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A role for NAADP in Ca2+- dependent pathways activated by VEGF in human endothelial cells.
No full texte release of Ca2+ from intracellular stores is a key process involved in a variety of signaling pathways. e
second messenger nicotinic acid adenine dinucleotide phosphate (NAADP) mobilizes Ca2+ from lysosomelike
acidic stores but not from IP3-sensitive or ryanodine-sensitive Ca2+ stores in different cell types. To
date, two receptors for NAADP have been discovered, namely TPC1 and TPC2. Interestingly, intracellular
calcium dynamics plays a central role in angiogenesis of endothelial cells (EC) which is primarily triggered
in response to growth factor such as vascular endothelial growth factor (VEGF). In addition to its well
known role in the formation of new blood vessels, VEGF is also involved in a number of different EC
functions such as proliferation, migration, regulation of vascular permeability and survival through the
binding to two receptors (VEGFR1 and VEGFR2) both stimulating intracellular calcium mobilization. e
aim of our study is to characterize the role of Ca2+ in VEGF-dependent signal transduction and to correlate
its intracellular signaling to specific biological functions. Our data propose the involvement of NAADP in
VEGFR2- but not VEGFR1-induced calcium mobilization. We show that both pharmacological inhibition of
NAADP signaling with Ned-19 (a reported specific antagonist of NAADP) and the use of small interfering
RNA (siRNA) targeting TPC1 and TPC2, significantly reduces VEGF-stimulated calcium release in Human
Umbilical Vein Endothelial Cells (HUVEC). Our data suggest that both Ned-19 and silencing of TPC
receptors by RNAi down regulates VEGF-stimulated ERK1/2 phosphorilation. Moreover, we observed that
Ned-19 modulates Akt activation and inhibits VEGF-induced migration of EC. All together our data suggest
that NAADP plays an important role in VEGF-induced Ca2+ signaling via tyrosine kinase receptor and open
new strategies for studying EC functions
Regulation of angiogenic functions by angiopoietins through calcium-dependent signaling pathways
Full text linkAngiopoietins are vascular factors essential for blood vessel assembly and correct organization and maturation. This study describes a novel calcium-dependent machinery activated through Angiopoietin-1/2-Tie receptor system in HUVECs monolayer. Both cytokines were found to elicit intracellular calcium mobilization. Targeting intracellular Ca(2+) signaling, antagonizing IP3 with 2-APB or cADPR with 8Br-cADPR, was found to modulate in vitro angiogenic responses to Angiopoietins in a specific way. 2-APB and 8Br-cADPR impaired the phosphorylation of AKT and FAK induced by Ang-1 and Ang-2. On the other hand, phosphorylation of ERK1/2 and p38, as well as cell proliferation, was not affected by either inhibitor. The ability of ECs to migrate following Angs stimulation, evaluated by "scratch assay," was reduced by either 2-APB or 8Br-cADPR following Ang-2 stimulation and only slightly affected by 2-APB in cells stimulated with Ang-1. These results identify a novel calcium-dependent machinery involved in the complex interplay regulating angiogenic processes showing that IP3- and cADPR-induced Ca(2+) release specifically regulates distinct Angs-mediated angiogenic steps
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
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
Ned-19 inhibition of parasite growth and multiplication suggests a role for NAADP mediated signalling in the asexual development of plasmodium falciparum
Full text linkBACKGROUND:
Although malaria is a preventable and curable human disease, millions of people risk to be infected by the Plasmodium parasites and to develop this illness. Therefore, there is an urgent need to identify new anti-malarial drugs. Ca2+ signalling regulates different processes in the life cycle of Plasmodium falciparum, representing a suitable target for the development of new drugs.
RESULTS:
This study investigated for the first time the effect of a highly specific inhibitor of nicotinic acid adenine dinucleotide phosphate (NAADP)-induced Ca2+ release (Ned-19) on P. falciparum, revealing the inhibitory effect of this compound on the blood stage development of this parasite. Ned-19 inhibits both the transition of the parasite from the early to the late trophozoite stage and the ability of the late trophozoite to develop to the multinucleated schizont stage. In addition, Ned-19 affects spontaneous intracellular Ca2+ oscillations in ring and trophozoite stage parasites, suggesting that the observed inhibitory effects may be associated to regulation of intracellular Ca2+ levels.
CONCLUSIONS:
This study highlights the inhibitory effect of Ned-19 on progression of the asexual life cycle of P. falciparum. The observation that Ned-19 inhibits spontaneous Ca2+ oscillations suggests a potential role of NAADP in regulating Ca2+ signalling of P. falciparum
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