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Compound 38, a novel potent and selective antagonist of adenosine A receptor, enhances arousal in mice.
Acta Pharmacol Sin
January 2025
Department of Pharmacology, School of Basic Medical Sciences, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Joint International Research Laboratory of Sleep, Fudan University, Shanghai, 200032, China.
Adenosine A receptor (AR) plays a pivotal role in the regulation of sleep-wake behaviors. We previously reported an AR selective antagonist compound 38 with an IC value of 29.0 nM.
View Article and Find Full Text PDFBidirectional histone monoaminylation dynamics regulate neural rhythmicity.
Nature
January 2025
Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Histone H3 monoaminylations at Gln5 represent an important family of epigenetic marks in brain that have critical roles in permissive gene expression. We previously demonstrated that serotonylation and dopaminylation of Gln5 of histone H3 (H3Q5ser and H3Q5dop, respectively) are catalysed by transglutaminase 2 (TG2), and alter both local and global chromatin states. Here we found that TG2 additionally functions as an eraser and exchanger of H3 monoaminylations, including H3Q5 histaminylation (H3Q5his), which displays diurnally rhythmic expression in brain and contributes to circadian gene expression and behaviour.
View Article and Find Full Text PDFEffects of time-of-day on the noradrenaline, adrenaline, cortisol and blood lipidome response to an ice bath.
Sci Rep
January 2025
Professorship of Exercise Biology, Department Health and Sport Sciences, TUM School of Medicine and Health, Technical University of Munich, Munich, Germany.
While the effect of time-of-day (morning versus evening) on hormones, lipids and lipolysis has been studied in relation to meals and exercise, there are no studies that have investigated the effects of time-of-day on ice bath induced hormone and lipidome responses. In this crossover-designed study, a group of six women and six men, 26 ± 5 years old, 176 ± 7 cm tall, weighing 75 ± 10 kg, and a BMI of 23 ± 2 kg/mhad an ice bath (8-12 °C for 5 min) both in the morning and evening on separate days. Absence from intense physical exercise, nutrient intake and meal order was standardized in the 24 h prior the ice baths to account for confounders such as diet or exercise.
View Article and Find Full Text PDFBiochar filtration of drug-resistant bacteria and active pharmaceutical ingredients to combat antimicrobial resistance.
Sci Rep
January 2025
School of Engineering and Materials Science, Queen Mary University of London, Mile End Road, London, E1 4NS, UK.
Antimicrobial resistance (AMR) is a major cause of death worldwide, with 1.27 M direct deaths from bacterial drug-resistant infections as of 2019. Dissemination of multidrug-resistant (MDR) bacteria in the environment, in conjunction with pharmapollution by active pharmaceutical ingredients (APIs), create and foster an environmental reservoir of AMR.
View Article and Find Full Text PDFStructural basis of THC analog activity at the Cannabinoid 1 receptor.
Nat Commun
January 2025
Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark.
Tetrahydrocannabinol (THC) is the principal psychoactive compound derived from the cannabis plant Cannabis sativa and approved for emetic conditions, appetite stimulation and sleep apnea relief. THC's psychoactive actions are mediated primarily by the cannabinoid receptor CB. Here, we determine the cryo-EM structure of HU210, a THC analog and widely used tool compound, bound to CB and its primary transducer, G.
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