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Many premalignant colorectal polyps in familial adenomatous polyposis arise polyclonally rather than from a single mutated cell, showing diverse early evolutionary trajectories that frequently occur without clonal APC or KRAS driver events.

In pelvic inflammatory disease, host immune responses to Neisseria gonorrhoeae damage Fallopian tube tissue and cause infertility. Here, Garcia et al. show that the cytokine IL-17C induces inflammatory responses, and peptidoglycan fragments reduce transcripts related to tissue integrity.

Metastatic dissemination contributes to the lethality in pancreatic ductal adenocarcinoma (PDAC). Here, the authors perform RNA-sequencing on patient derived circulating tumor cells (CTCs) and identify three major CTC subgroups, and show the therapeutic potential of targeting LIN28B/let-7 pathway to halt cancer metastasis.

Solar wind is highly structured yet variable. Close-up observations of the solar atmosphere reveal that the changing connectivity of multiple sources in the solar corona drives the observed complexity and variability in the inner heliosphere.

Dubois and colleagues assemble a large cohort of human pediatric high-grade glioma samples, identifying patterns of simple and complex structural variants and characterizing their role in tumor development and evolution.

Using data from a single time point, passenger-approximated clonal expansion rate (PACER) estimates the fitness of common driver mutations that lead to clonal haematopoiesis and identifies TCL1A activation as a mediator of clonal expansion.

Short-lived halogens have a substantial indirect cooling effect on climate and this cooling effect has increased since pre-industrial times owing to anthropogenic amplification of natural halogen emissions.

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.

Oxytocin promotes social behaviors, but its cortical targets remain unclear. Here, authors show that oxytocin activates local interneurons in the rat prefrontal cortex, enhancing sociability through top-down control of the basolateral amygdala.

Saturation genome editing of a cancer mutation hotspot in CTNNB1, the gene encoding β-catenin, reveals a gradient of effects of missense mutations on Wnt signaling.

Population-scale WGS reveals genetic determinants of persistent EBV DNA, linking immune regulation—especially antigen processing and MHC class II variation—to EBV persistence and heterogeneous disease associations.

Sabatino and colleagues examine expanded CD8⁺ T cell clonotypes from a small cohort of multiple sclerosis patients. They identified several cognate peptide epitopes that derive from Epstein–Barr virus, suggesting EBV reactivation may drive pathogenesis in these patients.

Large swathes of standing dead trees or ‘ghost forests’ can form owing to rising sea levels in coastal areas, but the extent to which this occurs is unclear. This study maps ghost forests at the individual tree level along the US Atlantic coastal region.

Achieving high resolution with optical neural interfaces is challenging. Here, the authors developed and chronically implanted 100-pixel microLED arrays on the surface of the mouse auditory cortex for optogenetic behavioural experiements.

The authors previously pinpointed OLAH (oleoyl-ACP-hydrolase) as a driver of life-threatening viral diseases. Here, the authors identify increased IL-18Rα expression on CD8⁺ T cells, which acquire a reduced cytotoxic signature, correlates with severe respiratory viral infection of influenza A virus, RSV and COVID-19.

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

Analysis of 97,691 high-coverage human blood DNA-derived whole-genome sequences enabled simultaneous identification of germline and somatic mutations that predispose individuals to clonal expansion of haematopoietic stem cells, indicating that both inherited and acquired mutations are linked to age-related cancers and coronary heart disease.

Patient-derived xenograft models (PDX) have been extensively used to study the molecular and clinical features of cancers. Here the authors present a cohort of 536 PDX models from 25 cancers, as well as their genomic and evolutionary profiles and their suitability for clinical trials.

Some cancers occur in spatially constrained tissues such as the mammary gland, and how the morphological features influence the evolution of the cancer is unclear. Here, the authors use mathematical modeling to study the question of competition for space and provide inferences on the mode of evolution of cancers in such tissues.

This paper compares the frequency and genetic basis of clonal hematopoiesis in 136,401 admixed American participants from the Mexico City Prospective Cohort with 416,118 largely European ancestry individuals from the UK Biobank cohort.

van der Sleen et al. introduce the use of an autoregressive null model to explain low-frequency variability in populations of marine fishes. Using time series of fisheries landings from a global database, their model shows that interannual sea surface temperature variation is integrated through each trophic level of the food web and can underlie observed low-frequency population dynamics.

Gene-based rare variant aggregation study with the levels of 1,294 plasma and 1,396 urine metabolites from paired specimens of 4,737 participants reveals graded effects of rare, putatively damaging variants on gene function and human traits.

Glioblastoma (GBM) is characterized by a high degree of heterogeneity and plasticity due to interplay with neural developmental programs. Here, the authors develop a model of GBM by introducing sequential oncogenic mutations in human neural stem cells and using this, identify INSM1 as a driver of a neural progenitor gene network promoting tumorigenesis.

The GLASS Consortium studies the evolutionary trajectories of 222 patients with a diffuse glioma to aid in our understanding of tumour progression and treatment failure

Few cancer drivers in non-coding regions have been identified so far. Here, the authors develop a transcription factor-aware burden test to predict non-coding variants and analyze the impact on transcription factor binding - especially ETS factors - as well as their impact on transcriptional activity.

