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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
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dc.contributor.advisor | 蕭信宏(Shin-Hong Shiao) | |
dc.contributor.author | Chia-Hao Chang | en |
dc.contributor.author | 張家豪 | zh_TW |
dc.date.accessioned | 2021-06-08T01:12:18Z | - |
dc.date.copyright | 2014-10-09 | |
dc.date.issued | 2014 | |
dc.date.submitted | 2014-08-15 | |
dc.identifier.citation | Anders, R. F., Adda, C. G., Foley, M. and Norton, R. S. (2010) 'Recombinant protein vaccines against the asexual blood stages of Plasmodium falciparum', Hum Vaccin 6(1): 39-53.
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(2008) 'Alternate hypothesis on the pathogenesis of dengue hemorrhagic fever (DHF)/dengue shock syndrome (DSS) in dengue virus infection', Exp Biol Med (Maywood) 233(4): 401-8. Olsauskas-Kuprys, R., Zlobin, A. and Osipo, C. (2013) 'Gamma secretase inhibitors of Notch signaling', Onco Targets Ther 6: 943-55. Pallavi, S. K., Ho, D. M., Hicks, C., Miele, L. and Artavanis-Tsakonas, S. (2012) 'Notch and Mef2 synergize to promote proliferation and metastasis through JNK signal activation in Drosophila', EMBO J 31(13): 2895-907. Park, J. H., Attardo, G. M., Hansen, I. A. and Raikhel, A. S. (2006) 'GATA factor translation is the final downstream step in the amino acid/target-of-rapamycin-mediated vitellogenin gene expression in the anautogenous mosquito Aedes aegypti', J Biol Chem 281(16): 11167-76. Pierfelice, T. J., Schreck, K. C., Eberhart, C. G. and Gaiano, N. (2008) 'Notch, neural stem cells, and brain tumors', Cold Spring Harb Symp Quant Biol 73: 367-75. Raikhel, A. (1992) Vitellogenesis in Mosquitoes. in K. Harris (ed.) Advances in Disease Vector Research, vol. 9: Springer New York. Raikhel, A. S. and Dhadialla, T. S. (1992) 'Accumulation of Yolk Proteins in Insect Oocytes', Annual Review of Entomology 37(1): 217-251. Raikhel, A. S., Kokoza, V. A., Zhu, J., Martin, D., Wang, S. F., Li, C., Sun, G., Ahmed, A., Dittmer, N. and Attardo, G. (2002) 'Molecular biology of mosquito vitellogenesis: from basic studies to genetic engineering of antipathogen immunity', Insect Biochem Mol Biol 32(10): 1275-86. Raikhel, A. S. and Lea, A. O. (1983) 'Previtellogenic development and vitellogenin synthesis in the fat body of a mosquito: an ultrastructural and immunocytochemical study', Tissue Cell 15(2): 281-99. Ranganathan, P., Weaver, K. L. and Capobianco, A. J. (2011) 'Notch signalling in solid tumours: a little bit of everything but not all the time', Nat Rev Cancer 11(5): 338-51. Rono, M. K., Whitten, M. M., Oulad-Abdelghani, M., Levashina, E. A. and Marois, E. (2010) 'The major yolk protein vitellogenin interferes with the anti-plasmodium response in the malaria mosquito Anopheles gambiae', PLoS Biol 8(7): e1000434. Sastre, M., Steiner, H., Fuchs, K., Capell, A., Multhaup, G., Condron, M. M., Teplow, D. B. and Haass, C. (2001) 'Presenilin-dependent gamma-secretase processing of beta-amyloid precursor protein at a site corresponding to the S3 cleavage of Notch', EMBO Rep 2(9): 835-41. Sirot, L. K., Hardstone, M. C., Helinski, M. E., Ribeiro, J. M., Kimura, M., Deewatthanawong, P., Wolfner, M. F. and Harrington, L. C. (2011) 'Towards a semen proteome of the dengue vector mosquito: protein identification and potential functions', PLoS Negl Trop Dis 5(3): e989. Suzanne, M., Perrimon, N. and Noselli, S. (2001) 'The Drosophila JNK pathway controls the morphogenesis of the egg dorsal appendages and micropyle', Dev Biol 237(2): 282-94. Tolle, M. A. (2009) 'Mosquito-borne diseases', Curr Probl Pediatr Adolesc Health Care 39(4): 97-140. Unni, S. K., Ruzek, D., Chhatbar, C., Mishra, R., Johri, M. K. and Singh, S. K. (2011) 'Japanese encephalitis virus: from genome to infectome', Microbes Infect 13(4): 312-21. WHO. (2012) ' 2012 World Malaria