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Neural Plasticity in Migraine Chronification.
Eur J Neurosci
January 2025
Faculty of Medicine, Collegium Medicum, Mazovian Academy in Plock, Plock, Poland.
Chronic migraine (CM) is the ultimate and most burdensome form of the transformation from episodic migraine (EM), called chronification. The mechanism behind migraine chronification is poorly known and difficult to explore as CM has the same spectrum of pathogenesis as EM and the EM-CM transition is bidirectional. Central sensitization (CS) is a key phenomenon in migraine: its mechanisms include disturbed neural plasticity, which is the ability of the nervous system to adapt to endo- and exogenous changes.
View Article and Find Full Text PDFProbing the Signal Transduction Mechanism of the Light-Activated Adenylate Cyclase OaPAC Using Unnatural Amino Acid Mutagenesis.
ACS Chem Biol
January 2025
Department of Chemistry, Stony Brook University, Stony Brook, New York 11794-3400, United States.
OaPAC, the photoactivated adenylyl cyclase from , is composed of a blue light using FAD (BLUF) domain fused to an adenylate cyclase (AC) domain. Since both the BLUF and AC domains are part of the same protein, OaPAC is a model for understanding how the ultrafast modulation of the chromophore binding pocket caused by photoexcitation results in the activation of the output domain on the μs-s time scale. In the present work, we use unnatural amino acid mutagenesis to identify specific sites in the protein that are involved in transducing the signal from the FAD binding site to the ATP binding site.
View Article and Find Full Text PDFSignal Transduction Pathway Mediating Carotid Body Dependent Sympathetic Activation and Hypertension by Chronic Intermittent Hypoxia.
Function (Oxf)
January 2025
Institute for Integrative Physiology, Department of Medicine, Pritzker School of Medicine, University of Chicago, Chicago, IL. 60637, USA.
Patients with obstructive sleep apnea (OSA) experience chronic intermittent hypoxia (CIH). OSA patients and CIH-treated rodents exhibit overactive sympathetic nervous system and hypertension, mediated through hyperactive carotid body (CB) chemoreflex. Activation of olfactory receptor 78 (Olfr78) by hydrogen sulfide (H2S) is implicated in CB activation and sympathetic nerve responses to CIH, but the downstream signaling pathways remain unknown.
View Article and Find Full Text PDFMetabolically Stable Adenylation Inhibitors of Biotin Protein Ligase as Antibacterial Agents.
J Med Chem
January 2025
Department of Medicinal Chemistry, University of Minnesota, 308 Harvard Street SE, Minneapolis, Minnesota 55455, United States.
The antibacterial agent Bio-AMS is metabolized in vivo through hydrolysis of the central acyl-sulfamide linker leading to high clearance and release of a moderately cytotoxic metabolite . Herein, we disclose analogues designed to prevent the metabolism of the central acyl-sulfamide moiety through steric hindrance or attenuation of the acyl-sulfamide electrophilicity. was identified as a metabolically stable analogue with a single-digit nanomolar dissociation constant for biotin protein ligase (BPL) and minimum inhibitory concentrations (MICs) against and ranging from 0.
View Article and Find Full Text PDFA DNA phosphorothioation pathway via adenylated intermediate modulates Tdp machinery.
Nat Chem Biol
January 2025
Department of Gastroenterology, Hubei Clinical Center and Key Laboratory of Intestinal and Colorectal Disease, TaiKang Center for Life and Medical Sciences, Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University, Wuhan, China.
In prokaryotes, the non-bridging oxygen in the DNA sugar-phosphate backbone can be enzymatically replaced by a sulfur atom, resulting in phosphorothioate (PT) modification. However, the mechanism underlying the oxygen-to-sulfur substitution remains enigmatic. In this study, we discovered a hypercompact DNA phosphorothioation system, TdpABC, in extreme thermophiles.
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