Recent advances in neutron reflectivity studies of biological membranes

Biological membranes are critical living interfaces which not only compartmentalise cells but also provide specific surfaces on which biochemical reactions take place. Their study is essential for our understanding of life and disease and also for the development of new pharmaceuticals. Because they are dynamic structures reliant on the surrounding aqueous phase for their activity, techniques which can probe them at a molecular scale under physiological conditions are crucial to understand their function. Here, I describe some of the recent developments in neutron reflectivity in this research area and suggest where future developments in the technology might be usefully directed.     

Analysis of a theoretical model for anisotropic enzyme membranes application to enzyme electrodes

A theoretical model of diffusion and reaction in an anisotropic enzyme membrane is presented with particular emphasis on the application of such membranes in enzyme electrodes. The dynamic response of systems in which the kinetics are linear, which comprises the practical operating regime for enzyme electrodes in analysis, is investigated via an analytic solution of the governing differential equations. The response is presented as a function of a single dimensionless group, Μ, that is the membrane modulus.     

Recent advances in sodium alginate-based membranes for dehydration of aqueous ethanol through pervaporation

Sodium alginate (SA) is a progressive material for membrane fabrication. The technological development of SA-based membranes has made a significant contribution to the separation techniques, especially in aqueous organic solutions. The outstanding performance of SA is attributed to its outstanding structural flexibility and hydrophilicity. In view of structural characteristics, SA membranes have immense utilization in the pervaporation separation of organics. Among various organics, dehydration of aqueous ethanol is employed as a standard to check the success of pervaporation (PV) membrane. Because ethanol and water have comparable molecular sizes, thus difficult to extract water from aqueous ethanol mixtures than it is for other organics. A literature survey shows that wide-ranging data are available on the PV performance of SA and its modified membranes. In this context, the present review addresses the recent advances made in SA membranes for enhanced ethanol dehydration performance during the last decade. Available data since 2010 has been compiled for grafted, crosslinked, blend, mixed matrix, and composite hybrid sodium alginate membranes in terms of separation factor, permeation flux, and pervaporation separation index PSI. The data are assessed with reference to the effect of feed composition, membrane selectivity, flux, and swelling behavior.     

Statistical mechanics of diffusion in polymers: Conductivity and electroosmosis in ion exchange membranes

The dependency of swelling of an ion exchange membrane and its ion-exchange capacity on the conductivity and electroosmosis are investigated. The analysis is based on a rigorous statistical mechanics theory employing the formalism of the generalized Nernst–Planck equation in the dusty gas membrane model. The simulation uses binary diffusivities computed from experimental data. Some unexpected conclusions can be drawn from the computed transport characteristics: at constant swelling of the polymeric membrane the equivalent conductivity decreases with the exchange capacity; the enhancement of conductivity by electroosmosis is rather poor, in all cases smaller than 15 %; conductivity of the material is more dependent on its exchange capacity than on swelling.

The calculations confirm that an optimized membrane with low electroosmosis is a highly charged membrane with low swelling. We show that the simple binary theories lead to wrong predictions of the conductivity even qualitatively. Finally, we propose a simple empirical theory, compatible with the generalized Nernst–Planck equation, where the diffusivities increase exponentially with swelling.     

Investigation of artificial biomembrane systems in biopartitioning micellar chromatography by method of mathematical design

An attempt to create and study an artificial membrane system was realized via biopartitioning micellar liquid chromatography. Towards this end the known formula of membrane permeability (on the basis of Fick's diffusion equation) was modified so that membrane permeability may be estimated in terms of chromatographic characteristics. The two-factoral experiments on the basis of mathematical design of second order were carried out. The regression equations are derived which describe the dependence of membrane permeability on the concentration of polyoxyethylene (23) lauryl ether in the mobile phase and its flow-rate for compounds with biomedical significance. Some regularities were revealed, which characterize the permeability of compounds of the different nature through membranes. The extremal dependence (with passing through minimum) of permeability on the concentration of non-ionic surfactant was observed for anionic compounds. The increasing character of permeability in relation with flow-rate of mobile phase was recognized for cationic samples. Both dependences were basically fulfilled for zwitterionic compounds.     

