Theoretical study of flow,pressure and solute concentration in double membrane systems

A model system consisting of two rigidly held membranes in series was investigated through the application of the Kedem and Katchalsky thermodynamic single membrane flow equations. This analysis results in predictions of the steady state flow properties as well as values for the solute concentration and pressure of the internal compartment when the system is under the influence of a constant solute concentration or hydrostatic pressure gradient. It is demonstrated that although the flow properties and internal compartment pressure are complicated functions of the membrane permeability coefficients and driving gradient across the system, the relationships are greatly simplified by the explicit appearance of the internal compartment steady state solute concentration in the equations. It is shown that the steady state volume flow rate depends on the absolute value of the solute concentration in the external compartments, as well as the solute concentration gradient across the system. The properties of non-linear dependence of volume flow on concentration gradient, and rectification of volume flow are discussed and shown to be independent properties of the system. For the system under the influence of a solute concentration gradient, the internal compartment pressure can be greater or less than the ambient pressure, and depends mainly on the order in which the membranes are encountered by the volume flow. These properties are qualitatively correlated with certain available experimental observations in biological systems.     

Effect of substance P and eledoisin on K+ efflux, amylase release and cyclic nucleotide levels in slices of rat parotid gland.

The undecapeptides, substance P and eledoisin, caused a rapid, concentration-dependent increase in K+ efflux and amylase release from parotid tissue slices. The effects were not blocked by beta-adrenergic, alpha-adrenergic, or cholinergic antagonists. Incubation buffer calcium was required for stimulation of K efflux and amylase release. The action of the undecapepides was independent of any effects on parotid cyclic AMP or cyclic GMP levels. Since the actions of the undecapeptides were Ca2+ dependent and no effects on cyclic nucleotide levels were discerned it was concluded that Ca2+ plays a primary role in agonist regulation of K+ efflux from the parotid.     

Comparable Long-Term Efficacy of Lopinavir/Ritonavir and Similar Drug-Resistance Profiles in Different HIV-1 Subtypes

Background

Analysis of potentially different impact of Lopinavir/Ritonavir (LPV/r) on non-B subtypes is confounded by dissimilarities in the conditions existing in different countries. We retrospectively compared its impact on populations infected with subtypes B and C in Israel, where patients infected with different subtypes receive the same treatment.

Methods

Clinical and demographic data were reported by physicians. Resistance was tested after treatment failure. Statistical analyses were conducted using SPSS.

Results

607 LPV/r treated patients (365 male) were included. 139 had HIV subtype B, 391 C, and 77 other subtypes. At study end 429 (71%) were receiving LPV/r. No significant differences in PI treatment history and in median viral-load (VL) at treatment initiation and termination existed between subtypes. MSM discontinued LPV/r more often than others even when the virologic outcome was good (p = 0.001). VL was below detection level in 81% of patients for whom LPV/r was first PI and in 67% when it was second (P = 0.001). Median VL decrease from baseline was 1.9±0.1 logs and was not significantly associated with subtype. Median CD4 increase was: 162 and 92cells/µl, respectively, for patients receiving LPV/r as first and second PI (P = 0.001), and 175 and 98, respectively, for subtypes B and C (P<0.001). Only 52 (22%) of 237 patients genotyped while under LPV/r were fully resistant to the drug; 12(5%) were partially resistant. In48%, population sequencing did not reveal resistance to any drug notwithstanding the virologic failure. No difference was found in the rates of resistance development between B and C (p = 0.16).

Conclusions

Treatment with LPV/r appeared efficient and tolerable in both subtypes, B and C, but CD4 recovery was significantly better in virologically suppressed subtype-B patients. In both subtypes, LPV/r was more beneficial when given as first PI. Mostly, reasons other than resistance development caused discontinuation of treatment.     

