1,720,985 research outputs found

    Effects of endothelin-1 on fibroblasts from type 2 diabetic patients: Possible role in wound healing and tissue repair

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    Endothelin-1 (ET-1) promotes the contractile ability of fibroblasts, essential for wound closure and reconstitution of the dermis. Wound healing is impaired in type 2 diabetic patients (D). We compared the effect of ET-1 on proliferative transforming growth factor (TGFbeta(1)) expression, fibronectin and laminin release), differentiative [alpha-smooth muscle actin (alpha-SMA) expression] and inflammatory [monocyte chemo-attractant protein (MCP-1) and interleukin-6 (IL-6) expression] responses in skin fibroblasts of healthy subjects (C) and D, testing the relative role of ET(A) and ET(B) receptors in mediating these responses. ET-1 did not influence TGFbeta(1), fibronectin or laminin production. alpha-SMA was more abundant and more stimulated in D, as well as MCP-1 and IL-6 expression and release. These effects were prevented by BMS-182874, selective antagonist of ET(A), more abundant than ET(B) in both cell strains and whose expression rose more in D than C upon stimulation with ET-1. This peculiar pattern of responses to ET-1, presumably acquired during the chronic in vivo exposure to hyperglycemia along the natural history of the disease, may partially explain the increased susceptibility of D to chronic ulcerations

    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

    Rosiglitazone increases matrix production and quenches inflammation: studies in human cells

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    BACKGROUND: Type 2 diabetes (T2D) is characterized by an accelerated atherogenesis, a process to which both proliferative and inflammatory responses contribute. Peroxisome proliferator-activated receptors-gamma (PPARgamma) agonists have both anti-proliferative and anti-inflammatory properties. We tested the effect of therapeutic doses of rosiglitazone on proliferative and inflammatory pathways in fibroblasts (HF) from five controls (C) and five T2D patients, and in aortic smooth muscle cells (hSMC). METHODS: Transforming growth factor-beta (TGFbeta) and interleukin-6 (IL-6) expression, and IL-6, laminin and fibronectin release were measured. To identify the involved intracellular signalling, extracellular signal-regulated kinases (ERK)1/2 phosphorylation and p38 activation were evaluated. RESULTS: Both phorbol 12-myristate 13-acetate (PMA) [a protein kinase C (PKC) activator] and rosiglitazone increased TGFbeta expression and fibronectin and laminin release in C and T2D patients. Rosiglitazone effect was reversed by its specific inhibitor Sr202. The combination PMA + rosiglitazone was additive in C, but not in T2D patients. IL-6 production was stimulated by PMA in both C and T2D patients; this effect was prevented by rosiglitazone in a Sr202-inhibitable manner. Experiments performed in hSMC yielded the same results. Rosiglitazone increased p38 activation more in C than in T2D patients; PMA-induced phosphorylation of ERK1/2 was similarly reduced in both cells. CONCLUSIONS: In HF and hSMC, rosiglitazone stimulates the synthesis of matrix components via enhanced TGFbeta expression; when combined with PMA, the resulting PKC activation is mediated by enhanced p38 phosphorylation. On the other hand, rosiglitazone quenches inflammation in both cell types, by counteracting PMA-induced phosphorylation of ERK1/2

    Extracellular adenosine 5'-triphosphate modulates insulin secretion via functionally active purinergic receptors of X and Y subtype

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    Extracellular nucleotides modulate several cell functions via specific receptors, P2X and P2Y. We explored the differential role of these receptors in the control of insulin secretion (InSec). In INS-1e cells grown in 11 mm glucose and then acutely exposed to 3.3, 7.5, 11, or 20 mm, coincubation with ATP, the global agonist of both P2X and P2Y receptors, induced a dose-dependent (P < 0.0001) reduction in insulin release (P < 0.0001) that was more marked at higher glucose concentrations (P < 0.0001 for the interaction). This effect was fully prevented (P < 0.0001) by incubating ATP-treated cells in the presence of apyrase, an ecto-ATP/ADPase. Uridine 5'-triphosphate (UTP), preferential agonist of P2Y receptors, significantly stimulated InSec at all glucose concentrations tested, whereas benzoyl-benzoyl ATP (BzATP), a strong and highly selective P2X(7) agonist, did not influence InSec. Oxidized ATP, which completely suppresses P2X activity, abolished the inhibitory effect of ATP on InSec. Similar results were obtained in MIN-6 cells. Stimulation with ATP, BzATP, and UTP dose-dependently increased Intracellular free Ca(2+) concentrations. By small interfering RNA we show P2X(3) and P2Y(4) as the main responsible inhibitory and promoting effect on InSec, respectively. Because P2X(7) is not directly involved in InSec, we tested whether the effect of ATP on hormone synthesis might be mediated by apoptosis. However, neither ATP nor BzATP induced either early or late apoptosis. We conclude that: 1) INS-1e cells express multiple purinergic receptors, 2) ATP reduces glucose-induced InSec as a net effect of inhibition through P2X and stimulation through P2Y receptors, and 3) P2X-mediated apoptosis is not involved in the inhibition of InSec

    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
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