A Molecular Thermodynamic Model of Coacervation in Solutions of Polycations and Oppositely Charged Micelles.

To guide the rational design of personal care formulations, we formulate a molecular thermodynamic model that predicts coacervation from cationic polymers and mixed micelles containing neutral and anionic surfactants and added salt. These coacervates, which form as a result of dilution of conditioning shampoos during use, deposit conditioning agents and other actives to the scalp or skin and also provide lubrication benefits. Our model accounts for mixing entropy, hydrophobic interactions of polycation with water, free energies of bindings of oppositely charged groups to micelles and polycations, and electrostatic interactions that capture connectivity of charged groups on the polycation chain and the micelle. The model outputs are the compositions of surfactants, polycation, salt, and water in the coacervate and in its coexisting dilute phase, along with the binding fractions and coacervate volume fraction. We study the effects of overall composition (of surfactant, polycation, and added salt), charge fractions on micelles and polycations, and binding free energies on the phase diagram of coacervates. Then, we perform coacervation experiments for three systems: sodium dodecyl sulfate (SDS)-JR30M, sodium methyl cocoyl taurate (Taurate)-JR30M, and sodium lauryl alaninate (Alaninate)-JR30M, where JR30M is a cationic derivative of hydroxyethylcellulose (cat-HEC), and rationalize their coacervation data using our model. For comparison with experiment, we also develop a parametrization scheme to obtain the requisite binding energies and Flory-Huggins χ parameter. We find that our model predictions agree reasonably well with the experimental data, and that the sulfate-free surfactants of Taurate and Alaninate display much larger 2-phase regions compared to SDS with JR30M.

Effect of deficit irrigation on physiological, biochemical, and yield characteristics in three baby corn cultivars (Zea mays L.).

The main problem in the production of crops in arid and semi-arid regions of the world is the lack of water and its effect on the plant in the form of drought stress. Cultivation of key crops such as corn, which also requires a lot of water, is not possible in these areas except by applying water consumption management methods. Among the most important of these methods is deficit irrigation. The effect of deficit irrigation on relative water content (RWC), malondialdehyde (MDA), compatible osmolytes (proline and soluble sugars), antioxidant enzymes, and yield was studied in three baby corn cultivars in a field experiment using a randomized complete block design (RCBD) with split-plots and three replications. Three levels of deficit irrigation (0, 20, and 40% deficit) constituted the main plots and three cultivars of baby corn (Challenger, Basin, and Passion) constituted the sub plots. Analysis of variance showed that deficit irrigation had a significant effect on all variables. Cultivar (Challenger, Basin and Passion) had a significant effect on proline (0%, 41.5% and 73.2%), carbohydrates (23.9%, 15.4% and 0%), and MDA content (0%, 26.1% and 41.2%), as well as peroxidase (POD) (0%, 136.1% and 227.9%) levels respectively. The interaction between deficit irrigation and cultivar had a significant effect on proline, carbohydrates, and POD. RWC decreased (26.9, 6.5 and 0%) with increasing irrigation deficit (0, 20 and 40%) respectively while proline (0, 23.7 and 64.8%), carbohydrates (0, 29.7 and 34.09%), catalase (CAT) (0, 20.8 and 70.1%), and POD (0, 55.05 and 113.2%) increased under the same conditions. Carbohydrate content was higher in the Basin and Challenger cultivars (21.71 and 19.07) and proline (145.9), POD (193.9), and MDA content (8.53) were higher in the Passion cultivar. Among the studied cultivars, the highest yield was achieved by the Passion cultivar (37.02 and 62.9% more than Challenger and Basin cultivars respectively). In general, the results showed that drought stress caused an increase in compatible osmolyte content and the activity of antioxidant enzymes. However, this increase could not offset the effects of drought stress on yield in the 40% deficit treatment.

Feasibility study of detecting some milk adulterations using a LED-based Vis-SWNIR photoacoustic spectroscopy system.

