1,721,094 research outputs found
The endocannabinoid system in ageing: A new target for drug development
No full textEndocannabinoids are a new class of lipids, which include amides, esters and ethers of long chain polyunsaturated fatty acids. Anandamide (N-arachidonoylethanolamine; AEA) and 2-arachidonoylglycerol are the main endogenous agonists of cannabinoid receptors able to mimic several pharmacological effects of Delta-tetrahydrocannabinol, the active principle of Cannabis saliva preparations like hashish and marijuana. AEA is released "on demand" from membrane lipids, and its activity at the receptors is limited by cellular uptake followed by intracellular hydrolysis. Together with AEA and congeners, the proteins which bind, synthesize, transport and hydrolyze AEA form the "endocannabinoid system". Endogenous cannabinoids are present in the central nervous system and in peripheral tissues, suggesting a physiological role as broad spectrum modulators. This review summarizes the main features of the endocannabinoid system, and the latest advances on its involvement in ageing of central and peripheral cells. In addition, the therapeutic potential of recently developed drugs able to modulate the endocannabinoid tone for the treatment of ageing and age-related human pathologies will be reviewed
L'epica spagnola medievale: aspetti della tradizione
No full textIl lascito diretto della poesia epica spagnola si riduce a due testi quasi completi, il Cantar de Mio Cid e le Mocedades de Rodrigo, a un frammento, il Roncesvalles, e a una redazione in cuaderna vía del poema di Fernán González; per il resto le leggende eroiche sono state assorbite nella prosa delle cronache. Dati interni e/o referti codicolocici indicano che la preservazione dei testi superstiti è stata assicurata, talora previa, profonda risemantizzazione, da centri monastici o diocesiani. Nel presente intervento, con incursioni nella tradizione della prosificazioni, si propone una mise au jour della questione
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
Cholesterol-dependent modulation of type 1 cannabinoid receptors in nerve cells
No full textType 1 cannabinoid receptors (CB1R) are G-protein-coupled receptors that mediate several actions of the endocannabinoid anandamide (N-arachidonoylethanolamine; AEA) in the central nervous system. Here we show that cholesterol enrichment of rat C6 glioma cell membranes reduces by approximately twofold the binding efficiency (i.e., the ratio between maximum binding and dissociation constant) of CB1R and that activation of CB1R by AEA leads to approximately twofold lower [S-35]GTP gamma S binding in cholesterol-treated cells than in controls. In addition, we show that CB1R-dependent signaling via adenylate cyclase and p42/p44 mitogen-activated protein kinase is almost halved by cholesterol enrichment. Unlike CB1R, the other AEA-binding receptor TRPV1, the AEA synthetase NAPE-PLD, and the AEA hydrolase FAAH are not modulated by cholesterol, whereas the catalytic efficiency (i.e., the ratio between maximal velocity and Michaelis-Menten constant) of the AEA membrane transporter AMT is almost doubled compared with control cells. These data demonstrate that, among the proteins of the "endocannabinoid system," only CB1R and AMT critically depend on membrane cholesterol content. This observation may have important implications for the role of CB1R in protecting nerve cells against (endo)cannabinoid-induced apoptosis. (c) 2005 Wiley-Liss, Inc
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
Anandamide regulates keratinocyte differentiation by inducing DNA methylation in a CB1 receptor-dependent manner
No full textAnandamide ( arachidonoylethanolamide, AEA) belongs to an important class of endogenous lipids including amides and esters of long chain polyunsaturated fatty acids, collectively termed "endocannabinoids." Recently we have shown that AEA inhibits differentiation of human keratinocytes, by binding to type-1 cannabinoid receptors (CB1R). To further characterize the molecular mechanisms responsible for this effect, we investigated the expression of epidermal differentiation-related genes after AEA treatment. We observed that keratin 1 and 10, transglutaminase 5 and involucrin are transcriptionally down-regulated by AEA. Most importantly, we found that AEA is able to decrease differentiating gene expression by increasing DNA methylation in human keratinocytes, through a p38, and to a lesser extent p42/44, mitogen-activated protein kinase-dependent pathway triggered by CB1R. An effect of AEA on DNA methylation because of CB1R-mediated increase of methyltransferase activity is described here for the first time, and we believe that the importance of this effect clearly extends beyond the regulation of skin differentiation. In fact, the modulation of DNA methylation by endocannabinoids may affect the expression of a number of genes that regulate many cell functions in response to these substances
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