wide scale.

Tan and colleagues conducted a single-cell multiomic analysis of T cell acute lymphoblastic leukemia and identified a treatment-resistant subpopulation of bone marrow progenitor-like blasts associated with poor outcomes.

Federated learning, a method for training artificial intelligence algorithms that protects data privacy, was used to predict future oxygen requirements of symptomatic patients with COVID-19 using data from 20 different institutes across the globe.

Stress inhibits  hair growth in mice through the release of the stress hormone corticosterone from the adrenal glands, which inhibits the activation of hair follicle stem cells by suppressing the expression of a secreted factor, GAS6, from the dermal niche.

Broadly neutralizing antibodies (bNAbs) are being evaluated for HIV post-exposure prophylaxis (PEP) in the setting of vertical transmission. Here, using a macaque model of perinatal SHIV infection, the authors show that PEP for infant macaques within 30–48 h of SHIV exposure is highly effective using either bNAbs or ART.

Of 12 serology assays tested, four detect antibodies in more than 80% of patients with COVID-19.

Deep-learning models for the automated measurement of retinal-vessel calibre in retinal photographs perform comparably to or better than expert graders in associations of measurements of retinal-vessel calibre with cardiovascular risk factors.

A new phylogenomic tree for butterflies is constructed using 391 genes from 2,300 species, representing 92% of genera. It suggests that butterflies originated around 100 million years ago in what is now the Americas and originally fed on Fabaceae.

Hagenbeek et al. identify a small-molecule pan-TEAD inhibitor that blocks the interaction between YAP/TAZ and TEAD proteins. They demonstrate that treatment with the inhibitor leads to antitumor activity and can synergize with KRAS G12C inhibition.

Stress induces hair greying in mice through depletion of melanocyte stem cells, which is mediated by the activation of sympathetic nerves rather than through immune attack or adrenal stress hormones.

The authors summarize the data produced by phase III of the Encyclopedia of DNA Elements (ENCODE) project, a resource for better understanding of the human and mouse genomes.

In a multicenter research program coordinated by the International Mouse Phenotyping Consortium, Spielmann et al. analyze the cardiac function and structure in ~4,000 monogenic mutant mice and identify 705 mouse genes involved in cardiac function, 75% of which have not been previously linked to cardiac heritable disease in humans. Using the UK Biobank human data, the authors validate the link between cardiovascular disease and some of the newly identified genes to illustrate the resource value and potential of their mutant mouse collection.

Nematode signals such as ascarosides are sensed by G protein-coupled receptors of a nematode-trapping fungus, resulting in fungal activation of cAMP–PKA signalling and trap development.

NEIL2, a mammalian DNA repair enzyme, has been reported to suppress infection induced inflammation. Here, the authors characterize its role in modulating the severity of SARS-CoV-2 infection.

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.

Macrophage infiltration and metabolic rewiring are associated with glioblastoma. Here the authors show that the glycolytic enzyme lactate dehydrogenase-A mediates macrophage-cancer cell crosstalk to promote glioblastoma progression.

The authors identify an increased hepatic NADH/NAD⁺ ratio as an underlying metabolic parameter that is shaped by human genetic variation and contributes causally to key metabolic traits and diseases.

Nsp15 is a uridine specific endoribonuclease present in all coronaviruses. Here, the authors determine the cryo-EM structures of SARS-CoV-2 Nsp15 in the apo and UTP-bound states, which together with biochemical experiments, mass spectrometry and molecular dynamics simulations provide insights into the catalytic mechanism of Nsp15 and its conformational dynamics.

Weaver and colleagues use breast cancer patient-derived organoids and mouse models to find an inhibitory role for the nuclear repressor NCOR2 in chemotherapy response and antitumor immunity, which can be targeted by blocking NCOR2–HDAC3 interaction.

Hyper-IgE syndrome is an autosomal dominant immunodeficiency that has been linked to mutations in stat3. This paper shows that stat3 mutant subjects fail to generate T_H17 cells, which may account for their susceptibility to recurrent infections.