Chronic myelomonocytic leukaemia is classified as proliferative (pCMML) or dysplastic based on the white blood cell counts but biological differences are unclear. Here, the authors show genetic, transcriptomic and epigenomic differences between these two subtypes establishing that pCMML is RAS-pathway driven and that inhibiting RAS-driven PLK1 expression is a viable therapeutic target.

Animal studies have shown that the nutritional status of parents can predispose the offspring to obesity and obesity-related diseases. Here the authors show that cardiac dysfunction induced by a high-fat diet persists for two generations in Drosophila, and that targeted expression of ATGL/bmm in the offspring, as well as inhibition of H3K27 trimethylation, is cardioprotective.

Multisystem inflammatory syndrome in children (MIS-C) onsets in COVID-19 patients with manifestations similar to Kawasaki disease (KD). Here the author probe the peripheral blood transcriptome of MIS-C patients to find signatures related to natural killer (NK) cell activation and CD8+ T cell exhaustion that are shared with KD patients.

Inherited mitochondrial DNA mutations can result in diverse clinical phenotypes. Here, the authors characterise a heteroplasmic tRNA^Ala mutation (m.5019A>G) in mice and demonstrate that macrophages carrying this mutation display altered function and metabolism in vitro, along with increased type I IFN release following LPS challenge in vivo.

CRISPR-Cas9 gene editing can induce a p53 mediated damage response. Here the authors investigate the possibility of selection of pre-existing cancer driver mutations during CRISPR-Cas9 knockout based gene editing and identify KRAS mutants that may confer a selected advantage to edited cells.

Clonal haematopoiesis (CH) has been associated with altered inflammatory profiles and increased risk of cardiovascular and malignant diseases. Here, the authors analyze patient data from two different cohorts and show that CH is associated with severe infections and severe Covid19.

An atlas study of adipose tissue in people with obesity undergoing weight loss and their lean counterparts reveals that weight loss reduces cell senescence but cannot reverse all the metabolic problems caused by obesity.

U.S. market data from 2012 to 2022 show that increasing transmission capacity is cost-effective. Benefits are often balanced across regions and concentrated during peak periods driven by short-term events, yet major barriers still prevent grid infrastructure from being developed.

Here, the authors examine the mechanisms behind cheatgrass’s successful invasion of North American ecosystems. Their genetic analyses and common garden experiments demonstrate that multiple introductions and migrations facilitated cheatgrass local adaptation.

Iron–sulfur minerals play critical roles in regulating nitrogen cycling under anoxic conditions. This study shows that pyrrhotite with abundant iron vacancies promotes electron transfer and microbial nitrate reduction to dinitrogen.

This study reconstructs the evolution of leaf venation networks, describing the transition from fewer, corrugated veins to high vein density and smoother loops. It also suggests herbivory as a potential driver of venation architectural changes.

Dissecting the adaptive exercise response of the neurogenic stem-cell niche in the dentate gyrus by single-nucleus RNA sequencing reveals the molecular mediators that underlie exercise’s protective effects in Alzheimer’s disease.

Dietary restriction promotes the expansion of effector T cells via ketone bodies, which enhances anti-tumour immunity and synergizes with immunotherapy in mice.

A pan-cancer epigenetic and transcriptomic atlas identifies epigenetic drivers associated with cancer transitions.

A consensus cell type atlas for the fly brain provides both an intellectual framework and open-source toolchains for brain-scale comparative connectomics.

Shlien and colleagues report on 300 patients from the SickKids Cancer Sequencing program and identify clinically actionable variants in 56% of the patients by profiling somatic and germline data at multiple clinical time points.

KRAB-zinc finger proteins repress retrotransposons and rapidly evolve in mammals. Here, the authors show that ERV insertions drive the emergence and diversification of new KZFP genes in mice, revealing a co-evolutionary mechanism between retroviruses and host repressors.

Lung cancer etiology has largely been studied in homogenous populations of European descent. Here, targeted sequencing in African American lung adenocarcinomas finds significantly higher prevalence of PTPRTand JAK2 mutations, validated independently by whole exome sequencing, highlighting potentially clinically actionable mutations in this population.

The relationship between pathogenic germline variation, clonal hematopoiesis (CH) and risk of hematologic malignancy is explored in 731,835 individuals across 6 cohorts. Carriers of variants in certain genes show distinct patterns of CH and increased risk of CH progression to malignancy.

In the past three decades, fish abundance, richness and uniqueness have diverged across cold and warm streams, and the effects on native fish communities of stream warming and increases in introduced fishes have magnified each other.

Using an adeno-associated virus–mediated, direct in vivo CRISPR screen, the authors mapped a quantitative landscape of glioblastoma suppressors. Their study revealed gene combinations that functionally drive gliomagenesis from normal glia in native mouse brains. The authors further demonstrate that mutational background can differentially influence gene expression and chemotherapeutic resistance.

Tan et al. identify PRDM16 as a key repressor of fibrotic switching in smooth muscle cells and show that its downregulation in atherosclerosis drives smooth muscle cells toward a synthetic fate, promoting fibrous plaques.