Candida albicans is a major fungal pathogen that causes serious systemic and mucosal infections in immunocompromised individuals. In yeast, histone H3 Lys56 acetylation (H3K56ac) is an abundant modification regulated by enzymes that have fungal-specific properties, making them appealing targets for antifungal therapy. Here we demonstrate that H3K56ac in C. albicans is regulated by the RTT109 and HST3 genes, which respectively encode the H3K56 acetyltransferase (Rtt109p) and deacetylase (Hst3p). We show that reduced levels of H3K56ac sensitize C. albicans to genotoxic and antifungal agents. Inhibition of Hst3p activity by conditional gene repression or nicotinamide treatment results in a loss of cell viability associated with abnormal filamentous growth, histone degradation and gross aberrations in DNA staining. We show that genetic or pharmacological alterations in H3K56ac levels reduce virulence in a mouse model of C. albicans infection. Our results demonstrate that modulation of H3K56ac is a unique strategy for treatment of C. albicans and, possibly, other fungal infections.

IL-10 is a potent anti-inflammatory cytokine interfering with antigen presentation by inducing the intracellular sequestration of MHC class II (MHC-II) molecules. Here we studied the contribution of membrane-associated RING-CH (MARCH) ubiquitin ligase family members to the IL-10-induced down-regulation of MHC-II molecules. We found that MARCH1 and MARCH8 proteins are the most potent family members for the downregulation of MHC-II surface expression in transfected cells, but only MARCH1 mRNA expression is strongly induced by IL-10 in human primary monocytes. We detected monoand poly-ubiquitinated forms of MHC-II molecules both in IL-10-treated monocytes and in cells transfected with MARCH1. We also show direct interaction between MHC-II and MARCH1 molecules in co-immunoprecipitation assays. Finally, we found that siRNAmediated knockdown of MARCH1 reverses IL-10-induced MHC-II down-regulation in primary monocytes. Thus, the immunosuppressive effect of IL-10 on antigen presentation is mediated through induced expression of MARCH1.

A novel class of aspartic peptidases known as fungal yapsins, whose first member ScYps1p was identified more than a decade ago in Saccharomyces cerevisiae, is characteristically modified by the addition of a glycophosphatidylinositol moiety and has a preference for cleaving substrates C-terminally to mono- and paired-basic residues. Over the years, several other members, first in S. cerevisiae and then in other fungi, have been identified. The implication of fungal yapsins in cell-wall assembly and/or remodelling had been suspected for many years. However, it is only very recently that studies performed on S. cerevisae and Candida albicans have confirmed their importance for cell-wall integrity. Here, we review 16 years of research, covering all fundamental aspects of these unique enzymes, in an effort to track their functional significance. We also propose a nomenclature for fungal yapsins based on their sequence identity with the founding members of this family, the S. cerevisiae yapsins.

Objectives: There are presently no data available concerning Internet addiction (IA) problems among adolescents in Canada and the province of Quebec. The goal of this study is thus to document and compare the influence of gender on Internet use and addiction.Method: The study data were collected from a larger research project on gambling among adolescents. Activities conducted online (applications used and time spent) as well as answers to the Internet Addiction Test (IAT) were collected from 3938 adolescents from grades 9 to 11. The two most often employed cut-off points for the IAT in the literature were documented: (40-69 and 70þ) and (50þ).Results: Boys spent significantly more time on the Internet than did girls. A greater proportion of the girls made intense use of social networks, whereas a greater proportion of the boys made intense use of massively multiplayer online role-playing games, online games, and adult sites. The proportion of adolescents with a potential IA problem varied according to the cut-off employed. When the cut-off was set at 70þ, 1.3% of the adolescents were considered to have an IA, while 41.7% were seen to be at risk. At a 50þ cut-off, 18% of the adolescents were considered to have a problem. There was no significant difference between the genders concerning the proportion of adolescents considered to be at risk or presenting IA problems. Finally, analysis of the percentile ranks would seem to show that a cut-off of 50þ better describes the category of young people at risk.

