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기도상피세포에서 17β-estradiol에 의한 MUC5B 유전자 발현의 신호전달
No full textDept. of Medicine/박사[한글]
MUC5B는 사람의 호흡기에서 주요 점액 성분의 하나이나 여러 기도질환에서 그 발현의 조절기전은 잘 알려져 있지 않다. 본 연구에서는 estradiol이 어떤 기전을 통하여 사람 코점막상피세포와 NCI-H292 세포에서 MUC5B 유전자 발현을 유도하는지 알아보고자 하였다. 17β-estradiol (E2)은 성호르몬으로 estrogen receptor α (ERα)와 결합하여 ERK-MAP kinase (MAPK)를 통하여 MUC5B 유전자 발현을 자극하였다. E2와 함께 ER길항제인 ICI 182, 780을 투여하면 E2에 의해 유도되는 ERK-MAPK 활성과 MUC5B 유전자의 발현이 모두 억제되었다. E2는 주요 MAP kinase중 p38과 JNK는 활성화시키지 않았으나 ERK1/2는 활성화시켰고 MEK1 길항제인 PD98059를 투여하였을 때 E2에 의한 ERK1/2활성과 MUC5B mRNA발현이 모두 억제되었다. 또한 siRNA로 ERK1 이나 ERK2를 knockdown시켰을 때E2에 의한 ERK1, ERK2의 활성과 MUC5B mRNA발현이 모두 억제되었다. Ras와 Raf의 dominant-negative construct로 transient transfection 시킨 세포에서도 E2에 의한 ERK1/2의 활성과 MUC5B mRNA발현이 모두 억제되었다. siRNA로 RSK1을 knockdown시켰을 때 E2에 의한 MUC5B mRNA발현이 억제되었다. siRNA로 CREB을 knockdown시켰을 때 E2에 의한 MUC5B mRNA발현이 억제되었다.일련의 MUC5B promoter construct를 제작하여 luciferase assay를 시행한 결과, -956bp 에서 -649bp사이에 존재하는 cAMP-response element (CRE) site가 ERK-MAPK 를 통한MUC5B 유전자 발현에 중요하다는 것을 알 수 있었다. E2를 처리하였을 때CREB이 -956bp에서 -753bp사이의 MUC5B promotor에 결합하는 것을 ChIP assay를 통하여 확인할 수 있었다. CREB은 또한 CRE site에 CREB- binding protein (CBP) 과 steroid receptor coactivator-1 (SRC-1)과 함께 결합하여 histone acetrylation과 MUC5B 유전자 발현을 증가시켰다. 따라서 17β-estradiol은 기도상피세포에서 estrogen receptor, Ras, Raf, MEK1, ERK1/2 MAPK, RSK1로 신호가 전달되며 CREB이 CBP, SRC-1과 함께 MUC5B promoter에 결합하여 MUC5B 유전자 발현을 유도한다.
[영문]
MUC5B is a major mucin of the human respiratory tract, and it is not clear how MUC5B expression is regulated in various airway diseases. The goal of this study was to determine the mechanisms by which E2 induces MUC5B gene expression in airway epithelial cells. It was found that 17-estradiol (E2), a sex hormone, stimulate MUC5B gene overexpression by interaction with estrogen receptor (ER ) and by acting through ERK-MAP kinase (MAPK). Co-treatment with E2 and ER antagonist ICI 182,780 blocked both E2-induced ERK-MAPK activation and MUC5B gene expression. It was also found that the activation of p90 ribosomal S 6 protein kinase 1 (RSK1), cAMP-response element-binding protein (CREB) and cAMP-response element (CRE) (-956 region of the MUC5B promoter) responsive signaling cascades via ERK-MAPK are crucial at the mediation MUC5B gene expression. This study further showed that CREB was recruited to CRE together with CREB- binding protein (CBP) and steroid receptor coactivator-1 (SRC-1). This coincided with increased histone H3 acetylation (AcH3) and up-regulation of MUC5B gene expression. Taken together, these studies give additional insights into the molecular mechanism of hormone-induced MUC5B gene expression and enhance our understanding of abnormal mucin secretion in response to hormonal imbalances.ope
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe 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
Full text link“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
Full text linkWe 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
Full text linkWe 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
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe 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
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
Author Under Sail The Imagination of Jack London, 1893-1902
No full textIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Intro -- Title Page -- Copyright Page -- Dedication -- Contents -- Acknowledgments -- Introduction -- 1. Spirit Truth -- 2. From Absorption to Theatricality and Back Again -- 3. "I Will Build a New Present" -- 4. Sons as Authors -- 5. Fathers as Publishers -- 6. The Daughter as Author -- 7. Lovers as Authors -- 8. At Sea with the Family -- 9. Yellow News, Yellow Stories -- 10. The Return Home -- Notes -- Bibliography -- Index -- About Jay WilliamsIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Description based on publisher supplied metadata and other sources.Electronic reproduction. Ann Arbor, Michigan : ProQuest Ebook Central, YYYY. Available via World Wide Web. Access may be limited to ProQuest Ebook Central affiliated libraries
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