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Philip A Gale - One of the best experts on this subject based on the ideXlab platform.
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fatty acid fueled transmembrane Chloride Transport
Journal of the American Chemical Society, 2019Co-Authors: Ethan N W Howe, Philip A GaleAbstract:Generation of chemical gradients across biological membranes of cellular compartments is a hallmark of all living systems. Here we report a proof-of-concept prototype transmembrane pumping system in liposomes. The pump uses fatty acid to fuel Chloride Transport, thus generating a transmembrane Chloride gradient. Addition of fatty acid to phospholipid vesicles generates a transmembrane pH gradient (pHin < pHout), and this electrochemical H+ potential is harnessed by an anionophore to drive Chloride efflux via H+/Cl– coTransport. Further addition of fatty acid efficiently fuels the system to continuously drive Chloride Transport against the concentration gradient, up to [Cl–]in 65 mM | [Cl–]out 100 mM, and is 1400 times more efficient than using an external fuel. Based on our findings from dissecting the H+/Cl– flux process with the use of different liposomal fluorescence assays, and supported by additional liposome-based 13C NMR and DLS studies; we proposed that the presence of an anionophore can induce as...
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tunable transmembrane Chloride Transport by bis indolylureas
Chemical Science, 2012Co-Authors: Cally J E Haynes, Stephen J Moore, Jennifer R Hiscock, Igor Marques, Paulo J Costa, Vitor Felix, Philip A GaleAbstract:A series of bis-indolylureas have been found to mediate Chloride Transport across vesicle bilayers. The anion Transport activity of these receptors may be readily modulated by small structural changes to the receptor scaffold as shown by the combination of experimental Chloride efflux studies and molecular dynamics simulations in water and POPC bilayers.
Jonas Hühn - One of the best experts on this subject based on the ideXlab platform.
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liposome based measurement of light driven Chloride Transport kinetics of halorhodopsin
Biochimica et Biophysica Acta, 2021Co-Authors: Hasin Feroz, Carol S. Baker, John P. Gajewski, Daniel J. Lugar, Sandeep B. Gaudana, Bryan Ferlez, Peter J Butler, Hossein Mohammadiarani, Tingwei Ren, Jonas HühnAbstract:We report a simple and direct fluorimetric vesicle-based method for measuring the Transport rate of the light-driven ions pumps as specifically applied to the Chloride pump, halorhodopsin, from Natronomonas pharaonis (pHR). Previous measurements were cell-based and methods to determine average single channel permeability challenging. We used a water-in-oil emulsion method for directional pHR reconstitution into two different types of vesicles: lipid vesicles and asymmetric lipid-block copolymer vesicles. We then used stopped-flow experiments combined with fluorescence correlation spectroscopy to determine per protein Cl- Transport rates. We obtained a Cl- Transport rate of 442 (±17.7) Cl-/protein/s in egg phosphatidyl choline (PC) lipid vesicles and 413 (±26) Cl-/protein/s in hybrid block copolymer/lipid (BCP/PC) vesicles with polybutadine-polyethylene oxide (PB12PEO8) on the outer leaflet and PC in the inner leaflet at a photon flux of 1450 photons/protein/s. Normalizing to a per photon basis, this corresponds to 0.30 (±0.07) Cl-/photon and 0.28 (±0.04) Cl-/photon for pure PC and BCP/PC hybrid vesicles respectively, both of which are in agreement with recently reported turnover of ~500 Cl-/protein/s from flash photolysis experiments and with voltage-clamp measurements of 0.35 (±0.16) Cl-/photon in pHR-expressing oocytes as well as with a pHR quantum efficiency of ~30%.
