1,720,958 research outputs found
Notch3 sostiene CXCR4 in membrana come meccanismo nella progressione della leucemia T-ALL
Get PDFSebbene l'iperattivazione del signaling di Notch è associata allo sviluppo della leucemia linfoblastica acuta a cellule T, i meccanismi che sono alla base della diffusione delle "cellule pre-leucemiche" non sono ancora ben chiari. Obbiettivo del nostro lavoro è stato quello di identificare le potenziali "cellule pre-leucemiche" e quali possono essere i meccanismi che guidano la loro diffusione. I nostri studi sono stati effettuati utilizzando topi transgenici che sovraesprimono il dominio intracellulare attivo di Notch3. In questo modello murino abbiamo osservato un aumento progressivo ed anomalo delle cellule T CD4+CD8+ nel sangue e poi nel midollo osseo. Queste cellule erano inoltre caratterizzate da un’elevata espressione in membrana dei recettori Notch3 e CXCR4. Il trapianto di tali cellule rivela la loro competenza nell'infiltrare la milza ed il midollo osseo di topi riceventi immuno-compromessi. Inoltre, i nostri dati in vitro, ottenuti con linee cellulari di leucemia umana T, dimostrano che l'espressione in superficie di CXCR4 è fondamentale per la capacità migratoria delle cellule CD4+CD8+, e che tale espressione è regolata da Notch3 attraverso la b-arrestina. Vista l’anomala fuoriuscita di tali cellule dal timo nelle prime fasi della leucemia, abbiamo effettuato esperimenti con un antagonista del recettore CXCR4, l’AMD3100. L'antagonismo in vivo del recettore impedisce la colonizzazione del midollo osseo da parte di tali cellule CD4+CD8+Notch3+CXCR4+ nei topi transgenici per Notch3, evidenziando ulteriormente l’importanza del recettore CXCR4 nella propagazione ed infiltrazione delle cellule CD4+CD8+. Quindi, l’iperespressione dei due recettori, Notch3 e CXCR4, su queste cellule T CD4+CD8+ "pre-leucemiche" probabilmente gioca un ruolo importante nelle fasi iniziali della progressione della malattia, contribuendo alla loro propagazione ed infiltrazione in organi linfoidi. Infine, i nostri dati suggeriscono che terapie combinate che contrastino precocemente il crosstalk intratimico Notch3/CXCR4, possano impedire la diffusione di cellule "pre-leucemiche" CD4+CD8+ e la progressione della malattia
Intrathymic Notch3 and CXCR4 combinatorial interplay facilitates T-cell leukemia propagation.
Get PDFNotch hyperactivation dominates T-cell acute lymphoblastic leukemia development, but the mechanisms underlying "pre-leukemic-cells" dissemination are still unclear. Here we describe how deregulated Notch3 signaling enhances CXCR4 cell-surface expression and migratory ability of CD4+CD8+ thymocytes, possibly contributing to “pre-leukemic” cell propagation, early in disease progression. In transgenic mice overexpressing the constitutively active Notch3 intracellular domain, we detect the progressive increase in circulating blood and bone marrow of CD4+CD8+-cells, characterized by high and combined surface expression of Notch3 and CXCR4. We report for the first time that transplantation of such CD4+CD8+-cells, reveals their competence in infiltrating spleen and bone marrow of immunocompromised recipient mice. We also show that CXCR4 surface expression is central to the migratory ability of CD4+CD8+-cells and that such an expression is regulated by Notch3 through -arrestin in human leukemia cells.
De novo, we propose that hyperactive Notch3 signaling by boosting CXCR4-dependent migration promotes anomalous egression of CD4+CD8+-cells from the thymus in early leukemia stages. In fact, in vivo CXCR4 antagonism prevents bone marrow colonization by such CD4+CD8+ cells in young Notch3 transgenic mice.
Therefore, our data suggest that combined therapies precociously counteracting intrathymic Notch3/CXCR4 crosstalk, may prevent dissemination of “pre-leukemic” CD4+CD8+-cells, by a “thymus-autonomous” mechanism
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
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
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