1,720,989 research outputs found
Need (more than) two to Tango: Multiple tools to adapt to changes in oxygen availability
Full text linkOxygen is a fundamental element for the life of a large number of living organisms allowing an efficient energetic utilization of substrates. Organisms relying on oxygen evolved complex structures for oxygen delivery and biochemical machineries dealing with its safe utilization and the ability to overcome the potentially harmful consequences of changes in oxygen availability. On fact, cells composing complex Eukaryotic organisms are set to live within an optimum narrow range of oxygen, quite specific for each cell type. Minute modifications of oxygen availability, either positive or negative, induce the expression of specific genes, the major actors of this responses being the transcription factors HIF and Nrf2 that control the attempt to cope with low oxygen (hypoxia) or to either high oxygen or to an oxygen “overflow,” respectively. This review describes the interaction between these two transcription factors and their interaction with the transcription factor NF-kB acting as a pivotal determinant of final cel
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
Palmitate-induced endothelial dysfunction is attenuated by cyanidin-3-O-glucoside through modulation of Nrf2/Bach1 and NF-κB pathways
No full textFree fatty acids (FFA), commonly elevated in diabetes and obesity, have been shown to impair endothelial functions and cause oxidative stress, inflammation, and insulin resistance. Anthocyanins represent one of the most important and interesting classes of flavonoids and seem to play a role in preventing cardiovascular diseases. Herein, we investigated the in vitro protective effects of cyanidin-3-O-glucoside (C3G) on cell signaling pathways in human umbilical vein endothelial cells (HUVECs) exposed to palmitic acid (PA), the most prevalent saturated FFA in circulation. Our data reported a significant augmentation of free radicals and oxidative stress in HUVECs exposed to PA for 3h, while C3G pretreatment improved intracellular redox status altered by FFA. Moreover, C3G significantly inhibited NF-κB proinflammatory pathway and adhesion molecules induced by PA, and these effects were attributed to the activation of Nrf2/EpRE pathway. In fact, C3G induced Nrf2 nuclear localization and activation of cellular antioxidant and cytoprotective genes at baseline and after PA exposure in endothelial cells. Our data confirm the hypothesis that natural Nrf2 inducers, such as C3G, might be a potential therapeutic strategy to protect vascular system against various stressors preventing several pathological conditions
Cyanidin-3-O-glucoside ameliorates palmitate-induced insulin resistance by modulating IRS-1 phosphorylation and release of endothelial derived vasoactive factors
No full textIncreased plasma levels of free fatty acids, including palmitic acid (PA), cause insulin resistance in endothelium characterized by a decreased synthesis of insulin-mediated vasodilator nitric oxide (NO), and by an increased production of the vasoconstrictor protein, endothelin-1. Several in vitro and in vivo studies suggest that anthocyanins, natural phenols commonly present in food and vegetables from Mediterranean Diet, exert significant cardiovascular health-promoting activities. These effects are possibly mediated by a positive regulation of the transcription factor Nrf2 and activation of cellular antioxidant and cytoprotective genes. The present study examined, at a molecular level, the effects of cyanidin-3-O-glucoside (C3G), a widely distributed anthocyanin, on PA-induced endothelial dysfunction and insulin resistance in human umbilical vein endothelial cells (HUVECs). Our results indicate that C3G pretreatment effectively reverses the effects of PA on PI3K/Akt axis, and restores eNOS expression and NO release, altered by PA. We observed that these effects were exerted by changes on the phosphorylation of IRS-1 on specific serine and tyrosine residues modulated by PA through the modulation of JNK and IKK activity. Furthermore, silencing Nrf2 transcripts demonstrated that the protective effects of C3G are directly related to the activation of Nrf2
Cyanidin-3-O-glucoside modulates intestinal inflammatory response induced by TNF-alpha: an approach based on in vitro epithelial and epithelial-endothelial co-culture models
No full textInflammatory Bowel Diseases (IBD) are chronic intestinal inflammatory disorders characterized by an excessive release of pro-inflammatory mediators, intestinal barrier dysfunction and altered permeability, and excessive activation of NF-κB cascade. IBD conventional therapies are insufficiently selective and associated to severe side effects. Phenolic compounds are considered to possess antioxidant and anti-inflammatory activities and are a great hope in prevention and treatment of chronic intestinal inflammation. In fact, the discovery of specific genes regulated by the Antioxidant Responsive Element (ARE) affected by antioxidants/electrophiles, led to the hypothesis that some phytochemicals may act as modulators of signal transduction pathways.
The aim of the present study was to evaluate the beneficial effects of Cyanidin-3-O-glucoside (C3G), an anthocyanin widely distributed in mediterranean diet, and the underlying mechanisms of action, in an vitro model of acute phase of intestinal inflammation using differentiated Caco-2 cells exposed to the proinflammatory cytokine TNF-α. Caco-2 cells exposure to TNF-α for 6 h activated IKK/NF-κB proinflammatory pathway, and induced COX-2 and IL6 expression. Interestingly, cells pretreatment for 24 h with C3G (20-40 μM) was effective in preventing TNF-α-induced changes. Our results also demonstrated that C3G improved intracellular redox status altered by TNF-α, and activated Nrf2/ARE pathway, at baseline and after TNF-α treatment. C3G increased Nrf2 nuclear translocation, and HO-1 and NQO1 expression and these effects can be associated to NF-κB pathway inhibition.
Epithelial cells are positioned in close proximity to various cell types, which places them in the unique position of providing signals to neighbouring cells located in the underlying mucosa, e.g. endothelial cells (EC), thereby possibly influencing the immunological response of the gut. A non-contact coculture system was used to investigate whether Caco-2 cells activated with TNF-α were able to provide signals that can induce EC dysfunction, and if C3G was able to prevent Caco-2-induced EC activation. Our results demonstrated that coculture of human umbilical vein endothelial cells (HUVECs) with TNF-α-stimulated Caco-2 cells led to a significant up-regulation of endothelial VCAM-1 and E-Selectin expression, accompanied by an increase in EC nuclear NF-κB p65 accumulation. Such evidence suggests that epithelial cells might activate neighboring EC to support leukocyte recruitment. Caco-2 pre-treatment with 20 μM C3G was effective in preventing EC adhesion molecules expression, and NF-κB p65 nuclear localization. Furthermore, inhibition of endothelial NF-κB activation using the IKK inhibitor wedelolactone resulted in a similar significant decrease of adhesion molecules expression. These data support the hypothesis that Caco-2 cell-produced factors exert their effects on endothelial dysfunction through activation of the NF-κB signaling pathway.
In conclusion, our data suggest that C3G may have protective effects against TNF-α-mediated intestinal mucosal damage acting as cell signaling modulator and inducing activation of the Nrf2/ARE pathway. Furthermore, inhibition of epithelial cells inflammation can protect from epithelial-induced EC activation, thus preventing the colonic inflammatory response and the subsequent immune cell recruitment during inflammation
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