Molecular dynamics simulation of the aqueous solvation shell of cellulose and xanthate ester derivatives

Gonzalo Riadi, Fernando González-Nilo. Centro de Bioinformática y Simulación Molecular, Universidad de Talca, Casilla 721, Talca, Chile.MD simulations of a pentasaccharide having D-glucopyranoside residues connected by (14)- glycosidic linkages, as a model of cellulose solvated in water, were carried out comparing the solvation of the hydroxyl group at C2 of the central ring of the pentamer and that of a single glucopyranose ring. MD simulations of 10 nsec were carried under NPT and periodic boundary conditions at 298 K and 1 atm. Explicit solvent (TIP3) and the force field CHARMM27 (modified for xanthate ester derivatives) were used in the molecular dynamics simulations. RDF calculations with respect to O2 of the central ring of the pentamer showed a well structured first solvation shell followed by secondary shells. When comparing the simulations of the pentamer to a single glucopyranose ring, it was observed that the solvation of O2 was lower for one repetitive unit, indicating that the pentamer had a stronger H-bond structure of water around O2 due to the cooperative effect of the neighboring residues. When the O2 of the central ring of the pentamer was substituted by a p-nitrobenzylxanthate moiety (pentXNB) there was a strong decrease in the hydration of the substituted O2 but the carbon and the sulfur of the thiocarbonyl group were clearly hydrated compared to the sulfur bridge. The global minimum energy conformation showed the p-nitrobenzyl group folded over the neighboring glucose ring. However, the simulations showed that the XNB group oscillates over the pentamer in periods of ca. 3000 psec

www.mdpi.org/molecules A Structure-Activity Study of Antibacterial Diterpenoids

Abstract: An analysis of the antibacterial activities of 15 terpenoids, eleven of which were previously described by us and four were extracted from the literature, suggested two structural requirements for activity of these and related compounds: a hydrophobic moiety, consisting of a substituted decalin skeleton, and a hydrophilic region possessing one hydrogen-bond-donor group. These structural requirements are responsible for an optimal insertion of these and related compounds into cell membranes, as suggested by the results of docking some of these compounds into a model phospholipid bilayer

On the dramatic increase with chain length of the oxidazability of linear saturated aliphatic alcohols on gold in alkaline media

© 2015 Elsevier Ltd. All rights reserved. The electrooxidation of linear saturated aliphatic alcohols from C1 to C8 on gold in alkaline media has been studied by cyclic voltammetry and with an electrochemical quartz crystal microbalance. The current density of alcohol oxidation very markedly increased and, correspondingly, the onset potential decreased, with increasing chain length, that is, with initially slightly increasing, and then constant, pKa. We attribute this oxidazability increase with chain length to the increasing hydrophobicity of the alcohol. Effectively, a molecular dynamics simulation of the hydration of alcohols and alcoholates shows that the hydrophobicity of the alcohols increases with increasing chain length. The higher activity of gold for the oxidation of organic, and also inorganic (CO), compounds in alkaline media is well known, and should be due to an activation of the gold surface by OH adsorption, and not to a change of the compounds themselves, the (majority) neutral alcohol being the oxidized species both in acid and alkaline media. At the potentials at which 1-heptanol oxidation starts, the mass in both base electrolyte and in 1-heptanol is at a minimum, or nearly so, which shows that water is driven away from the surface of gold prior to the oxidation of both gold and 1-heptanol.Peer Reviewe

Dissecting phosphatidylinositol 4,5-bisphosphate activation and thermosensation in TRP channels

