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Analysis of whole-genome sequencing data across 2,658 tumors spanning 38 cancer types shows that chromothripsis is pervasive, with a frequency of more than 50% in several cancer types, contributing to oncogene amplification, gene inactivation and cancer genome evolution.

Analysis of mitochondrial genomes (mtDNA) by using whole-genome sequencing data from 2,658 cancer samples across 38 cancer types identifies hypermutated mtDNA cases, frequent somatic nuclear transfer of mtDNA and high variability of mtDNA copy number in many cancers.

Aging impacts lung functionality and makes it more susceptible to chronic diseases. Combining proteomics and single cell transcriptomics, the authors chart molecular and cellular changes in the aging mouse lung, discover aging hallmarks, and predict the cellular sources of regulated proteins.

Simon Gayther and colleagues report 3 new risk variants for mucinous ovarian carcinoma (MOC) on the basis of an analysis of 1,644 MOC cases and 21,693 controls. They confirm an eQTL association between the HOXD9 promoter and risk SNPs at 2q31.1 using chromosome conformation capture analysis and show that HOXD9 overexpression associates with neoplastic transformation.

Oestrogen negative breast cancer is associated with a poor prognosis. In this study, the authors perform a meta-analysis of 11 breast cancer genome-wide association studies and identify four new loci associated with oestrogen negative breast cancer risk. These findings may aid in stratifying patients in the clinic.

A transancestral exome-wide association study for body-fat distribution identifies protein-coding variants that are significantly associated with waist-to-hip ratio adjusted for body mass index.

Observations from the Lucy spacecraft of the small main-belt asteroid (152830) Dinkinesh reveals unexpected complexity, with a longitudinal trough and equatorial ridge, as well as the discovery of the first contact binary satellite.

Genome-wide analysis identifies 32 loci associated with breast cancer susceptibility, accounting for estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 status and tumor grade.

An analysis of 85 Ebola virus sequences collected in Guinea from July to November 2014 provides insight into the evolution of the Ebola virus responsible for the epidemic in West Africa; the results show sustained transmission of three co-circulating lineages, each defined by multiple mutations.

Whole-genome sequencing of healthy human epithelial crypts from the small intestines of 39 individuals highlights APOBEC enzymes as a common contributor to the overall mutational burden in this tissue.

Whether and how slow wave activity (SWA) and the underlying membrane potential UP and DOWN states initiate mechanisms that augment memory functions in humans are not fully understood. Here authors used multineuron patch-clamp in alive human brain tissue, resected during neurosurgeries, to show that membrane potential UP/DOWN states, which mimic neural sleep activity, modulate axonal action potentials to boost synaptic strength and plasticity.

Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.

Here, the authors present the structure of an orphan lipase in complex with an endogenous C18 monoacylglycerol ester reaction intermediate derived from the expression host, which along with enzymatic assays enabled functional assignment as a prototypical long-chain monoacylglycerol lipase.

Solitons are nonlinear waves that exist in diverse forms of matter. Here, Husko et al. use near-field measurements to observe the spatio-temporal evolution of optical pulses in a nanophotonic semiconductor waveguide, demonstrating that nonlinear photo-carrier generation can induce fission of solitons.

Genome-wide association meta-analyses of waist-to-hip ratio adjusted for body mass index in more than 224,000 individuals identify 49 loci, 33 of which are new and many showing significant sexual dimorphism with a stronger effect in women; pathway analyses implicate adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution.

Precision measurements provide a sensitive test of fundamental constants and their uncertainties. Here the authors precisely measure the hyperfine structure splitting in bismuth ions, and report significant discrepancy with the theoretical prediction of quantum electrodynamics.

Brown and beige adipose tissues contribute to organismal energy expenditure by generating heat. Here, Klepac et al. survey G protein-coupled receptors in brown fat and show that G_q-coupled receptors inhibit expression of thermogenic proteins in mice and in human adipocytes.

Paul Pharoah, Joellen Schildkraut, Thomas Sellers and colleagues report a meta-analysis of genome-wide association studies for epithelial ovarian cancer and genotyping using the iCOGS array in 18,174 cases and 26,134 controls from 43 studies from the Ovarian Cancer Association Consortium. They identify three new ovarian cancer susceptibility loci, including one specific to the serous subtype, and their integrated molecular analysis of genes and regulatory regions at these loci suggests disease mechanisms.

In this study, the authors report that bat H9N2 influenza A virus replicates and transmits in ferrets, efficiently infects human lung explant cultures, evades MxA antiviral activity in mice, and has low antigenic similarity to seasonal N2, meeting pre-pandemic criteria.

Reduced glomerular filtration rate (eGFR) is a hallmark of chronic kidney disease. Here, Pattaro et al. conduct a meta-analysis to discover several new loci associated with variation in eGFR and find that genes associated with eGFR loci often encode proteins potentially related to kidney development.

West Nile Virus is emerging as an important pathogen in Europe, likely driven by recent climate and land-use changes. Here, the authors estimate the extent of the climate change-driven impact by modelling the change in West Nile Virus ecological suitability across the continent in the absence of climate change.

