Simulation of DNA bases in water: Comparison of the Monte Carlo algorithm with molecular mechanics force fields

The interaction between the nucleic acid bases and solvent molecules has an important effect in various biochemical processes. We have calculated total energy and free energy of the solvation of DNA bases in water by Monte Carlo simulation. Adenine, guanine, cytosine, and thymine were first optimized in the gas phase and then placed in a cubic box of water. We have used the TIP3 model for water and OPLS for the nucleic acid bases. The canonical (T, V, N) ensemble at 25°C and Metropolis sampling technique have been used. Good agreement with other available computational data was obtained. Radial distribution functions of water around each site of adenine, guanine, cytosine, and thymine have been computed and the results have shown the ability of the sites for hydrogen bonding and other interactions. The computations have shown that guanine has the highest value of solvation free energy and N7 and N6 in adenine and guanine, N3 in cytosine, and N3 and O4 in thymine have the largest radial distribution function. Monte Carlo simulation has also been performed using the CHARMM program under the same conditions, and the results of two procedures are compared.     

Molecular simulation study of PAMAM dendrimer composite membranes

Pure polysulfone (PSF) and its composites with chitosan (CST), hyaluronic acid (HA), conventional poly(amidoamine), and hydroxyl poly(amidoamine) dendrimers as the membranes for separation of the gases, methane, carbon dioxide, hydrogen sulfide, nitrogen, and oxygen have been studied by molecular dynamics (MD) and grand canonical Monte Carlo (GCMC) simulations. The transport properties (solubility, diffusivity, and permeability) of pure and gas mixtures in the membranes were calculated and the results of the simulations were compared with the available experimental data. The simulated structural properties of the pure and composite PSF membranes including occupied volume, free volume, surface area, fractional free volume (FFV), and radius of gyration (R _g ) were evaluated and their effects on the separability of the gases by the membranes were analyzed and interpreted by the obtained results.

Polishing low-biodegradable and saline industrial effluent in a full-scale horizontal subsurface flow constructed wetland: evaluation of bio-treatability and predictive power of kinetic models

Abstract

This study evaluates the bio-treatability performance and kinetic models of full-scale horizontal subsurface flow constructed wetland used for the tertiary treatment of composite industrial effluent characterized by high-salt content ranging from 5830 to 10,400 µS/cm and biochemical oxygen demand (BOD₅): chemical oxygen demand (COD) ratio below 0.2. The wetland vegetated with Phragmites australis was operated in a semi-arid climate under an average hydraulic loading rate of 63?mm/d. The results of a 4-year operation calculated based on the concentration of pollutants showed that the average removal efficiency of COD, BOD_5, and total suspended solids (TSS) were 17.5, 5.1, and 11.2%, respectively. The system reduced up to 6.5?±?0.7% of electrical conductivity presenting poor phyto-desalination potential without considering the contribution of evapotranspiration in water balance in contrast to satisfying performance for heavy metals reduction. The comparison of the kinetics of organic matter removal obtained by the first-order and Monod models paired with continuous stirred-tank reactor and plug flow regime showed that Monod-plug flow model provided the best fit with the constants of 2.01?g COD/m²·d and 0.3014?g BOD₅/m²·d with the best correlation coefficient of 0.610 and 0.968 between the predicted and measured concentrations, respectively. The low kinetic rates indicate that the process is capable of effluent polishing instead of purification due to the presence of organic compounds recalcitrant to biodegradation and a high level of salinity.     