The aim of this study is to evaluate a previousely developed photoacoustic spectroscopy system with light sources of visible to short-wave near infrared (Vis-SWNIR, 395-940 nm) for detection of adulterations in cow's milk including formalin, urea, hydrogen peroxide, starch, sodium hypochlorite, and detergent powder. The results of principal component analysis (PCA) showed a very good visual differentiation of different adulterations. The artificial neural networks (ANN) showed the highest classification accuracy (97.6 %) in detection of adulteration type and adulteration level (nearly 100 %). It can be generally concluded that the Vis-SWNIR photoacoustic spectroscopy system is a reliable and potent instrument for detecting various types of milk adulterations. Further studies are suggested with including cow's milk of different sources with probable variations in composition to generalize the findings of the present study. With the extension of the light sources to the range of long-wave NIR, the system can be applied as a diagnostic tool for quality evaluation of other liquid foods.

A multi-objective optimization using response surface model coupled with particle swarm algorithm on FSW process parameters.

In this study, multi-objective optimization of mechanical properties in friction-stir-welding of AH12 1050 aluminum alloy is performed using a combination of the response surface method and multi-objective particle swarm optimization algorithm. The process parameters are considered as tool pin diameter, shoulder diameter, rotational speed, feed speed, and tool tilt angle. The heat-affected zone's yield strength, fracture strain, impact toughness, and hardness on the advancing and retreating sides are selected as the objective functions. Threaded and simple conical pins are utilized to evaluate the effect of the pin geometry on the specimen mechanical properties. Optimization model outputs are in agree with the obtained experimental results. The effects of process parameters on the mechanical properties of the friction-stir-welded sheets are studied. Results reveal that the lower rotational speed and higher feed speed improve the material strength and hardness. Moreover, the microstructural analysis demonstrates that the proposed methodology can achieve a fine-grained structure with the minimum defects. Improvement in the material flow is observed for the threaded cylindrical pin compared with the conical pin due to the geometric shape of the tool pin leading to more functional mechanical properties. It is found that the combination of the response surface methodology and the multi-objective particle swarm algorithm led to the modeling and optimization of the process with outstanding accuracy and low experimental cost.

Geogenic and anthropogenic sources identification and ecological risk assessment of heavy metals in the urban soil of Yazd, central Iran.

Urban soil pollution with heavy metals is one of the environmental problems in recent years, especially in industrial cities. The aim of this study is to evaluate the role of geogenic and anthropogenic sources in the urban soil pollution in Yazd, Iran. For this purpose, 30 top-soil (0-10 cm) samples from Yazd within an area of 136.37 Km2 and population of nearly 656 thousand are collected, and the concentration of heavy elements is measured. To evaluate factors affecting the concentration of heavy elements in urban soils and determine their possible sources, Multivariate statistical analysis, including correlation coefficient, principal components analysis (PCA) and cluster analysis (CA) are performed. Enrichment Factor (EF), Geo-accumulation index (Igeo), and Modified potential ecological Risk Index (MRI) are used to assess the level and extension of contamination. Results of this study suggest that As, Cd, Pb and Zn are affected by anthropogenic source, while the concentrations of Fe, Mn, Ni, Cr, Co, Cu and Cs have come from mostly natural geologic sources. As, Cd and Pb are considerably enriched in the area, provided moderately enriched for the elements Mn, Zn and Cu. However, the other heavy elements show minimal enrichment. Igeo reveal that Co, Cr, Cs, Cu, Fe, Mn, Zn and Ni with negative values are unpolluted, Pb posed unpolluted to moderately polluted, and As and Cd represent high polluted. Based on the results of the ecological risk factor, the heavy metals of Mn, Ni, Cr, Zn and Cu have a low ecological risk level. More specifically, we find that Pb shows a moderated ecological risk in 39% of the urban soil in the studied area. As and Cd with respectively 100 and 72% contribution have considerable and very high ecological risk. According to the results of MRI, the area is in a very high ecological risk level, and appropriate management practice is essential to reduce the pollution of heavy elements in this area.

Extracting free energies of counterion binding to polyelectrolytes by molecular dynamics simulations.

