PKA Mediates Constitutive Activation of CFTR in Human Sweat Duct

The cystic fibrosis transmembrane conductance regulator (CFTR) Cl− channels are constitutively activated in sweat ducts. Since phosphorylation-dependent and -independent mechanisms can activate CFTR, we sought to determine the actual mechanism responsible for constitutive activation of these channels in vivo. We show that the constitutively activated CFTR Cl− conductance (gCFTR) in the apical membrane is completely deactivated following α-toxin permeabilization of the basolateral membrane. We investigated whether such inhibition of gCFTR following permeabilization is due to the loss of cytoplasmic glutamate or due to dephosphorylation of CFTR by an endogenous phosphatase in the absence of kinase activity (due to the loss of kinase agonist cAMP, cGMP or GTP through α-toxin pores). In order to distinguish between these two possibilities, we examined the effect of inhibiting the endogenous phosphatase activity with okadaic acid (10−8 M) on the permeabilization-induced deactivation of gCFTR. We show that okadaic acid (1) inhibits an endogenous phosphatase responsible for dephosphorylating cAMP but not cGMP or G protein-activated CFTR and (2) prevents deactivation of CFTR following permeabilization of the basolateral membrane. These results indicate that distinctly different phosphatases may be responsible for dephosphorylating different kinase-specific sites on CFTR. We conclude that the phosphorylation by PKA alone appears to be primarily responsible for constitutive activation of gCFTR in vivo

Effect of a single Dialysis session on plasma Lp(a) levels in patients on Maintenance haemodialysis

Background: 
Cardiovascular disease (CVD) is a major cause of mortality in End stage renal disease (ESRD) patients on Maintenance haemodialysis (MHD). Lp (a), is a specialized form of glycoprotein-LDL-cholesterol complex and is an independent risk factor for myocardial infarction. The risk is related to its atherogenic and thrombogenic properties. The present study was taken up to evaluate changes in Lp(a) and Lipid profile in patients undergoing hemodialysis session. 

Methodology: 
Twenty seven patients with end stage renal disease who were on maintenance hemodialysis were included. Plasma samples were collected hourly during a dialysis session with polysulfone membrane using bicarbonate dialysate. Plasma cholesterol, triglycerides, and Lp(a) were estimated on Beckmann CX9 Fully Automated Analyzer using commercial kits. Statistical analysis was performed using SPSS for windows version 11.5.

Results: 
Results of analysis of variance for repeated measures after correction for hemoconcentration where necessary revealed a decrease in Lp(a) (p=0.022) and triglycerides (p=0.001) levels and no change in cholesterol (p=0.48) levels.

Conclusion: 
Maintenance dialysis program is known to produce Dyslipidemia. Study of Lp(a) in dialysis patients is important as this is an independent risk marker. However there are very few reports on changes in Lp(a) due to the dialysis session. Our findings will be discussed in comparison with other reports.
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Effect of elevated in-service temperature on the mechanical properties and microstructure of particulate-filled epoxy polymers

In civil engineering applications, epoxy-based polymers are subject to different environmental conditions including in-service temperature, which might accelerate their degradation and limit their application ranges. Recently, different particulate fillers were introduced to enhance the mechanical properties and reduce the cost of epoxy-based polymers. This paper addresses the effect of in-service elevated temperature (from room temperature to 80o C) in particulate-filled epoxy based resin containing up to 60% by volume of fire retardant and fly ash fillers through a deep understanding of the microstructure and analysis of their mechanistic response. An improvement in the retention of mechanical properties at in-service elevated temperature was achieved by increasing the percentages of fillers. The retention of compressive and split tensile strength at 80o C for the mix containing 60% fillers was 72% and 52%, respectively, which was significantly higher than the neat epoxy. Thermo-dynamic analysis showed an increase in glass transition temperature with the inclusion of fillers, while these mixes also experienced less weight loss compared to neat epoxy, indicating better thermal stability. Scanning electron microscopy images showed the formation of dense microstructures for particulate-filled epoxy based resin at elevated temperatures. This indicates that the particulate filled epoxy resin exhibits better engineering properties at in-service elevated temperatures, increasing their durability and therefore their suitability for civil engineering applications. A simplified prediction equation based on power function was proposed and showed a strong correlation to the experimental compressive and splitting tensile strength at different levels of in-service elevated temperature

