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General anaesthetics have enjoyed long and widespread use but their molecular mechanism of action remains poorly understood. There is good evidence that their principal targets are pentameric ligand-gated ion channels (pLGICs) such as inhibitory GABA(A) (γ-aminobutyric acid) receptors and excitatory nicotinic acetylcholine receptors, which are respectively(More)
Replication Factor C (RFC) is required for the loading of Proliferating Cell Nuclear Antigen (PCNA) onto DNA during DNA replication, repair and recombination. RFC40, the second subunit of the RFC complex, and PCNA have been shown to be overexpressed in gestational trophoblastic diseases. Using RFC40 as the bait in a yeast two-hybrid screening, we have(More)
A prokaryotic member of the gamma-aminobutyric acid type A receptor superfamily (GLIC) was recently cloned from the cyanobacterium Gloeobacter violaceus, its function characterized, and its 3-dimensional x-ray diffraction crystal structure determined. We report its modulation by 9 anesthetics using 2-electrode voltage clamping in Xenopus laevis oocytes.(More)
Pentameric ligand-gated ion channels (pLGICs), which mediate chemo-electric signal transduction in animals, have been recently found in bacteria. Despite clear sequence and 3D structure homology, the phylogenetic distance between prokaryotic and eukaryotic homologs suggests significant structural divergences, especially at the interface between the(More)
INTRODUCTION Elevated concentrations of isovaleric (IVA), methylmalonic (MMA), and propionic acid are associated with impaired consciousness in genetic diseases (organic acidemias). We conjectured that part of the central nervous system depression observed in these disorders was due to anesthetic effects of these metabolites. We tested three hypotheses.(More)
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