The cavity models and the curvature dependence of the surface tension. Spherical cavities in anisotropic solvents

In the present work the solution process of globular solutes (xenon, cyclohexane, cyclooctane and adamantane) in n-alkane solvents is analyzed. New experimental data on solution enthalpies of adamantane in those solvents are presented. The cavity model previously proposed is corrected with respect to the dependence of the surface tension on the curvature radius of the microscopic cavity and a new equation is proposed to describe this dependence.     

Characterization of sodium dodecylsulphate and dodecylphosphocholine mixed micelles through NMR and dynamic light scattering

The complexity of biological membranes leads to the use of extremely simplified models in biophysical investigations of membrane‐bound proteins and peptides. Liposomes are probably the most widely used membrane models due, especially, to their versatility in terms of electric charge and size. However, liquid‐state NMR suffers the lack of such a model, because even the smallest liposomes slowly tumble in solution, resulting in a dramatic signals broadening. Micelles are typically used as good substitutes, with sodium dodecylsulphate (SDS) and dodecylphosphocholine (DPC) being the most widely employed surfactants. However, they are always used separately to mimic prokaryotic and eukaryotic membranes, respectively, and accurate investigations as a function of surface charge cannot be performed. In this work, the critical micelle concentration (CMC) of binary mixtures with different SDS/DPC ratios has been determined by following the chemical shift variation of selected ¹H and ³¹P NMR signals as a function of total surfactant concentration. The regular solution theory and the Motomura's formalism have been applied to characterize the micellization both in water and in phosphate buffer saline, and results were compared with those obtained directly from the experimental NMR chemical shift. The ζ‐potential and size distribution of the mixed micelles have been estimated with dynamic light scattering measurements. Results showed that SDS and DPC are synergic and can be used together to prepare mixed micelles with different negative/zwitterionic surfactants molar ratio. Copyright © 2013 John Wiley & Sons, Ltd.     

Quantification of DNA methylation and hydroxymethylation in Alzheimer's disease mouse model using LC‐MS/MS

Ambiguous alteration patterns of 5‐methylcytosine (5mC) and 5‐hydroxymethylcytosine (5hmC) involved in Alzheimer's disease (AD) obstructed the mechanism investigation of this neurological disorder from epigenetic view. Here, we applied a fully quantitative and validated LC‐MS/MS method to determine genomic 5mC and 5hmC in the brain cortex of 3 month‐aged (12, 15, and 18 month) AD model mouse and found significant increases of 5mC and 5hmC levels in different months of AD mouse when compared with age‐matched wild‐type control and exhibited rising trend from 12‐month to 18‐month AD mouse, thereby supporting genomic DNA methylation and hydroxymethylation were positively correlated with developing AD.     

Development of Abraham model correlations for enthalpies of solvation of organic solutes dissolved in 1,3-dioxolane

Published excess enthalpy of mixing data has been assembled from the chemical literature for binary mixtures containing 1,3-dioxalane. The experimental data were converted into partial molar enthalpies of solution and enthalpies of solvation for solutes dissolved in 1,3-dioxolane using standard thermodynamic relationships. The compiled enthalpy of solvation data for 59 different organic solutes was used to derive mathematical correlations based on the Abraham solvation parameter model. The derived correlations describe the experimental enthalpy of solvation data in 1,3-dioxolane to within a standard deviation of 2.0 kJ mol^?1.     

