sHSPdb: a database for the analysis of small Heat Shock Proteins

Background small Heat Shock Proteins (sHSP) is a wide proteins family. SHSP are found in all kingdoms and they play critical roles in plant stress tolerance mechanisms (as well as in pathogenic microorganisms and are implicated in human diseases). Results sHSPdb (small Heat Shock Proteins database) is an integrated resource containing non-redundant, full-length and curated sequences of sHSP, classified on the basis of amino acids motifs and physico-chemical properties. sHSPdb gathers data about sHSP defined by various databases (Uniprot, PFAM, CDD, InterPro). It provides a browser interface for retrieving information from the whole database and a search interface using various criteria for retrieving a refined subset of entries. Physicochemical properties, amino acid composition and combinations are calculated for each entry. sHSPdb provides automatic statistical analysis of all sHSP properties. Among various possibilities, sHSPdb allows BLAST searches, alignment of selected sequences and submission of sequences. Conclusions sHSPdb is a new database containing information about sHSP from all kingdoms. sHSPdb provides a classification of sHSP, as well as tools and data for the analysis of the structure - function relationships of sHSP. Data are mainly related to various physico-chemical properties of the amino acids sequences of sHSP. sHSPdb is accessible at http://forge.info.univ-angers.fr/~gh/Shspdb/index.php

Comparison of Amino Acids Physico-Chemical Properties and Usage of Late Embryogenesis Abundant Proteins, Hydrophilins and WHy Domain

Late Embryogenesis Abundant proteins (LEAPs) comprise several diverse protein families and are mostly involved in stress tolerance. Most of LEAPs are intrinsically disordered and thus poorly functionally characterized. LEAPs have been classified and a large number of their physico-chemical properties have been statistically analyzed. LEAPs were previously proposed to be a subset of a very wide family of proteins called hydrophilins, while a domain called WHy (Water stress and Hypersensitive response) was found in LEAP class 8 (according to our previous classification). Since little is known about hydrophilins and WHy domain, the cross-analysis of their amino acids physico-chemical properties and amino acids usage together with those of LEAPs helps to describe some of their structural features and to make hypothesis about their function. Physico-chemical properties of hydrophilins and WHy domain strongly suggest their role in dehydration tolerance, probably by interacting with water and small polar molecules. The computational analysis reveals that LEAP class 8 and hydrophilins are distinct protein families and that not all LEAPs are a protein subset of hydrophilins family as proposed earlier. Hydrophilins seem related to LEAP class 2 (also called dehydrins) and to Heat Shock Proteins 12 (HSP12). Hydrophilins are likely unstructured proteins while WHy domain is structured. LEAP class 2, hydrophilins and WHy domain are thus proposed to share a common physiological role by interacting with water or other polar/charged small molecules, hence contributing to dehydration tolerance

Analyse des déhydrines chez le champignon phytopathogène Alternaria brassicicola

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Enhanced direct oxidation of diclofenac (DCF) at a carbon paste electrode (CPE) modified with cellulose and its biodegradability by Scedosporium dehoogii

A novel carbon paste electrode modified with cellulose fibers and dedicated to diclofenac electroanalysis was prepared, optimized, and used for the determination of the kinetic parameters of DCF biodegradation by a filamentous fungus. The electrochemical response of the modified CPE was compared to that of the unmodified. This study conducted by cyclic voltammetry and linear sweep voltammetry allowed the optimization of the cellulose fibers modified CPE in terms of absence/presence of cellulose fibers, accumulation time (250 s), and initial potential (- 0.4 V/Ag/AgCl). Interestingly, in these conditions, the limit of detection observed through linear sweet voltammetry was found to be as low as 0.020 µmol L-1. This electrode was then used to follow the degradation of DCF. Our results demonstrated that among species belonging to the Scedosporium genus, S. dehoogii displayed the best assets in our process in terms of growth temperature and ability to metabolize DCF. More precisely, DCF biodegradation using S. dehoogii in the process revealed a kinetic of order of 1, a kinetic constant k of 0.012 day-1 and a half time of 57.8 days for an initial concentration of DCF of 1.65 ± 0.05 mg L-1 and at a temperature of 25°C. This study constitutes a solid proof of concept for future developments of fungal wastewater treatments for bioremediation of DCF which is refractory to standard bacterial-based bioprocesses

