1,720,982 research outputs found
Identification of Key Signaling Molecules Involved in the Activation of the Swelling-Activated Chloride Current in Human Glioblastoma Cells
No full textThe swelling-activated chloride current (I (Cl,Vol)) is abundantly expressed in glioblastoma (GBM) cells, where it controls cell volume and invasive migration. The transduction pathway mediating I (Cl,Vol) activation in GBM cells is, however, poorly understood. By means of pharmacological and electrophysiological approaches, on GL-15 human GBM cells we found that I (Cl,Vol) activation by hypotonic swelling required the activity of a U73122-sensitive phospholipase C (PLC). I (Cl,Vol) activation could also be induced by the membrane-permeable diacylglycerol (DAG) analog OAG. In contrast, neither calcium (Ca2+) chelation by BAPTA-AM nor changes in PKC activity were able to affect I (Cl,Vol) activation by hypotonic swelling. We further found that R59022, an inhibitor of diacylglycerol kinase (DGK), reverted I (Cl,Vol) activation, suggesting the involvement of phosphatidic acid. In addition, I (Cl,Vol) activation required the activity of a EHT1864-sensitive Rac1 small GTPase and the resulting actin polymerization, as I (Cl,Vol) activation was prevented by cytochalasin B. We finally show that I (Cl,Vol) can be activated by the promigratory fetal calf serum in a PLC- and DGK-dependent manner. This observation is potentially relevant because blood serum can likely come in contact with glioblastoma cells in vivo as a result of the tumor-related partial breakdown of the blood-brain barrier. Given the relevance of I (Cl,Vol) in GBM cell volume regulation and invasiveness, the several key signaling molecules found in this study to be involved in the activation of the I (Cl,Vol) may represent potential therapeutic targets against this lethal cancer
Identification of Key Signaling Molecules Involved in the Activation of the Swelling-Activated Chloride Current in Human Glioblastoma Cells
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Ruolo del canale potassio calcio-attivato di intermedia conduttanza nell'angiogenesi indotta da glioblastoma
No full textIl glioblastoma (GB), la forma piu frequente e letale dei tumori del cervello, è caratterizzato da un elevato grado di angiogenesi. I canali del potassio calcio-attivati di intermedia conduttanza (KCa3.1) sono altamente espressi nel GB umano, ma non nel cervello normale, suggerendo un ruolo importante del canale in questa patologia. Utilizzando impianti di GB nella membrana corio-allantoidea (CAM) di pollo come modello sperimentale dell'angiogenesi, abbiamo osservato che l'attivita del canale KCa3.1 è coinvollta nell'angiogenesi indotta dal GB. Infatti il TRAM-34, bloccante selettivo del canale KCa3.1, inibisce l'angiogenesi indotta da GB, misurata mediante l'incremento dell'indice di densità vascolare (IDV). Il TRAM-34 non mostra invece alcun effetto inibitorio sul normale sviluppo angiogenetico embrionale della CAM. Per comprendere il ruolo del canale KCa3.1 nel processo angiogenetico tumorale abbiamo studiato gli effetti di noti induttori dell'angiogenesi nel glioblastoma, come l'SDF-1 (fattore di derivazione stromale-1) e l'ipossia, sul canale KCa3.1. In cellule di GB le correnti KCa3.1 sono aumentate circa due volte dalla pre-incubazione con SDF-1 per 90 minuti. Il trattamento ipossico (P02 1-2% per 48 ore) nella linea di GB GL-15 e nella linea di fibroblasti trasformati con alte potenzialità angiogenetiche (NEH 3T3-EAG-1 g440s) induce in entrambe un significativo aumento dell'espressione della corrente KCa3.1 rispetto alla condizione normossica. Questi risultati indicano che il canale KCa3.1 è strettamente regolato dai segnali pro-angiogenetici, in linea con gli effetti anti-angiogenetici del TRAM-34 in modelli GB/CAM in vivo. Un modello interpretativo del ruolo del canale KCa3.1 nel processo angiogenetico indotto dal GB è proposto per spiegare i risultati presentati e pianificare la sperimentazione futura
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
Get PDF“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
Get PDFWe 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
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe 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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