Portrait of Ependymoma Recurrence in Children: Biomarkers of Tumor Progression Identified by Dual-Color Microarray-Based Gene Expression Analysis

BACKGROUND: Children with ependymoma may experience a relapse in up to 50% of cases depending on the extent of resection. Key biological events associated with recurrence are unknown. METHODOLOGY/PRINCIPAL FINDINGS: To discover the biology behind the recurrence of ependymomas, we performed CGHarray and a dual-color gene expression microarray analysis of 17 tumors at diagnosis co-hybridized with the corresponding 27 first or subsequent relapses from the same patient. As treatment and location had only limited influence on specific gene expression changes at relapse, we established a common signature for relapse. Eighty-seven genes showed an absolute fold change ≥2 in at least 50% of relapses and were defined as the gene expression signature of ependymoma recurrence. The most frequently upregulated genes are involved in the kinetochore (ASPM, KIF11) or in neural development (CD133, Wnt and Notch pathways). Metallothionein (MT) genes were downregulated in up to 80% of the recurrences. Quantitative PCR for ASPM, KIF11 and MT3 plus immunohistochemistry for ASPM and MT3 confirmed the microarray results. Immunohistochemistry on an independent series of 24 tumor pairs at diagnosis and at relapse confirmed the decrease of MT3 expression at recurrence in 17/24 tumor pairs (p = 0.002). Conversely, ASPM expression was more frequently positive at relapse (87.5% vs 37.5%, p = 0.03). Loss or deletion of the MT genes cluster was never observed at relapse. Promoter sequencing after bisulfite treatment of DNA from primary tumors and recurrences as well as treatment of short-term ependymoma cells cultures with a demethylating agent showed that methylation was not involved in MT3 downregulation. However, in vitro treatment with a histone deacetylase inhibitor or zinc restored MT3 expression. CONCLUSIONS/SIGNIFICANCE: The most frequent molecular events associated with ependymoma recurrence were over-expression of kinetochore proteins and down-regulation of metallothioneins. Metallothionein-3 expression is epigenetically controlled and can be restored in vitro by histone deacetylase inhibitors

Education thérapeutique en odontologie (prise en charge des patients adultes à risque carieux élevé)

Durant les vingt dernières années, une diminution de l'indice carieux dans la population générale a été constatée, notamment grâce à la qualité des traitements et à la mise en place d'actions de prévention. Néanmoins, la plupart des lésions carieuses sont observées dans des populations définies "à risque". L'éducation thérapeutique est un élément indispensable à intégrer à la prise en charge des patients adultes à risque carieux élevé. Elle est déjà présente dans de nombreux domaines de la médecine et a fait ses preuves. Son objectif est de trouver, avec le patient, des solutions adaptées à sa maladie afin qu'il les applique. Dans l'avenir, la formation des professionnels et la publication de recommandations sont nécessaires afin d'aboutir à une offre d'éducation thérapeutique harmonieuse.TOULOUSE3-BU Santé-Centrale (315552105) / SudocSudocFranceF

Dopaminergic neurons differentiating from LRRK2 G2019S induced pluripotent stem cells show early neuritic branching defects.

Some mutations of the LRRK2 gene underlie autosomal dominant form of Parkinson's disease (PD). The G2019S is a common mutation that accounts for about 2% of PD cases. To understand the pathophysiology of this mutation and its possible developmental implications, we developed an in vitro assay to model PD with human induced pluripotent stem cells (hiPSCs) reprogrammed from skin fibroblasts of PD patients suffering from the LRKK2 G2019S mutation. We differentiated the hiPSCs into neural stem cells (NSCs) and further into dopaminergic neurons. Here we show that NSCs bearing the mutation tend to differentiate less efficiently into dopaminergic neurons and that the latter exhibit significant branching defects as compared to their controls

Characterization of functional oligosaccharide mimics of the Shigella flexneri serotype 2a O-antigen: implications for the development of a chemically defined glycoconjugate vaccine.

International audienceProtection against reinfection with noncapsulated Gram-negative bacteria, such as Shigella, an enteroinvasive bacterium responsible for bacillary dysentery, is mainly achieved by Abs specific for the O-Ag, the polysaccharide part of the LPS, the major bacterial surface Ag. The use of chemically defined glycoconjugates encompassing oligosaccharides mimicking the protective determinants carried by the O-Ag, thus expected to induce an efficient anti-LPS Ab response, has been considered an alternative to detoxified LPS-protein conjugate vaccines. The aim of this study was to identify such functional oligosaccharide mimics of the S. flexneri serotype 2a O-Ag. Using protective murine mAbs specific for S. flexneri serotype 2a and synthetic oligosaccharides designed to analyze the contribution of each sugar residue of the branched pentasaccharide repeating unit of the O-Ag, we demonstrated that the O-Ag exhibited an immunodominant serotype-specific determinant. We also showed that elongating the oligosaccharide sequence improved Ab recognition. From these antigenicity data, selected synthetic oligosaccharides were assessed for their potential to mimic the O-Ag by analyzing their immunogenicity in mice when coupled to tetanus toxoid via single point attachment. Our results demonstrated that induction of an efficient serotype 2a-specific anti-O-Ag Ab response was dependent on the length of the oligosaccharide sequence. A pentadecasaccharide representing three biological repeating units was identified as a potential candidate for further development of a chemically defined glycoconjugate vaccine against S. flexneri 2a infection

L’émotion dans les expositions

L’émotion a toujours été présente au sein des musées, mais elle a longtemps été tenue pour la « folle du logis », qu’il fallait canaliser sinon supprimer. Il n’en va plus de même aujourd’hui, quand l’émotion fait partie d’une économie légitime de l’expérience de visite. Pareille émotion s’appuie sur la mobilisation des sens du visiteur par le conservateur ou par le commissaire d’exposition, sacrifie, le cas échéant, à différents rituels, et peut nourrir une pédagogie, sociale ou politique, au-delà du champ esthétique auquel elle était d’abord identifiée. Le numéro fait l’inventaire de ce tournant émotionnel au sein de la réflexion muséologique, de l’étude des publics et de la mission des institutions. Il montre combien l’émotion est désormais centrale dans un musée qui vise à donner du sens aux événements de la vie sociale, culturelle et politique. Emotion has always been present in museums, but for a long time it was considered to be the chatter of the mind, which had to be channelled if not suppressed. This is no longer the case today, when emotion is part of a legitimate economy of the visitor experience. Such emotion is based on the mobilization of the visitor’s senses by the curator, sacrificing, if need be, to different rituals, and can nourish a pedagogy, social or political, beyond the aesthetic field with which it was first identified. The issue takes stock of this emotional turning point in museological reflection, the study of audiences and the mission of institutions. It shows to what extent emotion is now central to the museum’s endeavour to give meaning to events in social, cultural and political life. La emoción siempre ha estado presente en los museos, pero durante mucho tiempo ha sido considerada como la loca del hogar, que había que canalizar, si no suprimir. Esto ya no es así hoy en día, cuando la emoción forma parte de una economía legítima de la experiencia de la visita. Una tal emoción se fundamenta en la movilización de los sentidos del visitante por el curador o el conservador, se sacrifica, si es necesario, a diferentes rituales, y puede alimentar una pedagogía, social o política, mas allá del campo estético, al cual se encontraba identificada en un comienzo. El número hace el inventario de este giro emocional, en el corazón de la reflexión museológica, del estudio de los públicos y la misión de las instituciones. Muestra cuán central es la emoción, en el afán del museo, por dar sentido a los eventos de la vida social, cultural y política