Intracellular delivery of phosphatidylinositol (3,4,5)-trisphosphate causes incorporation of glucose transporter 4 into the plasma membrane of muscle and fat cells without increasing glucose uptake

Insulin stimulates glucose uptake into muscle and fat cells by translocating glucose transporter 4 (GLUT4) to the cell surface, with input from phosphatidylinositol (PI) 3-kinase and its downstream effector Akt/protein kinase B. Whether PI 3,4,5-trisphosphate (PI(3,4,5)P(3)) suffices to produce GLUT4 translocation is unknown. We used two strategies to deliver PI(3,4,5)P(3) intracellularly and two insulin-sensitive cell lines to examine Akt activation and GLUT4 translocation. In 3T3-L1 adipocytes, the acetoxymethyl ester of PI(3,4,5)P(3) caused GLUT4 migration to the cell periphery and increased the amount of plasma membrane-associated phospho-Akt and GLUT4. Intracellular delivery of PI(3,4,5)P(3) using polyamine carriers also induced translocation of myc-tagged GLUT4 to the surface of intact L6 myoblasts, demonstrating membrane insertion of the transporter. GLUT4 translocation caused by carrier-delivered PI(3,4,5)P(3) was not reproduced by carrier-PI 4,5-bisphosphate or carrier alone. Like insulin, carrier-mediated delivery of PI(3,4,5)P(3) elicited redistribution of perinuclear GLUT4 and Akt phosphorylation at the cell periphery. In contrast to its effect on GLUT4 mobilization, delivered PI(3,4,5)P(3) did not increase 2-deoxyglucose uptake in either L6GLUT4myc myoblasts or 3T3-L1 adipocytes. The ability of exogenously delivered PI(3,4,5)P(3) to augment plasma membrane GLUT4 content without increasing glucose uptake suggests that input at the level of PI 3-kinase suffices for GLUT4 translocation but is insufficient to stimulate glucose transport.     

Impact of HIV-1 subtype and antiretroviral therapy on protease and reverse transcriptase genotype: results of a global collaboration

BackgroundThe genetic differences among HIV-1 subtypes may be critical to clinical management and drug resistance surveillance as antiretroviral treatment is expanded to regions of the world where diverse non-subtype-B viruses predominate.ConclusionGlobal surveillance and genotypic assessment of drug resistance should focus primarily on the known subtype B drug-resistance mutations.     

Breeding tomatoes for salt tolerance: inheritance of salt tolerance and related traits in interspecific populations

Summary Interspecific segregating populations derived from a cross between tomato (Lycopersicon esculentum) cv M82-1 -8 (M82) and the wild species L. pennellii accession LA-716 (Lpen716) were used to study the genetic basis of salt tolerance and its implications for breeding. BC₁ (M82 x (M82 x Lpen716)) and BC₁ S₁ (progenies of selfed BC₁ plants) populations were grown under arid field conditions and irrigated with water having electrical conductivities of 1.5 (control), 10 and 20 dSm^-1. The evaluation of salt tolerance was based on total fruit yield (TY), total dry matter (TD) and TD under salinity relative to the control (RD). Sodium, potassium and chloride concentrations were measured in the leaves and stems. The methods for estimating heritability were adapted to BC₁ plants and BC₁S₁ families. TY, TD and RD had heritability estimates of 0.3–0.45, indicating that salt tolerance can be improved by selection. Genetic correlations between traits indicated that high yield may be combined with salt tolerance and that ion contents are not likely to provide an efficient selection criteria for salt tolerance. Genetic correlations between performances under various salinity levels suggested that similar mechanisms affect the responses to salinity treatments of 10 and 20 dSm^-1. Responses to paper selection confirmed that salt tolerance of the tomato may be improved by selection, and that this selection should be based on dry matter and yield parameters under salinity.Passed away May 1986     

Photoacoustic and fluorescence measurements of the chilling response and their relationship to carbon dioxide uptake in tomato plants

