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Here, using computational integration of multi-omics data, the authors provide a detailed transcriptome and translatome of herpes simplex virus 1 (HSV-1), including previously unidentified ORFs and N-terminal extensions. The study also provides a HSV-1 genome browser and should be a valuable resource for further research.

Stalling of ribosomes by the nascent polypeptide chain is widely used to regulate gene expression. Here, Gersteuer et al determine cryo-EM structures of SecM-stalled ribosomes revealing the mechanism by which the SecM peptide arrests translation.

We uncover key processes of the genomic evolution of small cell lung cancer under therapy, identify the common ancestor as the source of clonal diversity at relapse and show central genomic patterns associated with drug response.

Translation of RAPP (Arg-AlaPro-Pro) motifs induces ribosome stalling. Here, structures of RAPP-stalled ribosomes reveal that RAPP motifs short circuit the ribosomal peptidyltransferase activity to induce stalling.

By studying individuals along a spectrum of cardiometabolic disease and adjusting for effects of lifestyle and medication, this investigation identifies alterations of the metabolome and microbiome from dysmetabolic conditions, such as obesity and type 2 diabetes, to ischemic heart disease.

Here, using clinical samples and autopsy tissues, the authors combine fast-colorimetric test (LAMP) for SARS-CoV-2 infection and large-scale shotgun metatranscriptomics for host, viral, and microbial profiling and provide a map of the viral genetic features of the New York City outbreak and associate specific host responses and gene expression perturbations with SARS-CoV-2 infection.

Sex differences in fasting glucose and insulin have been identified, but the genetic loci underlying these differences have not. Here, the authors perform a meta-analysis of genome-wide association studies to detect sex-specific and sex-dimorphic loci associated with fasting glucose and insulin.

Red blood cells (RBCs) are phagocytosed in the spleen in sickle cell disease and malaria. Here, Cao et al. show that high mannose N-glycans, exposed on diseased or oxidized RBC surfaces, bind mannose receptor CD206 on host cells, mediating phagocytosis.

An analysis of 2,173 individuals from the MetaCardis cohort quantifies the individual and combinatorial effects of a range of drugs on host health, metabolome and gut microbiome in cardiometabolic disease.

LKB1 regulates various cellular processes such as cell proliferation, energy homeostasis and cell polarity and is frequently downregulated in various tumours. Here the authors show that LKB1 activation requires direct binding to phospholipids and show this has an implication for carcinogenesis.

When the antibiotic erythromycin is bound to the ribosomal exit tunnel, ErmBL peptide translation stalls and allows translation of the downstream methyltransferase ErmB. Here the authors combine cryo-EM and molecular dynamics simulations to identify the underlying basis for the inhibition of peptide bond formation that results in ribosome stalling.

Prosaposin (PSAP) variants are linked to Parkinson’s disease (PD). Here, the authors report PSP changes in PD and lipid dyshomeostasis and PD-like phenotypes in mice lacking PSAP in dopamine neurons; PSAP overexpression counteracts experimental PD.

To overcome challenges posted by vast number of GPCR genes and redundancy, the authors disrupted nearly all GPCR-encoding genes in C. elegans, enabling effective examination of GPCR signaling and offering a valuable resource for the research community.

Through a CRISPR-activation screen, Ravid Lustig et al. show that GATA transcription factors activate long-range Xist enhancers to upregulate Xist expression and initiate X chromosome inactivation in early mouse embryos.

The pre-T-cell antigen receptor mediates early T-cell development and differentiation. These authors report its structure and explain how the head-to-tail dimeric arrangement allows the interaction of the pre-Tα domain with any variable β domain, and provides the basis for ligand-independent signalling.

This study identifies a molecular mechanism promoting fruit shape variation. Local meristem identity is maintained through autoregulatory activation of the STM gene to allow post-fertilization changes in fruit morphology.

A cross-sectional analysis of participants in the MetaCardis Body Mass Index Spectrum cohort finds that the higher prevalence of gut microbiota dysbiosis in individuals with obesity is not observed in those who take statin drugs.

The nuclear pore complex (NPC) is known to regulate p53 signaling and this has mainly been linked to peripheral NPC subunits. Here the authors show that Nup155 from the NPC inner ring regulates the p53 pathway by controlling p21 translation while also being a target of p53-mediated repression.

The coordination of interactions between multiple regulatory elements and genes within a chromatin domain remains poorly understood. Here, the authors use a method to detect multi-way chromatin interactions in a mouse model in which the α-globin domain is extended to include several additional genes, finding that the promoters do not form mutually exclusive interactions with the enhancers, but all interact simultaneously in a single complex.

Gut microbial metabolism of nutrients contributes to metabolic diseases, and the histidine metabolite imidazole propionate (ImP) is produced by type 2 diabetes (T2D) associated microbiome. Here the authors report that circulating ImP levels are increased in subjects with prediabetes or T2D in three European populations, and this increase associates with altered gut microbiota rather than dietary histidine.

Using shotgun metagenomics, cultivation and metabolic modelling, the authors construct the Salmon Microbial Genome Atlas as a resource for future studies on sustainable aquaculture.

This study shows that environmental conditions promote multicellular group formation in green algae and that retention of daughter cells reliant on nitrogen availability promotes fitness in the lab and in natural lake systems in Sweden.

Lind et al. investigate the causal relationship between plasma proteins and cardiovascular disease outcomes in patients of European and Chinese descent, identifying FGF5, PROCR and FURIN as promising targets for the development of new drugs.

Graphene energy transfer with vertical nucleic acids (GETvNA) is a general approach enabling dynamical observations of DNA structural changes and DNA–protein interactions with spatial resolution down to the Ångström scale.