We use all-atom molecular dynamics simulations to extract ΔGeff, the free energy of binding of potassium ions K+ to the partially charged polyelectrolyte poly(acrylic acid), or PAA, in dilute regimes. Upon increasing the charge fraction of PAA, the chains adopt more extended conformations, and simultaneously, potassium ions bind more strongly (i.e., with more negative ΔGeff) to the highly charged chains to relieve electrostatic repulsions between charged monomers along the chains. We compare the simulation results with the predictions of a model that describes potassium binding to PAA chains as a reversible reaction whose binding free energy (ΔGeff) is adjusted from its intrinsic value (ΔG) by electrostatic correlations, captured by a random phase approximation. The bare or intrinsic binding free energy ΔG, which is an input in the model, depends on the binding species and is obtained from the radial distribution function of K+ around the charged monomer of a singly charged, short PAA chain in dilute solutions. We find that the model yields semi-quantitative predictions for ΔGeff and the degree of potassium binding to PAA chains, α, as a function of PAA charge fraction without using fitting parameters.

In-vitro tumor microenvironment models containing physical and biological barriers for modelling multidrug resistance mechanisms and multidrug delivery strategies.

The complexity and heterogeneity of the three-dimensional (3D) tumor microenvironment have brought challenges to tumor studies and cancer treatment. The complex functions and interactions of cells involved in tumor microenvironment have led to various multidrug resistance (MDR) and raised challenges for cancer treatment. Traditional tumor models are limited in their ability to simulate the resistance mechanisms and not conducive to the discovery of multidrug resistance and delivery processes. New technologies for making 3D tissue models have shown the potential to simulate the 3D tumor microenvironment and identify mechanisms underlying the MDR. This review overviews the main barriers against multidrug delivery in the tumor microenvironment and highlights the advances in microfluidic-based tumor models with the success in simulating several drug delivery barriers. It also presents the progress in modeling various genetic and epigenetic factors involved in regulating the tumor microenvironment as a noticeable insight in 3D microfluidic tumor models for recognizing multidrug resistance and delivery mechanisms. Further correlation between the results obtained from microfluidic drug resistance tumor models and the clinical MDR data would open up avenues to gain insight into the performance of different multidrug delivery treatment strategies.

Predictive Biomarker Panel in Proliferative Lupus Nephritis- Two-Dimensional Shotgun Proteomics.

INTRODUCTION: Lupus nephritis (LN) is one of the most serious complications of systemic lupus erythematous (SLE). With no specific clinical or laboratory manifestation to predict response to treatment, this study was aimed to provide a panel of predictive biomarkers of response before initiation of treatment. METHODS: Liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis was performed on plasma and urine samples of 11 patients with biopsy proven proliferative LN at the time of biopsy. Unsupervised principal component analysis (PCA), orthogonal projection to latent structures discriminant analysis (OPLS-DA), gene ontology annotation and protein mapping were performed on 326 proteins in plasma and 1381 proteins in urine samples. RESULTS: Samples of eight patients achieved complete remission and three reached partial remission were analyzed. The mean 24-hour protein excretion was 3259 mg/day and the mean eGFR was 87.73 cc/min. OPLS-DA analysis of plasma samples showed a clear discrimination for complete and partial remission patients. Twenty plasma proteins and ten urine proteins with the highest fold changes and AUCs were selected as candidate biomarkers (IGHV1-18, PI16, IGHD, C3, FCER2, EPS8L2, CTTN, BLVRB). This plasma and urine biomarker panel is involved in oxidative stress, acute inflammation, reduction in regulatory T cells, complement pathway consumption, and proximal tubule bicarbonate reclamation. CONCLUSION: Our suggested panel of plasma and urine biomarkers can precisely discriminate patients with possibility of complete response to treatment. It seems that the higher indices of inflammation will associate with better chance of achieving complete remission.

Pollution, human health risk assessment and spatial distribution of toxic metals in urban soil of Yazd City, Iran.