Green micellar HPLC analysis of three angiotensin‐converting enzyme inhibitors in their mixtures with hydrochlorothiazide and modeling of their retention behavior by fitting to Foley's model

We present an environmentally friendly method for the analysis of three angiotensin‐converting enzyme inhibitors and hydrochlorothiazide simultaneously using a green micellar eluent for the first time. The chromatographic separation of enalapril maleate, lisinopril dihydrate, benazepril hydrochloride, and hydrochlorothiazide was implemented on an octadecyl silica column with a solution containing sodium dodecyl sulfate (0.12 M), 1‐propyl alcohol (10% v/v), triethylamine (0.3% v/v), and H₃PO₄ (0.02 M) at pH 3.6 as the mobile phase and UV detection at 210 nm. Validity of the method was confirmed and it exhibited good linearity within the ranges of 5.0–50.0 μg/mL for hydrochlorothiazide and 10.0–60.0 μg/mL for the three angiotensin‐converting enzyme inhibitors with a limit of detection of 0.39 to 1.15 μg/mL for all the studied drugs. The developed micellar high‐performance liquid chromatography method enables the quantification of the targeted angiotensin‐converting enzyme inhibitors in combined tablets with hydrochlorothiazide by isocratic elution. There is no need for special precautions to prevent broadening and splitting of their chromatographic peaks. The method fulfills the society rights for safe and green analytical methods. The retention behavior of the four studied drugs was fitted to Foley's model and their association equilibria to the micelles (K _AM) and to the surface‐modified stationary phase (K _AS) were calculated.     

Electrochemical Interpretation of Propagation of the Change in the Membrane Potential Using the Goldman‐Hodgkin‐Katz Equation

Nerve conduction has been frequently explained by the Hodgkin‐Huxley equation based on the flow of K⁺ and Na⁺ across the cell membrane. By considering the relation between the membrane potential and the membrane current based on the Goldman‐Hodgkin‐Katz equation, it becomes clear that the conventional analysis using the voltage‐clamp method is not correct and that the hyperpolarization condition is artificially made. Taking into account the channel functions and the electronic properties, we suggested a new propagation mechanism. When the nerve cell is excited by an external stimulus, the ligand‐gated channels at the synapse serve as an electric power source to propagate the change in the membrane potential to the synapse terminal along the axon and the voltage‐gated channels at the axon locally assist the directional propagation along the axon.     

四元交互体系Li+，K+/CL-，CO2-3-H2O在298 K时相平衡及物理化学性质研究

Zabuye Saline Lake, Tibet, China, is unrivalled in the world for its very high salinity, in particular, for the very high concentration of ions of lithium, potassium, and boron in the brine. It belongs to alkaline and carbonate-borate-type salt lake. As a part of the study on phase equilibrium of the 6component subsystem Li+, Na+, K+/C1-, CO2-3, B4O2-7-H2O of the brine system, a study on the reciprocal quaternary system Li+, K+/C1-, CO32-H2O at 298 K was done with isothermal dissolution equilibrium method in the present work. The phase equilibrium of the reciprocal quaternary system Li+,K+/C1, CO2-3-H2O at 298 K was studied with isothermal dissolution method in this work. The physicochemistry properties of the corresponding equilibrium solutions such as densities, viscosities, refractive index, conductivities and pH value were determined. The dried salt diagram of the system consists of four crystallization fields (KC1, Li2CO3, LiCI·H2O, K2CO3·3/2H2O) and five isothermal solubility curves.There are no double slat or solid solution found. Pitzer′s model of the electrolyte solution theory was used for parameterization from the results of solubility determination for subsystems and the prediction of solubilities for the reciprocal quaternary system was made. The solubility data of the experiment are in agreement with those calculated.     

Some model inhomogeneous electron liquid in D dimensions: relation between energy and chemical potential and a spatial generalisation of Kato's nuclear cusp theorem

After a brief survey on the application of the Thomas–Fermi statistical method to bare Coulomb potential satisfying Laplace equation in D dimensions, which then relates energy and chemical potential, we next focus attention on model atomic ions with merely one and two electrons in D dimensions. In particular, for a bare Coulomb field we use the nodeless radial eigenfunctions given by Herschbach in D dimensions to derive the spatial generalization of Kato's nuclear cusp theorem in D dimensions for D?>?1. The unbinding of H ^? as a function of dimensionality D is also briefly referred.     

