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DNA-sequencing data from primary tumours and paired metastases from participants in the TRACERx lung study and PEACE autopsy programme are used to analyse the metastatic diversity of advanced non-small cell lung cancer and the seeding patterns that underpin it.

The mode of action of eukaryotic initiation factor 5A (eIF5A), a translation factor activated by hypusination, remains to be characterized. Here, the authors suggest that hypusinated eIF5A is involved in mitochondrial metabolism and translation promoting prostate cancer progression.

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).

Tydeman et al. analyze pregnancy outcomes before the COVID-19 pandemic, during lockdowns, and after restrictions were lifted in >30,000 pregnancies from ethnically and socio-economically diverse individuals in the UK. Most pregnancy outcomes follow pre-pandemic temporal trends, either stable, increasing, or decreasing.

Longitudinal metatranscriptomics in a prospective cohort of 1,164 adults hospitalized for COVID-19 reveals that azithromycin offered no apparent anti-inflammatory benefit but enriched the respiratory microbiome with potential pathogens and antimicrobial resistance genes.

Robustness checks and reproduction of analyses with existing and updated data based on 110 articles in economics and political science journals with data and code-sharing requirements found high levels of robustness and reproducibility and determined that robustness was not dependent on author characteristics or data availability.

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.

Analysis of ancient human genomes from a Neolithic collective gallery grave in northern France points to population discontinuity and turnover between the third and fourth millennium BC.

Tailoring relativistic laser–plasma interactions on femtosecond timescales unlocks a direct route to extreme field generation using a coherent harmonic focus.

From 2014–2017, marine heatwaves caused global mass coral bleaching, where the corals lose their symbiotic algae. The authors find, this event exceeded the severity of all prior global bleaching events in recorded history, with approximately half the world’s reefs bleaching and 15% experiencing substantial mortality.

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.

Analysis of soundscape data from 139 globally distributed sites reveals that sounds of biological origin exhibit predictable rhythms depending on location and season, whereas sounds of anthropogenic origin are less predictable. Comparisons between paired urban–rural sites show that urban green spaces are noisier and dominated by sounds of technological origin.

Genome-wide association meta-analysis identifies 58 independent risk loci for major anxiety disorders among individuals of European ancestry and implicates GABAergic signaling as a potential mechanism underlying genetic risk for these disorders.

A phase 1 feasibility trial shows that bilateral deep brain stimulation within the central lateral thalamus can be safely applied and is associated with improved executive control.

This paper uses multiomics to profile a large cohort of meningioma samples to highlight the role of the tumor microenvironment in driving the epigenetic changes underpinning tumor classification and prediction of outcome.

Understanding the mechanisms behind clinical immunity to malaria is crucial for developing effective interventions. Here, the authors demonstrate that clinical immunity to Plasmodium vivax develops rapidly after a single controlled human malaria infection, reducing inflammatory responses and protecting against symptoms, while not significantly affecting parasite load.

Scourzic et al. show that germinal centre B cells display an enhanced ability to reprogram to induced pluripotent stem cells compared to mature B cells. This ability indicates their higher plasticity level and is T follicular helper cell-dependent.

Imprinting by influenza viruses can cause a deleterious shift of nearly the entire memory recall response against key, conserved epitopes.

Understanding the dual role of neuraminidase and hemagglutinin antibodies in influenza transmission is crucial for enhancing vaccine efficacy. Here, the authors use household transmission studies and mathematical models and find that neuraminidase immunity reduces infectivity, suggesting vaccines targeting both glycoproteins could lower community transmission and offer broader protection.

Lamin A/C in the nuclear lamina is identified as a regulator of cysteine catabolic flux, necessary for cell fate decisions and function.

High-depth sequencing of non-cancerous tissue from patients with metastatic cancer reveals single-base mutational signatures of alcohol, smoking and cancer treatments, and reveals how exogenous factors, including cancer therapies, affect somatic cell evolution.

Analyses of multiregional tumour samples from 421 patients with non-small cell lung cancer prospectively enrolled to the TRACERx study reveal determinants of tumour evolution and relationships between intratumour heterogeneity and clinical outcome.