Oscillatory dissipative conjugate heat and mass transfer in chemically-reacting micropolar flow with wall couple stress : a finite element numerical study

High temperature non-Newtonian materials processing provides a stimulating area for process engineering simulation. Motivated by emerging applications in this area, the present article investigates the time-dependent free convective flow of a chemically-reacting micropolar fluid from a vertical plate oscillating in its own plane adjacent to a porous medium. Thermal radiative, viscous dissipation and wall couple stress effects are included. The Rosseland diffusion approximation is used to model uni-directional radiative heat flux in the energy equation. Darcy’s model is adopted to mimic porous medium drag force effects. The governing two-dimensional conservation equations are normalized with appropriate variables and transformed into a dimensionless, coupled, nonlinear system of partial differential equations under the assumption of low Reynolds number. The governing boundary value problem is then solved under physically viable boundary conditions numerically with a finite element method based on the weighted residual approach. Graphical illustrations for velocity, micro-rotation (angular velocity), temperature and concentration are obtained as functions of the emerging physical parameters i.e. thermal radiation, viscous dissipation, first order chemical reaction parameter etc. Furthermore, friction factor (skin friction), surface heat transfer and mass transfer rates have been tabulated quantitatively for selected thermo-physical parameters. A comparison with previously published paper is made to check the validity and accuracy of the present finite element solutions under some limiting cases and excellent agreement is attained. Additionally, a mesh independence study is conducted. The model is relevant to reactive polymeric materials processing simulation

Effect Of A Dialysis Session On Plasma Branched Chain Aminio Acids In Hemodialysis Patients

Protein and amino acid (AA) metabolism is abnormal in End stage renal disease (ESRD). Hemodialysis (HD) procedure is a strong catabolic stimulus. Branched chain amino acids (BCAAs) can affect other AA levels by reducing AA efflux from muscle due to inhibition of muscle protein degradation. Essential amino acids and keto acid supplements including BCAA and branched-chain keto acid (BCKA) are proposed to decrease protein intake while maintaining protein status. This study was taken up to evaluate the effect of a dialysis session on plasma BCAA’s for which fifteen patients of ESRD on Maintenance HD, thrice a week were recruited into the study. Analysis was done on samples drawn at the beginning (pre-HD) and after the end of each dialysis session (post-HD). Plasma BCAA’s were estimated by Reverse phase High performance liquid chromatography using pre column derivatization with O-pthalaldehyde-Mercaptoethanol. A significant decrease in plasma concentration of Valine and Isoleucine were observed post-HD compared to the pre-HD levels (p<0.05). After correcting the data by creatinine, the decrease in plasma concentrations of Valine and Isoleucine were still found to be statistically significant. The percentage losses after the completion of HD were –24.45, –23.19, and –6.22% respectively for valine, isoleucine, and leucine. The lower reduction in leucine could be due to its appearance from muscle catabolism during the dialysis session. In conclusion, hemodialysis itself may influence dialysate amino acid losses and may have an effect on muscle protein breakdown and this negative protein can be reversed with nutritional supplementation

Outdoor experimental validation for ultra-high concentrator photovoltaic with serpentine-based cooling system