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Light-Driven Chloride Transport Kinetics of Halorhodopsin
Biophysical Journal, 2018Co-Authors: Hasin Feroz, Cécile Lefoulon, Carol S. Baker, John P. Gajewski, Daniel J. Lugar, Sandeep B. Gaudana, Bryan Ferlez, Peter J Butler, Jonas HühnAbstract:Abstract Despite growing interest in light-driven ion pumps for use in optogenetics, current estimates of their Transport rates span two orders of magnitude due to challenges in measuring slow Transport processes and determining protein concentration and/or orientation in membranes in vitro. In this study, we report, to our knowledge, the first direct quantitative measurement of light-driven Cl − Transport rates of the anion pump halorohodopsin from Natronomonas pharaonis ( Np HR). We used light-interfaced voltage clamp measurements on Np HR-expressing oocytes to obtain a Transport rate of 219 (± 98) Cl − /protein/s for a photon flux of 630 photons/protein/s. The measurement is consistent with the literature-reported quantum efficiency of ∼30% for Np HR, i.e., 0.3 isomerizations per photon absorbed. To reconcile our measurements with an earlier-reported 20 ms rate-limiting step, or 35 turnovers/protein/s, we conducted, to our knowledge, novel consecutive single-turnover flash experiments that demonstrate that under continuous illumination, Np HR bypasses this step in the photocycle.
Jacky Jacquot - One of the best experts on this subject based on the ideXlab platform.
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enhanced f508del cftr channel activity ameliorates bone pathology in murine cystic fibrosis
American Journal of Pathology, 2014Co-Authors: Carole Le Henaff, Frederic Velard, Olivier Tabary, Caroline Marty, Pierre J Marie, Jacky JacquotAbstract:In patients with cystic fibrosis (CF), rib and thoracic vertebral fractures can have adverse effects on lung health because the resulting pain and debilitation can impair airway clearance. The F508del mutation in the CF transmembrane conductance regulator ( Cftr ) gene induces an osteopenic phenotype in humans and mice. N -butyldeoxynojyrimicin (miglustat), an approved drug for treating type 1 Gaucher disease, was found to normalize CFTR-dependent Chloride Transport in human F508del CFTR lung cells and in nasal mucosa of F508del CF mice. Herein, we investigated whether targeting F508del-CFTR may rescue the skeletal osteopenic phenotype in murine CF. We found that oral administration of low-dose miglustat (120 mg/kg once a day for 28 days) improved bone mass and microarchitecture in the lumbar spine and femur in F508del mice. The increased bone density was associated with an increased bone formation rate and reduced bone resorption. This effect was associated with increased 17β-estradiol but not with insulin-like growth factor 1 serum levels in miglustat-treated F508del mice. Exposure of primary F508del osteoblasts to miglustat partially restored the deficient CFTR-dependent Chloride Transport in these bone-forming cells. This study provides evidence that reversal of CFTR-dependent Chloride Transport in osteoblasts normalizes bone mass and microarchitecture in murine CF. These findings may provide a potential therapeutic strategy to prevent or correct the bone disease in patients with CF.
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enhanced f508del cftr channel activity ameliorates bone pathology in murine cystic fibrosis
American Journal of Pathology, 2014Co-Authors: Carole Le Henaff, Frederic Velard, Olivier Tabary, Caroline Marty, Pierre J Marie, Jacky JacquotAbstract:In patients with cystic fibrosis (CF), rib and thoracic vertebral fractures can have adverse effects on lung health because the resulting pain and debilitation can impair airway clearance. The F508del mutation in the CF transmembrane conductance regulator ( Cftr ) gene induces an osteopenic phenotype in humans and mice. N -butyldeoxynojyrimicin (miglustat), an approved drug for treating type 1 Gaucher disease, was found to normalize CFTR-dependent Chloride Transport in human F508del CFTR lung cells and in nasal mucosa of F508del CF mice. Herein, we investigated whether targeting F508del-CFTR may rescue the skeletal osteopenic phenotype in murine CF. We found that oral administration of low-dose miglustat (120 mg/kg once a day for 28 days) improved bone mass and microarchitecture in the lumbar spine and femur in F508del mice. The increased bone density was associated with an increased bone formation rate and reduced bone resorption. This effect was associated with increased 17β-estradiol but not with insulin-like growth factor 1 serum levels in miglustat-treated F508del mice. Exposure of primary F508del osteoblasts to miglustat partially restored the deficient CFTR-dependent Chloride Transport in these bone-forming cells. This study provides evidence that reversal of CFTR-dependent Chloride Transport in osteoblasts normalizes bone mass and microarchitecture in murine CF. These findings may provide a potential therapeutic strategy to prevent or correct the bone disease in patients with CF.
Ha Won Song - One of the best experts on this subject based on the ideXlab platform.
