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Bacteriophages (phages), viral predators of bacteria, generate selection pressure that causes bacteria to evolve defence systems. Type I, II and III restriction enzymes cleave incoming non-modified phage DNAs. Phages have evolved to defend against these restriction systems by modifying their DNA so that they are no longer suitable substrates. Type IV restriction enzymes have evolved to recognize and cleave modified DNA. We have recently characterized and solved the first structure for the Type IV GmrSD-family enzymes, using the BrxU homologue from . Though promiscuous in target modifications, little is known about BrxU substrate preference. We used modified DNAs in assays to characterize the substrate preferences of BrxU and investigate the impact of the GmrSD-inhibitor IPI* on BrxU activity. These data extend our knowledge of phage-host interactions and inform mechanistic studies on the reaction cycle of BrxU and GmrSD homologues.This article is part of the discussion meeting issue 'The ecology and evolution of bacterial immune systems'.
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http://dx.doi.org/10.1098/rstb.2024.0072 | DOI Listing |
Nat Aging
September 2025
Department of Clinical Molecular Biology, University of Oslo and Akershus University Hospital, Lørenskog, Norway.
Beyond their classical functions as redox cofactors, recent fundamental and clinical research has expanded our understanding of the diverse roles of nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP) in signaling pathways, epigenetic regulation and energy homeostasis. Moreover, NAD and NADP influence numerous diseases as well as the processes of aging, and are emerging as targets for clinical intervention. Here, we summarize safety, bioavailability and efficacy data from NAD-related clinical trials, focusing on aging and neurodegenerative diseases.
View Article and Find Full Text PDFExp Neurobiol
August 2025
Institute of Medical Science, Ajou University School of Medicine, Suwon 16499, Korea.
Neural tumors represent diverse malignancies with distinct molecular profiles and present particular challenges due to the blood-brain barrier, heterogeneous molecular etiology including epigenetic dysregulation, and the affected organ's critical nature. KCC-07, a selective and blood-brain barrier penetrable MBD2 (methyl CpG binding domain protein 2) inhibitor, can suppress tumor development by inducing p53 signaling, proven only in medulloblastoma. Here we demonstrate KCC-07 treatment's application to other neural tumors.
View Article and Find Full Text PDFAdv Drug Deliv Rev
September 2025
Biochemistry, CUNY Graduate Center, The City University of New York, 365 Fifth Avenue, New York, NY 10016, United States; Molecular, Cellular, and Developmental Biology, CUNY Graduate Center, The City University of New York, 365 Fifth Avenue, New York, NY 10016, United States; Chemistry, CUNY Gradua
Targeted drug delivery significantly enhances therapeutic efficacy across various diseases, particularly in cancer treatments, where conventional approaches such as chemotherapy and radiotherapy often cause severe side effects. In this context, nucleic acid aptamers-short, single-stranded DNA or RNA oligonucleotides capable of binding specific targets with high affinity-have emerged as promising tools for precision drug delivery and therapy. Aptamers can be selected against whole, living cells using SELEX and chemically modified for diverse applications.
View Article and Find Full Text PDFMikrochim Acta
September 2025
Department of Public Health Laboratory Sciences, College of Public Health, Hengyang Medical School, University of South China, 28 Changsheng West Road, Hengyang, 421001, Hunan, China.
We systematically evaluated the DNA adsorption and desorption efficiencies of several nanoparticles. Among them, titanium dioxide (TiO₂) nanoparticles (NPs), aluminum oxide (Al₂O₃) NPs, and zinc oxide (ZnO) NPs exhibited strong DNA-binding capacities under mild conditions. However, phosphate-mediated DNA displacement efficiencies varied considerably, with only TiO₂ NPs showing consistently superior performance.
View Article and Find Full Text PDFJ Am Chem Soc
September 2025
Life-like Materials and Systems, University of Mainz, Duesbergweg 10-14, 55128 Mainz, Germany.
Transmembrane signaling is essential for cellular communication, yet reconstituting such mechanisms in synthetic systems remains challenging. Here, we report a simple and robust DNA-based mechanism for transmembrane signaling in synthetic cells using cholesterol-modified single-stranded DNA (Chol-ssDNA). We discovered that anchored Chol-ssDNA spontaneously flips across the membrane of giant unilamellar lipid vesicles (GUVs) in a nucleation-driven, defect-mediated process.
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