Gender-based violence against women in contemporary France: domestic violence and forced marriage policy since the Istanbul Convention

ABSTRACT: In 2014, France ratified the Council of Europe’s Convention on Preventing and Combating Violence against Women and Domestic Violence (the Istanbul Convention) and passed the Law for Equality between Women and Men to bring French law into line with it. The Law for Equality between Women and Men situates the fight against violence against women within a broader context of the need to address inequalities between women and men. This is not new at the international level, but it is new to France. When the structural, transformative understandings of violence against women found in international texts are translated into national laws, policy documents and implementation on the ground, they might challenge widespread ideas about gender relations, or they might be diluted in order to achieve consensus. To what extent has French violence against women policy moved into line with UN and Council of Europe initiatives which present violence against women as both a cause and a consequence of gendered power relations? Have internationally accepted concepts of gender and gender-based violence been incorporated into French policy debates and, if so, how? What implications, if any, does all this have for the continued struggle in France and elsewhere to eliminate violence a gainst women? RÉSUMÉ: En 2014, la France a ratifié la Convention du Conseil de l’Europe sur la prévention et la lutte contre la violence à l’égard des femmes et la violence domestique (dite Convention d’Istanbul) et a adopté dans la foulée la loi pour l’égalité réelle entre les femmes et les hommes afin de mettre en conformité la législation française. Cette loi place la lutte contre la violence à l’égard des femmes dans un contexte de lutte contre les inégalités de genre. Si cela est loin d’être une nouveauté à l’échelle internationale, cela l’est en France. Lorsque les conceptions structurelles et transformatrices de la violence à l’égard des femmes présentes dans les textes internationaux sont traduites à l’échelle nationale en lois, documents d’orientation et mesures de mise en œuvre sur le terrain, elles peuvent alors remettre en question des idées largement répandues sur les rapports de genre, ou au contraire être édulcorées afin d’aboutir à un consensus. Dans quelle mesure la politique de la France relative à la violence à l’égard des femmes s’est-elle alignée sur les initiatives de l’ONU et du Conseil de l’Europe qui présentent ce type de violence comme étant à la fois une cause et une conséquence des rapports de force liés au genre? Le genre et la violence fondée sur le genre, qui sont des concepts internationalement reconnus, ont-ils été intégrés dans les débats politiques français, et si oui, de quelle manière? Quelles en sont les implications le cas échéant sur la poursuite, en France et ailleurs, de la lutte pour éliminer la violence à l’égard des femmes

Angiotensin-Converting Enzyme (ACE) Gene Insertion/Deletion Polymorphism and ACE Inhibitor-Related Cough: A Meta-Analysis

Objective: An insertion/deletion (I/D) variant in the angiotensin-converting enzyme (ACE) gene was associated with ACE inhibitor (ACEI)-related cough in previous studies. However, the results were inconsistent. Our objective was to assess the relationship between the ACE I/D polymorphism and ACEI-related cough by meta-analysis and to summarize all studies that are related to ACE I/D polymorphism and ACEI-cough and make a summary conclusion to provide reference for the researchers who attempt to conduct such a study. Methods: Databases including PubMed, EMbase, Cochrane Library, and China National Knowledge Infrastructure, were searched for genetic association studies. Data were extracted by two independent authors and pooled odds ratio (OR) with 95% confidence interval (CI) was calculated. Metaregression and subgroup analyses were performed to identify the source of heterogeneity. Results: Eleven trials, including 906 cases (ACEI-related cough) and 1,175 controls, were reviewed in the present meta-analysis. The random effects pooled OR was 1.16 (95% CI: 0.78-1.74, p = 0.46) in the dominant model and 1.61 (95% CI: 1.18-2.20, p = 0.003) in the recessive model. Heterogeneity was found among and within studies. Metaregression indicated that the effect size was positively associated with age and negatively associated with follow-up duration of ACEI treatment. Subgroup analysis revealed a significant association between ACE I/D polymorphism and ACEI-related cough in studies with mean age >60 y, but not in studies with mean age 2 mo or in studies in Caucasians. No heterogeneity was detected in these two subgroups. Conclusions: Synthesis of the available evidence supports ACE I/D polymorphism as an age-dependent predictor for risk of ACEI-related cough