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factors influencing Chloride Transport and Chloride threshold level for the prediction of service life of concrete structures
International Journal of Structural Engineering, 2010Co-Authors: Ha Won Song, Seungwoo PackAbstract:In this study, the influence of parametric values on the risk of steel corrosion in concrete was quantitatively calculated in terms of the sensitivity to service life of concrete structures subjected Chloride attack. Prior to the analysis, a thorough literature review on the Chloride threshold level (CTL) for steel corrosion and the rate of Chloride Transport was performed to define the influencing factors. As a result, it was found that the CTL can be quantitatively represented in the form of total Chloride content by weight of cement, reflecting both the corrosiveness and inhibition effect. For Chloride Transport, diffusion is the main driving force for Chloride ions in concrete, although other driving forces such as permeation and sorption simultaneously exist. Finally, the sensitivity analysis of parametric values using the Fick's second law for the prediction of service life of concrete structures due to Chloride induced corrosion found that the concrete cover depth is the most influencing to the time to corrosion, followed by the surface Chloride concentration, apparent diffusion coefficient and the CTL.
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prediction of time dependent Chloride Transport in concrete structures exposed to a marine environment
Cement and Concrete Research, 2010Co-Authors: Seungwoo Pack, Min Sun Jung, Ha Won SongAbstract:Abstract A survey of 11 concrete bridges located in a marine environment at 0.65–48.65 years was examined in terms of Chloride Transport. As a result, the apparent diffusion coefficient ( D ) and the surface Chloride concentration ( C S ) are time dependent; the D exponentially decreased with time and the C S increased in the form of a logarithm function to time. Using these data, governing equations for the D and C S were derived to predict the Chloride Transport in a long term. The time dependent model indicated the higher Chloride ingresses in ordinary Portland cement (OPC) concrete than the time independent model, due to a build-up of the C S with time, but ground granulated blast furnace slag (GGBS) concrete indicated a similar range of the Chloride ingresses, due to the rapid decrease in the D . To ensure the accuracy of the model that the present study suggested, the fitted model was compared to the well known model of the LIFE 365 together with a Chloride profile obtained from an in-situ examination. Then it was found that the model in the present study well predicted the rate of Chloride Transport, while the LIFE 365 indicated a poor description of the Chloride ingress in a long term, due to a constant C S and an overwhelming rapid decrease in the D .
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factors influencing Chloride Transport in concrete structures exposed to marine environments
Cement & Concrete Composites, 2008Co-Authors: Ha Won SongAbstract:Abstract The present study concerns a literature review regarding Chloride Transport in terms of the diffusion coefficient (D) and surface Chloride content (CS) in concrete structures exposed to a marine environment. In addition, a refined model is proposed for D and CS for time-dependent Chloride Transport. It is found that both D and CS are time-dependent: D decreases and CS increases with time, due to further cement hydration development. D and CS are significantly influenced by concrete mix proportion, air void content in concrete, curing methods, degree of exposure to seawater and climate. Blended cement concretes are beneficial in decreasing D, but increase CS, presumably due to a refinement of the concrete pore structures and Chloride binding. An increase in the air void content in concrete increases D, but decreases CS. The CS depends on curing methods such as water, membrane and aeration. The degree of exposure to seawater does not have a clear relationship with CS: higher exposure levels did not result in a higher level of CS. Exposure in tropical areas results in higher CS in concrete jetty structures with a similar level of D, mainly due to an increased temperature and concentration of salinity. Based on these findings, a refined model for CS was proposed to provide more realistic prediction of the build-up of Chlorides by Chloride Transport in concrete structures exposed to marine environments.
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factors influencing Chloride Transport in concrete structures exposed to marine environments
Cement & Concrete Composites, 2008Co-Authors: Ha Won Song, Changhong Lee, Ki Yong AnnAbstract:Abstract The present study concerns a literature review regarding Chloride Transport in terms of the diffusion coefficient ( D ) and surface Chloride content ( C S ) in concrete structures exposed to a marine environment. In addition, a refined model is proposed for D and C S for time-dependent Chloride Transport. It is found that both D and C S are time-dependent: D decreases and C S increases with time, due to further cement hydration development. D and C S are significantly influenced by concrete mix proportion, air void content in concrete, curing methods, degree of exposure to seawater and climate. Blended cement concretes are beneficial in decreasing D , but increase C S , presumably due to a refinement of the concrete pore structures and Chloride binding. An increase in the air void content in concrete increases D , but decreases C S . The C S depends on curing methods such as water, membrane and aeration. The degree of exposure to seawater does not have a clear relationship with C S : higher exposure levels did not result in a higher level of C S . Exposure in tropical areas results in higher C S in concrete jetty structures with a similar level of D , mainly due to an increased temperature and concentration of salinity. Based on these findings, a refined model for C S was proposed to provide more realistic prediction of the build-up of Chlorides by Chloride Transport in concrete structures exposed to marine environments.
