1,720,972 research outputs found

    Batimastat reduces Mycobacterium tuberculosis-induced apoptosis in macrophages

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    In this study, we report evidences that Mycobacterium tuberculosis (MTB)-induced apoptosis in macrophages is reduced by a broad-spectrum hydroxamic acid-based matrix metalloproteinase (MMP) inhibitor, Batimastat (BB-94). In particular, we show that BB-94 administration to MTB-infected macrophages inhibits apoptosis and the downmodulation of membrane CD14 expression. Moreover, the addition of broad spectrum matrix metalloproteinase inhibitor to cell culture, during MTB infection, decreases the release of soluble TNF-alpha and leads to a simultaneous increase of membrane TNF-alpha. These results show that MTB-induced apoptosis in macrophages is reduced by a MMP inhibitor and most probably is related to TNF-alpha release. This identifies BB-94 as a simultaneous anti-apoptotic and anti-inflammatory molecule during MTB infection

    CpG oligodeoxynucleotides promote phospholipase D dependent phagolysosome maturation and intracellular mycobacterial killing in M. tuberculosis infected type II alveolar epithelial cells

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    CpG oligodeoxynucleotides have been previously shown to enhance antimycobacterial response in human monocytes/macrophages. The present study reports evidences showing the capability of CpG oligodeoxynucleotides to induce (i) host phospholipase D (PLD) activation, (ii) PLD dependent reactive oxygen intermediate production, (iii) PLD dependent phagolysosome maturation and (iv) PLD dependent intracellular mycobacterial killing in type II alveolar epithelial cells. These are the first evidences showing that alveolar epithelial cells may represent efficient effecter cells during primary innate antimycobacterial immune response

    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

    Analysis of T cells repertoire and clinical course of EAE after pretreatment with CNS antigens with asymmetric liposomes

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    Objective: Experimental Autoimmune Encephalomyelitis (EAE) is the murine model of Multiple Sclerosis. Phospholipids have been shown to effectively modulate the immune response. We studied the effect of asymmetric liposomes on recruitment of CNS-specific T lymphocytes in EAE and on disease clinical course. Methods: T cell repertoire analysis: Female SJL mice were pretreated s.c. with liposomes with or without PLP139-151. Mice were immunized s.c. 15 days after pretreatment with PLP139-151 in PBS emulsified 1:1 in CFA. Ten days later T cells from draining lymph nodes were cultured in the presence or absence of PLP139 for 3 days. The analysis of specific TCR-β repertoire were performed using immunoscope technique (Ria et al. 2006). EAE induction: Female SJL mice were pretreated s.c. with liposomes or with plp139-151 and liposomes and were immunized 15 days after to induce EAE with PLP139-151 emulsified 1:1 with CFA 4x. Clinical score was evaluated following published criteria (Touhy et al. 1988). Results: The immunoscope analysis of the PLP139-151 specific TR-β repertoire showed some interesting results: mice treated with Liposomes and PLP 139-151 recruited less frequently CD4+ T cells carrying the semiprivate rearrangement VB4-Jb1.6 than mice of the control group; There were no differences in the recruitment of CD4+ T cells carrying the public rearrangement VB10-Jb1.1. Furthermore, administration of Liposomes and PLP139-151 decreased usage of CD8+ cells carrying the public and semi-private rearrangements VB17-Jb1.6 and VB20-Jb2.3. Surprisingly we observed that the pre-immune TCR-β repertoire, which is usually depleted after immunization with PLP (Penitente et al. 2008), was still preserved in the group of mice pretreated with Liposomes and PLP 139-151. When EAE was induced after pre-treatment with liposomes in the presence or absence of PLP139-151, We observed a significant difference in the clinical score of the disease. In particular the group of mice previously treated with Liposomes + PLP139-151 presented a lower severity of the symptoms at the onset of the disease. Conclusions: Although the observed differences in the recruitment of T lymphocytes can justify the different clinical course of the disease, further studies are needed to understand the mechanism through which co-administration of antigens with asymmetric liposomes modifies immune responses

    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

    Sphingosine 1-phosphate promotes antigen processing and presentation to CD4+ T cells in Mycobacterium tuberculosis-infected monocytes

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    Sphingosine 1-phosphate (S1P) has recently been described to induce antimycobacterial activity. The present study analyses the role played by S1P in antigen presentation of monocytes and in the next activation of Mycobacterium tuberculosis (MTB)-specific CD4+ T cell response. Results reported herein show that S1P stimulation of MTB-infected monocytes (i) inhibits intracellular mycobacterial growth, (ii) enhances phagolysosome maturation and the transit of mycobacteria in MHC class II compartments, (iii) increases the frequency of MTB-specific CD4+CD69+ T cells, expressing the inflammatory homing receptor CCR5, derived from tuberculosis patients and PPD+, BCG naïve, healthy subjects, and (iv) induces IFN-gamma production in CD4+CD69+CCR5+ T cells derived from PPD+ healthy individuals, only. Altogether, these results show that S1P promotes antigen processing and presentation in monocytes, increases the frequency of MTB-specific CD4+ T cells and can regulate IFN-gamma production by antigen specific CD4+ T cells in the course of active disease

    Author Index

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