345 research outputs found

    CD44 acts as a signalling platform controlling tumour progression and metastasis

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    CD44 proteins emerge as major signal transduction controller. CD44 isoforms participate in several signalling pathways ranging from growth factor-induced signalling to Wnt-regulated pathways. The role of CD44 in tumour progression and metastasis is most likely linked to its function as a signalling hub. More and more evidence suggests as well that CD44 is not only a mere cancer stem cell marker but is directly involved in tumour and metastasis initiation. It is foreseeable that a link between the expression of CD44 on cancer stem cells and its function as a regulator of cell signalling will be drawn in a near future

    Haploinsufficiency of c-met in cd44(-/-) mice identifies a collaboration of CD44 and c-met in vivo

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    Recent evidence has shown that the activation of receptor tyrosine kinases is not only dependent on binding of their ligands but in addition requires adhesion molecules as coreceptors. We have identified CD44v6 as a coreceptor for c-Met in several tumor and primary cells. The CD44v6 ectodomain is required for c-Met activation, whereas the cytoplasmic tail recruits ERM proteins and the cytoskeleton into a signalosome complex. Here we demonstrate that c-Met (and hepatocyte growth factor and Gab1) is haploinsufficient in a cd44(-/-) background, as the cd44(-/-); met(-/-) (and cd44(-/-); hgf(+/-) and cd44(-/-); gab1(+/-)) mice die at birth. They have impaired synaptic transmission in the respiratory rhythm-generating network and alterations in the phrenic nerve. These results are the first genetic data showing that CD44 and c-Met collaborate in vivo and that they are involved in synaptogenesis and axon myelination in the central and peripheral nervous systems

    Fighting pancreatic cancer

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    Henri Rousseau: visual narratives

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    O presente estudo procura descrever e interpretar o fenômeno de interação entre pintura e escrita na obra do artista francês autodidata Henri Rousseau (1844-1910), conhecido como o Aduaneiro. Criador múltiplo, embora reconhecido hoje mormente como pintor de relevância ímpar na evolução da arte moderna, dedicou-se simultaneamente à música e à dramaturgia. A experiência da escrita, em particular, desdobra-se em seu trabalho em uma vertente complexa: a composição de versos e sentenças destinados a completar a inteligência de seus quadros, verdadeiros textos da imagem ou legendas, propriamente ditas, que cumprem função interpretante. Acredita-se, por conseguinte, que uma análise aprofundada da dinâmica entre imagens e palavras na criação de significado verificada na obra do Aduaneiro, tendo em vista uma determinada disposição narrativa, sugere efetivamente novas leituras do percurso figurativo configurado entre o visual e o verbal, assim como dos efeitos poéticos que resultam da associação dessas duas categorias. Em síntese, trata-se de considerar que tal fenômeno projeta um universo referencial expandido, formado a partir de elementos comuns às composições pictóricas e verbais realizadas pelo artista.The aim of this study is to describe and interpret the phenomenon of interaction between painting and writing in the work of the self-taught French artist Henri Rousseau (1844-1910), called the Douanier. Multiple creator, although today recognized mainly as a painter of distinctive relevance in the evolution of modern art, he devoted himself simultaneously to music and dramaturgy. The experience of writing, in particular, unfolds in his work in a complex aspect: the composition of verses and sentences intended to complete the intelligence of his paintings, true texts of the image or properly captions accomplishing an interpretative function. Therefore, it is believed that an in-depth analysis of the dynamics between images and words in the creation of meaning verified in the Douanier\'s work, in view of a certain narrative disposition, effectively suggests new readings of the figural process configured between the visual and the verbal, as well as the poetic effects resulting from the association of these two categories. In brief, it is a matter of considering that this phenomenon projects an expanded referential universe, formed from elements common to the pictorial and verbal compositions realized by the artist

    Investigation of documents persistency on the Web

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    @inproceedings{CI-Lancieri-2004-2, author = {Lancieri, Luigi and Lecouvey, Mathieu and Glasse, Veronique}, title = {Investigation of documents persistency on the Web}, booktitle = {International conference E-Society 2004 (ES2004), IADIS}, year = {2004}, address = {Spain} }International audienc

    Live cell imaging shows hepatocyte growth factor-induced Met dimerization

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    Koschut D, Richert L, Pace G, Niemann H, Mely Y, Orian-Rousseau V. Live cell imaging shows hepatocyte growth factor-induced Met dimerization. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH. 2016;1863(7):1552-1558.The canonical model of receptor tyrosine kinase (RTK) activation assumes that ligand-induced dimerization of inactive receptor monomers is a prerequisite for autophosphorylation. For several RTK families, recent results of fluorescence microscopy provided evidence for preformed receptor dimers that may or may not require ligand binding for kinase activity. Here we report, for the first time, the application of advanced quantitative fluorescence microscopy techniques to study changes in the oligomerization state of the RTK Met in response to stimulation by its endogenous ligand hepatocyte growth factor (HGF). We used inducible C-terminal fusions be, tween Met and enhanced green fluorescent protein (EGFP) or red fluorescent protein (RFP) in combination with fluorescence resonance energy transfer (FRET)-based fluorescence-lifetime imaging microscopy (FLIM) and fluorescence correlation spectroscopy (FCS). A small fraction of HGF-independent Met dimers appeared to be present in cells even at low receptor density. At high receptor density, both the fraction of Met dimers and the level of Met autophosphorylation increased in the absence of HGF. Stimulation with HGF at low receptor density significantly increased the fraction of Met dimers on live cells. We found no indications of Met oligomers larger than dimers. Our findings thus confirm a model of Met activation through HGF-induced dimerization and at the same time they support previous reports of Met dimers in unstimulated cells. The tools established in this work will be useful to further characterize the mechanism of Met activation and to define the contribution of co-receptors. (C) 2016 Elsevier B.V. All rights reserved

    Implementation and evaluation of a psychoeducational program for parents recently reunified with their children: a case study

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    This dissertation focuses on the process of designing, implementing and evaluating a parenting program for single parents with a history of mental illness who have been separated from their children, within the context of a residence at a human services agency in an urban setting. Maher’s program planning and evaluation framework and a case study approach were used to facilitate the process. Principles of attachment theory informed the curriculum created for the program. This dissertation was conducted with an intention to contribute to the attachment literature and to expand knowledge about the needs of parents with a history of mental illness who have lost custody of their children. Maher’s program planning and evaluation framework consists of four phases: clarification, design, implementation and evaluation. During the Clarification Phase, an assessment of the parents’ needs and the relevant context was conducted. The needs assessment revealed that parents at the residence had significant past histories of trauma and poor parenting that negatively affected their skills as parents. Additionally, it was determined that many parents struggled to connect emotionally with their children and to provide appropriate discipline. A program design was then created based on the needs identified in the Clarification Phase. The program was entitled the Attachment Based Parenting Program and consisted of a psychoeducation group designed to teach parents skills to improve attachment with their children and to provide appropriate discipline. A description of the program and its implementation is further detailed in this dissertation. The program was implemented over the course of 12 weeks in the Fall of 2008 and involved 10 parents. Following the program implementation, an evaluation was conducted. Results of the evaluation revealed that the program provided some value to the participants: (a) parents were able to process their own history; (b) parents were able to better understand ways in which prior traumas affected their ability to connect with their children; and (c) parents learned new skills to improve their connection to their children. Constraints of the dissertation are noted and recommendations are provided for future design and implementation of the program.Psy.DIncludes bibliographical referencesby Veronique Nicole Le
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