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Induction of Early Growth Response (Egr)-1 by Epstein-Barr Virus Lytic Transactivator Zta
No full textEB病毒的生活史中存在兩種狀態：潛伏期和溶裂期。根據過去的研究，當EB病毒進入溶裂期時可能造成細胞的改變。為了解溶裂期進行時對於細胞環境的影響，我們實驗室使用微矩陣分析法偵測先前建立的293A潛伏期與溶裂期細胞株中，並比較細胞基因表現之差異。結果發現，相較於潛伏期細胞，溶裂期細胞中可以偵測到較高量的Egr-1基因產物。利用西方墨點分析實驗，證實溶裂期細胞中Egr-1蛋白質質表現確實高於潛伏期細胞中。另一方面，在使用針對Zta專一性之siRNA表現質體(siZ1)抑制溶裂期發生時，即無法偵測到Egr-1蛋白質質量增高的現象。據此，推測當細胞中的EB病毒進入溶裂期時可引發Egr-1蛋白質質表現量上升。為進一步探討Egr-1蛋白質質量之增加是否受到病毒溶裂期基因產物的影響，利用單一基因轉染的方式將溶裂期病毒蛋白質質表現於不含EB病毒的細胞株中，並偵測Egr-1蛋白質質之表現。由實驗結果得知，在NPC-TW01和NPC-TW04細胞中，Zta蛋白質質可明顯促進細胞中Egr-1蛋白質量增加。同樣地，在先前實驗室所建立之Zta誘發性細胞株(HONE-1-52)也觀察到相同結果。進一步，利用報導質體實驗分析，也能證實Zta可以轉活化Egr-1啟動子之活性。根據以上結果得知，Zta蛋白質可以利用轉錄層級的機制調控Egr-1基因，並促進其蛋白質之表現。為了解Zta啟動Egr-1基因的詳細機制，利用一系列Egr-1啟動子的刪除突變報導質體進行分析，發現啟動子上–503bp~–438bp和–438bp~–395bp的區域對於Zta活化Egr-1啟動子而言是重要的。根據過去文獻記載以及利用軟體分析後知道-452bp~-438bp區域中存在兩個可能的ZREs (Zta response elements)，而-431bp~-407bp間存在一Elk-1/SRF結合位置。另一方面，由過去研究Egr-1基因的調控，已知細胞受到血清或者生長因子的刺激下，可以藉由活化的Ras/Raf/Mek/Erk/Elk訊息路徑啟動Egr-1基因表現。有趣的是，在HONE-1-52細胞中，Zta確實可使Erk蛋白質的磷酸化的程度增加。而加入Erk抑制劑時，即使Zta蛋白質表現也無法有效活化Egr-1基因，代表Erk的磷酸化對於Zta啟動Egr-1基因而言相當重要。綜合以上結果，EB病毒溶裂期轉活化子Zta可能藉由直接與啟動子之結合以及間接活化Erk訊息誘發細胞中Egr-1基因之表現。然而，就目前為止，Zta所引發的Egr-1蛋白質表現其生物功能仍然未知，需要日後投入更多的研究工作以探討之。Epstein-Barr virus (EBV) contains two phases in its life cycle: latent and lytic stages. According to previous studies, the progression of lytic cycle may affect many cellular events. To address this issue, we performed a microarray analysis on two groups of EBV-infected 293 cells that were distinguished into latent and lytic clones. We found that the expression of early growth response-1 (Egr-1), a zinc finger transcription factor, was increased in lytic clones, but not in latent clones. Immunoblot analysis confirmed that Egr-1 protein expression was associated with EBV lytic cycle. Zta is an immediate-early protein encoded by BZLF1 gene and plays a significant role to initiate viral lytic cascades. By using BZLF1-targetd siRNA to block EBV lytic progression, the expression of Egr-1 protein was reduced. Therefore, we suggested that the expression of Egr-1 protein was the downstream event of EBV lytic cycle. Furthermore, by using single gene transfection assay, we identified that Zta could induce Egr-1 protein expression in two EBV-negative cell lines, NPC-TW01 and NPC-TW04. In addition, in a Zta-inducible cell line (HONE-1-52), Egr-1 protein was also induced during Zta expression. As the regulator of EBV lytic cycle, Zta also affects the cellular gene expression at transcriptional level either by directly binding to a consensus DNA sequence or indirectly activating cellular signaling pathways. According to the reporter assays, Zta could activate Egr-1 promoter. By analysis of the deletion mutants of Egr-1 promoter, two regions relative to the transcriptional start site, -503bp~-438bp and –438bp~-395bp, were proven to critical for Zta-mediated activation. These two promoter regions contained putative ZREs (Zta response elements) and Elk-1/SRF binding site, respectively. The Elk-1/SRF binding site was crucial for Egr-1 gene expression upon Ras/Raf/Mek/Erk/Elk signaling pathway triggered by serum and many growth factors. Interestingly, Zta could dramatically increase the phosphorylattion status of Erk-1 protein in our study. In the presence of Erk phosphorylation inhibitos, PD98059 and U0126, Zta-induced Egr-1 protein expression was decreased significantly. Taken together, we demonstrate that the EBV lytic transactivator Zta can induce the expression of cellular Egr-1 gene, and the mechanism is dependent on direct DNA binding and indirect Erk signal activation. The biological meanings of Zta-induced Egr-1 protein remain be investigated in future study.摘要 ................................................. I
Abstract ............................................ III
目錄 ................................................ V
序論 ................................................. 1
EB病毒 ............................................... 1
發現歷史，病毒分類以及相關疾病 ....................... 1
EB病毒結構以及基因體 ................................. 2
EB病毒生活史 ......................................... 2
Zta蛋白質............................................. 4
基因調控 ............................................. 4
蛋白質結構與功能 ...................................... 5
Egr-1蛋白質 ........................................... 7
發現歷史 .............................................. 7
蛋白質結構 ............................................ 7
基因調控 .............................................. 8
EB病毒溶裂期與Egr-1蛋白質 ............................. 9
目的 .................................................. 10
材料 .................................................. 11
藥品 (Chemicals) ...................................... 11
套裝試劑 (Kits) ....................................... 12
抗體 (Antibodies) ..................................... 13
溶液 (Solutions) ...................................... 13
方法 .................................................. 15
細胞 (Cells) ........................................ 15
細胞培養以及處理 (Cell culture and treatments)....... 15
質體 (Plasmids) .................................... 16
建構Egr-1啟動子之刪除突變質體 (Construction of the deletion mutants of
Egr-1 promoter) ..................................... 16
製備大量質體DNA (Preparation of plasmid DBNA in large scale) ............... 17
暫時性轉染 (Transient transfection) ................ 19
西方墨點分析法 (Immunoblot analysis) ............... 19
報導基因分析 (Reporter gene assay) ................. 20
結果 ................................................. 22
討論 ................................................. 29
表與圖 ............................................... 34
參考文獻 ............................................. 5
Going Beyond Counting First Authors in Author Co-citation Analysis
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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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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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