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Current photoproximity labelling methods often require metal-based catalysts to map protein interactomes but, owing to their toxicity, they have limited intracellular applicability. A deazaflavin cofactor has now been developed as a biocompatible alternative for diazirine activation inside living cells, offering accurate mapping of protein interactors and dynamics with excellent spatio-temporal control.

By studying dynamic folding intermediates on the human ribosome, Pellowe et al. show that newly made domains help each other to fold but do not stably interact until synthesis is complete, avoiding interdomain misfolding.

Exponential growth of toxigenic Streptococcus pyogenes M1_UK lineage accounted for most of the 2022/2023 invasive infection upsurge in the UK. Authors provide evidence that M1_UK first emerged in 2008, has genetic evidence of enhanced fitness, and has disseminated to 3 continents.

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.

Here, the authors show that physiological alpha-synuclein supports mitochondrial ATP homeostasis via interactions with ATP synthase and AK2, whereas its disease-linked mutants, truncated forms, and aggregates lose these interactions.

Nanoparticles (NPs) hold promise for therapeutic applications, but their interactions with biological environments remain poorly understood. Here, the authors reveal that the glycosylation of the biomolecular corona, particularly sialic acid content, significantly influences NP interactions with cellular uptake processes, offering new insights into predicting NPs’ biological fate.

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).

BRCA1 and BRCA2 are well known breast cancer predisposition genes, however, many variants have not yet been classified for their pathogenicity. Here, the authors analyse a large combined cohort to provide evidence of variant pathogenicity.

A multi-ancestry genome-wide association study for age at menarche followed by fine mapping and downstream analysis implicates 665 pubertal timing genes, such as the G-protein-coupled receptor 83 (GPR83) and other genes expressed in the ovaries involved in the DNA damage response.

Sadhu et al. identify and functionally validate ferredoxin-1 (FDX1) as a determinant of cholesterol metabolism and cardiovascular risk in Asian populations.

Break-induced telomere synthesis initiates recruitment of the SNM1A nuclease, which promotes DNA end resection that in turn allows template switching to enable bypass of lesions.

Whole-genome sequencing and phenotype data sharing are introduced in a national health system to streamline diagnosis and to discover coding and non-coding variants that cause rare diseases.

In the first results from an ongoing global cancer screening data repository, screening program organization was better overall in Europe compared to other continents; however, there were substantial gaps in implementation across both high- and low-resource settings.

The interaction of Toll-like receptor 4 (TLR4) results in recruitment of proteinacious adapter molecules to the cell membrane. Here Hering and colleagues show that sphinganine recruits adaptor protein MyD88 to TLR4 in the macrophage membrane and the absence of sphinganine in murine models disrupts TLR4 driven inflammation.

CDK4/6 inhibitors (CDK4/6i) have improved cancer patient outcomes but shown limited benefits for those with triple-negative breast cancer (TNBC). Here, the authors report that CDK4/6 inhibition prevents CDK4 enhanced mitochondria-endoplasmic reticulum interactions, inhibiting mitochondrial apoptosis and driving resistance to CDK4/6i in TNBC models.

DISCOVER-Seq+ is a high-sensitivity method for the detection of off-target effects of CRISPR genome editing.

This Pediatric Cell Atlas study analyzes temporal cortex single-nucleus RNA sequencing datasets from eight diverse donors from 4 to 50 years of age, describing gene expression dynamics over the course of brain maturation.

Post-acute COVID-19 condition is difficult to quantify because it includes a range of symptoms that may have other causes. In this study, the authors use primary care data from England and Catalonia, Spain, to estimate the incidence of the condition and identify symptoms that occur more frequently following infection than in uninfected controls.

In this study, Aggarwal and colleagues perform prospective sequencing of SARS-CoV-2 isolates derived from asymptomatic student screening and symptomatic testing of students and staff at the University of Cambridge. They identify important factors that contributed to within university transmission and onward spread into the wider community.

Cells from embryonic, fetal, paediatric and adult human intestinal tissue are analysed at different locations along the intestinal tract to construct a single-cell atlas of the developing and adult human intestinal tract, encompassing all cell lineages.

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.

As proof of principle, an analysis using a suite of human-aligned immunocompetent mouse models of hepatocellular carcinoma identifies a promising therapeutic candidate, cladribine, which acts in a highly effective subtype-specific manner in combination with standard-of-care therapy.

A genome-wide association study of critically ill patients with COVID-19 identifies genetic signals that relate to important host antiviral defence mechanisms and mediators of inflammatory organ damage that may be targeted by repurposing drug treatments.

The impact of modifiable lifestyle factors on the risk of post-COVID-19 sequelae is not well understood. Here, the authors perform a prospective cohort study amongst UK Biobank participants and show that a healthy lifestyle is associated with lower risk of post-COVID-19 sequelae across multiple organ systems.

T cell responses can be generated to either pathogen infection or from priming with a vaccine. Here the authors compare T cell generation, phenotype and single cell transcriptome of participants vaccinated with a mpox vaccine or infected with the virus showing that the virus induced T cells showed more effective function and phenotype.

Eye2Gene’s next-generation phenotyping of multimodal images increases diagnostic yield for inherited retinal diseases by improving screening, phenotype-driven variant prioritization and automatic similarity matching in phenotypic space to drive gene discovery.

Transgenerational transmission of acquired immunological traits has been demonstrated in invertebrates and plants but not mammals. Katzmarski et al. demonstrate that trained immunity that protects against heterologous infections can be transmitted to F2 offspring.

Sea level data and models of solid Earth effects and ocean thermal expansion are used to show that global mean sea level and Antarctic ice volume were likely higher and smaller, respectively, in the mid-late Holocene than at the preindustrial.

The genomic landscape of hereditary SDHB-mutant pheochromocytomas (PC) and paragangliomas (PG) remains to be explored. Here, the authors perform multiomic analysis on 94 tumours from 79 patients and identify the molecular features of metastatic disease and treatment response.

Swimming animals are generally assumed to generate forward thrust by pushing surrounding water rearwards. Here, Gemmell et al.show that efficient swimming in lampreys and jellyfish is achieved primarily through suction, as vortex-associated low pressure regions are synchronized by undulations of the body.

The HOX gene cluster is responsible for anteroposterior axis patterning in an evolutionarily conserved manner. Here they examine HOX gene expression in human embryos and show that neural-crest derivatives retain the anatomical HOX code of their origin while also adopting the code of their destination.

While the ribosome has been harnessed for synthetic biology, designing ribosomes has remained challenging. Here, the authors demonstrate a community science approach for rational design of ribosomes with beneficial properties.