Image noise is a common problem in light microscopy, and denoising is a key step in microscopic imaging pipelines. Lequyer et al. propose a self-supervised denoising method and apply it to diverse imaging and analysis pipelines.

Using patient-derived colorectal cancer tumour enteroids, Schwartz et al. find that ectopic expression of hepcidin in the tumour epithelium establishes an axis to sequester iron to maintain the nucleotide pool and sustain proliferation.

Cryo-EM structures of the multienzyme complex between the endoribonuclease Las1 and the polynucleotide kinase Grc3 reveal two molecular switches that coordinate nuclease and kinase function.

Immunotherapies have shown limited efficacy in patients with glioma. Here, based on an in vivo kinome knockout CRISPR screen, the authors show that checkpoint kinase 2 promotes CD8 T cell immune evasion and that its depletion or inhibition improve survival and response to PD1/PDL1 blockade in preclinical glioma models.

Discovery of causal variants for monogenic disorders has been facilitated by whole exome and genome sequencing, but does not provide a diagnosis for all patients. Here, the authors propose a Full Spectrum of Intolerance to Loss-of-Function (FUSIL) categorization that integrates gene essentiality information to aid disease gene discovery.

The Omicron variant evades vaccine-induced neutralization but also fails to form syncytia, shows reduced replication in human lung cells and preferentially uses a TMPRSS2-independent cell entry pathway, which may contribute to enhanced replication in cells of the upper airway. Altered fusion and cell entry characteristics are linked to distinct regions of the Omicron spike protein.

Packaging split Cas9 into AAVs increases cargo capacity and allows for efficient genome editing and gene activation in vivo. AAV–split-Cas9 activates the host immune system but does not trigger the extensive cellular damage observed with delivery of Cas9 via DNA electroporation.

In two patient-derived xenograft models of colorectal cancer and a mouse model of autochthonous soft-tissue sarcoma, dietary restriction of methionine influences the outcome of cancer and interacts with antimetabolite and radiation therapies, through effects on one-carbon metabolism.

The increasing accessibility of single cell omics technologies beyond transcriptomics demands parallel advances in analysis. Here, the authors introduce STREAM, a pipeline for reconstruction and visualization of differentiation trajectories from both single-cell RNA-seq and ATAC-seq data.

Phenotypic screening for serine hydrolase inhibitors capable of modulating lipid storage coupled with target deconvolution identifies carboxylesterase 3 as having a role in regulating adipocyte function, with enzyme inhibition causing positive outcomes in mouse models of obesity and diabetes.

microbeMASST is a tool to associate known and unknown metabolites to microbial producers leveraging untargeted metabolomics data.

Ring ATPase translocases that operate on disordered substrates adopt lockwasher architectures and use a hand-over-hand mechanism. By challenging the dsDNA packaging motor of bacteriophage ϕ29 with hybrid and dsRNA, the authors propose that the motor cycles between planar and lock-washer structures.

A randomized trial in patients hospitalized with COVID-19 showed no benefit and potentially increased harm associated with the use of convalescent plasma, with subgroup analyses suggesting that the antibody profile in donor plasma is critical in determining clinical outcomes.

The Somatic Mosaicism across Human Tissues Network aims to create a reference catalogue of somatic mosaicism across different tissues and cells within individuals.

Cheung, Zhang et al. examine the association between secondhand smoke exposure and changes in the retinal vasculature among children aged 6 to 8, in a population-based cohort study. Children exposed to secondhand smoke have wider retinal arteriolar and venular calibers compared to those in smoke-free homes.

Miyazaki, Gharib, Hsu et al. use a combined cell-specific luciferase reporter system and chemo-selective substrate to identify mouse tissues at risk of renal injury. The platform can be used to identify cell-specific pathophysiological events and transcriptional changes, finding potential therapeutic targets.

This Resource introduces a new public database that enables researchers to re-analyse a large corpus of studies into meta-cognitive confidence judgements.