1,721,161 research outputs found

    EFFECTS OF A PSORIATIC INFLAMMATORY MICROENVIRONMENT ON KERATINOCYTE MORPHOLOGY IN 3D AND 2D BIOLOGICAL EXPERIMENTAL MODELS OF NORMAL HUMAN SKIN

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    The interplay between proinflammatory circulating cytokines and keratinocytes is a crucial event in the development and progression of psoriatic lesions. However, the early phases of the pathogenesis of psoriasis are still to be elucidated, in particular regarding the epidermal barrier. A pivotal role is played by tight junctions (TJs), i.e. claudin-mediated intercellular attachment structures, localized in the upper granular layer. A barrier impairment associated to an alteration in TJ proteins is described in psoriasis as a response to a proinflammatory microenvironment. We investigated by immunofluorescence analysis the modulation of the expression of claudin 1 (CLDN-1), a transmembrane integral TJ protein, and of Zonula Occludens 1 (ZO-1), a scaffold plaque protein, after the incubation with MIX, a combination of interleukin (IL)-17, IL-22, IL-23, tumor necrosis factor (TNF)-alpha, for 24 (T24) and 48 (T48) hours. We considered as experimental models the standardized 3D organotypic cultures of normal human skin (n=7) and in vitro cultures of primary normal human keratinocytes (n=3) in basal or differentiating cell growth conditions. On skin bioptic samples, ultrastructural analysis by transmission electron microscopy (TEM) was performed. In control skin samples, CLDN-1 immunopositivity increased from the basal layer upwards, but its expression was early reduced in the basal and suprabasal layers starting from T24 in MIX-incubated group. At this time point, ZO-1 expression in control samples increased gradually, starting from the basal layers towards the epidermal surface and the incubation with MIX induced its immunopositivity in the basal and suprabasal layers. At T24, CLDN-1 expression was unaffected by MIX in undifferentiated and also calcium- differentiated keratinocytes. Unexpectedly, undifferentiated cells relocated ZO-1 at cell-cell contact points after the incubation with MIX, and in calcium-differentiated keratinocytes, ZO-1 synthesis was stimulated, too. By TEM, after MIX incubation, the overall architecture of the epidermal compartment was maintained, but apoptosis and enlargement of intercellular spaces were evident. The present results strongly suggest that the i) broadening of ZO-1 expression and ii) the downregulation of CLDN-1, typical features of psoriasis, can be induced as early as 24 hours in both models, suggesting that they represent a valid experimental approach. To complete this study, the effect of this microenvironment on keratinocyte proliferation and differentiation will be investigated, obtaining further insights into the early processes leading to the formation/progression of psoriatic plaques. Donetti E, Cornaghi L, Gualerzi A, Baruffaldi Preis FW, Prignano F. An innovative three-dimensional model of normal human skin to study the proinflammatory psoriatic effects of tumor necrosis factor-alpha and interleukin-17. Cytokine; 2014; 68:1-8. Donetti E, Cornaghi L, Arnaboldi F, Ricceri F, Pescitelli L, Maiocchi M, Carriero F, Baruffaldi Preis FW, Prignano F. Epidermal barrier reaction to an in vitro psoriatic microenvironment. Exp Cell Res; 2017; 15:180-188. Donetti E, Lombardo G, Baruffaldi Preis FW, Cornaghi L, Pescitelli L, Prignano F. 3D skin model to investigate the early epidermal morphological psoriatic features. J Transl Sci; 2019; doi: 10.15761/JTS.1000361 Riva F, Casasco A, Nespoli E, Cornaglia AI, Casasco M, Faga A, Scevola S, Mazzini G, Calligaro A Generation of human epidermal constructs on a collagen layer alone. Tissue Eng; 2007; 13: 2769-79. Riva F, Casasco A, Casasco M, Calligaro A, Cornaglia AI. Growth and stratification of epithelial cells in minimal culture conditions. Methods Mol Biol; 2010; 585:25-43

    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

    Structural parameters and mechanical strength of cancellous bone in the femoral head in osteoarthritis do not depend on age

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    For normal bone, aging has been associated with a decrease of both density and failure strength, and with the development of pathologies such as osteoporosis. Conversely, it has been reported that another common disease, osteoarthritis, may alter these age-related changes in cancellous bone, suggesting that it may have a protective role against osteoporosis and the correspondent fracture risk. It was reported that in the principal compressive region of the femoral head in osteoarthritis the bone density does not depend on age. However, it is not clear if this independence on age of the cancellous bone density corresponds also to a reduced dependence on age of the strength to failure. The present work examined cancellous bone from the principal compressive region of the femoral head of 37 patients having severe osteoarthritis. The aim was (1) to investigate the dependence on age of both the structural parameters and the ultimate stress and (2) to investigate the relationships between the ultimate stress and the structural parameters. Using X-ray microcomputed tomography, three-dimensional structural parameters, such as bone volume fraction, direct trabecular thickness and structure model index were calculated. Then the specimens were compressed to failure to determine the ultimate stress. It was found that none of the investigated structural parameters did depend on age, and also the ultimate stress did not depend on age (p>0.05 for all regressions on age). In addition, the ultimate stress was significantly correlated with the structural parameters, primary with the minimum bone volume fraction and the average bone volume fraction (R(2)=0.95 and R(2)=0.84, respectively). These findings show that severe osteoarthritis or a related factor may change the age dependences of both the structural parameters and the mechanical properties usually reported for normal cancellous bone. These results suggest for this pathology to have a protective role against the age-related decrease in density, the age-related deterioration of the microarchitecture and the age-related decrease of the failure strength for the cancellous bone in the principal compressive region of the human femoral head

    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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