M.B.A. / Please refer to full text to view abstract

在不同的模型體系和疾病microRNA-199a (miR-199a)的功能和基因表達都不盡相同而且相當複雜。它在人基因組中有個表達位點，分別是位於19 號染色體的miR-199a-1 和1 號染色體的miR-199a-2。這個位點可以產生相同的miRNA (miR-199a-3p 和miR-199a-5p)。造成miR-199a不同表達和功能的原因尚未清楚。但是，很有可能是由於個位點不同的調節機制和miR-199a 在不同的細胞和組織中可變的作用对象。在睾丸生殖細胞腫瘤(簡稱睾丸癌)和膠質母細胞瘤(簡稱膠質瘤)中研究miR-199a 的啟動子甲基化發現，在睾丸癌中miR-199a-1 和-2 共同的啟動子過甲基化導致miR-199a 表達低。而在膠質瘤中，只有miR-199a-2，而不是miR-199a-1 的啟動子低甲基化與miR-199a 的高表達相關。除啟動子甲基化，在幹細胞分化過程中升高表達的miR-199a 被證實是通過轉因子Twist1 的調控；循环通Twist1-miR-199a-5p-HIF1α控制miR-199a-5p 促進成骨分化的作用。miR-199a 的功能是通過其下游目標 (靶基因) 而成的。因此, 目標分子的功能控制miR-199a 在同的模型體系和疾病中的作用。我應用基因組學和蛋白組學的方法尋找miR-199a-5p 在睾丸癌中的下游目標(靶基因)。MAFB 被指出和證明是miR-199a-5p 在睾丸癌中的靶基因，而miR-199a 抗腫瘤細胞增殖活性的作用是通過MAFB 發揮的。通過研究miR-199a 在用系統中的調控機制和作用目標，我希望用miR-199a 作為模型明miRNA 生物學的複雜多樣性。 / microRNA-199a (miR-199a) has been shown to have diverse biological functions and behave quite differently in different physiological systems and diseases. It is encoded by two loci in the human genome, miR-199a-1 in chromosome 19 and miR-199a-2 in chromosome 1. Both loci give rise to the same miRNAs (miR-199a-5p and miR-199a-3p). The underlying mechanism responsible for the diverse action of the miRNA is not clear. However, it is likely contributed by differential regulation of the two genomic loci and variable targets of the miRNA in different cells and tissues. Studies on the promoter methylation of miR-199a in testicular germ cell tumors (TGCTs) and glioblastomas (gliomas) demonstrated that hypermethylation of both loci of miR- 199a resulted in its reduced expression in TGCTs, while hypomethylation of miR-199a-2 but not -1 in gliomas might lead to its elevated expression. In addition to DNA methylation, the functions of transcription factors in controlling the expression of miR-199a through a Twist1- miR-199a-5p-HIF1α cyclic pathway were demonstrated to play significant roles during me nchymal stem cell differentiation. The functions of miR-199a are mediated by the actions of its downstream targets. Both genomic and proteomic approaches were applied to study the targets of miR-199a-5p in TGCTs. A putative target of miRNA-199a-5p, MAFB, was identified and confirmed to be responsible for the anti-tumor proliferation activity of the microRNA. By studying the mechanisms that control the expressions of miR-199a and its various downstream targets in different systems, it is hoped that miR-199a could be used as a model to illustrate the complexity of miRNA biology. / Detailed summary in vernacular field only. / Gu, Shen. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2013. / Includes bibliographical references (leaves 144-163). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts also in Chinese. / Abstract --- p.I / 摘要 --- p.II / Acknowledgements --- p.III / Abbreviations --- p.VIII / Chapter 1 --- p.1 / Chapter 1.1 --- miRNAs - small yet powerful molecules --- p.2 / Chapter 1.1.1 --- Biogenesis and processing of miRNA --- p.2 / Chapter 1.1.2 --- Detection of miRNA expression --- p.7 / Chapter 1.1.3 --- Identification of putative miRNA targets --- p.11 / Chapter 1.2 --- miR-199a - an example revealing the complexity of the miRNA world --- p.19 / Chapter 1.2.1 --- miR-199a - standing out among thousands --- p.19 / Chapter 1.2.2 --- Regulation of miR-199a expression --- p.20 / Chapter 1.2.3 --- miR-199a in carcinogenesis --- p.24 / Chapter 1.2.4 --- miR-199a in cardiogenesis --- p.33 / Chapter 1.2.5 --- miR-199a in stem cell differentiation and embryo development --- p.34 / Chapter 1.2.6 --- Other functions of miR-199a --- p.35 / Chapter 1.3 --- Project overview --- p.38 / Chapter 2 --- p.39 / Chapter 2.1 --- Introduction --- p.40 / Chapter 2.2 --- Materials and methods --- p.42 / Chapter 2.3 --- Results --- p.49 / Chapter 2.3.1 --- Dysregulation of miR-199a in tumors were controlled by DNA methylation --- p.49 / Chapter 2.3.2 --- Transcriptome changes upon miR-199a-5p in TGCTs --- p.58 / Chapter 2.3.3 --- Identification of MAFB as a putative target of miR-199a-5p in TGCTs --- p.63 / Chapter 2.3.4 --- MAFB is highly expressed in malignant testicular tumor and negatively correlated with miR-199a-5p --- p.67 / Chapter 2.3.5 --- MAFB knockdown suppresses tumor cell growth in vitro --- p.69 / Chapter 2.4 --- Discussion --- p.70 / Chapter 3 --- p.75 / Chapter 3.1 --- Introduction --- p.76 / Chapter 3.2 --- Materials and methods --- p.81 / Chapter 3.3 --- Results --- p.86 / Chapter 3.3.1 --- Expression of miR-199a during MSC osteogenesis --- p.86 / Chapter 3.3.2 --- Functions of miR-199a on osteogenesis of hMSCs --- p.90 / Chapter 3.3.3 --- Involvement of HIF1α, Twist1 and miR-199a-5p during osteogenesis of hMSC at early stage and late stage of differentiation --- p.94 / Chapter 3.3.4 --- Up-regulation of miR-199a-5p was related to hypoxia enhanced osteogenesis at early stage --- p.99 / Chapter 3.3.5 --- miR-199a-5p inhibited HIF1α-Twist1 pathway to increase osteogenesis at late stage --- p.103 / Chapter 3.4 --- Discussion --- p.107 / Chapter 4 --- p.111 / Chapter 4.1 --- Overview of the project --- p.112 / Chapter 4.2 --- Summary and conclusion --- p.115 / Chapter 4.3 --- Future work --- p.116 / Chapter Supplementary Materials --- p.117 / Chapter Supplementary Table 2.1 --- p.118 / Chapter Supplementary Table 2.2 --- p.129 / Chapter Supplementary Table 2.3 --- p.142 / References --- p.144

