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    Intestinal neuromuscular function adaptation to ischemia/reperfusion injury: relevance of the microbiota-gut interplay

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    Intestinal ischemia/reperfusion (IR) injury represents an important clinical problem, inducing severe damage to the enteric nervous system and to the neuromuscular intestinal function. Recently, we have focused on hyaluronan (HA), an extracellular matrix component, as a new modulator of the neuroadaptive changes of enteric neuronal circuitries in the inflamed gut. In this study, we evaluated HA involvement in myenteric neuron derangements after IR injury. After IR, a gradual deposition of HA was observed along the intestinal layers, with the highest deposition occurring in the external longitudinal muscle with the myenteric plexus, which was associated to HA synthase2 upregulation. IR-induced HA deposition was reduced by treatment with 4MU, a HA synthesis inhibitor. After IR, the expression levels of HA targets, TLR2, TLR4 and CD44 increased in the muscularis externa with the myenteric plexus more than in submucosal and mucosal layers and were sensitive to 4MU. The efficiency of the intestinal transit was significantly reduced in IR and further reduced in the 4MU-treated IR group. Carbachol (CCh), electrical field stimulated (EFS) contractions and EFSinduced non-adrenergic-non-cholinergic (NANC) relaxations were reduced after I/R. In this condition, 4MU increased EFS contractions towards control values, but did not affect CCh-induced contractions neither NANC on-relaxations. Main alterations in the neurochemical coding of excitatory (tachykinergic) and inhibitory pathways (iNOS, VIPergic) were also observed after IR and were influenced by 4MU administration. Overall, our data suggest that, after an intestinal IR damage, changes of HA homeostasis in specific myenteric neuron populations may participate in neuromuscular function derangement

    Natural Products with Toll-Like Receptor 4 Antagonist Activity

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    Toll-Like Receptors (TLRs) are the innate immunity receptors that play an activating role when interacting with molecules released by bacteria and viruses (PAMPs, pathogen-associated molecular patterns) or with molecules released by injured cells and tissues (DAMPs, danger-associated molecular patterns). TLR triggering leads to the induction of proinflammatory cytokines and chemokines, driving the activation of both innate and adaptive immunity. In particular, Toll-Like Receptor 4 (TLR4) has been described to be involved in the inflammatory processes observed in several pathologies (such as ischemia/reperfusion injury, neuropathic pain, neurodegenerative diseases, and cancer). Molecules obtained by natural sources have been discovered to exert an anti-inflammatory action by targeting TLR4 activation pathways. This review focuses on TLR4 antagonists obtained from bacteria, cyanobacteria, and plants

    The Effect of Cyanobacterial LPS Antagonist (CyP) on Cytokines and Micro-RNA Expression Induced by Porphyromonas gingivalis LPS

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    Lipopolysaccharide (LPS) from Porphyromonas gingivalis (Pg-LPS) is a key bacterial structure involved in the maintenance of a chronic pro-inflammatory environment during periodontitis. Similar to other gram-negative LPS, Pg-LPS induces the release of pro-inflammatory cytokines through interaction with Toll-Like Receptor 4 (TLR4) and is able to stimulate negative TLR4 regulatory pathways, such as those involving microRNA (miRNA). In this work, we employed CyP, an LPS with TLR4-MD2 antagonist activity obtained from the cyanobacterium Oscillatoria planktothrix FP1, to study the effects on pro-inflammatory cytokine production and miRNA expression in human monocytic THP-1 cells stimulated with Pg-LPS or E. coli LPS (Ec-LPS). Results showed that CyP inhibited TNF-α, IL-1β and IL-8 expression more efficiently when co-incubated with Pg-LPS rather than with Ec-LPS. The inhibition of pro-inflammatory cytokine production was maintained even when CyP was added 2 h after LPS. The analysis of the effects of CyP on miRNA expression showed that, although being an antagonist, CyP did not inhibit miR-146a induced by Pg-LPS or Ec-LPS, whereas it significantly inhibited miR-155 only in the cultures stimulated with Ec-LPS. These results suggest that CyP may modulate the pro-inflammatory response induced by Pg-LPS, not only by blocking TLR4-MD2 complex, but also by preserving miR-146a expression

    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

    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

    Dispelling the Myths Behind First-author Citation Counts

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    We 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

    Author Index

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