The paper describes the reactivity of fluorescein isothiocyanate towards the N-terminus of cytochromes P450 2B4 and 1A2 in solution, in the natural membrane of microsomes and in proteoliposomes (cholate and ultrasonic). The results obtained indicate, that the N-terminus of microsomal or proteoliposomal cytochromes P-450 2B4 and 1A2 spans the membrane only once and faces the vesicles interior. It was suggested that of major importance in orientation of N-terminal residues in the membrane is not the hydrophobic segment itself but rather the positively charged fragment, following it.
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Proc Natl Acad Sci U S A
November 2024
Department of Biochemistry, Rosalind and Morris Goodman Cancer Institute, McGill University, Montreal, QC H3A 1A3, Canada.
A critical host response against viral infections entails the activation of innate immune signaling that culminates in the production of antiviral proteins. DNA viruses are sensed by the cytosolic pattern recognition receptor cyclic GMP-AMP synthase (cGAS), which initiates a signaling pathway that results in production of proinflammatory cytokines such as Interferon-β (IFN-β) and activation of the antiviral response. Precise regulation of the antiviral innate immune response is required to avoid deleterious effects of its overactivation.
View Article and Find Full Text PDFPhys Med Biol
February 2024
Department of Engineering Physics, Polytechnique Montréal, Montréal, QC H3T 1J4, Canada.
A rise in blood flow velocity variations (i.e. pulsatility) in the brain, caused by the stiffening of upstream arteries, is associated with cognitive impairment and neurodegenerative diseases.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
November 2023
Max Planck Institute of Microstructure Physics, Weinberg 2, Halle, 06120, Germany.
Toxicol Appl Pharmacol
October 2023
Department of Medical Chemistry and Biochemistry, Faculty of Medicine and Dentistry, Palacky University, Hnevotinska 3, 77515 Olomouc, Czech Republic. Electronic address:
This study examined the biotransformation of phytocannabinoids in human hepatocytes. The susceptibility of the tested compounds to transformations in hepatocytes exhibited the following hierarchy: cannabinol (CBN) > cannabigerol (CBG) > cannabichromene (CBC) > cannabidiol (CBD). Biotransformation included hydroxylation, oxidation to a carboxylic acid, dehydrogenation, hydrogenation, dehydration, loss/shortening of alkyl, glucuronidation and sulfation.
View Article and Find Full Text PDFAm J Hum Genet
March 2020
Department of Human Genetics, McGill University, Montreal, QC H3A 1B1, Canada; Centre for Clinical Epidemiology, Department of Epidemiology, Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, QC H3T 1E2, Canada; Department of Medicine, McGill University Montreal, QC H3G 1Y6, Canada; Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, QC H3A 1A2, Canada; Department of Twin Research and Genetic Epidemiology, King's College London, London WC2R 2LS, UK. Electronic address:
We aimed to increase our understanding of the genetic determinants of vitamin D levels by undertaking a large-scale genome-wide association study (GWAS) of serum 25 hydroxyvitamin D (25OHD). To do so, we used imputed genotypes from 401,460 white British UK Biobank participants with available 25OHD levels, retaining single-nucleotide polymorphisms (SNPs) with minor allele frequency (MAF) > 0.1% and imputation quality score > 0.
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