Molecular basis of differential target regulation by miR-96 and miR-182: the Glypican-3 as a model

Besides the fact that miR-96 and miR-182 belong to the miR-182/183 cluster, their seed region (UUGGCA, nucleotides 2–7) is identical suggesting potential common properties in mRNA target recognition and cellular functions. Here, we used the mRNA encoding Glypican-3, a heparan-sulfate proteoglycan, as a model target as its short 3′ untranslated region is predicted to contain one miR-96/182 site, and assessed whether it is post-transcriptionally regulated by these two microRNAs. We found that miR-96 downregulated GPC3 expression by targeting its mRNA 3′-untranslated region and interacting with the predicted site. This downregulatory effect was due to an increased mRNA degradation and depended on Argonaute-2. Despite its seed similarity with miR-96, miR-182 was unable to regulate GPC3. This differential regulation was confirmed on two other targets, FOXO1 and FN1. By site-directed mutagenesis, we demonstrated that the miRNA nucleotide 8, immediately downstream the UUGGCA seed, plays a critical role in target recognition by miR-96 and miR-182. Our data suggest that because of a base difference at miRNA position 8, these two microRNAs control a completely different set of genes and therefore are functionally independent

The PTEN Phosphatase Controls Intestinal Epithelial Cell Polarity and Barrier Function: Role in Colorectal Cancer Progression

The PTEN phosphatase acts on phosphatidylinositol 3,4,5-triphosphates resulting from phosphatidylinositol 3-kinase (PI3K) activation. PTEN expression has been shown to be decreased in colorectal cancer. Little is known however as to the specific cellular role of PTEN in human intestinal epithelial cells. The aim of this study was to investigate the role of PTEN in human colorectal cancer cells.Caco-2/15, HCT116 and CT26 cells were infected with recombinant lentiviruses expressing a shRNA specifically designed to knock-down PTEN. The impact of PTEN downregulation was analyzed on cell polarization and differentiation, intercellular junction integrity (expression of cell-cell adhesion proteins, barrier function), migration (wound assay), invasion (matrigel-coated transwells) and on tumor and metastasis formation in mice. Electron microscopy analysis showed that lentiviral infection of PTEN shRNA significantly inhibited Caco-2/15 cell polarization, functional differentiation and brush border development. A strong reduction in claudin 1, 3, 4 and 8 was also observed as well as a decrease in transepithelial resistance. Loss of PTEN expression increased the spreading, migration and invasion capacities of colorectal cancer cells in vitro. PTEN downregulation also increased tumor size following subcutaneous injection of colorectal cancer cells in nude mice. Finally, loss of PTEN expression in HCT116 and CT26, but not in Caco-2/15, led to an increase in their metastatic potential following tail-vein injections in mice.Altogether, these results indicate that PTEN controls cellular polarity, establishment of cell-cell junctions, paracellular permeability, migration and tumorigenic/metastatic potential of human colorectal cancer cells

Séries de suicide impliquant des adolescents et des jeunes : culture et transmission intergénérationnelle

Cette analyse porte sur deux séries de suicides d’adolescents et de jeunes adultes, l’une dans un village des Premières Nations et l’autre dans un milieu traditionnel québécois. La méthodologie repose en premier lieu sur une validation des cas à partir des rapports de coroners*

Littératie communautaire : analyse de la production documentaire et revue de la littérature

Cet article vise à clarifier le concept de littératie communautaire et en produire une définition afin de mieux comprendre ses champs d’étude et d’action. La méthodologie repose sur une recherche documentaire comprenant une analyse bibliométrique et une revue systématique de la littérature réalisée sur un corpus de textes anglo-américains, incluant quelques textes en français, et hispanophones. Les résultats de cette recherche révèlent que le concept de littératie communautaire s’appuie sur une série de dimensions constitutives : la différence et la diversité, la situation locale, un dispositif critique et éthique, la délimitation et le continuum des littératies. Cette analyse documentaire particulièrement complète et ces résultats permettront d’enrichir les approches théoriques et pratiques tout en favorisant l’engagement des différents actrices et acteurs en matière de littératie communautaire.This article aims to clarify the concept of community literacy and produce a definition in order to better understand its fields of study and action. The methodology is based on a literature search including a bibliometric analysis and a systematic review of the literature conducted on a corpus of Anglo-American and Spanish-language texts. The results of this research reveal that the concept of community literacy is based on a series of constitutive dimensions: difference and diversity, locality, critical and ethical agency, delineation and continuum of literacies. This comprehensive review of the literature and these findings will enrich theoretical and practical approaches while fostering the engagement of different actors in community literacy

Artcité : When Montréal Turns Into a Museum

Pocket-sized catalogue for the event Artcité, for which 55 works from the collection of the Musée d’art contemporain de Montréal (including the Lavalin collection) were paired according to certain affinities; one installed in the Museum and its counterpart in an unusual site elsewhere in the city (businesses, offices, shops, churches, etc.). Each work is documented with a photograph and a short analytical text, with biographical references on the artist. D. Bumbaru provides architectural and historical notes on each of the 23 off-site locations and their rapport with the urban environment. Index of names (artists, artworks and exhibition sites)