1,721,272 research outputs found

    The role of acetaldehyde in mediating effects of alcohol on expression of endogenous opioid system genes in a neuroblastoma cell line

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    Ethanol (EtOH) alters neural activity through interaction with various neurotransmitters and neuromodulators. The endogenous opioid system seems to play a key role in the activities of EtOH, since the opioid antagonist naltrexone (ReVia) attenuates craving. We have investigated the transcriptional regulation of opioid system genes in response to EtOH exposure for up to 96 h in human neuroblastoma SH-SY5Y cells using quantitative real-time polymerase chain reaction. We observed a significant decrease in the expression of opioid peptide precursors (proopiomelanocortin, proenkephalin, and prodynorphin) and of the kappa opioid receptor after 48 and 72 h of EtOH exposure (10 and 40 mM). These alterations were not present when the EtOH metabolism was blocked by 4-methylpyrazole. To evaluate whether the effects evoked by EtOH were possibly due to the first product of EtOH metabolism, cells were exposed to 0.4 mM acetaldehyde. We observed the same pattern of changes for prodynorphin, proenkephalin, and the kappa opioid receptor as after 72 h exposure to EtOH. These results contribute to our understanding of EtOH action at a cellular level and provide evidence of the role of acetaldehyde in mediating some of the EtOH-induced effects

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The 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

    A role for epigenetic mechanisms in the regulation of prodynorphin expression by alcohol

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    Background and Aim: Alcohol alters several neurotransmitter systems within the brain and accumulated evidences indicate the endogenous opioid system as an important target of its action. We studied, in vitro and in vivo the molecular alterations occurring in the prodynorphin gene following different exposures to alcohol. Methods: Human neuroblastoma SH-SY5Y cells were exposed to low, clearly not intoxicating, and high etha- 208 European Opioid Conference 2011, Kraków, Poland nol concentrations at different time points. Sprague Dawley rats received alcohol intragastrically trying to mimic human drinking that establishes tolerance and dependence conditions. Real-time RT-PCR was used to assess the abundance of mRNAs of interest. DNA methylation was analyzed by Methylation Specific-Real Time PCR and bisulfite-Pyrosequencing. Specific histone modifications at gene promoters were evaluated by Chromatin ImmunoPrecipitation. Results: In the cellular model we demonstrated a temporal relationship between selective chromatin modifications induced by ethanol or acetaldehyde, and changes in prodynorphin gene expression were demonstrated. In the amygdala complex of alcoholtreated rats differential changes in prodynorphin gene expression changes were observed depending on the time of exposure; consistently, we propose potential epigenetic mechanisms responsible for these alterations, at least upong short ethanol exposure. Conclusion: Our findings indicate a linkage between gene expression alterations and epigenetic modulation in prodynorphin promoter, thus adding novel information on how the opioid system can be affected by alcohol in several ways. Studies are ongoing to evaluate the chromatin remodelling in the neuroplasticity occurring in the progression of alcohol abuse. It will be also of value to study the ability of epigenetic modulators in reverting dynorphin genetic/epigenetic alterations and alcohol abuse-related behaviours. Moreover, opioid drugs already available in alcoholism treatment could also have possible epigenetic modulating properties

    Variations on the Author

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    “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

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    We 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
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