Giles et al. developed a method for noninvasive absorbance measurement of mitochondrial hemes to monitor the mitochondrial membrane potential in the perfused heart. They then applied this approach to show how the mitochondrial membrane potential changed during cardiac ischemia.

Sarcomas are morphologically heterogeneous tumours rendering their classification challenging. Here the authors developed a classifier using DNA methylation data from several soft tissue and bone sarcoma subtypes, which has the potential to improve classification for research and clinical purposes.

Integrated multi-omic analyses using samples from the TRACERx study highlight cross-talk between DNA hypermethylation and genomic lesions in non-small cell lung cancer.

A study of several longitudinal birth cohorts and cross-sectional cohorts finds only moderate overlap in genetic variants between autism that is diagnosed earlier and that diagnosed later, so they may represent aetiologically different conditions.

A two-species eco-evolutionary model based on consumer–resource interactions and quantitative genetic inheritance shows how evolution among competitors changes the components of stable coexistence.

A longitudinal evolutionary analysis of 126 lung cancer patients with metastatic disease reveals the timing of metastatic divergence, modes of dissemination and the genomic events subject to selection during the metastatic transition.

Phylogenomic analysis of 7,923 angiosperm species using a standardized set of 353 nuclear genes produced an angiosperm tree of life dated with 200 fossil calibrations, providing key insights into evolutionary relationships and diversification.

Venous tumour thrombus can occur within renal cell carcinoma, and can require complex additional surgery and treatment. Here, the authors analyse multiparametric data from patients treated with axitinib and develop a machine learning model to predict neoadjuvant treatment response.

Openshaw and colleagues find myeloid inflammation and complement activation signatures in patients with long COVID who were previously hospitalized.

Mutations in the NRF2-KEAP1 pathway is found to be related with therapeutic resistance and poor outcomes of non-small cell lung cancer (NSCLC). Here this group reports that cystine/glutamate antiporter system xc−, controlled by NRF2, can be non-invasively imaged by positron emission tomography thereby providing a sensitive and specific marker of NRF2 activation in advanced preclinical models of NSCLC.

Immune lymphocyte estimation from nucleotide sequencing (ImmuneLENS) infers B cell and T cell fractions from whole-genome sequencing data. Applied to the 100,000 Genomes Project datasets, circulating T cell fraction provides sex-dependent and prognostic insights in patients.

Cross-culturally, humans have extensive childcare systems that help parents raise their children. Page et al. examine 1,701 alloparent–child dyads in Agta people, finding that both kin selection and reciprocity are important predictors of alloparenting.

This study identifies a set of risk factors that fully mediate and uniquely contribute to the relationship between sex assigned at birth and posttraumatic stress disorder severity.

Resting T cells are difficult to manipulate, and are a reservoir for latent HIV. Here, the authors develop a lipid nanoparticle formulation with the ability to transfect resting primary human T cells, enabling delivery of mRNAs that result in reactivation of latent HIV. This could help development of HIV cure strategies.

This study tests a key hypothesis of cerebellar motor correction, showing that inputs to the cerebellum that drive errors during skilled movements are rapidly adjusted over trials to enhance motor accuracy.

Hepatitis C virus (HCV) variability and its phenotypic consequences aren’t well studied in relation to viral replication fitness and disease severity. Here, the authors identify a replication-enhancing domain in non-structural protein 5A, linking high replication fitness to severe disease outcomes, with implications for understanding HCV pathogenesis in immunocompromised patients.

Genome-wide ancient DNA data from individuals from the Middle Bronze Age to Iron Age documents large-scale movement of people from the European continent between 1300 and 800 bc that was probably responsible for spreading early Celtic languages to Britain.

Combination of epidemiology, preclinical models and ultradeep DNA profiling of clinical cohorts unpicks the inflammatory mechanism by which air pollution promotes lung cancer

Results of the TRACERx study shed new light into the association between body composition and body weight with survival in individuals with non-small cell lung cancer, and delineate potential biological processes and mediators contributing to the development of cancer-associated cachexia.

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.

Whole-genome sequencing analysis of individuals with primary immunodeficiency identifies new candidate disease-associated genes and shows how the interplay between genetic variants can explain the variable penetrance and complexity of the disease.