Heavy metal pollution significantly reduces the quality of the environment and threatens human health, especially in industrial cities. This study investigated toxic metals concentrations, pollution levels and human health risks assessment of urban soils in Yazd City, as an industrial city in center of Iran. Soil surface samples (0-10 cm) were collected from 30 points in the area for geochemical analysis. The concentrations of heavy metals were determined using an inductively coupled plasma mass spectrometry (ICP-MS). The values of the mean concentrations of toxic metals (mg kg-1) in the urban soils decrease in the order of Zn (83.9) > Pb (34.5) > Cr (32.6) > Cu (23.5) > Ni (23.4) > As (5.86) > Co (4.86) > Cd (0.27). The mean concentration of Zn, Pb, As and Cd elements was higher than the background and the crust values. A pollution assessment by Geo-accumulation Index (Igeo), Pollution Index (PI), Contamination Degree (CD), the Integrated Pollution Index (IPI), the Pollution Load Index (PLI) and Integrated Nemerow Pollution Index (INPI) showed that As, Cd and Pb were moderately enriched and the study area polluted considerably by these toxic metals. Based on PI results, 88.9% of the urban soil samples highly polluted by As. Overall, the quality of the urban soil in Yazd City is clearly affected by toxic metals. Due to the prevailing wind direction, the route of the north-south highway of Iran and the population density and traffic of the northwestern and southern areas of the study area were found the highest level of pollution indicators (IPI > 1.8; LPI > 1.3; CD > 15 and INPI > 4.3). The results of Pearson correlation analysis indicated that all pollution evaluation indicators were influenced by As and Cu, and showed high significant correlation with these two elements, while neither of them had a significant relationship with Pb and was found also a weak link statistically with Cd. Health risk assessment of toxic metals has been performed in both carcinogenic and non-carcinogenic sectors. The results indicate that oral intake is the main pathway that toxic metals can harm human health for both the child and adults. The carcinogenic risks (RI) of adults and child by toxic metals were as follows: Ni > Pb > Cr > As > Cd. Hazard quotients (HQ) and hazard index (HI) values for child also were higher than these for adults. Generally, the results demonstrated that the potential carcinogenic health risks for adults of toxic metals were in an acceptable range in study area, whereas for Cr, Ni and Pb with RI > 10-4, the risk of cancer in child probably increases.

Overcharging of polyelectrolyte complexes: an entropic phenomenon.

Overcharging in complex coacervation, in which a polyelectrolyte complex coacervate (PEC) initially containing equal moles of the cationic and anionic monomers absorbs a large excess of one type of polyelectrolyte species, is predicted using a recently developed thermodynamic model describing complexation through a combination of reversible ion binding on the chains and long-range electrostatic correlations. We show that overcharging is favored roughly equally by the translational entropy of released counterions and the binding entropy of polyelectrolytes in the polyelectrolyte complex, thus helping resolve competing explanations for overcharging in the literature. We find that the extent of overcharging is non-monotonic in the concentration of added salt and increases with both strength of ion-pairing between polyions and chain hydrophobicity. The predicted extent of overcharging of the PEC is directly compared with that of multilayers made of poly(diallyldimethylammonium), PDADMA, and poly(styrene-sulfonate), PSS, overcompensated by the polycation in two different salts: KBr and NaCl. Accounting for the specificity of salt ion interactions with the polyelectrolytes, we find good qualitative agreement between theory and experiment.

Epigenetic regulation and transcriptional memory in development; selection facilitating prudence.

The epigenetic mechanisms regulating developmental gene expression are examples of a strategy to generate unique expression profiles with global regulators controlling several genes. In a simplified view, a common set of tools, that include DNA motif recognizing proteins (recruiters), binding/interacting surfaces (ARPs- actin related proteins), epigenetic writers (histone methyltransferases, acetylases), readers (chromatin remodeling proteins, PRC1 members) and erasers (demethylases, deacetylases) form complexes which not only regulate transcription, but also retain the transcriptional memory through mitosis. There are two arms of epigenetic regulation: covalent modification of DNA and the post-translational modification of histones. In this review, we discuss both of these aspects briefly to illustrate functional diversity. We discuss our efforts at utilization of the genome sequence data for de novo identification of new players and their functional validation in this remarkable process.

Quantitative Assessment of Thermodynamic Theory in Elucidating the Behavior of Water under Hydrophobic Confinement.

