317 research outputs found

    Met signaling mutants as tools for developmental studies

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    The Met receptor is widely expressed in embryonic and adult epithelial tissues; its ligand (hepatocyte growth factor/scatter factor, HGF/SF) is expressed in the mesenchymal component of various organs. The generation of hgf and met null mice has revealed an essential role for this ligand-receptor pair in the development of the placenta, liver, and limb muscles. However the early lethality of the null mutants has precluded analysis of Met function in late development. To extend the possible observation period, we generated mutant metalleles of different severity. This was done by impairing the ability of the receptor to transduce the HGF/SF signal, via mutation of consensus sequences in the multifunctional docking site present in the C-terminal tail of the receptor. Mice expressing a Met mutant still active as a kinase, but unable to recruit its effectors, died in mid-gestation with the same phenotype as the metknockout, proving the importance of phosphotyrosine-SH2 interactions in vivo. Mice expressing a Met receptor with partial loss of signaling function survived until birth and revealed novel aspects of HGF/SF-Met function during muscle development

    Ontology-based identification of music for places

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    The final publication is available at Springer via http://dx.doi.org/10.1007/978-3-642-36309-2_37Proceedings of the International Conference on Information and Communication Technologies in Tourism in Innsbruck, Austria, January 22-25, 2013Place is a notion closely linked with the wealth of human experience, and invested by values, attitudes, and cultural influences. In particular, many places are strongly linked to music, which contributes to shaping the perception and the meaning of a place. In this paper we propose a computational approach for identifying musicians and music suited for a place of interest (POI). We present a knowledge-based framework built upon the DBpedia ontology, and a graph-based algorithm that scores musicians with respect to their semantic relatedness to a POI and suggests the top scoring ones. We found that users appreciate and judge as valuable the musician suggestions generated by the proposed approach. Moreover, users perceived compositions of the suggested musicians as suited for the POIs

    Reprodução induzida e criação de larvas de híbridos interespecíficos e intragenérico da ordem siluriforme (Pisces).

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    O presente trabalho tem como objetivo analisar a resposta à indução artificial da reprodução em exemplares de cachapinta, híbrido resultante do cruzamento de Pseudoplatystoma corruscans X Pseudoplatystoma reticulatum no cruzamento intergenérico entre fêmea deste produto híbrido e macho de jundiá (Leiarius marmoratus), para verificar a produção de gametas viáveis, quantidade de larvas eclodidas, percentual de sobrevivência e crescimento das larvas e consequentemente a produção de exemplares para estudos genéticos.Organizado por: Sílvio Ricardo Maurano; AQUACIÊNCIA 2012

    Cell delivery of Met docking site peptides inhibit angiogenesis and vascular tumor growth

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    Hepatocyte growth factor (HGF) and its receptor Met are responsible for a wide variety of cellular responses, both physiologically during embryo development and tissue homeostasis, and pathologically, particularly during tumor growth and dissemination. In cancer, Met can act as an oncogene on tumor cells, as well as a pro-angiogenic factor activating endothelial cells and inducing new vessel formation. Molecules interfering with Met activity could be valuable therapeutic agents. Here we have investigated the antiangiogenic properties of a synthetic peptide mimicking the docking site of the Met carboxyl-terminal tail, which was delivered into the cells by fusion with the internalization sequences from Antennapedia or HIV-Tat. We showed that these peptides inhibit ligand-dependent endothelial cell proliferation, motility, invasiveness and morphogenesis in vitro to an even greater extent and with much less toxicity than the Met inhibitor PHA-665752, which correlated with interference of HGF-dependent downstream signaling. In vivo, the peptides inhibited HGF-induced angiogenesis in the matrigel sponge assay and impaired xenograft tumor growth and vascularization in Kaposi's sarcoma. These data show that interference with the Met receptor intracellular sequence impairs HGF-induced angiogenesis, suggesting the use of antidocking site compounds as a therapeutic strategy to counteract angiogenesis in cancer as well as in other diseases

    The Dynamics of Democracy, Development and Cultural Values

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    Over the past decades many countries have experienced rapid changes in their economies, their democratic institutions and the values of their citizens. Comprehensive data measuring these changes across very different countries has recently become openly available. Between country similarities suggest common underlying dynamics in how countries develop in terms of economy, democracy and cultural values. We apply a novel Bayesian dynamical systems approach to identify the model which best captures the complex, mainly non-linear dynamics that underlie these changes. We show that the level of Human Development Index (HDI) in a country drives first democracy and then higher emancipation of citizens. This change occurs once the countries pass a certain threshold in HDI. The data also suggests that there is a limit to the growth of wealth, set by higher emancipation. Having reached a high level of democracy and emancipation, societies tend towards equilibrium that does not support further economic growth. Our findings give strong empirical evidence against a popular political science theory, known as the Human Development Sequence. Contrary to this theory, we find that implementation of human-rights and democratisation precede increases in emancipative values
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