Report. '. Wolter, J. (2013) 'The Notch Signaling Pathway in Embryogenesis', Embryo Project Encyclopedia. Xu, J. and Gridley, T. (2012) 'Notch Signaling during Oogenesis in Drosophila melanogaster', Genet Res Int 2012: 648207. Zecchini, V., Brennan, K. and Martinez-Arias, A. (1999) 'An activity of Notch regulates JNK signalling and affects dorsal closure in Drosophila', Curr Biol 9(9): 460-9. Zhu, X., Zhang, J., Tollkuhn, J., Ohsawa, R., Bresnick, E. H., Guillemot, F., Kageyama, R. and Rosenfeld, M. G. (2006) 'Sustained Notch signaling in progenitors is required for sequential emergence of distinct cell lineages during organogenesis', Genes Dev 20(19): 2739-53. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/18569 | - |
dc.description.abstract | 蚊子是許多重要傳染疾病的媒介,例如瘧疾、登革熱、黃熱病、西尼羅病毒熱、絲蟲病等。然而其中只有黃熱病已發展出疫苗,而且現有的抗瘧疾藥物也逐漸開始產生抗藥性,因此,藉由控制病媒蚊的數量以減緩疾病傳播的替代性策略是現今努力的目標之一。在蚊子的生活史中,蚊卵產出後需要經過一段時間,卵殼才會黑化及硬化,以保護其內的胚胎。在本實驗室先前的研究中發現,當我們以RNAi的方式抑制埃及斑蚊Notch的表現,會造成部分的卵無法黑化及硬化,此外不論這些卵黑化與否,絕大部分的卵皆無法順利孵化。在哺乳類動物及果蠅的研究中發現Notch是一個高度保留的訊息傳遞路徑,在胚胎發育與決定細胞分化扮演重要的角色。過去的研究證實,典型的Notch訊息傳遞路徑是藉由配體 (ligand)與受體 (receptor) Notch相互結合後,引發Notch被切割,再進一步與下游的CSL共同調控下游基因的表現,而近年的文獻也指出Notch可以在無配體結合的情況下,或是不需要CSL的參與,即可誘發下游基因的表現,但詳細的調控機制至今仍不清楚。因此我們在本研究中想深入探討埃及斑紋Notch調控蚊子生殖能力的分子機制。我們使用Notch訊息路徑的抑制劑來抑制Notch訊息路徑的活化,結果顯示卵殼的黑化與卵的孵化率皆受到明顯抑制,但我們以RNAi的方式分別抑制Notch的配體 (Delta和Serrate) 與下游的轉錄因子CSL,結果卻發現對卵殼黑化無明顯影響。因此我們推測Notch調控卵殼黑化及胚胎發育可能經由非典型的Notch訊息路徑。因此,我們使用JNK的抑制劑來抑制JNK的磷酸化,結果發現卵殼的黑化受到明顯抑制。此外,過去文獻指出,參與卵殼黑化硬化的卵殼過氧化酵素 (chorion peroxidase) 可催化卵殼上酪胺酸 (tyrosine) 的相互鍵結,而我們以JNK抑制劑處理蚊子後,其所產出黑化受到明顯抑制的卵,我們發現其卵殼過氧化酵素的活性有明顯下降的情形。未來我們將進一步釐清Notch調控卵殼黑化及胚胎發育的詳細分子機制,本研究成果將有助於制定蚊媒疾病防治的新策略。 | zh_TW |
dc.description.abstract | Notch signaling pathway is an evolutionary highly conserved cell-cell signaling pathway. Notch acts as both transmembrane receptor and transcription activator. In canonical pathway, Notch is activated after the binding of ligand to the extracellular domain. This specific binding induces proteolytic cleavage and release of the intracellular domain (Notch intracellular domain, NICD). The binding of NICD to the transcription factor, such as CSL, leads to the activation of target genes. It has been reported that Notch signaling may activate through a ligand or CSL independent (non-canonical) mechanism. However, its detail mechanism remains largely unknown. Our previous results demonstrated that silencing of Notch in the mosquito Aedes aegypti resulted in significant inhibition of egg tanning and hatching rate. In this study, we attempted to further investigate the detail regulation machinery of Notch signaling in the reproduction of Aedes aegypti. To further confirm the role of Notch signaling in egg tanning and embryogenesis, we made use of DAPT, a Notch signaling inhibitor, to examine the effect on mosquito reproduction. To elucidate the role of non-canonical Notch signal in the mosquito reproduction, a non-canonical pathway factor (JNK) was inhibited by SP600125 to examine the effect on egg tanning. Our results showed that inhibition of JNK activity resulted in the reduction of egg tanning and hatching rate. Interestingly, the activity of chorion peroxidase, which catalyzing chorion protein cross-linking during chorion hardening, was also reduced in non-tanning eggs. In the future, we will investigate the non-canonical Notch-mediated mosquito reproduction. Data revealed by this study will be crucial for future study on vector competence and vector control in the field. | en |
dc.description.provenance | Made available in DSpace on 2021-06-08T01:12:18Z (GMT). No. of bitstreams: 1 ntu-103-R01445202-1.pdf: 7190294 bytes, checksum: b02595011c5a2d6028d5099cab344903 (MD5) Previous issue date: 2014 | en |
dc.description.tableofcontents | Acknowledgement i
