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Exploring the Ascorbate Requirement of the 2-Oxoglutarate-Dependent Dioxygenases.
J Med Chem
January 2025
Ma̅tai Ha̅ora - Centre for Redox Biology and Medicine, Department of Biomedical Science and Pathology, University of Otago, Christchurch, Christchurch 8140, New Zealand.
In humans, the 2-oxoglutarate-dependent dioxygenases (2-OGDDs) catalyze hydroxylation reactions involved in cell metabolism, the biosynthesis of small molecules, DNA and RNA demethylation, the hypoxic response and the formation of collagen. The reaction is catalyzed by a highly oxidizing ferryl-oxo species produced when the active site non-heme iron engages molecular oxygen. Enzyme activity is specifically stimulated by l-ascorbic acid (ascorbate, vitamin C), an effect not well mimicked by other reducing agents.
View Article and Find Full Text PDFA Quantitative First Passage Time Model for Tubular Microfluidic Immunoassays.
ACS Sens
January 2025
Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China.
Solid-phase immunosorbent reactions, such as ELISA, are widely used for detecting, identifying, and quantifying protein markers. However, traditional centimeter scale well-based immunoreactors suffer from low surface-to-volume (S/V) ratios, leading to large sample consumption and a long assay time. Microfluidic technologies, particularly tubular microfluidic immunoreactors, have emerged as promising alternatives due to their high S/V ratios.
View Article and Find Full Text PDFSIV monoclonal antibody administration spanning treatment interruption in macaques delays viral rebound and selects escape variants.
Proc Natl Acad Sci U S A
February 2025
U.S. Military HIV Research Program, Center for Infectious Disease Research, Walter Reed Army Institute of Research, Silver Spring, MD 20910.
HIV-1 envelope broadly neutralizing antibodies represent a promising component of HIV-1 cure strategies. To evaluate the therapeutic efficacy of combination monoclonal antibodies (mAbs) in a rigorous nonhuman primate model, we tested different combinations of simian immunodeficiency virus (SIV) neutralizing mAbs in SIVmac251-infected rhesus macaques. Antiretroviral therapy-suppressed animals received anti-SIV mAbs targeting multiple Env epitopes spanning analytical treatment interruption (ATI) in 3 groups (n = 7 each): i) no mAb; ii) 4-mAb combination; and iii) 2-mAb combination.
View Article and Find Full Text PDFComputational analysis of the effect of a binding protein (RbpA) on the dynamics of Mycobacterium tuberculosis RNA polymerase assembly.
PLoS One
January 2025
Molecular Biophysics Unit, Indian Institute of Science, Bengaluru, Karnataka, India.
Article Synopsis
- RbpA is a critical protein for Mycobacterium tuberculosis growth, impacting transcription and antibiotic response, but its regulatory mechanisms are not fully understood.
- Significant structural changes in RNA polymerase occur when it interacts with RbpA, revealing important amino acids for transcription regulation and dynamic behavior of the complex.
- The study identifies potential ligands for RbpA's interaction site, laying the groundwork for future research on developing inhibitors that target RbpA's regulatory role in transcription.
Extended receptor repertoire of an adenovirus associated with human obesity.
PLoS Pathog
January 2025
Department of Clinical Microbiology, Umeå University, Umeå, Sweden.
Human adenovirus type 36 (HAdV-D36) has been putatively linked to obesity in animals and has been associated with obesity in humans in some but not all studies. Despite extensive epidemiological research there is limited information about its receptor profile. We investigated the receptor portfolio of HAdV-D36 using a combined structural biology and virology approach.
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