Narayanan Neithalath - One of the best experts on this subject based on the ideXlab platform.
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an electrical impedance investigation into the Chloride ion Transport resistance of alkali silicate powder activated slag concretes
Cement & Concrete Composites, 2013Co-Authors: Deepak Ravikumar, Narayanan NeithalathAbstract:Abstract The Chloride Transport resistance of alkali silicate powder activated slag concretes is evaluated. Two different Na2O-to-source material ratios (n) and two SiO2-to-Na2O ratios of the activator (Ms) are used on concretes proportioned using two slag contents (300 kg/m3 and 400 kg/m3). Rapid Chloride permeability (RCP) and non-steady state migration (NSSM) tests are used to evaluate the Chloride Transport behavior. Alkali silicate powder activated concretes demonstrate comparable or better Chloride Transport resistance than OPC concretes when evaluated using RCP and NSSM tests. The relationships between the activator parameter, n·Ms, and the critical pore sizes (dc) or the RCP and NSSM values demonstrate similar trends showing the influence of dc in determining the ionic Transport response. Electrical impedance spectroscopy (EIS) is used to relate the material response before and after the Transport tests, and equivalent circuit models are used to extract the parameters that relate to the pore structure. EIS coupled with circuit modeling clearly brings out the differences between the RCP and NSSM test on their influences in the microstructure of alkali activated slag concretes.
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relating rapid Chloride Transport parameters of concretes to microstructural features extracted from electrical impedance
Cement and Concrete Research, 2010Co-Authors: Narayanan Neithalath, Jitendra JainAbstract:Abstract The rapid Chloride Transport parameters such as the rapid Chloride permeability (RCP) and non-steady state migration coefficient are related to the material microstructural parameters in this paper. Electrical impedance spectroscopy and associated equivalent circuit modeling are used to extract the microstructural features of the plain concrete as well as concretes modified with varying amounts of Class F fly ash or silica fume. A methodology is developed in this paper that utilizes the ratios of RCP values and the ratios of effective conductivities to pore solution conductivities of plain and modified concretes, to quantify the relative influence of pore solution conductivity and pore structure on the RCP values. The resistance attributable to the connected pores is extracted from an equivalent circuit model for the impedance spectra of concretes, which is found to relate well to the rapid Chloride Transport parameters as well as the microstructural parameters. Based on the experimental results and electrical circuit models, it is shown that a reduction in pore connectivity has a higher impact on the rapid Chloride Transport parameters than a reduction in the porosity, and reduction in pore sizes is more consequential than porosity reduction in reducing pore connectivity.
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Chloride Transport in fly ash and glass powder modified concretes influence of test methods on microstructure
Cement & Concrete Composites, 2010Co-Authors: Jitendra Jain, Narayanan NeithalathAbstract:This paper discusses the influence of rapid Chloride Transport test methods on the microstructure and the measured Chloride penetration resistance of concretes containing fly ash or fine glass powder as partial cement replacement materials. Rapid Chloride permeability (RCP), non-steady-state migration (NSSM), and steady state conduction (SSC) tests are performed on plain and modified concretes. The glass powder modified concretes demonstrate similar or lower RCP values as compared to the fly ash modified concretes of the same cement replacement level whereas the steady state conductivities are lower for the fly ash modified mixtures. The NSSM coefficients are lower for the fly ash modified concretes even when the initial conductivities are similar to those of plain or glass powder modified concretes. Chloride binding under the conditions of NSSM test, that influence the microstructure and the Transport parameter, is quantified using thermal analysis and XRD patterns as well as an electrical circuit model for the impedance response. The resistance of connected pores (Rc) extracted from the model adequately captures the changes in microstructure with time and with Chloride Transport. The changes in Rc between the start and finish of the NSSM test also indicate microstructural alteration in fly ash modified concretes.