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nCDase and SphK-1 localization in vesicles shed by tumour cells and their biological roles.
No full textSphingolipid metabolism is a dynamic process resulting in the formation of a number of bioactive metabolites
including ceramide, ceramide-1-phosphate, sphingosine e sphingosine-1-phosphate (S1P). (Pyne and Pyne; Biochem. J.
2000; 349:385-402).
Following sphingomyelinase activation, sphingomyelin is hydrolyzed to ceramide, which is considered to be an
inducer of cell growth arrest, differentiation and apoptosis. (Hannun et. al 1996; Science: 274:1855-1859). Ceramidase
catalyzes the deacylation of ceramide to produce a free fatty acid and sphingosine. The enzyme sphingosine kinase
(SphK) catalyzes the formation of S1P from sphingosine and ATP (Olivera et al. J.Biol.Chem. 1998; 273:12576-
12583).
Two distinct SphK isoforms, SphK1 and SphK2, have been cloned and characterized. (Liu et.al. J.Biol.Chem. 2000;
275: 19513-19520) and recently, alternatively spliced variants of human SphK1 and SphK2, differing in their amino
terminal portions, have also been described (Billich et. al J.Biol.Chem. 2003; 278; 47408-47415). SphK1 and SphK2
differ in their relative tissue distribution, sub cellular localization and biochemical activities, consistent with distinct
biologic functions for these two enzymes (Saba et al. Circ. Res. 2004; 94:724-734). SphK2 presents a nuclear
localization signal sequence and is localized in the cell nucleus (Igarashi et. al. J.Biol.Chem 2003; 278: 46832-46839).
SphK1 is primarily localized in the cytosol. PMA and TNFα induce the phosphorylation of SphK1 Ser 225, through the
activation of MAPK and ERK1/2. Phosphorylation of SphK1results in its plasma membrane localization and in its
activation. (Pitson et al. Embo J. 2003; 22: 5491-550). SphK1 is a cell surface-active kinase and an extracellular
protein.
As several secreted proteins, like for instance FGF-1 and FGF-2, SphK1 molecule lacks a conventional leader
secretion signal sequence. The mechanism of its release from the cell occurs via a non classical pathway independent of
the endoplasmic reticulum/Golgi system but requiring functional actin dynamics (Ancellin et al J.Biol.Chem. 2002;
277: 6667-6675). SphK1 activity, and therefore production of S1P at the cell periphery and/or in the extracellular
medium, was shown to regulate a wide variety of cellular processes, including promotion of cell proliferation, survival
and motility (Olivera et al. J.Biol.Chem. 2003; 278: 46452-46460). S1P is an important proangiogenic factor and its
ability to promote capillary morphogenesis in endothelial cell is significantly enhanced when S1P is associated with
FGF-2 (Harvey et al. J Lab. Clin. Med 2002; 140: 188-198).
Since we already reported that FGF-2 release occurs by vesicle shedding (Taverna et. al. J.Biol.Chem. 2003; 278:
51911-51919), we hypothesized and tried to demonstrate the possibility that S1P is produced in shed vesicles and that it
exerts a synergic role with vesicle associated FGF-2, in the induction of endothelial cell differentiation. We also
considered the hypothesis that enzymes involved in sphingolipid degradation could play a role in vesicle shedding.
Our experimental dates indicate:
· nCDase and SphK1 are both present in shed vesicles in biologically active forms, together with their lipidic
substrates.
· The enzymes of sphingolipid metabolism are not involved in the process of vesicle shedding.
· In SK Hep-1 hepatocarcinoma cells, which we used in most of our experiments, FGF-2 and both nCDase and
SphK1 are simultaneously released in shed vesicles.
· Shed vesicles exert chemiotactic effects on endothelial cells and have the ability to promote their
morphogenesis in capillary-like structures.
· Since these effects are typical of both FGF-2 and S1P, to neutralize effects of vesicle-associated FGF-2, we
denatured the protein components of vesicles by a 10 minutes treatment at 100 C°. This treatment is known todenature FGF-2 (Vemuri et al. 1994; J Pharm Pharmacol. 46: 481-486) while S1P is reported to be
stable at temperatures below 120 C° (Harvey et al. J Lab. Clin. Med 2002; 140: 188-198). Heat treatment
substantially decreased the chemiotactic effect of vesicles but only had a small effect on their capability to
induce formation of capillary-like structures.
· Promotion of endothelial cell morphogenesis was increased in vesicles shed by cells overexpressing SphK1
and it was decreased in cells expressing a dominant negative SphK1 isoform.
In summary our dates show that shed vesicles are vehicles for both FGF-2 and SphK1 secretion, and that FGF-2
and S1P, produced in the vesicle membrane by the joined catalytic action of nCDase and SphK1, exert a synergic
action on endothelial cells inducing angiogenesis
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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