CO2在Na2Cr2O7溶液中的平衡溶解度模型

为研究重铬酸钠(Na₂Cr₂O₇)对CO₂溶解的影响, 本文在带有搅拌的气液相高压平衡釜内, 采用静态法测定了温度在313.2-333.2 K, 压力在0.1-1.9 MPa 范围内, 重铬酸钠浓度分别为0、0.361、0.650、0.901 mol·kg^-1 时, CO₂ 在Na₂Cr₂O₇溶液中的溶解度. 结果表明: (1) Na₂Cr₂O₇对CO₂ 的溶解有盐析效应; (2) CO₂ 在Na₂Cr₂O₇溶液中的溶解符合亨利定律, 并且CO₂溶解度是温度和Na₂Cr₂O₇浓度的函数, 且用改进的Setschenow方程和Peng-Robinson-Pitzer (PR-Pitzer)方程拟合了在此温度、压力及重铬酸钠浓度范围内的实验数据, 拟合效果较好, 并且其平均相对误差分别为4.24%和3.32%.     

Protonation of carbonate in aqueous tetraalkylammonium salts at 25 degrees C

Protonation constants of carbonate were determined in tetramethylammonium chloride (Me₄NCl_aq 0.1 ≤ I/mol kg⁻¹ ≤ 4) and tetraethylammonium iodide (Et₄NI_aq 0.1 ≤ I/mol kg⁻¹ ≤ 1) by potentiometric ([H⁺]-glass electrode) measurements. Dependence of protonation constants on ionic strength was taken into account by modified specific ion interaction theory (SIT) and by Pitzer models. Literature data on the protonation of carbonate in NaCl_aq (0.1 ≤ I/mol kg⁻¹ ≤ 6) were also critically analysed. Both protonation constants of carbonate follow the trend Et₄NI > Me₄NCl > NaCl. An ion pair formation model designed to take into account the different protonation behaviours of carbonate in different supporting electrolytes was also evaluated.     

Integration of metabolomics and network pharmacology to validate the mechanism of Schisandra chinensis（Turcz.）Baill - Acorus tatarinowii Schott ameliorating the Alzheimer's disease by regulating the aromatase activity to affect local estrogen in brain of AD model rats

Alzheimer's disease (AD) is a latent and progressive neurodegenerative disease. Schisandra chinensis（Turcz.）Baill - Acorus tatarinowii Schott (Sc-At) are effective in treating neurological disorders.Purpose of this study is to explore the mechanism of Sc-At in AD treatment. First, untargeted ultra-performance liquid chromatography quadrupole-time of flight/mass spectrometer (UPLC-QTOF/MS) metabolomics was employed to detect the rat brain metabolism. Then, network pharmacology was used to determine the potential anti-AD targets. Bioinformatics, and molecular docking were conducted for further analysis. A MetScape study examined the association between differential metabolites and potential targets. Finally, the targeted ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) metabolomics and the potential protein activity studies were carried out to elucidate the mechanisms. The results showed that Sc-At improved the neuronal cell alignment disorder in hippocampal CA1 region of AD rats. In brain metabolomics, 30 differential metabolites were screened in the study model versus blank group. The network pharmacology analyzed 54 targets of Sc-At anti-AD where, 14 were correlated with amyloid β-protein (Aβ). Aromatase was selected as an important hub target having the best binding power in molecular docking simulation predictions and also correlated with Aβ. Further tests showed that the brain aromatase activity, and the downstream product 17β-Estradiol levels were elevated in AD rats treated with Sc-At. This work may provide new perspectives for the pharmacological effects and the action mechanisms of natural compounds extracts in treating AD progression.