Available enzymatic CO2 reduction strategies are not suitable for aerobic microorganisms and many industrial settings. Here, the authors design a new metabolic pathway that can operate under fully aerobic conditions, ambient CO2 levels, and seamlessly integrate with well-established C1-assimilation pathways.

Physical characterisation of proteins is challenging. Here the authors report single-molecule microfluidic diffusional sizing (smMDS) to enable calibration-free single-molecule diffusional-sizing based monitoring of protein hydrodynamic radii even within heterogenous multicomponent mixtures.

Similarities in cancers can be studied to interrogate their etiology. Here, the authors use genome-wide association study summary statistics from six cancer types based on 296,215 cases and 301,319 controls of European ancestry, showing that solid tumours arising from different tissues share a degree of common germline genetic basis.

Smallholder farmers will be impacted substantially by climate change and need to adapt. Agent-based modelling shows that interventions, particularly cash transfer paired with risk transfer mechanisms, lead to increased migration and uptake of cash crops, with higher income and lower inequality.

Use of an enhanced suite of marine ecosystem models and Earth system model outputs from Phase 6 of the Coupled Model Intercomparison Project (CMIP6) reveals greater decline in mean global ocean animal biomass than previously projected under both strong-mitigation and high-emissions scenarios.

A trans-ancestry meta-analysis of GWAS of glycemic traits in up to 281,416 individuals identifies 99 novel loci, of which one quarter was found due to the multi-ancestry approach, which also improves fine-mapping of credible variant sets.

Genome-wide association analyses of intracranial and nine subcortical brain volumes in 74,898 participants of European ancestry identify 254 independent loci and yield polygenic scores accounting for brain variation across ancestries.

Minguet and colleagues systematically examine how individual CD3 chains of the TCR–CD3 complex can improve chimeric antigen receptor (CAR) T cell performance.

This mass spectrometry-based proteomic study profiles the plasma proteome in 2,147 children and adolescents and reveals its association with age, sex, puberty, body mass index and genetics.

Plasmodium falciparum Snf2L is an ISWI-related ATPase that actively repositions P. falciparum nucleosomes in vivo.

CtBP is a transcriptional master co-repressor with oncogenic activity. Here, the authors use structural and biophysical methods to show that CtBP interacts with RAI2 through SLiMs that induce CtBP polymerization and inactivation.

There are many available ways to rank species for conservation prioritization. Here the authors identify species of mammals and birds that are both spatially restricted and functionally distinct, finding that such species are currently insufficiently protected and disproportionately sensitive to current and future threats.

Over 170 susceptibility loci have been identified by genome-wide association studies in breast cancer. Here, the authors interrogated the role of risk-associated variants from non-breast tissue, and using expression quantitative trait loci, identify potential target genes of known breast cancer susceptibility variants, as well as 11 regions not previously known to be associated with breast cancer risk.

In a large cohort of patients who underwent non-cardiac surgery, postoperative prescription of oral anticoagulation medication decreased the risk of stroke in patients with postoperative atrial fibrillation (POAF), especially for patients deemed to be at high risk for POAF based on a newly developed risk score.

Federated learning (FL) has emerged as a potential solution to train machine learning models in multiple clinical datasets while preserving patient privacy. Here, the authors develop an MRI-based FL platform for pediatric posterior fossa brain tumors—FL-PedBrain—and evaluate it on a diverse multi-center cohort.

Although vaccination drops COVID-19 mortality in older adults, post-vaccine fatal COVID-19 in nursing home outbreaks was linked to Delta, Gamma and Mu variants, persistently detected in aerosols. Mortality was predicted by IFNB1 or age, ORF7a and ACE2 mRNAs.

The production of ribosomes is a precisely orchestrated energy consuming cellular process of highest priority. Here, the authors use cryo-EM to show that bacterial ribosomal subunits, self-assembled from their purified RNA and protein components, mature along parallel pathways.

Complex experimental protocols often require multi-modal data acquisition with precisely aligned timing, as well as behaviour-dependent interventions. Here, authors describe a software with an intuitive user interface for flexible data acquisition without dedicated synchronisation hardware.

Histone deacetylase (HDAC) inhibitors, a class of cancer therapeutics, cause thrombocytopenia via an unknown mechanism. Here, the authors show that HDAC6 inhibition impairs proplatelet formation in human megakaryocytes, and show that this is linked to hyperacetylation of the actin-binding protein cortactin.

The hippocampus in mammalian brain varies in size across individuals. Here, Hibar and colleagues perform a genome-wide association meta-analysis to find six genetic loci with significant association to hippocampus volume.

This report from the 1000 Genomes Project describes the genomes of 1,092 individuals from 14 human populations, providing a resource for common and low-frequency variant analysis in individuals from diverse populations; hundreds of rare non-coding variants at conserved sites, such as motif-disrupting changes in transcription-factor-binding sites, can be found in each individual.

Here the authors apply machine learning approaches to Alzheimer’s genetics, confirm known associations and suggest novel risk loci. These methods demonstrate predictive power comparable to traditional approaches, while also offering potential new insights beyond standard genetic analyses.

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.

Serology is an important way to monitor SARS-CoV-2 infection in the population and support vaccine development. Here the authors develop a multiplex immunoassay including spike and nucleocapsid proteins of SARS-CoV-2 and the endemic human coronaviruses with high specificity and sensitivity.