1,720,958 research outputs found
CCL5 activates a orphan G-protein coupled receptor 75 in human neuroblastoma SH-SY5Y cell line. 15-19 NOVEMBER, WASHINGTON DC
No full textThe chemokine CCL5 inhibits entry of M-tropic HIV strains into macrophages/microglia by affecting the binding of the envelop protein gp120 to the co-receptor CCR5. Interestingly, CCL5 also prevents neuronal cell death mediated by the T-tropic gp120 and the viral protein Tat, which have no affinity for CCR5. Thus, CCL5 could be used to reduce HIV-associated neurocognitive disorder (HAND). Nevertheless, the mechanism of action of CCL5 remains to be fully characterized. Recent studies have shown that CCL5 activates a G-protein coupled receptor 75 (GPR75) which encodes for a 540 amino-acid orphan receptor of the Gq α family. In the present study, we examined the interaction of CCL5 and GPR75 in neuroblastoma SH-SY5Y cells that do not express other receptors for CCL5, such as CCR5, CCR3, and CCR1. CCL5 then promoted GPR75 internalization within few minutes. In addition, CCL5 elicited a significant dose-dependent increase in pro-survival pathways, such as the phosphatidylinositol 3-kinase (PI3K) and the extracellular signal-regulated kinases (ERK1/2). Akt and ERK1/2 phosphorylation were blocked by the specific pathway inhibitors, Wortmannin and U73 122, respectively, but not by pertuxin toxin, suggesting that CCL5 activate a Gq-coupled receptor. In conclusion, we hypothesize that CCL5-GPR75 signaling could further activate a neuroprotective mechanism that could explain the multiple pro-survival roles of CCL5 in reducing gp120 and Tat cell death
Morphine induces the release of CCL5 from astrocytes: Potential neuroprotective mechanism against the HIV protein gp120
No full textA number of human immunodeficiency virus type-1 (HIV) positive subjects are also opiate abusers. These individuals are at high risk to develop neurological complications. However, little is still known about the molecular mechanism(s) linking opiates and HIV neurotoxicity. To learn more, we exposed rat neuronal/glial cultures prepared from different brain areas to opiate agonists and HIV envelope glycoproteins gp120IIIB or BaL. These strains bind to CXCR4 and CCR5 chemokine receptors, respectively, and promote neuronal death. Morphine did not synergize the toxic effect of gp120IIIB but inhibited the cytotoxic property of gp120BaL. This effect was blocked by naloxone and reproduced by the mu opioid receptor agonist DAMGO. To examine the potential mechanism(s) of neuroprotection, we determined the effect of morphine on the release of chemokines CCL5 and CXCL12 in neurons, astrocytes, and microglia cultures. CCL5 has been shown to prevent gp120BaL neurotoxicity while CXCL12 decreases neuronal survival. Morphine elicited a time-dependent release of CCL5 but failed to affect the release of CXCL12. This effect was observed only in primary cultures of astrocytes. To examine the role of endogenous CCL5 in the neuroprotective activity of morphine, mixed cerebellar neurons/glial cells were immunoneutralized against CCL5 prior to morphine and gp120 treatment. In these cells the neuroprotective effect of opiate agonists was blocked. Our data suggest that morphine may exhibit a neuroprotective activity against M-tropic gp120 through the release of CCL5 from astrocytes
CCL5 activates a orphan G-protein coupled receptor 75 Neuroprotective effect of CCL5 via the G-protein coupled receptor 75 (GPR75) activation. 20th Meeting of Society of NeuroImmune Pharmacology (SNIP). 26-29 March, 2014 New Orleans, U.S.A.
No full textThe chemokine CCL5 affects the binding of the envelop protein gp120 to the co-receptor CCR5. CCL5 also
prevents neuronal cell death mediated by the X4 gp120 and Tat, which have no affinity for CCR5. The mechanism
of action of this chemokine remains to be fully characterized. Recent studies and preliminary data have shown that
CCL5 activates a GPR75 which belongs to the Gqα family. This receptor is more abundant in the brain than in the
immune organs. Moreover, CCL5 activates various pro-survival signaling molecules, including inositol
triphosphate, phosphatidylinositol 3-kinase and its downstream targets, protein kinase B (Akt) and extracellular
signal-regulated kinases (ERK1/2), in SH-SY5Y human neuroblastoma cells. These cells do not express CCR5,
CCR3 and CCR1, receptors known to bind to CCL5. Moreover, CCL4, CCL7 and CCL3, other chemokines that
bind to CCR5, CCR3 and CCR1, failed to activate these signaling molecules in SH-SY5Y cells. Akt and ERK1/2
phosphorylation were blocked by the Wortmannin and U73122, inhibitors of Akt and ERK1/2, respectively. At the
same time these responses were insensitive to pertussis toxin, a Gi inhibitor, suggesting that CCL5 activates a
GPCR coupled to Gq proteins. Therefore, GPR75 could explain the neuroprotective activity of CCL5 against gp120
and Tat. The discovery and characterization of compounds that prevent or limit the neurodegeneration that follows
HIV infection of the brain is a great challenge for HIV research. Thus, the results provide new mechanistic insight
which can be instrumental in addressing this challenge. Supported by NS 079172, NS 074916, DA 03228
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
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
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