1,720,990 research outputs found
Dual effect of hypochlorite in the modification of high density lipoproteins
No full textHDL-cholesterol levels are inversely correlated to the risk of cardiovascular disease. In recent years the concept that not only the quantity, but also the quality of HDL is related to their atheroprotective function has gained momentum. In fact several studies have showed that HDL can shift their properties from anti-atherogenic to pro-atherogenic upon chemical or enzymatic "modification". However, not all kind of modifications affect the antiatherogenic properties of HDL. For example, tyrosylation of HDL improves its ability to remove cholesterol from cultured cells and inhibits mice atherosclerotic lesion formation; oxidation of HDL(3) with 15-lipoxygenase or with copper ions for short time induce the formation of pre-β-migrating particles that are highly effective as cholesterol acceptors from lipid laden cells. Myeloperoxidase modifies HDL and apoA-I and reduces their ability to promote ABCA1-mediated cholesterol efflux. In the present study we show that modification with low concentration HOCl (a myeloperoxidase product) induces the formation of pre-β-migrating particles, thus improving the function of HDL in the reverse cholesterol transport, without affecting the anti-inflammatory activity. At higher HOCl concentration, pre-β-migrating particles were not detectable and the anti-inflammatory properties of HDL were lost. These findings suggest that during early phases of inflammation, when a low HOCl concentration is generated, changes in HDL occur that increase their ability to remove cholesterol and sparing anti-inflammatory properties; later during acute inflammation, when higher HOCl concentration are present changes in HDL occur that severely decrease their ability to remove cholesterol from macrophages and to protect endothelial cells from pro-inflammatory stimuli
Modification of HDL3 by mild oxidative stress increases ATP-binding cassette transporter 1-mediated cholesterol efflux
Full text linkOBJECTIVE: Elevated levels of high-density lipoprotein (HDL) cholesterol are inversely related to the risk of cardiovascular disease. The anti-atherosclerotic function of HDL is mainly ascribed to its role in reverse cholesterol transport, and requires the integrity of HDL structure. Experimental evidence suggests that the ability of HDL to promote removal of excess cholesterol from peripheral cells is impaired upon oxidation. On the other hand, tyrosylation of HDL enhances its protective function, suggesting that not all forms of modified lipoprotein may be atherogenic. In the present study we investigated the effect of a mild oxidation of HDL(3) on its function as cholesterol acceptor. METHODS AND RESULTS: A mild oxidative stress (induced by 15 min exposure of HDL(3) to 1 microM Cu(++) or to 15-lipoxygenase) caused the formation of pre-beta-migrating particles. Compared to native lipoprotein, mildly modified HDL(3) induced a significant ATP-binding cassette transporter 1 (ABCA1)-mediated increase of cholesterol and phospholipids efflux from J774 macrophages. This effect was abolished by an inhibitor of ABCA1-mediated lipid efflux (glyburide) and was absent in Tangier fibroblasts. CONCLUSIONS: A mild oxidative modification of HDL(3) may improve its function as cholesterol acceptor, increasing ABCA1-mediated lipid efflux from macrophages, a process that may reduce foam cell formation
Liver X receptor and retinoic X receptor agonists modulate the expression of genes involved in lipid metabolism in human endothelial cells
No full textThe cooperation of liver X receptors (LXRs) alpha and beta, and retinoic X receptor (RXR) modulate the expression of several genes involved in lipid metabolism in hepatocyte and macrophages. Using cDNA microarray technology, we have shown previously that several of these genes are also expressed in endothelial cells. In the present study, we investigated whether the activation of LXR and RXR affects the expression of genes involved in lipid metabolism in human endothelial cells. Relative expression of ABCA-1, CETP, SR-B1, EL, LPL, PLTP, ApoE and LDLR was investigated in HUVECs, human fibroblasts (hFB) and HepG2 cells by quantitative real-time PCR. For CETP and EL mRNA expression, the results were HUVECs > hFB > HEPG2; for PLTP, LDLR and LPL: hFB > HUVECs > HEPG2; for SR-B1 and ApoE: HEPG2 > HUVECs > hFB; and for ABCA-1 HEPG2: > hFB > HUVECs. Incubation of HUVECs with LXR agonists as 22-(R)-hydroxycholesterol (22-(R)-HC) or T0901317-induced ABCA1 (20.1- and 17.8-fold), LPL (3.46- and 7.03-fold) and CETP (6.34- and 3.98-fold) expression; EL, LDLR and SR-B1 expression was induced only upon incubation with T0901317 (2.40-, 2.83- and 2.19-fold, respectively) while 22-(R)-HC had no effect on EL and SR-B1 expression (0.8- and 0.9-fold) and decreased LDLR expression (0.4-fold). No effect of either 22-(R)-HC or T0901317 on PLTP and ApoE expression was observed. The RXR agonist, 9-cis retinoic acid (9CRA) alone induced the expression of CETP, LPL and SR-B1 (2.8-, 8.2- and 2.4-fold). No effect of 9CRA on ABCA-1, EL, PLTP, ApoE, and LDLR expression was observed. Association of 9CRA with 22-(R)-HC or T0901317 increased the expression of CETP and LPL while no effect on ABCA-1 or LDLR was observed. Activation of LXRs and RXRs in endothelial cells represents a new target of LXR and RXR agonist in the arterial wall. Modulation of gene expression in the endothelium should be taken into account when studying the effects of LXR and RXR agonists on lipid metabolism in the arterial wall
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
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