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    S-nitrosoglutathione potentiates protein S-nitrosation under oxidative stress, a potential improvement of NO storage into smooth muscle cells

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    Introduction To counteract NO deficiency occurring with oxidative stress (OS) in cardiovascular diseases, administration of S-nitrosothiols (RSNO) like S-nitrosoglutathione (GSNO), the main storage form of NO in tissues [1], represents an alternative to other NO-donors, with no tolerance nor OS induction. However, their ability to regulate NO bioavailability under OS is unknown. As S-nitrosation of proteins, the formation of high molecular weight RSNOs, is also considered as a form of NO storage in tissues [2], we evaluated whether an administration of GSNO will regulate protein S-nitrosation in an OS model of rat smooth muscle cells. Material and methods A rat smooth muscle cell line (SMC A-10) was stimulated by 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH; 50 mM, 2 h, 37°C) to mimic OS. Intracellular thiol status as content of reduced glutathione (GSH) (2,3-naphthalene dicarboxaldehyde assay) and reduced thiol containing proteins (Ellman’s method) were monitored. The activity of γ-glutamyl transpeptidase (GGT), specifically implied in GSNO catabolism, was measured using L-γ-glutamyl-p-nitroanilide as chromogenic substrate. Then, the thiol status modifications and intracellular peptides/proteins S-nitrosation (2,3-diaminonaphthalene/Hg2+assay) were monitored in stressed SMC incubated for 1 h with 50 μM GSNO. S-nitrosated proteins were purified (biotin switch technique) and identified by mass spectrometry. Results Under OS, the intracellular content of reduced thiols was greatly decreased for GSH (59±4 to 29 ± 5 nmol/mg proteins, n = 3) compared to proteins (148 ± 6 to 125 ± 4 nmol/mg proteins, n = 3), with no impact of GSNO. However, GSNO increased the global content of intracellular S-nitrosated peptides/proteins upon OS (0.53 ± 0.04 to 1.07±0.09 nmol/mg proteins, n = 3). Although the GGT activity decreased (1.35 ± 0.20 to 0.39±0.14 nmol/min/mg proteins) under OS, it was still implied at 38±5% (using serine borate complex, a GGT specific inhibitor) into the intracellular peptides/proteins S-nitrosation. The final mass spectrometry identification revealed that 71 proteins were S-nitrosated under control condition and this rose to 93 under OS. Discussion/conclusion The increase in intracellular S-nitrosated proteins in smooth muscle cells submitted to OS and treated with GSNO can be the starting point for GSNO to restore the NO pool. How and when this NO pool can be released has to be further evaluated. References 1. Maron BA et al. Antioxid Redox Signal (2013) 18, 270-287. 2. Rayner BS et al. J Biol Chem (2005) 280, 9985-9993

    S-nitrosoglutathione potentiates protein S-nitrosation under oxidative stress, a potential improvement of NO storage into smooth muscle cells

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    Cardiovascular diseases are associated with oxidative stress and reduced nitric oxide (NO) bioavailability. The ability of NO donors like S-nitrosoglutathione (GSNO) to regulate NO bioavailability under oxidative stress is poorly studied. Here, we monitored protein S-nitrosation (Pr-SNO), a post-translational protein modification in smooth muscle cells exposed to GSNO under oxidative stress. Intracellular thiol redox status in relation with the extent and distribution of GSNO-induced intracellular Pr-SNO (LC-MALDI MS) were assessed. The role of the gammaglutamyl transferase (GGT), a redox enzyme metabolizing GSNO, in Pr-SNO formation was also studied. GSNO prevented the oxidation of proteins SH groups. Concomitantly, a 2-fold increase of GSNO-dependent Pr-SNO formation still depending on GGT activity was observed. Mass spectrometry identified 51 proteins S-nitrosated by GSNO under oxidative stress (vs 32 in basal condition), including a higher number of cytoskeletal proteins (17 vs 8 in basal condition) related to cell morphogenesis and movement. Furthermore, additional proteins belong to cell adhesion and protein trafficking were S-nitrosated under oxidative stress. Oxidative stress modifies the extent and distribution of GSNO induced Pr-SNO formation, a NO storage form in tissue. Further studies will likely elucidate the pathophysiological significance of these observations

    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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    koamabayili/VECTRON-author-checklist: VECTRON author checklist

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    We have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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