Human physiologically based pharmacokinetic model for ACE inhibitors: ramipril and ramiprilat

BACKGROUND: The angiotensin-converting enzyme (ACE) inhibitors have complicated and poorly characterized pharmacokinetics. There are two binding sites per ACE (high affinity "C", lower affinity "N") that have sub-nanomolar affinities and dissociation rates of hours. Most inhibitors are given orally in a prodrug form that is systemically converted to the active form. This paper describes the first human physiologically based pharmacokinetic (PBPK) model of this drug class. METHODS: The model was applied to the experimental data of van Griensven et. al for the pharmacokinetics of ramiprilat and its prodrug ramipril. It describes the time course of the inhibition of the N and C ACE sites in plasma and the different tissues. The model includes: 1) two independent ACE binding sites; 2) non-equilibrium time dependent binding; 3) liver and kidney ramipril intracellular uptake, conversion to ramiprilat and extrusion from the cell; 4) intestinal ramipril absorption. The experimental in vitro ramiprilat/ACE binding kinetics at 4°C and 300 mM NaCl were assumed for most of the PBPK calculations. The model was incorporated into the freely distributed PBPK program PKQuest. RESULTS: The PBPK model provides an accurate description of the individual variation of the plasma ramipril and ramiprilat and the ramiprilat renal clearance following IV ramiprilat and IV and oral ramipril. Summary of model features: Less than 2% of total body ACE is in plasma; 35% of the oral dose is absorbed; 75% of the ramipril metabolism is hepatic and 25% of this is converted to systemic ramiprilat; 100% of renal ramipril metabolism is converted to systemic ramiprilat. The inhibition was long lasting, with 80% of the C site and 33% of the N site inhibited 24 hours following a 2.5 mg oral ramipril dose. The plasma ACE inhibition determined by the standard assay is significantly less than the true in vivo inhibition because of assay dilution. CONCLUSION: If the in vitro plasma binding kinetics of the ACE inhibitor for the two binding sites are known, a unique PBPK model description of the Griensven et. al. experimental data can be obtained

Computational and Statistical Analyses of Amino Acid Usage and Physico-Chemical Properties of the Twelve Late Embryogenesis Abundant Protein Classes

Late Embryogenesis Abundant Proteins (LEAPs) are ubiquitous proteins expected to play major roles in desiccation tolerance. Little is known about their structure - function relationships because of the scarcity of 3-D structures for LEAPs. The previous building of LEAPdb, a database dedicated to LEAPs from plants and other organisms, led to the classification of 710 LEAPs into 12 non-overlapping classes with distinct properties. Using this resource, numerous physico-chemical properties of LEAPs and amino acid usage by LEAPs have been computed and statistically analyzed, revealing distinctive features for each class. This unprecedented analysis allowed a rigorous characterization of the 12 LEAP classes, which differed also in multiple structural and physico-chemical features. Although most LEAPs can be predicted as intrinsically disordered proteins, the analysis indicates that LEAP class 7 (PF03168) and probably LEAP class 11 (PF04927) are natively folded proteins. This study thus provides a detailed description of the structural properties of this protein family opening the path toward further LEAP structure - function analysis. Finally, since each LEAP class can be clearly characterized by a unique set of physico-chemical properties, this will allow development of software to predict proteins as LEAPs