1,721,396 research outputs found

    The control of ribosomal RNA synthesis in mammalian cells

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    The biogenesis of ribosomes is a fundamental process that occurs in all living cells. In mammalian cells, it is a highly complex process consisting of the coordinated synthesis and assembly of four ribosomal RNAs (rRNAs) with about 80 ribosomal proteins (RPs). More than 150 non-ribosomal proteins are involved in the processing of rRNAs. The main focus of this project is to use adult rat ventricular cardiomyocytes (ARVCs) as a model to address how mTOR complex 1 (mTORC1) and other signalling pathways regulate the synthesis of rRNAs.A new technique has been developed to monitor the synthesis of new rRNAs using 4-thiouridine (4-SU) and I have applied it in both HeLa cells and heart muscle cells to study the control of ribosome synthesis. HeLa cells were treated with different mTOR inhibitors to identify effects on the transcription and/or decay of rRNA. We analysed both the synthesis rate and the decay rate of new RNAs made by Pol I and Pol III using real-time RT-PCR. Interestingly, rapamycin not only blocked the synthesis of 18S, 28S and 5S rRNA, but also induced the decay of newly synthesized rRNAs. This demonstrates that mTORC1 regulates Pol I and Pol III transcription, as well as the decay of rRNA.In cardiomyocytes, hypertrophic agents such as phenylephrine (PE) strongly activate protein synthesis and lead to heart cell growth. The boost of protein synthesis drives the increase of cell size and leads to hypertrophy. Cardiac hypertrophy (CH) is a major risk factor for heart failure. Therefore, it is important to understand the mechanisms that how hypertrophic agents which cause the overgrowth of heart muscle increase ribosome production. Although it is known that inhibiting mTORC1 largely blocks the rapid activation of protein synthesis by PE, here it did not affect the synthesis of new 18S rRNAs. However, inhibitors of the MEK/Erk pathway and p90RSK each block the new rRNA synthesis. These data reveal that, in contrast to many other types of cell, ribosome biogenesis is controlled by MEK/ERK/p90RSK signalling, not mTORC1, in cardiomyocytes. Taken together, the data presented here may provide cues for potential valuable therapy of cardiac left ventricular hypertrophy

    CUHK electronic theses & dissertations collection

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    by Zhang Ze Sheng."October 2001."Thesis (Ph.D.)--Chinese University of Hong Kong, 2001.Includes bibliographical references (p. 157-174).Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web.Mode of access: World Wide Web.Abstracts in English and Chinese

    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

    p90RSKs mediate the activation of ribosomal RNA synthesis by the hypertrophic agonist phenylephrine in adult cardiomyocytes

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    Cardiac hypertrophy involves the growth of heart muscle cells and is driven by faster protein synthesis which involves increased ribosome biogenesis. However, the signaling pathways that link hypertrophic stimuli to faster ribosome production remain to be identified.Here we have investigated the signaling pathways which promote ribosomal RNA synthesis in cardiomyocytes in response to hypertrophic stimulation. We employed a new non-radioactive labeling approach and show that the hypertrophic agent phenylephrine (PE) stimulates synthesis of 18S rRNA (made by RNA polymerase I) and 5S rRNA (produced by RNA polymerase III) in adult cardiomyocytes. In many settings, rRNA synthesis is driven by rapamycin-sensitive signaling through mammalian target of rapamycin complex 1 (mTORC1). However, the activation of rRNA synthesis by PE is not inhibited by rapamycin, indicating that its regulation involves other signaling pathways.PE stimulates MEK/ERK signaling in these cells. Inhibition of this pathway blocks the ability of PE to activate synthesis of 18S and 5S rRNA. Furthermore, BI-D1870, an inhibitor of the p90RSKs, protein kinases which are activated by ERK, blocks PE-activated rRNA synthesis, as did a second p90RSK inhibitor, SL0101. BI-D1870 also inhibits the PE-stimulated association of RNA polymerase I with the rRNA promoter.These findings show that signaling via MEK/ERK/p90RSK, not mTORC1, drives rRNA synthesis in adult cardiomyocytes undergoing hypertrophy. This is important both for our understanding of the mechanisms that control ribosome production and, potentially, for the management of cardiac hypertrophy

    Vibration control of a semiactive vehicle suspension system based on extended state observer techniques

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    A feedback control method based on an extended state observer (ESO) method is implemented to vibration reduction in a typical semiactive suspension (SAS) system using a magnetorheological (MR) damper as actuator. By considering the dynamic equations of the SAS system and the MR damper model, an active disturbance rejection control (ADRC) is designed based on the ESO. Numerical simulation and real-time experiments are carried out with similar vibration disturbances. Both the simulation and experimental results illustrate the effectiveness of the proposed controller in vibration suppression for a SAS system. © 2014 Ze Zhang et al

    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
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