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Tumour hypoxia in driving genomic instability and tumour evolution.
Nat Rev Cancer
January 2025
Translational Oncogenomics Laboratory, Cancer Research UK Manchester Institute, University of Manchester, Manchester, UK.
Intratumour hypoxia is a feature of all heterogenous solid tumours. Increased levels or subregions of tumour hypoxia are associated with an adverse clinical prognosis, particularly when this co-occurs with genomic instability. Experimental evidence points to the acquisition of DNA and chromosomal alterations in proliferating hypoxic cells secondary to inhibition of DNA repair pathways such as homologous recombination, base excision repair and mismatch repair.
View Article and Find Full Text PDFStructure and function of a near fully-activated intermediate GPCR-Gαβγ complex.
Nat Commun
January 2025
Department of Molecular Biosciences, University of South Florida, 4202 E Fowler Ave, Tampa, FL, 33620, USA.
Unraveling the signaling roles of intermediate complexes is pivotal for G protein-coupled receptor (GPCR) drug development. Despite hundreds of GPCR-Gαβγ structures, these snapshots primarily capture the fully activated complex. Consequently, the functions of intermediate GPCR-G protein complexes remain elusive.
View Article and Find Full Text PDFIFN-γ licenses normal and pathogenic ALPK1/TIFA pathway in human monocytes.
iScience
January 2025
CIRI, Centre International de Recherche en Infectiologie, Inserm U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, University Lyon, F-69007 Lyon, France.
Alpha-kinase 1 (ALPK1) is an immune receptor sensing the bacterial nucleotide sugar ADP-heptose. ALPK1 phosphorylates TIFA leading to its oligomerization and downstream NF-κB activation. Specific mutations in are associated with an autoinflammatory syndrome termed ROSAH and with spiradenoma (skin cancers with sweat gland differentiation).
View Article and Find Full Text PDFTwo-pore channel regulators - Who is in control?
Front Physiol
January 2025
Walther Straub Institute of Pharmacology and Toxicology, Faculty of Medicine, Ludwig-Maximilians-University, Munich, Germany.
Two-pore channels (TPCs) are adenine nucleotide and phosphoinositide regulated cation channels. NAADP activates and ATP blocks TPCs, while the endolysosomal phosphoinositide PI(3,5)P activates TPCs. TPCs are ubiquitously expressed including expression in the innate as well as the adaptive immune system.
View Article and Find Full Text PDFElectrochemical aptasensor for the selective detection of vancomycin based on nanostructured "in-lab" printed electrodes.
Mikrochim Acta
January 2025
Department of Analytical Chemistry, Faculty of Pharmacy, "Iuliu Hațieganu" University of Medicine and Pharmacy, 4 Pasteur Street, 400349, Cluj-Napoca, Romania.
A label-free, flexible, and disposable aptasensor was designed for the rapid on-site detection of vancomycin (VAN) levels. The electrochemical sensor was based on lab-printed carbon electrodes (C-PE) enriched with cauliflower-shaped gold nanostructures (AuNSs), on which VAN-specific aptamers were immobilized as biorecognition elements and short-chain thiols as blocking agents. The AuNSs, characterized by scanning electron microscopy (SEM) and atomic force microscopy (AFM), enhanced the electrochemical properties of the platform and the aptamer immobilization active sites.
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