1,721,136 research outputs found
Grb10/Nedd4 complex regulates ligand-induced ubiquitination and stability of the IGF-I Receptor
Full text linkThe adapter protein Grb10 belongs to a superfamily of related proteins, including Grb7, -10, and -14 and Caenorhabditis elegans Mig10. Grb10 is an interacting partner of the insulin-like growth factor I receptor (IGF-IR) and the insulin receptor (IR). Previous work showed an inhibitory effect of mouse Grb10 (mGrb10α) on IGF-I-mediated mitogenesis (A. Morrione et al., J. Biol. Chem. 272:26382-26387, 1997). With mGrb10α as bait in a yeast two-hybrid screen, mouse Nedd4 (mNedd4-1), a ubiquitin protein ligase, was previously isolated as an interacting protein of Grb10 (A. Morrione et al., J. Biol. Chem. 274:24094-24099, 1999). However, Grb10 is not ubiquitinated by Nedd4 in cells. Here we show that in mouse embryo fibroblasts overexpressing Grb10 and the IGF-IR (p6/Grb10), there is a strong ligand-dependent increase in ubiquitination of the IGF-IR compared with that in parental cells (p6). This increased ubiquitination is associated with a shorter half-life and increased internalization of the IGF-IR. The IGF-IR is stabilized following treatment with both MG132 and chloroquine, indicating that both the proteasome and lysosomal pathways mediate degradation of the receptor. Ubiquitination of the IGF-IR likely occurs at the plasma membrane, prior to the formation of endocytic vesicles, as it is insensitive to dansylcadaverine, an inhibitor of early endosome formation in IGF-IR endocytosis. Grb10 coimmunoprecipitates with the IGF-IR and endogenous Nedd4 in p6/Grb10 cells, suggesting the presence of a Grb10/Nedd4/IGF-IR complex. Ubiquitination of the IGF-IR in p6/Grb10 cells is severely impaired by overexpression of a catalytically inactive Nedd4 mutant (Nedd4-CS), which also stabilizes the receptor. Likewise, overexpression of a Grb10 mutant lacking the Src homology 2 (SH2) domain impaired ubiquitination of the IGF-IR in parental p6 and p6/Grb10 cells, indicating that Grb10 binding to Nedd4 is critical for ubiquitination of the receptor. These results suggest a role for the Grb10/Nedd4 complex in regulating ubiquitination and stability of the IGF-IR, and they suggest that Grb10 serves as an adapter to form a bridge between Nedd4 and the IGF-IR. This is the first demonstration of regulation of stability of a tyrosine kinase receptor by the Nedd4 (HECT) family of E3 ligases.Temple University. College of Science and TechnologyBiolog
Mortalità infantile nelle necropoli altomedievali di Campochiaro Vicenne e Morrione (CB, Molise).
No full textLe necropoli di Campochiaro, Vicenne e Morrione, costituiscono un ampio complesso barbarico datato al VII secolo d.C. (Ceglia, 2000). Lo studio archeologico e antropologico della necropoli di Vicenne ha messo in luce una realtà sociale che riflette il contesto di drammatiche trasformazioni proprie dell’Alto Medioevo: emerge l’immagine di una società multietnica, gerarchizzata, coinvolta in attività belliche e sottoposta a condizioni di vita dure (Belcastro et. al, 2003, 2007). In questo contesto vengono presentati i dati relativi alla distribuzione della mortalità infantile delle due necropoli, un parametro che fornisce importanti indicazioni sul generale benessere e sullo stato di salute della popolazione. Gli scavi di Campochiaro hanno portato alla luce 167 sepolture nell’area di Vicenne e 234 nell’area di Morrione. Pratiche di sepoltura differenziale degli infanti non sembrano avere luogo in questi siti e sulla base di questo dato il campione in esame non sarebbe stato quindi selezionato rispetto alla popolazione vivente. Lo studio dei reperti ha evidenziato una mortalità dei subadulti compresa tra il 25% e il 35% nelle due aree. In entrambe le necropoli i decessi sono concentrati nei primi otto anni di vita. Si tratta di un dato di mortalità alto, che esprime le difficili condizioni di crescita all’interno di questa popolazione, ma confrontabile con i valori osservati per l’Europa altomedioevale (Barbiera e Dalla Zuanna, 2007, Del Panta et al., 1997)
Mortalità infantile nelle necropoli altomedievali di Campochiaro Vicenne e Morrione (CB, Molise)
No full textLe necropoli di Campochiaro, Vicenne e Morrione, costituiscono un ampio complesso barbarico
dell’Italia meridionale (Molise) datato al VII secolo d.C. (Ceglia, 2000). Lo studio archeologico e
antropologico della necropoli di Vicenne ha restituito l’immagine di una società caratterizzata da una
singolare multiculturalità, strutturata gerarchicamente in virtù dell’attività bellica, e in condizioni di
vita e salute difficili (Belcastro et. al, 2003, 2007). Nel presente lavoro si espongono i dati relativi alla
distribuzione della mortalità infantile delle due necropoli, un parametro che fornisce importanti
indicazioni sullo stato di salute della popolazione. Gli scavi di Campochiaro hanno portato alla luce
167 sepolture nell’area di Vicenne e 234 nell’area di Morrione. L’età degli individui in crescita è stata
stimata applicando i comuni metodi antropologici. Lo studio dei reperti ha evidenziato valori di
mortalità compresi tra il 30% e il 35%, un dato che indica condizioni di crescita difficili e che ben si
inquadra con quelli del periodo per l’Europa altomedioevale (cfr. Barbiera e Dalla Zuanna, 2007, Del
Panta et al., 1997)
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Orexins and Prostate Cancer: State of the Art and Potential Experimental and Therapeutic Perspectives
Full text linkProstate cancer (PCa) is the second most common cancer in humans. Peptides have recently been used as targeted therapeutics in cancers, due to their extensive multi-functional applications. Two hypothalamic peptides, orexins A (OXA) and B (OXB) and their specific receptors, orexin receptor 1 (OX1R) and 2 (OX2R), orchestrate several biological processes in the central nervous system and peripheral organs. However, in addition to their role in physiological responses, orexins are involved in numerous inflammatory and/or neoplastic pathologies. The presence and expression of orexins in different cancer models, including prostate cancer, and their role in inducing pro- or anti-apoptotic responses in tumor cell lines, suggest that the orexinergic system might have potential therapeutic action or function as a diagnostic marker in PCa. In addition to the traditional animal models for studying human PCa, the canine model might also serve as an additional tool, due to its clinical similarities with human prostate cancer
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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