This is the final version. Available from Elsevier via the DOI in this record.With demand for renewable energy growing, concentrator photovoltaic thermal hybrids have great potential. Maximising concentration ratios through the deployment of multi-stage optics can yield high power outputs from multi-junction solar cells. To prevent damaging thermal stress and to enable extraction of thermal energy, a capable cooling system is necessary. The primary objective of this study is to maximise the effective concentration ratio over a solar cell and calibrate the system to optimise the energetic and exergetic efficiencies. The capability of the serpentine-based cooling system is investigated for each concentrator optic configuration. Originality is found in the presentation of the 3-stage optic, and the use of outdoor real-world experimental data to validate a computational model. This model uses both ray tracing, heat and mass transfer simulations to enhance the understanding of system operation and enable accurate prediction of performance under various conditions. Results show focal spot shape is more important than raw optical efficiency for electrical output, making the 3-stage optic superior to the other configurations in most regards. An effective concentration of over 1200 × is achieved. Higher exergetic efficiencies are consistently found in the double serpentine configuration, though variation does not exceed ±0.3% when only changing cooling system geometry.Engineering and Physical Sciences Research CouncilSaudi Arabia Culture Bureau in the U

Indoor experimental analysis of Serpentine-Based cooling scheme for high concentration photovoltaic thermal systems

This is the final version. Available on open access from Elsevier via the DOI in this record.Data availability statement: Data will be made available on request.High concentration photovoltaic thermal hybrids are expected to play an important role in meeting growing energy demands. When approaching concentrations over 1000 suns, a cooling system is needed to maximise both the thermal and electrical performance of the multi-junction solar cell without producing excessive parasitic losses. This study develops a novel simulation model to provide an in-depth understanding of the functionality of a concentrated photovoltaic thermal hybrid system with serpentine-based cooling systems. An ultra-high concentrator photovoltaic optic irradiance profile (peak effective concentration ratio: ∼1500 suns) is considered within the simulation model, which has been validated through indoor experimentation. The effectiveness of cooling is also evaluated through maximum thermal stresses generated in the multi-junction solar cell. The double serpentine design was deemed the highest performing, primarily because of the single serpentine’s excessive pressure drop. Copper as the heat sink material yielded superior performance because of its higher thermal conductivity. The maximum total exergetic efficiency achieved by the receiver was ∼ 10.9% with this configuration. Compared to some examples in the literature this value may seem low, however, it is more accurate due to the inclusion of a specific irradiance profile. All serpentine-based cooling systems could maintain the recommended operating temperature.Engineering and Physical Sciences Research Council (EPSRC)Saudi Arabia Culture Bureau, U

Using zeta-potential measurements to quantify peptide partition to lipid membranes

© The Author(s) 2011. This article is published with open access at Springerlink.com.Open Access: This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.Many cellular phenomena occur on the biomembranes. There are plenty of molecules (natural or xenobiotics) that interact directly or partially with the cell membrane. Biomolecules, such as several peptides (e.g., antimicrobial peptides) and proteins, exert their effects at the cell membrane level. This feature makes necessary investigating their interactions with lipids to clarify their mechanisms of action and side effects necessary. The determination of molecular lipid/water partition constants (Kp) is frequently used to quantify the extension of the interaction. The determination of this parameter has been achieved by using different methodologies, such as UV-Vis absorption spectrophotometry, fluorescence spectroscopy and ζ-potential measurements. In this work, we derived and tested a mathematical model to determine the Kp from ζ-potential data. The values obtained with this method were compared with those obtained by fluorescence spectroscopy, which is a regular technique used to quantify the interaction of intrinsically fluorescent peptides with selected biomembrane model systems. Two antimicrobial peptides (BP100 and pepR) were evaluated by this new method. The results obtained by this new methodology show that ζ-potential is a powerful technique to quantify peptide/lipid interactions of a wide variety of charged molecules, overcoming some of the limitations inherent to other techniques, such as the need for fluorescent labeling.This work was partially supported by project PTDC/QUI/ 69937/2006 from Fundação para a Ciência e Tecnologia-Ministério da Ciência, Tecnologia e Ensino Superior (FCT-MCTES, Portugal), and by Fundação Calouste Gulbenkian (Portugal). JMF and MMD also thank FCT-MCTES for grants IMM/BT/37-2010 and SFRH/BD/41750/2007, respectively