A macroscopic thermodynamics-based theory that can quantitatively describe the behavior of water confined between hydrophobic solutes has so far remained elusive. In this work, we progress toward this goal by comparing the predictions of macroscopic theory with the results from computer simulations. We have determined free energy profiles of water confined between two nanometer-sized surfaces of varying hydrophobicity using molecular simulations and have estimated thermodynamic properties such as contact angle, line tension, and size of the critical vapor tube from independent simulations. We show that the scaling of free energy barrier to evaporation is fairly well captured by the factor ( D/2 + λ/ϒLV)2, where D is the confinement gap and λ/ ϒLV is the ratio of line-tension and liquid-vapor surface tension. The radius of the critical vapor tube necessary for nucleating evaporation scales by the factor ( D/2 + λ/ϒLV). Exclusion of the line-tension term from thermodynamic theory leads to a qualitative disagreement between theoretical predictions and results from molecular simulations. We also demonstrate that macroscopic theory that includes the line-tension term is able to quantitatively match the entire free energy profile associated with the formation of a vapor-tube inside the confined region for conditions when the vapor state is the most stable state. The match is however only qualitatively correct for the conditions when the liquid state is more stable. Overall, the conclusion is that the inclusion of line-tension in macroscopic theory is necessary to describe the behavior of water under nanoscale confinement between two hydrophobic solutes.

Human PRE-PIK3C2B, an intronic cis-element with dual function of activation and repression.

The Polycomb/Trithorax Responsive Elements (PRE/TREs) are the cis-regulatory sequences that interact with both repressive (PcG) as well as activating (TrxG) complexes. However, most of the mammalian PREs are demonstrated to interact with the repressive polycomb (PcG) complexes only. We have carried out an unbiased search for proteins interacting with human PRE-PIK3C2B (hPRE-PIK3C2B) based on DNA affinity purification followed by mass spectrometry and identified MLL, MLL4 and WDR87 among other proteins in three biological replicates in HEK, U87 and HeLa cell lines. The hPRE-PIK3C2B interacts with the members of multiple activating complexes (COMPASS-like). The increase in the interaction of MLL and MLL4 on depletion of YY1 and the increase in the enrichment of YY1 and EZH2 upon MLL knockdown at the hPRE-PIK3C2B indicate the dual occupancy and suggest a concentration dependent enrichment of the activator or the repressor complex at hPRE-PIK3C2B. Further, we show that the hPRE-PIK3C2B interacts with the Drosophila homologues of PcG and TrxG proteins in transgenic flies. Here, we found that there is an increased enrichment of Pc (Polycomb) in comparison to Trx (TrxG protein) at hPRE-PIK3C2B in the Drosophila transgenic flies and this seems to be the default state while the balance is tipped towards the trithorax complex in PcG mutants. To the best of our knowledge, this is one of the early demonstrations of human PRE acting as a TRE without any sequence alteration.

Beneficial Effect of Leptin on Spatial Learning and Memory in Streptozotocin-Induced Diabetic Rats.

BACKGROUND: Diabetes mellitus is a chronic disease which may be accompanied by cognitive impairments. The expression of the obesity gene (ob) is decreased in insulin-deficient diabetic animals and increased after the administration of insulin or leptin. Plasma leptin levels are reduced in the streptozotocin (STZ)-induced diabetic rats. Therefore, the deleterious effects of diabetes on memory may be due to the reduction of leptin. AIMS: Investigate the effect of subcutaneous injection of leptin on spatial learning and memory in STZ-induced diabetic rats. STUDY DESIGN: Animal experimentation. METHODS: The rats were divided into three groups: 1-control, 2- diabetic, and 3- diabetic-leptin. Diabetes was induced in groups 2 and 3 by STZ injection (55 mg/kg) intraperitoneally (i.p). The animals received leptin (0.1 mg/kg) or saline subcutaneously (s.c) for 10 days before behavioral studies. Then, they were examined in the Morris water maze over 3 blocks after 3 days of the last injection of leptin. RESULTS: The travelled path length and time spent to reach the platform significantly increased in the diabetic group (p<0.001) and decreased with leptin treatment (p<0.01 & p<0.001 respectively); also, a significant increase in path length and time was observed between the diabetic-leptin group and the diabetic group (p<0.01, p<0.001, respectively) in the probe test. CONCLUSION: Leptin can exert positive effects on memory impairments in diabetic rats.

