The 4 functional segments of Factor H: Role in physiological target recognition and contribution to disease DOI Creative Commons
Peter F. Zipfel,

Karin Heidenreich

The Journal of Immunology, Journal Year: 2025, Volume and Issue: unknown

Published: May 12, 2025

Abstract Factor H controls proximal complement activation, and its dysfunction leads to diseases that often manifest in the kidney. Structural functional analyses have identified 4 distinct segments: an N-terminal regulatory unit, a cell binding segment with combined low-affinity C3b heparin sites, C-terminal recognition or sensor unit overlapping C3b/C3d sites. Three segments are linked diseases. The is affected C3 glomerulopathy antineutrophil cytoplasmic antibody–associated vasculitis. second includes Y402H polymorphism of age-related macular degeneration, associated different types cancer, targeted by pathogens. involved atypical hemolytic uremic syndrome, FHR1:FHR3 deficient autoantibody–positive syndrome form exploited function modulated like protein 1 FHR1, 2 plasma proteins share H. This interplay critical for fine-tuning local complement. Understanding H’s physiological role, as well impact absence, mutations, autoantibody targeting, provides insights into disease mechanisms opportunities therapeutic intervention using full-length H, fragments, complement-modulatory compounds.

Language: Английский

Anticancer Plant Secondary Metabolites Evicting Linker Histone H1.2 from Chromatin Activate Type I Interferon Signaling DOI Open Access
Olga Vlasova, Irina Antonova, Khamis Magomedova

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(1), P. 375 - 375

Published: Jan. 4, 2025

Previously we discovered that among 15 DNA-binding plant secondary metabolites (PSMs) possessing anticancer activity, 11 compounds cause depletion of the chromatin-bound linker histones H1.2 and/or H1.4. Chromatin remodeling or multiH1 knocking-down is known to promote upregulation repetitive elements, ultimately triggering an interferon (IFN) response. Herein, using HeLa cells and applying fluorescent reporter assay with flow cytometry, immunofluorescence staining quantitative RT-PCR, studied effects PSMs both evicting from chromatin not influencing their location in nucleus. We found (1) 8 PSMs, histone chromatin, activated significantly type I IFN signaling pathway out these resveratrol, berberine, genistein, delphinidin, naringenin curcumin also caused LINE1 expression. Fisetin quercetin, which induced eviction only signaling, but expression; (2) curcumin, sanguinarine kaempferol, causing significant H1.4 presence activate less intensively without any changes (3) four did eviction, displayed neither activation nor enhancement Thus, have shown for first time destabilization observed by accompanied expression often impacts this activation.

Language: Английский

Citations

0
Immunoredox model for interpretation and prediction of human diseases DOI
Young Jun Kim, Hyungdon Lee,

Sofian Abdul-Nasir

et al.

Molecular & Cellular Toxicology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 13, 2025

Language: Английский

Citations

0
Bridging peptide presentation and T cell recognition with multi-task learning DOI
Li Su, Duolin Wang, Dong Xu

et al.

Nature Machine Intelligence, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 20, 2025

Language: Английский

Citations

0
Prediction of the infecting organism in peritoneal dialysis patients with acute peritonitis using interpretable Tsetlin Machines DOI Creative Commons
Olga Tarasyuk, Anatoliy Gorbenko, Matthias Eberl

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: March 5, 2025

Abstract Motivation The analysis of complex biomedical datasets is becoming central to understanding disease mechanisms, aiding risk stratification and guiding patient management. However, the utility computational methods often constrained by their lack interpretability accessibility for non-experts, which particularly relevant in clinically critical areas where rapid initiation targeted therapies key. Results To define diagnostically immune signatures peritoneal dialysis patients presenting with acute peritonitis, we analysed a comprehensive array cellular soluble parameters cloudy effluents. Utilising Tsetlin Machines (TMs), logic-based machine learning approach, identified pathogen-specific fingerprints different bacterial groups, each characterised unique biomarker combinations. Unlike traditional ‘black box’ models such as artificial neural networks, TMs clear, logical rules dataset that pointed towards distinctly nuanced responses types infection. This demonstrates unambiguously even when infecting same anatomical location causing indistinguishable symptoms, type pathogens interacts specific way body’s system. Importantly, these could be easily visualised facilitate interpretation, thereby not only enhancing diagnostic accuracy but also potentially allowing rapid, accurate transparent decision-making based on patient’s profile. capacity help deliver clear actionable insights early support informed treatment choices advance conventional microbiological culture results, thus antibiotic stewardship contributing improved outcomes. Availability implementation All underlying tools present are available at https://github.com/anatoliy-gorbenko/biomarkers-visualization . anonymised data this article will shared reasonable request corresponding authors.

Language: Английский

Citations

0
The 4 functional segments of Factor H: Role in physiological target recognition and contribution to disease DOI Creative Commons
Peter F. Zipfel,

Karin Heidenreich

The Journal of Immunology, Journal Year: 2025, Volume and Issue: unknown

Published: May 12, 2025

Abstract Factor H controls proximal complement activation, and its dysfunction leads to diseases that often manifest in the kidney. Structural functional analyses have identified 4 distinct segments: an N-terminal regulatory unit, a cell binding segment with combined low-affinity C3b heparin sites, C-terminal recognition or sensor unit overlapping C3b/C3d sites. Three segments are linked diseases. The is affected C3 glomerulopathy antineutrophil cytoplasmic antibody–associated vasculitis. second includes Y402H polymorphism of age-related macular degeneration, associated different types cancer, targeted by pathogens. involved atypical hemolytic uremic syndrome, FHR1:FHR3 deficient autoantibody–positive syndrome form exploited function modulated like protein 1 FHR1, 2 plasma proteins share H. This interplay critical for fine-tuning local complement. Understanding H’s physiological role, as well impact absence, mutations, autoantibody targeting, provides insights into disease mechanisms opportunities therapeutic intervention using full-length H, fragments, complement-modulatory compounds.

Language: Английский

Citations

0