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

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

Proper patterning of the optic fissure requires the sequential activity of BMP7 and SHH

12 páginas, 8 figuras.The optic disc develops at the interface between optic stalk and retina, and enables both the exit of visual fibres and the entrance of mesenchymal cells that will form the hyaloid artery. In spite of the importance of the optic disc for eye function, little is known about the mechanisms that control its development. Here, we show that in mouse embryos, retinal fissure precursors can be recognised by the expression of netrin 1 and the overlapping distribution of both optic stalk (Pax2, Vax1) and ventral neural retina markers (Vax2, Raldh3). We also show that in the absence of Bmp7, fissure formation is not initiated. This absence is associated with a reduced cell proliferation and apoptosis in the proximoventral quadrant of the optic cup, lack of the hyaloid artery, optic nerve aplasia, and intra-retinal misrouting of RGC axons. BMP7 addition to organotypic cultures of optic vesicles from Bmp7-/- embryos rescues Pax2 expression in the ventral region, while follistatin, a BMP7 antagonist, prevents it in early, but not in late, optic vesicle cultures from wild-type embryos. The presence of Pax2-positive cells in late optic cup is instead abolished by interfering with Shh signalling. Furthermore, SHH addition re-establishes Pax2 expression in late optic cups derived from ocular retardation (or) embryos, where optic disc development is impaired owing to the near absence of SHH-producing RGC. Collectively, these data indicate that BMP7 is required for retinal fissure formation and that its activity is needed, before SHH signalling, for the generation of PAX2-positive cells at the optic disc.This study was supported by grants from Spanish Ministerio de Educación y Ciencia (BFU-2004-01585) and the European Union (QLG3-CT-2001-01460) to P.B., and in part by a grant from Fight for Sight, UK to J.C.S. J.M. was supported by a predoctoral fellowship from the Comunidad Autónoma de Madrid (CAM) and an EMBO short-term fellowship.Peer reviewe

Resistance of the tomato to TYLCV

* Contrat CEE DGXII-TS2-A-055 F (CD)International audienc

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

Broadway: A Case-Based System for Cooperative Information Browsing on the World-Wide-Web.

: The World Wide Web is a huge hypermedia where finding relevant documents is not an easy task. In this paper, we present our case-based system for cooperative information browsing, called BROADWAY. BROADWAY follows a group of users during their navigations on the WWW (proxy-based architecture) and advise them by displaying a list of potentially relevant documents to visit next. BROADWAY uses case-based reasoning to reuse precise experiences derived from past navigations with a time-extended situation assessment: the advice are based mainly on similarity of ordered sequence of past accessed documents. In addition, the dynamic of the WWW is addressed in the reuse step and with a specific method for case forgetting. 1. Introduction The World Wide Web (WWW) [15] is an hypermedia of heterogeneous and dynamic documents. This virtual space is growing more and more every day, offering to the user a huge amount of data [4]. Two kinds of methods can be used to locate a relevant document throu..