Immobilization of recombinant nanobiofiber CS3 fimbriae onto alginate beads for improvement of cadmium biosorption

A cell surface display system with metalbinding properties was previously developed using CS3 fimbriae, which are hollow tubes 20 nm-thick and 2 nm in diameter. In this study, hybrid CS3 pili were separated from recombinant Escherichia coli and entrapped in calcium alginate gel beads in order to improve their stabilization and also adsorption of heavy metals. The surface morphology of the gel beads containing pili was investigated by scanning electron microscopy (SEM). Immunofluorescence microscopy was employed to confirm the attachment of nanobiofibers to the alginate beads. The effects of three variables (sodium alginate concentration, protein to alginate mass ratio, and bead size) at two levels each on Cd²⁺ biosorption efficiency were investigated by full factorial experimental design. A second-order polynomial equation modeled the design space for the process response of cadmium removal capacity. The optimal values of the factors were obtained as follows: 1% sodium alginate concentration, 0.25 protein to alginate mass ratio, and a 6 mm bead size. Under these conditions, Cd²⁺ was adsorbed at 45.45 mg/g to the nanobiofiber. The results indicate that the immobilized recombinant hybrid CS3 pili may be an appropriate biosorbent for removal of heavy metals from polluted aquatic environments.     

Dressings Combined with Injection of Meglumine Antimoniate in the Treatment of Cutaneous Leishmaniasis: A Randomized Controlled Clinical Trial

Background

Cutaneous leishmaniasis (CL) is a neglected infectious disease and a major health problem in several developing countries. Despite some reasonable explanation for their potential benefits, there is only trace evidence regarding the role of dressings in the treatment of CL.

Methods

This randomized, assessor-blind, controlled, clinical trial was conducted in an endemic area for CL caused by Leishmania major in Iran to assess the efficacy of administration of weekly intralesional meglumine antimoniate (i.l.MA) either alone or combined with application of a silver or a non-silver polyester dressing on their lesions for 6 weeks. After screening of 241 patients with CL lesions, 83 eligible patients with 158 lesions were randomly allocated in three arms of the study. Eligibility criteria included parasitologically confirmed CL, age of 12 to 60 years; willingness to participate, duration of lesion<3 months, number of lesions<5, largest ulcer diameter<5 cm. Pregnant or lactating women were excluded. The primary outcome was absolute risk reduction (ARR) based on the proportion of complete healing, which was defined as more than 75% reduction in the size of the lesion compared with baseline in each group at the termination of treatment and 1 month later.

Findings

ARR (95% Confidence Interval [CI]) in i.l.MA versus i.l.MA+non-silver dressing groups was 5.98% (−7.07% to 20.25%), between i.l.MA versus i.l.MA+silver dressing groups was −0.23% (−13.53% to 14.82%), and between i.l.MA+non-silver dressing versus i.l.MA+silver dressing groups was −6.21%(−18.28% to 6.52%) after 6 weeks of treatment. ARR (95% CI) in i.l.MA versus i.l.MA+non-silver dressing groups was −2.22% (−22.12% to 18.10%), between i.l.MA versus i.l.MA+silver dressing groups was 3.64% (−15.36% to 22.82%), and between i.l.MA+non-silver dressing versus i.l.MA+silver dressing groups was 5.86% (−12.86% to 24.31%) 1 month later.

Conclusion

It could not be demonstrated that the efficacy of i.l.MA was improved by either dressing.

Trial Registration

Iranian Registry of Clinical Trials (IRCT.ir) IRCT138707201166N2.     

Tropisetron But Not Granisetron Ameliorates Spatial Memory Impairment Induced by Chronic Cerebral Hypoperfusion

Neurochemical Research - Tropisetron and Granisetorn are 5-HT3 antagonists with antiemetic effects. Tropisetron also has a partial agonistic effect on alpha-7 nicotinic acetylcholine receptors...     

Docosahexaenoic acid suppresses migration of triple-negative breast cancer cell through targeting metastasis-related genes and microRNA under normoxic and hypoxic conditions

