Ptch2/Gas1 and Ptch1/Boc differentially regulate Hedgehog signalling in murine primordial germ cell migration.

Gas1 and Boc/Cdon act as co-receptors in the vertebrate Hedgehog signalling pathway, but the nature of their interaction with the primary Ptch1/2 receptors remains unclear. Here we demonstrate, using primordial germ cell migration in mouse as a developmental model, that specific hetero-complexes of Ptch2/Gas1 and Ptch1/Boc mediate the process of Smo de-repression with different kinetics, through distinct modes of Hedgehog ligand reception. Moreover, Ptch2-mediated Hedgehog signalling induces the phosphorylation of Creb and Src proteins in parallel to Gli induction, identifying a previously unknown Ptch2-specific signal pathway. We propose that although Ptch1 and Ptch2 functionally overlap in the sequestration of Smo, the spatiotemporal expression of Boc and Gas1 may determine the outcome of Hedgehog signalling through compartmentalisation and modulation of Smo-downstream signalling. Our study identifies the existence of a divergent Hedgehog signal pathway mediated by Ptch2 and provides a mechanism for differential interpretation of Hedgehog signalling in the germ cell niche

Activation of BMP-Smad1/5/8 Signaling Promotes Survival of Retinal Ganglion Cells after Damage In Vivo

While the essential role of bone morphogenetic protein (BMP) signaling in nervous system development is well established, its function in the adult CNS is poorly understood. We investigated the role of BMP signaling in the adult mouse retina following damage in vivo. Intravitreal injection of N-Methyl-D-aspartic acid (NMDA) induced extensive retinal ganglion cell death by 2 days. During this period, BMP2, -4 and -7 were upregulated, leading to phosphorylation of the downstream effector, Smad1/5/8 in the inner retina, including in retinal ganglion cells. Expression of Inhibitor of differentiation 1 (Id1; a known BMP-Smad1/5/8 target) was also upregulated in the retina. This activation of BMP-Smad1/5/8 signaling was also observed following light damage, suggesting that it is a general response to retinal injuries. Co-injection of BMP inhibitors with NMDA effectively blocked the damage-induced BMP-Smad1/5/8 activation and led to further cell death of retinal ganglion cells, when compared with NMDA injection alone. Moreover, treatment of the retina with exogenous BMP4 along with NMDA damage led to a significant rescue of retinal ganglion cells. These data demonstrate that BMP-Smad1/5/8 signaling is neuroprotective for retinal ganglion cells after damage, and suggest that stimulation of this pathway can serve as a potential target for neuroprotective therapies in retinal ganglion cell diseases, such as glaucoma

Perturbations of MicroRNA Function in Mouse Dicer Mutants Produce Retinal Defects and Lead to Aberrant Axon Pathfinding at the Optic Chiasm

During development axons encounter a variety of choice points where they have to make appropriate pathfinding decisions. The optic chiasm is a major decision point for retinal ganglion cell (RGC) axons en route to their target in order to ensure the correct wiring of the visual system. MicroRNAs (miRNAs) belong to the class of small non-coding RNA molecules and have been identified as important regulators of a variety of processes during embryonic development. However, their involvement in axon guidance decisions is less clear.We report here that the early loss of Dicer, an essential protein for the maturation of miRNAs, in all cells of the forming retina and optic chiasm leads to severe phenotypes of RGC axon pathfinding at the midline. Using a conditional deletion approach in mice, we find in homozygous Dicer mutants a marked increase of ipsilateral projections, RGC axons extending outside the optic chiasm, the formation of a secondary optic tract and a substantial number of RGC axons projecting aberrantly into the contralateral eye. In addition, the mutant mice display a microphthalmia phenotype.Our work demonstrates an important role of Dicer controlling the extension of RGC axons to the brain proper. It indicates that miRNAs are essential regulatory elements for mechanisms that ensure correct axon guidance decisions at the midline and thus have a central function in the establishment of circuitry during the development of the nervous system

Web Usage Mining: Sequential Pattern Extraction with a Very Low Support

Abstract. The goal of this work is to increase the relevance and the interestingness of patterns discovered by a Web Usage Mining process. Indeed, the sequential patterns extracted on web log files, unless they are found under constraints, often lack interest because of their obvious content. Our goal is to discover minority users ’ behaviors having a coherence which we want to be aware of (like hacking activities on the Web site or a users ’ activity limited to a specific part of the Web site). By means of a clustering method on the extracted sequential patterns, we propose a recursive division of the problem. The developed clustering method is based on patterns summaries and neural networks. Our experiments show that we obtain the targeted patterns whereas their extraction by means of a classical process is impossible because of a very weak support (down to 0.006%). The diversity of users ’ behaviors is so large that the minority ones are both numerous and difficult to locate

Résultats de la thoracoscopie dans les pleurésies purulentes : une expérience monocentrique de 33 cas.

Le but de ce travail était d’évaluer les résultats de la vidéothoracoscopie dans les pleurésies purulentes à travers notre pratique courante. De 2005 à 2013, notre étude rétrospective a permi de colliger 33 patients pris en charge chirurgicalement par vidéothoracoscopie. Les patients ont été répartis en deux groupes, ceux qui ont achevé la procédure par vidéothoracoscopie et ceux qui ont eu une conversion en thoracotomie. Trente trois patients ayant été l’objet d’une vidéothoracoscopie pour pleurésies purulentes après échec du traitement médical, avec une prédominance masculine (ratio 3,71) et un âge moyen de (58 16,27), ont été répartis entre le stade II et stade III avant la chirurgie (23 cas soit 69,7% et 10 cas soit 30,3%) et au moment de la chirurgie (16 cas soit 48,5% et 17 cas soit 51,5%). Le taux de conversion en thoracotomie a été de 30,3%. En comparant le groupe thoracoscopie seule et le groupe conversion en thoracotomie, il est apparu que seul le stade de la pleurésie purulente a constitué un facteur déterminant dans la conversion (p<0,001). Nous avons également trouvé une discordance entre la classification pré-opératoire et la classification post-opératoire de la pleurésie. Trois (3) patients de stade II ont été opérés par thoracoscopie seule et trois (3) ont eu une re-intervention pour récidive ; la mortalité était nulle. La vidéothoracoscopie a été une technique performante dans la prise en charge des pleurésies purulentes, tant sur le plan diagnostique que sur le plan thérapeutique avec une morbidité et une mortalité faibles.Mots clés : pleurésies purulentes, vidéothoracoscopie, conversion.English AbstractTo evaluate the results of videothoracoscopy approach in thoracic empyema through our practice. From 2005 to 2013, our retrospective study with prospective collection of data allowed to record 33 patients who underwent surgery by taking videothoracoscopy. We have divided the patients into two groups, those who have completed the procedure videothoracoscopy and those who needed a conversion to thoracotomy. 33 patients underwent videothoracoscopy for empyema after failure of medical treatment, with a male predominance (ratio 3.71) and an average age (58 16.27); divided between stage II and stage III before surgery (23 cases or 69.7%, and 10 cases or 30.3%) and at the time of surgery (16 cases or 48.5%, and 17 cases or 51.5%). The conversion rate to thoracotomy is (30.3%). Thoracoscopic group versus conversion group to thoracotomy, it appears that only the stage of empyema was the sole factor in the conversion (p <0.001). We also found a difference between the preoperative classification and the classification postoperatively. Three patients with stage II operated by thoracoscopy alone and three had a reoperation for recurrence, mortality was null. The videothoracoscopy approach seems to be effective in the management of empyema, both diagnostic and therapeutic terms with a low morbidity and mortality.Key words: empyema, videothoracoscopy, conversio