The functional diversity of Drosophila Ino80 in development.

Ino80 is well known as a chromatin remodeling protein with the catalytic function of DNA dependent ATPase and is highly conserved across phyla. Ino80 in human and Drosophila is known to form the Ino80 complex in association with the DNA binding protein Ying-Yang 1 (YY1)/Pleiohomeotic (Pho) the Drosophila homologue. We have earlier reported that Ino80 sub-family of proteins has two functional domains, namely, the DNA dependent ATPase and the DNA binding domain. In the background of the essential role of dIno80 in development, we provide evidence of Pho independent function of dIno80 in development and analyze the dual role of dIno80 in activation as well as repression in the context of the homeotic gene Scr (sex combs reduced) in imaginal discs. This differential effect of dIno80 in different imaginal discs suggests the contextual function of dIno80 as an Enhancer of Trithorax and Polycomb (ETP). We speculate on the role of dIno80 as a chromatin remodeler on one hand and a potential recruiter of epigenetic regulatory complexes on the other.

Effect of exogenous leptin on serum levels of lipids, glucose, renal and hepatic variables in both genders of obese and streptozotocin-induced diabetic rats.

OBJECTIVES: Leptin exerts various effects on appetite and body weight. Disruption of the obesity gene is precedent to fatness. Insulin or glucose elevates leptin, but streptozotocin reduces it. However, controversial data exist for the effects of leptin on diabetes and leptin level in each gender. Leptin can damage the kidney function but little evidence exists for its hepatic effects. The aim of this study was to investigate the probable sex-dependent differences in blood sugar levels, lipid profile, and renal and hepatic biochemical factors in the obesity and streptozotocin-induced diabetic rats after leptin administration. MATERIALS AND METHODS: Wistar rats of both sexes were randomly divided into two groups, namely obese and diabetic rats. Each group was further divided into male and female subgroups. Extra fat and carbohydrate was added to the diet to induce obesity. Furthermore, streptozotocin (55 mg/kg, IP) was injected to induce diabetes. The treatment groups received leptin (0.1 mg/kg SC) for 10 days, and then, blood samples were taken from the orbital sinus for laboratory evaluations. RESULTS: Leptin resulted in a significant weight loss in both sexes (P<0.001), food intake reduction in male rats (P<0.05), LDL reduction in female rats (obese (P<0.05) and diabetic (P<0.001)), and glucose level decline in the female diabetic rats (P<0.001). However, total protein concentration, LFT (liver function tests), urea and creatinin concentrations among different groups did not show any significant changes. CONCLUSION: Leptin caused some discrepant results, especially regarding the LDL and glucose levels in diabetic female rats.

Identification and Validation of a Putative Polycomb Responsive Element in the Human Genome.

Epigenetic cellular memory mechanisms that involve polycomb and trithorax group of proteins are well conserved across metazoans. The cis-acting elements interacting with these proteins, however, are poorly understood in mammals. In a directed search we identified a potential polycomb responsive element with 25 repeats of YY1 binding motifthatwe designate PRE-PIK3C2B as it occurs in the first intron of human PIK3C2B gene. It down regulates reporter gene expression in HEK cells and the repression is dependent on polycomb group of proteins (PcG). We demonstrate that PRE-PIK3C2B interacts directly with YY1 in vitro and recruits PRC2 complex in vivo. The localization of PcG proteins including YY1 to PRE-PIK3C2B in HEK cells is decreased on knock-down of either YY1 or SUZ12. Endogenous PRE-PIK3C2B shows bivalent marking having H3K27me3 and H3K4me3 for repressed and active state respectively. In transgenic Drosophila, PRE-PIK3C2B down regulates mini-white expression, exhibits variegation and pairing sensitive silencing (PSS), which has not been previously demonstrated for mammalian PRE. Taken together, our results strongly suggest that PRE-PIK3C2B functions as a site of interaction for polycomb proteins.