There is insufficient evidence with respect to the effect of the standard anticancer therapeutic agents as well as common dietary supplements on the expression of such genes and microRNAs (miRNAs). Therefore, this study was aimed to study the effect of applying linoleic acid (LA) and docosahexaenoic acid (DHA) fatty acids alone or combined with Taxol on the expression of the matrix metalloproteinase (MMP)-9, MMP-2, vimentin, and talin2 genes, tumor-suppressor miR-194 and, onco-miR-106b in triple-negative breast cancer cell line, known as MDA-MB-231. MDA-MB-231 as metastatic breast cancer cell line was cultured and treated using 0.3 μM Taxol, 100 μM DHA, and 50 μM LA for 24 hours, alone or combined with Taxol under the normoxic and hypoxic conditions. Cells were harvested, after RNA extraction and complementary DNA synthesis, analysis of the expression levels of the studied genes and miRNAs was done through the use of the quantitative real-time polymerase chain reaction (qRT-PCR). Wound healing assay and Western blot analysis were also performed for confirmation. The results of qRT-PCR showed that treating the MDA-MB-231 cells with DHA caused an increase in the miR-194 expression and a decrease in the miR-106b expression, leading to the downregulation of the MMP-2 and MMP-9, and vimentin, and upregulation of the talin2 under the normoxic and hypoxic conditions. The results of the wound healing scratch assay revealed that the administration of the DHA and the DHA-Taxol combination caused the repression of cell migration in comparison with the control groups under the normoxic and hypoxic conditions. The results of the Western blot analysis demonstrated that DHA and the DHA-Taxol combination caused an increase in the expression of the talin2 protein rather than the control cells under both normoxic and hypoxic conditions. This study showed that DHA has significant antimetastatic effects against the triple-negative breast cancer cells. DHA could serve as a promising supplementation for suppressing the breast cancer cell migration, especially under the hypoxic condition.     

Sucrose self-administration and CNS activation in the rat

We have previously reported that administration of insulin into the arcuate nucleus of the hypothalamus decreases motivation for sucrose, assessed by a self-administration task, in rats. Because the pattern of central nervous system (CNS) activation in association with sucrose self-administration has not been evaluated, in the present study, we measured expression of c-Fos as an index of neuronal activation. We trained rats to bar-press for sucrose, according to a fixed-ratio (FR) or progressive-ratio (PR) schedule and mapped expression of c-Fos immunoreactivity in the CNS, compared with c-Fos expression in handled controls. We observed a unique expression of c-Fos in the medial hypothalamus (the arcuate, paraventricular, retrochiasmatic, dorsomedial, and ventromedial nuclei) in association with the onset of PR performance, and expression of c-Fos in the lateral hypothalamus and the bed nucleus of stria terminalis in association with the onset of FR performance. c-Fos expression was increased in the nucleus accumbens of both FR and PR rats. Our study emphasizes the importance of both hypothalamic energy homeostasis circuitry and limbic circuitry in the performance of a food reward task. Given the role of the medial hypothalamus in regulation of energy balance, our study suggests that this circuitry may contribute to reward regulation within the larger context of energy homeostasis.     

Nutritional state and collective motion: from individuals to mass migration

In order to move effectively in unpredictable or heterogeneous environments animals must make appropriate decisions in response to internal and external cues. Identifying the link between these components remains a challenge for movement ecology and is important in understanding the mechanisms driving both individual and collective motion. One accessible way of examining how internal state influences an individual''s motion is to consider the nutritional state of an animal. Our experimental results reveal that nutritional state exerts a relatively minor influence on the motion of isolated individuals, but large group-level differences emerge from diet affecting inter-individual interactions. This supports the idea that mass movement in locusts may be driven by cannibalism. To estimate how these findings are likely to impact collective migration of locust hopper bands, we create an experimentally parametrized model of locust interactions and motion. Our model supports our hypothesis that nutrient-dependent social interactions can lead to the collective motion seen in our experiments and predicts a transition in the mean speed and the degree of coordination of bands with increasing insect density. Furthermore, increasing the interaction strength (representing greater protein deprivation) dramatically reduces the critical density at which this transition occurs, demonstrating that individuals'' nutritional state could have a major impact on large-scale migration.     

Implications of a histone code mimic in epigenetic signaling

In this issue of Molecular Cell, Sampath et al. show a lysine methylase exhibits substrate promiscuity and variability in degree of product methylation (Sampath et al., 2007). Two lysines are found to be automethylated in G9a, and one is H3K9-like and can establish a docking site for HP1 chromodomain.