Gonzalez Nilo, Danilo and Gonzalez, Wendy. Centro de Bioinformatica y Simulacion Molecular, Universidad de Talca, Talca, Chile.Phosphatidylinositol 4,5-bisphosphate (PIP2) is able to regulate the activity of many ion channels, transporters and enzymes. In particular, the activation of several TRP channels has been shown to be PIP2-dependent. For the case of TRPM8, this activation is supposed to be possible through a direct the interaction between PIP2 and key positively charged residues present in the TRP Domain. Because of the high sequence similarity among Transient Receptor Potential (TRP) channels on their TRP Domain, that region has been proposed as a common PIP2 binding site. In this work, we have exchanged different segments of the C-terminal region between TRPM8 and TRPV1 trying to understand the role of PIP2 during temperature activation of the channel. A chimera dubbed TRPM8(CTV1686-752) is activated by PIP2 and is able to confer the phenotype of heat activation. PIP2 sensitivity disappears when charges R701 and K710 were neutralized. When the exchanged fragment reached a length of 11 amino acid TRPM8(CTV1741-752), temperature dependence disappears. Together, our findings suggest the existence of different activation domains for temperature, PIP2 and voltage. Here, we also provide a simple interpretation for Channel-PIP2 interaction using a refined full-atom molecular model of TRPV1, and PIP2 docking analysis. (Supported by Fondecyt Grants Nº 3060003 (GO), 1040254 (FG) and 103-0830 (RL)

Stigma towards mental illness and substance use issues in primary health care: Challenges and opportunities for Latin America

Stigma towards mental illness and addictive disorders is a global problem and one of the main obstacles in tackling this issue remains the effective integration of mental health services into primary health care (PHC). In Latin America, information has significantly increased on the existence of stigma; however, little is known about effective interventions to prevent stigma and promote recovery-oriented practices in PHC. The aim of this study is to understand the existing evidence regarding mental health stigma in PHC with a special focus on the Latin American region. A scoping review of the literature related to mental health stigma in PHC was conducted. Two hundred and seventeen articles were evaluated; 74 met inclusion criteria and 14 additional articles were selected from references of search results. Results were subdivided into five different perspectives: users, family members and significant others, health professionals, contextual factors, and potential effective interventions. Only nine studies were based in Latin America, and only one described an intervention to reduce stigma in mental health services, not specifically in PHC. We found an urgent need to develop interventions to understand and reduce stigma in PHC settings, especially in Latin America

Validation of the Opening Minds Scale and patterns of stigma in Chilean primary health care.

ObjectivesStigma toward people with mental health problems (MHP) in primary health care (PHC) settings is an important public health challenge. Research on stigma toward MHP is relatively scarce in Chile and Latin America, as are instruments to measure stigma that are validated for use there. The present study aims to validate the Opening Minds Scale for Health Care Professionals (OMS-HC) among staff and providers in public Chilean PHC clinics, and examine differences in stigma by sociodemographic characteristics.Methods803 participants from 34 PHC clinics answered a self-administered questionnaire. Confirmatory factor analysis was completed. Average 15-item OMS-HC scores were calculated, and means were compared via t-test or ANOVA to identify group differences. Correlations of OMS-HC scores with other commonly used stigma scores were calculated to evaluate construct validity.ResultsThe 3-factor OMS-HC structure was confirmed in this population. The average OMS-HC (α = 0.69) score was 34.55 (theoretical range 15-75). Significantly lower (less stigmatizing) mean OMS-HC scores were found in those with additional training and/or personal experience with MHP.ConclusionThe validated, Spanish version of OMS-HC can be of use to further research stigma toward MHP in Chile and Latin America, advancing awareness and inspiring interventions to reduce stigma in the future

Dissection of the components for PIP2 activation and thermosensation in TRP channels

Phosphatidylinositol 4,5-bisphosphate (PIP2) plays a central role in the activation of several transient receptor potential (TRP) channels. The role of PIP2 on temperature gating of thermoTRP channels has not been explored in detail, and the process of temperature activation is largely unexplained. In this work, we have exchanged different segments of the C-terminal region between cold-sensitive (TRPM8) and heat-sensitive (TRPV1) channels, trying to understand the role of the segment in PIP2 and temperature activation. A chimera in which the proximal part of the C-terminal of TRPV1 replaces an equivalent section of TRPM8 C-terminal is activated by PIP2 and confers the phenotype of heat activation. PIP2, but not temperature sensitivity, disappears when positively charged residues contained in the exchanged region are neutralized. Shortening the exchanged segment to a length of 11 aa produces voltage-dependent and temperature-insensitive channels. Our findings suggest the existence of different activation domains for temperature, PIP2, and voltage. We provide an interpretation for channel–PIP2 interaction using a full-atom molecular model of TRPV1 and PIP2 docking analysis