1,720,973 research outputs found

    Modulation of the proteolytic activity of matrix metalloproteinase-2 (gelatinase A) on fibrinogen

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    Modulation of the proteolytic activity of matrix metalloproteinase-2 (gelatinase A) on fibrinogen Susanna MONACO*, Magda GIOIA*†, Janet RODRIGUEZ‡, Giovanni Francesco FASCIGLIONE*, Donato DI PIERRO*, Giulio LUPIDI§, Ludwig KRIPPAHL_, Stefano MARINI* and Massimo COLETTA*†1 *Department of Experimental Medicine and Biochemical Sciences, University of Roma Tor Vergata, Via Montpellier 1, I-00133 Roma, Italy, †Interuniversity Consortium on the Metal Chemistry in Biological Systems (CIRCMSB), P.za Umberto I 1, I-70100 Bari, Italy, ‡Laboratorio de Farmacologia, Centro de Quimica Farmaceutica, 200 y 21, Atabey, 21, Atabey, Playa, P.O. Box 16042, La Habana, Cuba, §Department of Molecular, Cellular and Animal Biology, University of Camerino, Via F. Camerini 2, I-62032 Camerino, Italy, and _Departamento de Quimica, Faculdade de Ciencias e Tecnologia, Universidade Nova de Lisboa, 2829-516 Monte de Caparica, Portugal The proteolytic processing of bovine fibrinogen by MMP-2 (gelatinase A), which brings about the formation of a product unable to form fibrin clots, has been studied at 37◦C. Catalytic parameters, although showing a somewhat lower catalytic efficiency with respect to thrombin and plasmin, indeed display values indicating a pathophysiological significance of this process. A parallel molecular modelling study predicts preferential binding of MMP-2 to the β-chain of fibrinogen through its haemopexin-like domain, which has been directly demonstrated by the inhibitory effect in the presence of the exogenous haemopexin-like domain. However, the removal of this domain does not impair the interaction between MMP-2 and fibrinogen, but it dramatically alters the proteolytic mechanism, producing different fragmentation intermediates. The investigation at various pH values between 6.0 and 9.3 indicates a proton-linked behaviour,which is relevant for interpreting the influence on the process by environmental conditions occurring at the site of an injury. Furthermore, the action of MMP-2 on peroxynitrite-treated fibrinogen has been investigated, a situation possibly occurring under oxidative stress. The chemical alteration of fibrinogen, which has been shown to abolish its clotting activity, brings about only limited modifications of the catalytic parameters without altering the main enzymatic mechanism. Key words: fibrinogen, fragmentation, gelatinase A, kinetics, molecular modelling, pH-dependence

    Effect of axial coordination on the kinetics of assembly and folding of the two halves of horse heart cytochrome C.

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    The kinetics of the assembly of two complementary fragments of oxidized horse heart cytochrome c (cyt c), namely the heme-containing fragment-(1-56) and the fragment-(57-104), have been characterized at different pH values. At neutral pH the fragment-(1-56) is hexacoordinated and has two histidines axially ligated to the heme-Fe(III) (Santucci, R., Fiorucci, L., Sinibaldi, F., Polizio, F., Desideri, A., and Ascoli, F. (2000) Arch. Biochem. Biophys. 379, 331-336), thus mimicking what occurs in the folding intermediate of cyt c. The kinetics of the formation of the complex between the two fragments are characterized at pH 7.0 by a slow rate constant that is independent of the concentration of the reactants; conversely, at a low pH the kinetics are much faster and depend on the concentration of the fragments. This behavior suggests that the rate-limiting step observed in the recombination process of the fragments at neutral pH (that leads to the final coordination of Met-80) has to be ascribed to the detachment of the "misligated" histidine. Thus, the faster recombination rate at a low pH can be related to the fact that histidine is protonated and not able to coordinate to the metal. Furthermore, the independence of the rate constant on the concentration of the reactants observed at pH 7.0 can be accounted for by the occurrence of a conformational transition, which takes place immediately after the two fragments collapse together, likely simulating what induces the detachment of the misligated histidine during cytochrome folding

    Gelatinolytic activity in gingival crevicular fluid and saliva of growing patients with Marfan syndrome: a case-control study

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    Aim of the study was to evaluate the gelatinolytic activity in the saliva and gingival crevicular fluid from a sample group of subjects with Marfan syndrome

    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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