中文摘要 iii Abstract iv Table of Contents vi List of Figures xi List of Tables xiv Chapter 1. Introduction 1 1.1 Mosquito-borne diseases 1 1.1.1 Malaria 3 1.1.2 Dengue fever 5 1.2 Life cycle of Aedes aegypti 6 1.3 Vitellogenesis of mosquitoes 7 1.4 Notch signaling pathway 9 1.5 Chorion hardening 11 1.6 Research aim and hypothesis 12 Chapter 2. Materials and Methods 13 2.1 Materials and methods 13 2.1.1 Rearing and blood feeding of Aedes aegypti 13 2.1.2 RNA extraction 14 2.1.3. Reverse transcription (RT) 15 2.1.4. Polymerase chain reaction (PCR) 15 2.1.5. Quantitative polymerase chain reaction (Q-PCR) 16 2.1.6. Double-stranded RNA preparation 17 2.1.7. RNAi-mediated silencing and evaluation of silencing efficiency 19 2.1.8. Kinase inhibitor injection 20 2.1.9. Western blot analysis 20 2.1.10. Hatching assay 21 2.1.11. Scanning electron microscopy 22 2.2 Reagents 22 2.2.1 10% sugar solution 22 2.2.2 Avertin 23 2.2.3 LB broth 23 2.2.4 Ammonium acetate stop solution 23 Chapter 3. Results 24 3.1 The protein expression of Notch intracellular domain (NICD) after a blood meal 24 3.2 Notch silencing reduced the transcription levels of vitellogenin in female mosquitoes. 25 3.3 Treatment of γ-secretase inhibitor, DAPT, resulted in the reduced egg production with Notch silencing mosquitoes. 26 3.4 Treatment of γ-secretase inhibitor, DAPT, resulted in the decreasing melanization rate with Notch silencing mosquitoes. 27 3.5 Treatment of γ-secretase inhibitor, DAPT, resulted in the decreasing hatching rate with Notch silencing mosquitoes. 28 3.6 Treatment of γ-secretase inhibitor, DAPT, resulted in the collapsed micorpyle structure under SEM with Notch silencing mosquitoes. 29 3.7 Silencing of components of Notch signaling pathway does not affect the egg production. 30 3.8 Silencing of components of Notch signaling pathway does not affect the melanization rate. 30 3.9 Silencing of components of Notch signaling pathway does not affect the hatching rate. 31 3.10 JNK phoshorylation inhibition leaded to reduced egg production of female mosquitoes. 32 3.11 JNK phoshorylation inhibition leaded to reduced egg melanization of female mosquitoes. 33 3.12 JNK phoshorylation inhibition leaded to reduced egg hatching rates of female mosquitoes. 34 3.13 JNK phoshorylation inhibition affected micropyle structure of eggs. 35 3.14 JNK phoshorylation inhibition affected eggs fertility. 36 3.15 The effect of JNK phosphorylation rate in female mosquitoes treated with DAPT. 36 3.16 The melanization rates of eggs in complementation of JNK phosphorylation by Puc silencing. 37 3.17 Both DAPT and SP600125 treatments affected the length of eggs. 38 3.18 Egg chorion peroxidase activity of female mosquitoes injected with JNK inhitor blocking JNK phoshorylation 39 Chapter 4. Discussion 41 4.1 The expression of Notch in the mosquito Aedes aegypti. 41 4.2 Notch silencing reduced vitellogenin expressions affecting egg production. 42 4.3 The inhibition of Notch signaling pathway through DAPT treatment resulted in the similar phenotypes of Notch silencing mosquitoes. 43 4.4 Non-canonical Notch signaling pathway regulated the reproduction of mosquitoes. 44 4.5 Proposed mechanism of non-canonical Notch signaling pathway in mosquito Aedes aegypti. 48 Figures 50 Tables 82 References 84 | |
dc.language.iso | en | |
dc.title | 非典型Notch訊息調控埃及斑蚊卵殼黑化之研究 | zh_TW |
dc.title | A non-canonical Notch signaling regulates egg melanization in the mosquito Aedes aegypti | en |
dc.type | Thesis | |
dc.date.schoolyear | 102-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 張俊哲(Chun-che Chang),余明俊(Ming-Jiun Yu) | |
dc.subject.keyword | 埃及斑蚊,Notch,JNK,黑化,卵殼過氧化酵素, | zh_TW |
dc.subject.keyword | Aedes aegypti,Notch,JNK,melanization,chorion peroxidase, | en |
dc.relation.page | 92 | |
dc.rights.note | 未授權 | |
dc.date.accepted | 2014-08-15 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 微生物學研究所 | zh_TW |
顯示於系所單位: | 微生物學科所 |
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