1,720,956 research outputs found

    Genetic and epigenetic effect of estrogen on mesenchymal stem cell maintenance and differentiation

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    Cataloged from PDF version of article.Includes bibliographical references leaves 126-143.Mesenchymal stem cells (MSCs) have the potential to differentiate into multiple cell types and immune privileged characteristics. These features make MSCs a hope in tissue engineering and cell based treatment applications. Tremendous amount of studies were carried out in order to produce an ideal biomaterial as a scaffold for cell transplantation. In recent studies, carbon nanotubes (CNT) were identified as a novel scaffold array due to their unique physical, chemical and electrical properties among the other biomaterials.The effect of estrogen hormone on the regulation of MSC maintenance, proliferation and differentiation was reported. However, its role in maintenance of MSCs on scaffold materials such as CNTs and the genetic and epigenetic regulation of MSC differentiation have not fully been elucidated. Therefore our aim was to examine the possible role of estrogen in the MSCs’ maintenance seeded on CNT surfaces and genetic and epigenetic regulation of the key transcription factors involved in adipogenic, osteogenic and chondrogenic differentiaton of MSCs. Our results revealed the enhanced effect of estrogen on the viability of MCSs which were seeded and incubated on multiwalled carbon nanotubes (MWCNT). In addition we demonstrated that passaging causes decrease of cell viability and the number of attached cells on CNT materials. We have also shown the effect of estrogen on the epigenetic and genetic regulation of MSC differentiation. Estrogen treatment decreased the expression of major adipogenic transcription factors; C/EBPα, FABP4, PPARγ, Adipsin and increased key osteogenic transcription factor RUNX2 in MSCs from both normal female and ovariectomized rats, suggesting inhibitory and stimulatory effect of estrogen on adipogenesis and osteogenesis respectively. We have also shown that the subcellular localization of PPARγ and ETS1 is changed in response to estrogen deficiency. Among modified histones, we found that H3K27me2, H3K27me3 and H3K36me2 protein levels were reduced after estrogen treatment both in female and ovariectomized animals. In addition, ChIP analysis showed that estrogen treatment caused an increase in H3K27me2, H3K27me3 and ERα levels at the promoters of C/EBPα, FABP4, PPARγ, Adipsin and RUNX2. Bisulfite sequencing analysis revealed that in the absence of estrogen, DNA hypermethylation was established in C/EBPα and PPARγ promoters whereas in ERα promoters CpG hypomethylation was observed after estrogen treatment. In conclusion, estrogen causes epigenetic and genetic changes in maintenace and differentiation of MSCs. Understanding the effect of estrogen on the genetic and epigenetic regulation of the major transcription factors may lead to clues for new treatment in chronic diseases such as obesity, osteoporosis and ostearthiritis.Bitirim, Ceylan Verd

    Increased free Zn2+ correlates induction of sarco(endo)plasmic reticulum stress via altered expression levels of Zn2+‐transporters in heart failure

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    Zn2+‐homoeostasis including free Zn2+ ([Zn2+]i) is regulated through Zn2+‐transporters and their comprehensive understanding may be important due to their contributions to cardiac dysfunction. Herein, we aimed to examine a possible role of Zn2+‐transporters in the development of heart failure (HF) via induction of ER stress. We first showed localizations of ZIP8, ZIP14 and ZnT8 to both sarcolemma and S(E)R in ventricular cardiomyocytes (H9c2 cells) using confocal together with calculated Pearson's coefficients. The expressions of ZIP14 and ZnT8 were significantly increased with decreased ZIP8 level in HF. Moreover, [Zn2+]i was significantly high in doxorubicin‐treated H9c2 cells compared to their controls. We found elevated levels of ER stress markers, GRP78 and CHOP/Gadd153, confirming the existence of ER stress. Furthermore, we measured markedly increased total PKC and PKCα expression and PKCα‐phosphorylation in HF. A PKC inhibition induced significant decrease in expressions of these ER stress markers compared to controls. Interestingly, direct increase in [Zn2+]i using zinc‐ionophore induced significant increase in these markers. On the other hand, when we induced ER stress directly with tunicamycin, we could not observe any effect on expression levels of these Zn2+ transporters. Additionally, increased [Zn2+]i could induce marked activation of PKCα. Moreover, we observed marked decrease in [Zn2+]i under PKC inhibition in H9c2 cells. Overall, our present data suggest possible role of Zn2+ transporters on an intersection pathway with increased [Zn2+]i and PKCα activation and induction of HF, most probably via development of ER stress. Therefore, our present data provide novel information how a well‐controlled [Zn2+]i via Zn2+ transporters and PKCα can be important therapeutic approach in prevention/treatment of HF

    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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