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How Do Gepotidacin and Zoliflodacin Stabilize DNA-Cleavage Complexes with Bacterial Type IIA Topoisomerases? 2. A Single Moving Metal Mechanism.
Int J Mol Sci
December 2024
Medicines Discovery Institute, Cardiff University, Cardiff CF10 3AT, UK.
DNA gyrase is a bacterial type IIA topoisomerase that can create temporary double-stranded DNA breaks to regulate DNA topology and an archetypical target of antibiotics. The widely used quinolone class of drugs use a water-metal ion bridge in interacting with the GyrA subunit of DNA gyrase. Zoliflodacin sits in the same pocket as quinolones but interacts with the GyrB subunit and also stabilizes lethal double-stranded DNA breaks.
View Article and Find Full Text PDFBridging health registry data acquisition and real-time data analytics.
Front Med (Lausanne)
December 2024
Department II of Internal Medicine and Center for Molecular Medicine Cologne, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany.
The number of clinical studies and associated research has increased significantly in the last few years. Particularly in rare diseases, an increased effort has been made to integrate, analyse, and develop new knowledge to improve patient stratification and wellbeing. Clinical databases, including digital medical records, hold significant amount of information that can help understand the impact and progression of diseases.
View Article and Find Full Text PDFα-Catenin force-sensitive binding and sequestration of LZTS2 leads to cytokinesis failure.
J Cell Biol
March 2025
Department of Pulmonary Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Epithelial cells can become polyploid upon tissue injury, but mechanosensitive cues that trigger this state are poorly understood. Using an Madin Darby Canine Kidney (MDCK) cell knock-out/reconstitution system, we show that α-catenin mutants that alter force-sensitive binding to F-actin or middle (M)-domain promote cytokinesis failure and binucleation, particularly near epithelial wound-fronts. We identified Leucine Zipper Tumor Suppressor 2 (LZTS2), a factor previously implicated in abscission, as a conformation sensitive proximity partner of α-catenin.
View Article and Find Full Text PDFDevelopment of GaN-Based, 6.6 kW, 450 V, Bi-Directional On-Board Charger with Integrated 1 kW, 12 V Auxiliary DC-DC Converter with High Power Density.
Micromachines (Basel)
December 2024
Department of Electrical, Electronic, and Information Engineering "Guglielmo Marconi", University of Bologna, 40136 Bologna, Italy.
Automotive-grade GaN power switches have recently been made available in the market from a growing number of semiconductor suppliers. The exploitation of this technology enables the development of very efficient power converters operating at much higher switching frequencies with respect to components implemented with silicon power devices. Thus, a new generation of automotive power components with an increased power density is expected to replace silicon-based products in the development of higher-performance electric and hybrid vehicles.
View Article and Find Full Text PDFMedication non-adherence: reflecting on two decades since WHO adherence report and setting goals for the next twenty years.
Front Pharmacol
December 2024
Syreon Research Institute, Budapest, Hungary.
Background: Non-adherence to medication remains a persistent and significant challenge, with profound implications for patient outcomes and the long-term sustainability of healthcare systems. Two decades ago, the World Health Organization (WHO) dedicated its seminal report to adherence to long-term therapies, catalysing notable changes that advanced both research and practice in medication adherence. The aim of this paper was to identify the most important progress made over the last 2 decades in medication adherence management and to initiate a discussion on future objectives, suggesting priority targets for the next 20 years.
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