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We have recently identified and characterized the bacterial cyclic nucleotide gated (bCNG) subfamily of the larger mechanosensitive channel of small conductance (MscS) superfamily of ion channels. The channel domain of bCNG channels exhibits significant sequence homology to the mechanosensitive subfamily of MscS in the regions that have previously been used as a hallmark for channels that gate in response to mechanical stress. However, we have previously demonstrated that three of these channels are unable to rescue Escherichiacoli from osmotic downshock. Here, we examine an additional nine bCNG homologues and further demonstrate that the full-length bCNG channels are unable to rescue E. coli from hypoosmotic stress. However, limited mechanosensation is restored upon removal of the cyclic nucleotide binding domain. This indicates that the C-terminal domain of the MscS superfamily can drive channel gating and further highlight the ability of a superfamily of ion channels to be gated by multiple stimuli.
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http://dx.doi.org/10.1016/j.bbrc.2011.12.049 | DOI Listing |
RMD Open
December 2024
David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA.
Interstitial lung disease (ILD) associated with rheumatoid arthritis or with connective tissue diseases such as systemic sclerosis can be collectively named systemic autoimmune rheumatic disease-associated ILDs (SARD-ILDs) or rheumatic musculoskeletal disorder-associated ILDs. SARD-ILDs result in substantial morbidity and mortality, and there is a high medical need for effective therapies that target both fibrotic and inflammatory pathways in SARD-ILD. Phosphodiesterase 4 (PDE4) hydrolyses cyclic AMP, which regulates multiple pathways involved in inflammatory processes.
View Article and Find Full Text PDFPLoS One
December 2024
Chakri Naruebodindra Medical Institute, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bang Phli, Samut Prakarn, Thailand.
Secretory diarrhea, a major global health concern, particularly among young children, is often characterized by excessive chloride secretion through the cystic fibrosis transmembrane conductance regulator (CFTR) channel. Nornidulin, a fungus-derived natural product from Aspergillus unguis, has previously been shown to inhibit cAMP-induced Cl- secretion in T84 cells (human intestinal cell lines). However, the cellular mechanism of nornidulin in inhibiting cAMP-induced Cl- secretion and its anti-secretory efficacy is still unknown especially in a human colonoid model, a preclinical model recapitulating intestinal physiology in humans.
View Article and Find Full Text PDFOrg Biomol Chem
December 2024
Institute of Organic Chemistry, Albert-Ludwigs-Universität Freiburg, Albertstraße 21, 79104 Freiburg im Breisgau, Germany.
We introduce two water-soluble excited state intramolecular proton transfer (ESIPT) based fluorescent turn-on probes responding to inorganic polyphosphates. These ESIPT probes enable specific detection of short-chain inorganic polyphosphates over a range of different condensed phosphates. The probes are weakly emissive in their off-state due to the blocking of ESIPT by Cu coordination.
View Article and Find Full Text PDFBiol Pharm Bull
December 2024
Laboratory of Clinical and Translational Physiology, Kyoto Pharmaceutical University.
Mucociliary clearance (MCC) is a host defense mechanism of the respiratory system. Beating cilia plays a crucial role in the MCC process and ciliary beat frequency (CBF) is activated by several factors including elevations of the intracellular cAMP concentration ([cAMP]), intracellular Ca concentration ([Ca]), and intracellular pH (pH). In this study, we investigated whether an artichoke-extracted component cynaropicrin could be a beneficial compound for improving MCC.
View Article and Find Full Text PDFCell Rep
December 2024
Department of Anesthesiology, Huashan Hospital, Fudan University, Shanghai 200040, China. Electronic address:
Dissociation, characterized by altered consciousness and perception, underlies multiple mental disorders, but the specific neuronal subtypes involved remain elusive. In mice, we find that dissociation-inducing doses of ketamine significantly inhibit retrosplenial cortex (RSC) parvalbumin interneurons (PV-INs), enhancing delta oscillations (1-3 Hz) and delta-gamma phase-amplitude coupling (δ-γ PAC) and inducing dissociation-like behaviors. Optogenetic inhibition of RSC PV-INs triggers delta oscillations, δ-γ PAC, and some dissociation-like behaviors without ketamine.
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