16 research outputs found
Identification of epigenetic factors regulating the mesenchyme to epithelium transition by RNA interference screening in breast cancer cells
Alternances codiques et éducation en Outre-mer français : Guadeloupe, Guyane, Saint-Martin
Alternances codiques et éducation dans les département et collectivités d'outre-mer: Guadeloupe, Guyane, Saint-Martin
Nonobstant leur diversité sur le plan linguistique et socioculturel, les contextes d'enseignement dans les départements et collectivités de l'outre-mer français présentent de nombreux points communs, et notamment la présence de plusieurs langues entrainant des phénomènes de contacts comme les alternances codiques (désormais AC). Ainsi, dans ces contextes bi et plurilingues, la question de la gestion des langues au cours des interactions didactiques est centrale et concerne tous les acteurs : élèves, parents, enseignants, formateurs, conseillers pédagogiques, inspecteurs de l'Éducation nationale... Si l'utilisation des langues régionales et de l'AC dans les situations d'enseignement a longtemps été interdite et considérée comme un manque de maitrise ou de respect, les travaux actuels tendent à considérer ces phénomènes comme des marques de mobilisation des ressources langagières et de construction de compétences plurilingues en vue de l'enseignement et de l'apprentissage de savoirs, tant dans les disciplines dites linguistiques (français, langue vivante étrangère, langue vivante régionale...) que non linguistiques (sciences de la vie et de la terre, histoire, mathématiques, éducation physique et sportive...). C'est pourquoi nous avons relevé, transcrit puis analysé des corpus de parole issus de situations d'enseignement aux Antilles et en Guyane françaises, afin d'analyser les AC en classe et de proposer des pistes de réflexion didactiques et pédagogiques, mais également éducatives, culturelles et sociales en contextes bi- et plurilingues
Additional file 1: of Identification of epigenetic factors regulating the mesenchyme to epithelium transition by RNA interference screening in breast cancer cells
Raw Data. An excel file containing 10 spreadsheets. Each spreadsheet has the name of the figure in which the data were used. (XLS 788 kb
Coffinite formation from UO 2+x
International audienceMost of the highly radioactive spent nuclear fuel (SNF) around the world is destined for final disposal in deep-mined geological repositories. At the end of the fuel’s useful life in a reactor, about 96% of the SNF is still UO2. Thus, the behaviour of UO2 in SNF must be understood and evaluated under the weathering conditions of geologic disposal, which extend to periods of hundreds of thousands of years. There is ample evidence from nature that many uranium deposits have experienced conditions for which the formation of coffinite, USiO4, has been favoured over uraninite, UO2+x, during subsequent alteration events. Thus, coffinite is an important alteration product of the UO2 in SNF. Here, we present the first evidence of the formation of coffinite on the surface of UO2 at the time scale of laboratory experiments in a solution saturated with respect to amorphous silica at pH = 9, room temperature and under anoxic conditions
Hijacking DNA methyltransferase transition state analogues to produce chemical scaffolds for PRMT inhibitors
International audienceDNA, RNA and histone methylation is implicated in various human diseases such as cancer or viral infections, playing a major role in cell process regulation, especially in modulation of gene expression. Here we developed a convergent synthetic pathway starting from a protected bromomethylcytosine derivative to synthesize transition state analogues of the DNA methyltransferases. This approach led to seven 5-methylcytosine-adenosine compounds that were, surprisingly, inactive against hDNMT1, hDNMT3Acat, TRDMT1 and other RNA human and viral methyltransferases. Interestingly, compound 4 and its derivative 2 showed an inhibitory activity against PRMT4 in the micromolar range. Crystal structures showed that compound 4 binds to the PRMT4 active site, displacing strongly the S-adenosyl-l-methionine cofactor, occupying its binding site, and interacting with the arginine substrate site through the cytosine moiety that probes the space filled by a substrate peptide methylation intermediate. Furthermore, the binding of the compounds induces important structural switches. These findings open new routes for the conception of new potent PRMT4 inhibitors based on the 5-methylcytosine-adenosine scaffold.This article is part of a discussion meeting issue 'Frontiers in epigenetic chemical biology'
Recommended from our members
The oral-facial-digital syndrome gene C2CD3 encodes a positive regulator of centriole elongation.
Centrioles are microtubule-based, barrel-shaped structures that initiate the assembly of centrosomes and cilia. How centriole length is precisely set remains elusive. The microcephaly protein CPAP (also known as MCPH6) promotes procentriole growth, whereas the oral-facial-digital (OFD) syndrome protein OFD1 represses centriole elongation. Here we uncover a new subtype of OFD with severe microcephaly and cerebral malformations and identify distinct mutations in two affected families in the evolutionarily conserved C2CD3 gene. Concordant with the clinical overlap, C2CD3 colocalizes with OFD1 at the distal end of centrioles, and C2CD3 physically associates with OFD1. However, whereas OFD1 deletion leads to centriole hyperelongation, loss of C2CD3 results in short centrioles without subdistal and distal appendages. Because C2CD3 overexpression triggers centriole hyperelongation and OFD1 antagonizes this activity, we propose that C2CD3 directly promotes centriole elongation and that OFD1 acts as a negative regulator of C2CD3. Our results identify regulation of centriole length as an emerging pathogenic mechanism in ciliopathies