Pyruvate carboxylases are homotetrameric enzymes in eukaryotes and most bacteria. Here, the authors report the structure of an unusual two-subunit form of the enzyme from the Gram-negative bacterium Methylobacillus flagellates, revealing an unexpected α₂β₄stoichiometry.

The direct detection of metabolites secreted by cells can indicate how cellular dynamics affects population development. Here, the authors present an integrated circuit-based method for electrochemical imaging of redox-active signalling molecules with spatial resolution within bacterial colonies.

By complementing spatial transcriptomics with high-resolution proteomics, Kaufmann et al. tracked a gradient of disease severity across the brains of patients with progressive multiple sclerosis, uncovering new therapeutic opportunities to slow disease.

Long-read single-cell RNA sequencing is capable of detecting isoform-level gene expression and genomic alterations such as mutations and gene fusions, thereby providing cell-specific genotype-phenotype information. Here, the authors use long-read scRNA-seq on metastatic ovarian cancer samples and detect cell-type specific isoforms and gene fusions that may otherwise be misclassified in short-read data.

The role of hypoxia inducible factors in infection and immune response is unclear. Here, the authors study their impact on the regulation of T cells responses during Mycobacteria tuberculosis infection using transcriptomics, flow cytometry and in vivo infection.

The detailed mechanisms of action of bactericidal antibiotics remain unclear. Here, Wong et al. show that these antibiotics induce cytoplasmic condensation through membrane damage and outflow of cytoplasmic contents, as well as accumulation of reactive metabolic by-products and lipid peroxidation, as part of their lethality.

Faster sinking rates can enhance bacterial degradation of organic particles in the ocean due to flow-induced removal of waste products, according to laboratory experiments and modelling of the marine carbon pump.

Variation among RNA transcript isoforms can be generated from alternative start and polyadenylation sites, and results in RNAs and proteins with different properties being generated from the same genomic sequence; here a new method termed transcript isoform sequencing is described in yeast, and the method allows a fuller exploration of transcriptome diversity across the compact yeast genome.

Integration of differential and conventional RNA sequencing and transposon mutant fitness data for Bacteroides thetaiotaomicron grown under 15 different conditions provides an expression atlas, expands the regulatory RNA repertoire and reveals that the small RNA MasB regulates susceptibility to tetracyclines.

Myoglobin is a hemeprotein that reversibly binds oxygen and gives muscle its red color. Here, the authors report a genetic variant in the MB gene that associates with myoglobinopathy, an autosomal dominant progressive myopathy, and altered oxygen binding properties of the mutant protein.

The cytokine IFNα is expressed in the islets of individuals with type 1 diabetes and contributes to local inflammation and destruction of beta cells. Here, the authors provide a global multiomics view of IFNα-induced changes in human beta cells at the level of chromatin, mRNA and protein expression.

Pre-clinical cell culture models capturing the heterogeneity of childhood kidney tumours are limited. Here, the authors establish and characterise an organoid biobank of tumour and matched normal organoid cultures from over 50 children with different subtypes of kidney cancer.

Bacteroides thetaiotaomicron is a human gut microbe and an emergent model organism. Here, Ryan et al. generate single-nucleotide resolution RNA-seq data for this bacterium and map transcription start sites and noncoding RNAs, one of which modulates expression of metabolic enzymes.

ABC exporters hydrolyze ATP to pump substrates across membranes, but critical steps of the transport mechanism remain poorly understood. Here, the authors solve the crystal structure of outward-facing TM287/288 with the help of a state-specific sybody and gain insights into the role of the extracellular gate.

By combining a yeast single-cell RNA-seq method that counts transcript start sites in a strand- and isoform-specific manner with index sorting, the authors uncover a linear relationship between cell size and RNA content and extreme cell heterogeneity in the expression of metabolic genes.

Histone deacetylase 3 (HDAC3) is a regulator of lipid homeostasis in several tissues, however, its role in intestinal lipid metabolism was not yet known. Here the authors study intestine specific HDAC3 knock out mice and report that these animals have increased fatty acid oxidation and undergo remodeling of the intestinal epithelial cell lipidome.

A survey of 136 factors that may influence cytokine secretion identify smoking, cytomegalovirus latent infection and body mass index as influential factors, with varying effects on innate and adaptive immunity.

Future aquatic ecosystems will be impacted synergistically by large-scale environmental changes, such as climate change and increased humic content. Now research shows that community responses are determined by food-chain length and that the top trophic level, and every second level below that, can be expected to benefit from climate change, whereas trophic levels in between are likely to suffer.

Bicuspid aortic valve (BAV) is the most common human congenital cardiovascular malformation. Here, the authors perform a genome-wide association study for BAV and identify risk variants in the gene region of cardiac-specific transcription factor GATA4 and implicate GATA4 in heart valve development.

Gilean McVean and colleagues report the results of a large-scale clinical genome sequencing project spanning a broad spectrum of disorders. They identify factors influencing successful genetic diagnosis and highlight the challenges of interpreting findings for genetically heterogeneous disorders.

High salt intake changed the gut microbiome and increased T_H17 cell numbers in mice, and reduced intestinal survival of Lactobacillus species, increased the number of T_H17 cells and increased blood pressure in humans.

Increased potential for branched-chain amino acid and lipopolysaccharide biosynthesis in the gut microbiome of insulin-resistant individuals suggests that changes in the serum metabolome induced by dysbiosis, and driven by only a handful of species, contribute to the development of diabetes.

Aetiology of colitis is highly complex and incompletely understood. Here the authors show in mouse models that A20 deubiquitinase limits pro-inflammatory cytokine production in myeloid cells while inhibiting proapoptotic response to these cytokines in enterocytes, and that only upon losing both functions intestinal pathologies develop.

A comprehensive analysis of the thymic medulla identifies a tuft-cell-like thymic epithelial cell population that is necessary for shaping thymic function.