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La Grille de dépistage de la consommation problématique d’alcool et de drogues chez les adolescents (DEP-ADO) a été créée pour répondre aux besoins des milieux de pratique québécois. Cet article rapporte les résultats de deux études portant sur les qualités psychométriques de la DEP-ADO. Une première étude a révélé que l’outil était pertinent et possédait une très bonne validité d’apparence, tant auprès des intervenants que des jeunes. Une seconde étude a été menée auprès de 673 élèves de 14 à 17 ans provenant de trois écoles secondaires du Québec et de 64 jeunes inscrits dans des centres de réadaptation en toxicomanie pour évaluer la structure factorielle, la fidélité et la validité de l’outil. Les résultats indiquent que les qualités psychométriques de la DEP-ADO sont nettement satisfaisantes et se comparent avantageusement à celles constatées auprès des autres outils de repérage de la consommation abusive de substances psychoactives chez les adolescents (validité de construit, cohérence interne, fidélité test-retest et inter modes de passation, validité critériée concomitante). Fait intéressant, les analyses factorielles ont permis d’identifier, en plus d’un facteur global, trois facteurs dont le sens clinique est bien identifiable (consommation d’alcool et de cannabis, consommation d’autres drogues, conséquences de la consommation de substances psychoactives). Tout en confirmant de façon globale la validité et la fidélité de la version originale, l’étude a également permis d’y apporter des améliorations et d’ouvrir des perspectives nouvelles sur l’utilisation qui peut en être faite.The chart used to screen problem consumption of alcohol and drugs among adolescents (La Grille de dépistage de la consommation problématique d’alcool et de drogues chez les adolescents/DEP-ADO) was created to meet the needs of drug addiction centres in Quebec. This article reports on the results of two studies on the psychometric qualities of the DEP-ADO. The first demonstrated that the tool was pertinent and appeared to have excellent face validity, for practitioners as well as youth. The second study, involving 673 students from 14 to 17 years of age from three secondary schools in Quebec and 64 youth registered in drug addiction rehabilitation centres, was carried out to evaluate the factor pattern, reliability and the validity of the tool. The results indicated that the psychometric qualities of the DEP-ADO were clearly satisfactory and compare advantageously to those of other screening tools for abusive consumption of psychoactive substances among adolescents (construct validity, internal consistency, test-retest and intermodal execution reliability, concomitant criterion referenced validity). It is interesting that, in addition to an overall factor, the factorial analyses enabled the identification of three factors the clinical meaning of which was clearly identifiable (consumption of alcohol and cannabis, consumption of other drugs, consequences of the consumption of psychoactive substances). While generally confirming the v...

Mineral carbonation of ultramafic rocks provides an environmentally safe and permanent solution for CO(2) sequestration. In order to assess the carbonation potential of ultramafic waste material produced by industrial processing, we designed a laboratory-scale method, using a modified eudiometer, to measure continuous CO(2) consumption in samples at atmospheric pressure and near ambient temperature. The eudiometer allows monitoring the CO(2) partial pressure during mineral carbonation reactions. The maximum amount of carbonation and the reaction rate of different samples were measured in a range of experimental conditions: humidity from dry to submerged, temperatures of 21 and 33 °C, and the proportion of CO(2) in the air from 4.4 to 33.6 mol %. The most reactive samples contained ca. 8 wt % CO(2) after carbonation. The modal proportion of brucite in the mining residue is the main parameter determining maximum storage capacity of CO(2). The reaction rate depends primarily on the proportion of CO(2) in the gas mixture and secondarily on parameters controlling the diffusion of CO(2) in the sample, such as relative saturation of water in pore space. Nesquehonite was the dominant carbonate for reactions at 21 °C, whereas dypingite was most common at 33 °C.