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Microbial constituents in the gastrointestinal tract, the urine and prostate tissue are being linked with clinical differences in prostate cancer, and a recent meta-analysis has linked periodontal disease to this cancer. Several hypotheses exist regarding how specific bacteria can contribute towards the development of prostate cancer. Recovering microbial genomes, and their genomic features, from clinical samples and investigating fine-scale taxonomy is a critical first step in investigating...

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Cys2-His2-zinc-finger proteins (C2H2-ZFPs) form the largest class of human transcription factors, yet their potential roles in higher-order genome organization remain poorly defined. To date, only a few C2H2-ZFPs, e.g. CTCF, have been implicated in chromatin organization. Here, we systematically examined the global relationship between C2H2-ZFPs and long-range chromatin interactions (LRIs). By integrating ChIP-seq datasets for 216 C2H2-ZFPs with genome-wide chromatin interaction maps, we find...

CONCLUSIONS: Our study identified differences in MLH1 and MSH2 cancer development which may suggest distinct mechanisms impacting CRC. The inverse relationship between adenoma detection and CRC risk in MSH2 carriers enhances our understanding of the adenoma-carcinoma sequence, while the lack of association in MLH1 carriers suggests alternative carcinogenic pathways requiring further study.

Prostate cancer is a common malignancy with a heterogeneous disease course. Prior studies have identified a paucity of point mutations in protein-coding genes and only a few clinically relevant driver alterations. Here, using the Pan Prostate Cancer Group whole genome sequencing dataset from 1001 men, we perform an integrative analysis of cancer driver genes by quantifying recurrent genomic alterations among small mutations, structural variants, and copy number alterations in 961 primary...

Ever since the observation of a robust heriditary component of autism, the scientific community has invested efforts and resources toward the identification of genetic variation associated with this condition. The current chapter provides an overview of of these efforts in a historical context, outlining how increasingly precise methods to query the genome along with unprecedented levels of international collaboration are starting to eludicate the complex genetic architecture of autism.

The first observation of a new meson state decaying into B_{c}^{+} and a photon is presented using a dataset of pp collisions at a center-of-mass energy sqrt[s]=13 TeV collected by the ATLAS detector at the Large Hadron Collider, corresponding to an integrated luminosity of 140 fb^{-1}. The B_{c}^{+} mesons are reconstructed from a three-muon final state from B_{c}^{+}→J/ψ(μ^{+}μ^{-})μ^{+}ν_{μ}X decays, along with photons reconstructed via conversions to electron-positron pairs in the detector...

CONCLUSIONS: CDK4/6 inhibitors are good candidates for further preclinical and clinical evaluation in combination with radiation in HPV-negative SCCs due to their effects on cell cycle phase in cells with Rb protein activity and low p16 levels. The long-term viability assay allows for efficient testing of drug/radiation combinations and can be considered for future experiments as part of a bench-to-bedside translational pipeline.

Chlorinated benzenes are persistent groundwater contaminants whose anaerobic transformation can depend on organohalide-respiring microorganisms embedded within metabolically interconnected communities. Here, we asked which microorganisms and metabolic functions characterize a Dehalobacter-containing dechlorinating community, and whether bioinformatics and genome-resolved metabolic modeling could identify candidate interactions supporting organohalide respiration. To address these questions, we...

Neuronal microexons are a highly conserved class of alternative splicing events enriched in genes with critical functions in nervous system biology^(1,2). Microexon splicing is often disrupted in the brains of autistic individuals, and mice with microexon deficiencies display autism-like phenotypes^(1,3,4). However, the full landscape of microexons is not known, and the impact of genetic variation on these exons has not been systematically investigated. Here, through extensive transcriptome...

Dysregulated immune activation at the vascular surface drives microvascular inflammation and tissue injury in many diseases, yet current therapies do not restore immune regulation at the blood-vessel interface. Terminal sialic acids engage inhibitory Siglec receptors on circulating immune cells and function as endogenous glyco-immune checkpoint ligands. Loss of sialylation on vascular endothelial cells during injury disrupts this regulatory axis and promotes vascular damage. Here, we introduce a...

BACKGROUND: Antineutrophil cytoplasmic antibody-associated vasculitis (AAV) is a complex autoimmune disease with distinct clinical and serological subtypes. Previous genome-wide association studies (GWAS) have identified several susceptibility loci, particularly within the major histocompatibility complex (MHC), but the broader genetic architecture and causal variants underlying AAV remain incompletely defined.

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Stroboscopic light stimulation (SLS) reliably evokes geometric visual hallucinations and, in some contexts, altered-state experiences. Its increasing use in research, public, recreational and exploratory clinical settings creates a need for proportionate safety guidance. The main concern is a visually triggered seizure in a susceptible individual; reported non-epileptic responses include discomfort or distress. We combined a retrospective survey of safety practices and reported events across...

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CONCLUSIONS: Pediatric CPA exhibits a dynamic, progressive course in which conversative management often leads to clinical deterioration. ISR was the most effective treatment for improving ischemic symptoms, highlighting the role of hypoperfusion in CPA. Collaborative prospective studies are needed to determine optimal management strategies for pediatric CPA.

DNA motif discovery and, particularly, computational modeling of transcription factor binding motifs, has been a mecca of algorithmic bioinformatics for several decades. Here, we report the results of the largest open community challenge in Inferring BInding Specificities (IBIS), where participants all over the world were invited to construct binding specificity models from multi-assay experimental data for poorly studied human transcription factors. The submissions were rigorously tested...

This Letter presents a combination of searches for Higgs boson pair (HH) production performed by the ATLAS and CMS Collaborations using proton-proton collision datasets recorded at sqrt[s]=13 TeV during the Large Hadron Collider Run 2, corresponding to integrated luminosities ranging between 126 and 140 fb^{-1}. The upper limit at the 95% confidence level on the total HH signal strength, defined as the ratio of the measured cross section to the standard model (SM) prediction, corresponds to 2.5,...

Cerebrospinal fluid (CSF) is the biofluid most proximal to the central nervous system (CNS), yet its proteomic organization across neurological disease remains unresolved. We assembled a meta-atlas of 35 CSF proteomic datasets (2016-2026) comprising 10,560 quality-controlled samples spanning neurodegenerative, neuroinflammatory, neuro-oncological, infectious and structural-injury contexts. Meta-analysis of cross-cohort detection defined a 747-protein core mass-spectrometry-accessible CSF...

Mass-spectrometry-based proteomics is rapidly advancing, becoming fast, affordable, and increasingly accessible to environmental scientists. This perspective outlines how proteomics can illuminate biotransformation processes and sublethal organism-level effects, and highlights future opportunities enabled by emerging technologies. Our goal is to give a concise overview on realistic expectations of current capabilities while inspiring scientists to adapt and develop novel proteomic approaches...