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Thesis (M.B.A.)--Boston University / PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you. / 2031-01-01

Lun Miu-chi. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2004. / Includes bibliographical references (leaves 37-42). / Abstracts in English and Chinese. / Acknowledgment --- p.i / Table of contents --- p.ii / Abstract --- p.iv / Chapter Chapter 1: --- Introduction / Relationship Harmony --- p.1 / Previous Research on Relationship Harmony --- p.1 / Relationship Harmony in Groups --- p.3 / The Five-Factor Model of Personality and Relationship Harmony --- p.5 / "Relationship Harmony, Interpersonal Attraction, and Group Cohesiveness" --- p.8 / "Relational Experiences, Group Cohesiveness, and Group Performance" --- p.11 / The Nonindependence Issue --- p.12 / Chapter Chapter 2: --- Method / Participants --- p.14 / Measures --- p.14 / Analytical Strategy --- p.17 / Chapter Chapter 3: --- Results / Table 1: Descriptive statistics of the variables Self-report RH --- p.18 / Table 2: Correlation matrix of the variables --- p.19 / Table 3: Results regarding self-report RH Other-given RH --- p.20 / Table 4: Results regarding other-given RH Self-report Liking --- p.22 / Table 5: Results regarding self-report liking Other-given Liking --- p.24 / Table 6: Results regarding other-given liking Individual's Attraction to Group --- p.24 / Table 7: Results regarding individual's attraction to the group Perception of Group Integration --- p.26 / Table 8: Results regarding perception of group integration Group Performance Outcome --- p.27 / Table 9: Results regarding the mediating role of group integration between group relationship harmony and group performance --- p.29 / Chapter Chapter 4: --- Discussion / Personality Correlates of Relationship Harmony and Interpersonal Attraction --- p.30 / "Relationship Harmony, Interpersonal Attraction, and Group Cohesiveness" --- p.33 / "Relational Constructs, Group Cohesiveness, and Group Performance" --- p.34 / Future Research Direction --- p.35 / Reference --- p.37 / Appendixes / Chapter Appendix 1: --- The Interpersonal Liking Scale --- p.43 / Chapter Appendix 2: --- The Group Interaction Measure --- p.44

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This research is a case study based on an entrepreneurship located in Henderson, Kentucky called HorseFeathers Gifts. HorseFeathers Gifts supplies handmade, vintage-inspired jewelry and accessories to customers all over the world. The case study documents the path taken by HorseFeathers Gifts’ owners, showing exactly how the entrepreneurship reached the successful position that it currently holds. Based on the case studies available and a review of the literature, it is apparent that no other case studies like this one exist. Information for this case was gathered by interviewing both owners of HorseFeathers Gifts. The interviews helped me to learn about the business’ story from the day it was first engendered until the present day. This case study displays the business’ processes, successes, and failures, and ultimately gives struggling or aspiring entrepreneurs advice on how to better their own chances of business survival.

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1 / Xiaoye Su