The response of tomato plants to various chilling treatments was studied using two approaches for the measurement of photosynthetic activity. One involved the use of a portable fluorometer for the measurement of in-vivo chlorophyll fluorescence, while the other employed a newly introduced photoacoustic system which allowed changes in oxygen evolution to be followed in a leaf disc. A strong correlation was found between results obtained by each system and those obtained by a conventional open gas-exchange system for the determination of CO₂ uptake. Both systems of measurements could readily distinguish between the effects of chilling in the dark (at 3° C for 18 h) and chilling at high photon flux density (2000 mol m^-2 s^-1 for 5h at 5° C). Chilling in the dark had practically no effect on the quantum yield of oxygen evolution, chlorophyll fluorescence or CO₂ uptake, while chilling at excessively high photon flux density resulted in a sharp reduction (50–70%) in the quantum yields obtained. The results support the view that photosystem II cannot be the primary site of damage by chilling in the dark, although it is significantly affected by chilling at high light intensity.Abbreviations DCMU 3-(3,4-dichlorophenyl)-1,1-dimethylurea - PA photoacoustic - PFD photon flux density - PSII photosystem II     

Oxidative stress disrupts insulin-induced cellular redistribution of insulin receptor substrate-1 and phosphatidylinositol 3-kinase in 3T3-L1 adipocytes. A putative cellular mechanism for impaired protein kinase B activation and GLUT4 translocation

In a recent study we have demonstrated that 3T3-L1 adipocytes exposed to low micromolar H2O2 concentrations display impaired insulin stimulated GLUT4 translocation from internal membrane pools to the plasma membrane (Rudich, A., Tirosh, A., Potashnik, R., Hemi, R., Kannety, H., and Bashan, N. (1998) Diabetes 47, 1562-1569). In this study we further characterize the cellular mechanisms responsible for this observation. Two-hour exposure to approximately 25 microM H2O2 (generated by adding glucose oxidase to the medium) resulted in disruption of the normal insulin stimulated insulin receptor substrate (IRS)-1 and phosphatidylinositol (PI) 3-kinase cellular redistribution between the cytosol and an internal membrane pool (low density microsomal fraction (LDM)). This was associated with reduced insulin-stimulated IRS-1 and p85-associated PI 3-kinase activities in the LDM (84 and 96% inhibition, respectively). The effect of this finding on the downstream insulin signal was demonstrated by a 90% reduction in insulin stimulated protein kinase B (PKB) serine 473 phosphorylation and impaired activation of PKBalpha and PKBgamma. Both control and oxidized cells exposed to heat shock displayed a wortmannin insensitive PKB serine phosphorylation and activity. These data suggest that activation of PKB and GLUT4 translocation are insulin signaling events dependent upon a normal insulin induced cellular compartmentalization of PI 3-kinase and IRS-1, which is oxidative stress-sensitive. These findings represent a novel cellular mechanism for the induction of insulin resistance in response to changes in the extracellular environment.     

Increase in femaleness of three cucurbits by treatment with Ethrel,an ethylene releasing compound

Summary The application of Ethrel (2-chloroethane phosphonic acid), an ethylene-releasing compound, to monoecious cultivars of cucumber and squash and an andromonoecious cultivar of muskmelon, caused a shift towards femaleness in all three species. The increase in femaleness manifested itself in several symptoms: a decrease in the number of staminate (male) flowers, an increase in the number of pistillate (female) or hermaphrodite (perfect) flowers, and a change in flowering pattern, namely, formation of female flowers at lower nodes in cucumber and squash, and formation of hermaphrodite flowers on the main axis in muskmelon where normally only male flowers are formed in this cultivar.     

Impact of Lipase, Bile Salts, and Polysaccharides on Properties and Digestibility of Tuna Oil Multilayer Emulsions Stabilized by Lecithin–Chitosan

The influence of lipase, bile salts, and polysaccharides (pectin and maltodextrin) on the properties and digestibility of lecithin/chitosan-stabilized tuna oil-in-water multilayer emulsions were studied when they were subjected to an in vitro digestion model. All emulsions became unstable to creaming after passing through the digestion model, as deduced from the formation of large visible brown clumps on the top of the emulsions. The release of free fatty acids and glucosamine from the emulsions suggested that lecithin/chitosan-coated droplets were degraded by lipase under simulated gastrointestinal conditions. The amount of free fatty acids released per unit amount of emulsion was higher when bile salt was included in the digestion model or anionic polysaccharide (pectin) was present in the emulsions. These results have important implications for the utilization of multilayered emulsions for the encapsulation, protection, and delivery of n-3 fatty acids and other bioactive lipids.