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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 吳金洌 | |
dc.contributor.author | Wei-Lun Wang | en |
dc.contributor.author | 汪惟倫 | zh_TW |
dc.date.accessioned | 2021-06-13T02:19:59Z | - |
dc.date.available | 2014-08-05 | |
dc.date.copyright | 2011-08-05 | |
dc.date.issued | 2011 | |
dc.date.submitted | 2011-08-01 | |
dc.identifier.citation | Adams, J. M. & S. Cory, (1998) The Bcl-2 protein family: arbiters of cell survival. Science (New York, N.Y 281: 1322-1326.
Altmann, S. M., M. T. Mellon, D. L. Distel & C. H. Kim, (2003) Molecular and functional analysis of an interferon gene from the zebrafish, Danio rerio. Journal of virology 77: 1992-2002. Ambros, V., (2004) The functions of animal microRNAs. Nature 431: 350-355. Bala, S., M. Marcos, K. Kodys, T. Csak, D. Catalano, P. Mandrekar & G. Szabo, (2011) Up-regulation of microRNA-155 in macrophages contributes to increased tumor necrosis factor {alpha} (TNF{alpha}) production via increased mRNA half-life in alcoholic liver disease. The Journal of biological chemistry 286: 1436-1444. Bartel, D. P., (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116: 281-297. Bazzoni, F., M. Rossato, M. Fabbri, D. Gaudiosi, M. Mirolo, L. Mori, N. Tamassia, A. Mantovani, M. A. Cassatella & M. Locati, (2009) Induction and regulatory function of miR-9 in human monocytes and neutrophils exposed to proinflammatory signals. Proceedings of the National Academy of Sciences of the United States of America 106: 5282-5287. Benedict, C. A., (2003) Viruses and the TNF-related cytokines, an evolving battle. Cytokine & growth factor reviews 14: 349-357. Benedict, C. A., T. A. Banks & C. F. Ware, (2003) Death and survival: viral regulation of TNF signaling pathways. Current opinion in immunology 15: 59-65. Benedict, C. A., P. S. Norris & C. F. Ware, (2002) To kill or be killed: viral evasion of apoptosis. Nat Immunol 3: 1013-1018. Berghe, T. V., N. Vanlangenakker, E. Parthoens, W. Deckers, M. Devos, N. Festjens, C. J. Guerin, U. T. Brunk, W. Declercq & P. Vandenabeele, (2010) Necroptosis, necrosis and secondary necrosis converge on similar cellular disintegration features. Cell death and differentiation 17: 922-930. Chen, P. C., J. L. Wu, G. M. Her & J. R. Hong, (2010) Aquatic birnavirus induces necrotic cell death via the mitochondria-mediated caspase pathway. Fish & shellfish immunology 28: 344-353. Chiu, C. L., J. L. Wu, G. M. Her, Y. L. Chou & J. R. Hong, (2010) Aquatic birnavirus capsid protein, VP3, induces apoptosis via the Bad-mediated mitochondria pathway in fish and mouse cells. Apoptosis. Choy, E. Y., K. L. Siu, K. H. Kok, R. W. Lung, C. M. Tsang, K. F. To, D. L. Kwong, S. W. Tsao & D. Y. Jin, (2008) An Epstein-Barr virus-encoded microRNA targets PUMA to promote host cell survival. J Exp Med 205: 2551-2560. Das, B. K., B. Collet, M. Snow & A. E. Ellis, (2007) Expression kinetics of ISG15 and viral major capsid protein (VP2) in Atlantic cod (Gadus morhua L.) fry following infection with infectious pancreatic necrosis virus (IPNV). Fish & shellfish immunology 23: 825-830. Degterev, A., J. Hitomi, M. Germscheid, I. L. Ch'en, O. Korkina, X. Teng, D. Abbott, G. D. Cuny, C. Yuan, G. Wagner, S. M. Hedrick, S. A. Gerber, A. Lugovskoy & J. Yuan, (2008) Identification of RIP1 kinase as a specific cellular target of necrostatins. Nat Chem Biol 4: 313-321. Der, S. D., A. Zhou, B. R. Williams & R. H. Silverman, (1998) Identification of genes differentially regulated by interferon alpha, beta, or gamma using oligonucleotide arrays. Proceedings of the National Academy of Sciences of the United States of America 95: 15623-15628. Dinarello, C. A., (1997) Interleukin-1. Cytokine & growth factor reviews 8: 253-265. Dobos, P., (1977) Virus-specific protein synthesis in cells infected by infectious pancreatic necrosis virus. Journal of virology 21: 242-258. Dobos, P., (1995) Protein-primed RNA synthesis in vitro by the virion-associated RNA polymerase of infectious pancreatic necrosis virus. Virology 208: 19-25. Dobos, P., B. J. Hill, R. Hallett, D. T. Kells, H. Becht & D. Teninges, (1979) Biophysical and biochemical characterization of five animal viruses with bisegmented double-stranded RNA genomes. Journal of virology 32: 593-605. Duncan, R., C. L. Mason, E. Nagy, J. A. Leong & P. Dobos, (1991) Sequence analysis of infectious pancreatic necrosis virus genome segment B and its encoded VP1 protein: a putative RNA-dependent RNA polymerase lacking the Gly-Asp-Asp motif. Virology 181: 541-552. Duncan, R., E. Nagy, P. J. Krell & P. Dobos, (1987) Synthesis of the infectious pancreatic necrosis virus polyprotein, detection of a virus-encoded protease, and fine structure mapping of genome segment A coding regions. Journal of virology 61: 3655-3664. Erkel, G., T. Anke & O. Sterner, (1996) Inhibition of NF-kappa B activation by panepoxydone. Biochemical and biophysical research communications 226: 214-221. Everett, H. & G. McFadden, (1999) Apoptosis: an innate immune response to virus infection. Trends in microbiology 7: 160-165. Farrow, S. N. & R. Brown, (1996) New members of the Bcl-2 family and their protein partners. Curr Opin Genet Dev 6: 45-49. Feldmann, M., (2008) Many cytokines are very useful therapeutic targets in disease. J Clin Invest 118: 3533-3536. Festjens, N., T. Vanden Berghe, S. Cornelis & P. Vandenabeele, (2007) RIP1, a kinase on the crossroads of a cell's decision to live or die. Cell death and differentiation 14: 400-410. Festjens, N., T. Vanden Berghe & P. Vandenabeele, (2006) Necrosis, a well-orchestrated form of cell demise: signalling cascades, important mediators and concomitant immune response. Biochim Biophys Acta 1757: 1371-1387. Fiers, W., R. Beyaert, W. Declercq & P. Vandenabeele, (1999) More than one way to die: apoptosis, necrosis and reactive oxygen damage. Oncogene 18: 7719-7730. Garner, J. N., B. Joshi & R. Jagus, (2003) Characterization of rainbow trout and zebrafish eukaryotic initiation factor 2alpha and its response to endoplasmic reticulum stress and IPNV infection. Developmental and comparative immunology 27: 217-231. Garofalo, M., G. L. Condorelli, C. M. Croce & G. Condorelli, (2010) MicroRNAs as regulators of death receptors signaling. Cell death and differentiation 17: 200-208. Garofalo, M., G. Di Leva, G. Romano, G. Nuovo, S. S. Suh, A. Ngankeu, C. Taccioli, F. Pichiorri, H. Alder, P. Secchiero, P. Gasparini, A. Gonelli, S. Costinean, M. Acunzo, G. Condorelli & C. M. Croce, (2009) miR-221&222 regulate TRAIL resistance and enhance tumorigenicity through PTEN and TIMP3 downregulation. Cancer Cell 16: 498-509. Goetz, F. W., J. V. Planas & S. MacKenzie, (2004) Tumor necrosis factors. Developmental and comparative immunology 28: 487-497. Gottwein, E. & B. R. Cullen, (2010) A human herpesvirus microRNA inhibits p21 expression and attenuates p21-mediated cell cycle arrest. Journal of virology 84: 5229-5237. Han, J. & B. Beutler, (1990) The essential role of the UA-rich sequence in endotoxin-induced cachectin/TNF synthesis. Eur Cytokine Netw 1: 71-75. Han, J., T. Brown & B. Beutler, (1990) Endotoxin-responsive sequences control cachectin/tumor necrosis factor biosynthesis at the translational level. J Exp Med 171: 465-475. Hayden, M. S. & S. Ghosh, (2004) Signaling to NF-kappaB. Genes Dev 18: 2195-2224. He, S., L. Wang, L. Miao, T. Wang, F. Du, L. Zhao & X. Wang, (2009) Receptor interacting protein kinase-3 determines cellular necrotic response to TNF-alpha. Cell 137: 1100-1111. Hedrick, R. P., N. Okamoto, T. Sano & J. L. Fryer, (1983) Biochemical characterization of eel virus european. J Gen Virol 64 (Pt 6): 1421-1426. Herman, B., A. L. Nieminen, G. J. Gores & J. J. Lemasters, (1988) Irreversible injury in anoxic hepatocytes precipitated by an abrupt increase in plasma membrane permeability. FASEB J 2: 146-151. Hirono, I., B. H. Nam, T. Kurobe & T. Aoki, (2000) Molecular cloning, characterization, and expression of TNF cDNA and gene from Japanese flounder Paralychthys olivaceus. J Immunol 165: 4423-4427. Hiscott, J., T. L. Nguyen, M. Arguello, P. Nakhaei & S. Paz, (2006) Manipulation of the nuclear factor-kappaB pathway and the innate immune response by viruses. Oncogene 25: 6844-6867. Hitomi, J., D. E. Christofferson, A. Ng, J. Yao, A. Degterev, R. J. Xavier & J. Yuan, (2008) Identification of a molecular signaling network that regulates a cellular necrotic cell death pathway. Cell 135: 1311-1323. Holland, M. C. & J. D. Lambris, (2002) The complement system in teleosts. Fish & shellfish immunology 12: 399-420. Holler, N., R. Zaru, O. Micheau, M. Thome, A. Attinger, S. Valitutti, J. L. Bodmer, P. Schneider, B. Seed & J. Tschopp, (2000) Fas triggers an alternative, caspase-8-independent cell death pathway using the kinase RIP as effector molecule. Nat Immunol 1: 489-495. Hong, J. R., H. Y. Gong & J. L. Wu, (2002) IPNV VP5, a novel anti-apoptosis gene of the Bcl-2 family, regulates Mcl-1 and viral protein expression. Virology 295: 217-229. Hong, J. R., B. J. Guan, G. M. Her, O. Evensen, N. Santi & J. L. Wu, (2008) Aquatic birnavirus infection activates the transcription factor NF-kappaB via tyrosine kinase signalling leading to cell death. Journal of fish diseases 31: 451-460. Hong, J. R., Y. L. Hsu & J. L. Wu, (1999a) Infectious pancreatic necrosis virus induces apoptosis due to down-regulation of survival factor MCL-1 protein expression in a fish cell line. Virus research 63: 75-83. Hong, J. R., L. J. Huang & J. L. Wu, (2005) Aquatic birnavirus induces apoptosis through activated caspase-8 and -3 in a zebrafish cell line. Journal of fish diseases 28: 133-140. Hong, J. R., T. L. Lin, Y. L. Hsu & J. L. Wu, (1998) Apoptosis precedes necrosis of fish cell line with infectious pancreatic necrosis virus infection. Virology 250: 76-84. Hong, J. R., T. L. Lin, J. Y. Yang, Y. L. Hsu & J. L. Wu, (1999b) Dynamics of nontypical apoptotic morphological changes visualized by green fluorescent protein in living cells with infectious pancreatic necrosis virus infection. Journal of virology 73: 5056-5063. Hong, J. R. & J. L. Wu, (2002) Induction of apoptotic death in cells via Bad gene expression by infectious pancreatic necrosis virus infection. Cell death and differentiation 9: 113-124. Huang, J., F. Wang, E. Argyris, K. Chen, Z. Liang, H. Tian, W. Huang, K. Squires, G. Verlinghieri & H. Zhang, (2007) Cellular microRNAs contribute to HIV-1 latency in resting primary CD4+ T lymphocytes. Nat Med 13: 1241-1247. Huang, Q., K. Gumireddy, M. Schrier, C. le Sage, R. Nagel, S. Nair, D. A. Egan, A. Li, G. Huang, A. J. Klein-Szanto, P. A. Gimotty, D. Katsaros, G. Coukos, L. Zhang, E. Pure & R. Agami, (2008) The microRNAs miR-373 and miR-520c promote tumour invasion and metastasis. Nat Cell Biol 10: 202-210. Huising, M. O., T. van der Meulen, G. Flik & B. M. Verburg-van Kemenade, (2004) Three novel carp CXC chemokines are expressed early in ontogeny and at nonimmune sites. European journal of biochemistry / FEBS 271: 4094-4106. Jenner, R. G. & R. A. Young, (2005) Insights into host responses against pathogens from transcriptional profiling. Nat Rev Microbiol 3: 281-294. Jeurissen, S. H., F. Wagenaar, J. M. Pol, A. J. van der Eb & M. H. Noteborn, (1992) Chicken anemia virus causes apoptosis of thymocytes after in vivo infection and of cell lines after in vitro infection. Journal of virology 66: 7383-7388. Jopling, C. L., S. Schutz & P. Sarnow, (2008) Position-dependent function for a tandem microRNA miR-122-binding site located in the hepatitis C virus RNA genome. Cell Host Microbe 4: 77-85. Jopling, C. L., M. Yi, A. M. Lancaster, S. M. Lemon & P. Sarnow, (2005) Modulation of hepatitis C virus RNA abundance by a liver-specific MicroRNA. Science (New York, N.Y 309: 1577-1581. Kain, S. R., K. Mai & P. Sinai, (1994) Human multiple tissue western blots: a new immunological tool for the analysis of tissue-specific protein expression. BioTechniques 17: 982-987. Karin, M. & A. Lin, (2002) NF-kappaB at the crossroads of life and death. Nat Immunol 3: 221-227. Kelly, R. K. & P. C. Loh, (1972) Electron microscopical and biochemical characterization of infectious pancreatic necrosis virus. Journal of virology 10: 824-834. Kerr, J. F., (1971) Shrinkage necrosis: a distinct mode of cellular death. J Pathol 105: 13-20. Khatri, M. & J. M. Sharma, (2006) Infectious bursal disease virus infection induces macrophage activation via p38 MAPK and NF-kappaB pathways. Virus research 118: 70-77. Kim, Y. S., M. J. Morgan, S. Choksi & Z. G. Liu, (2007) TNF-induced activation of the Nox1 NADPH oxidase and its role in the induction of necrotic cell death. Mol Cell 26: 675-687. Kobayashi, T., J. Lu, B. S. Cobb, S. J. Rodda, A. P. McMahon, E. Schipani, M. Merkenschlager & H. M. Kronenberg, (2008) Dicer-dependent pathways regulate chondrocyte proliferation and differentiation. Proceedings of the National Academy of Sciences of the United States of America 105: 1949-1954. Kumar, G., D. K. Srivastava & W. Tefera, (1994) A 70- to 80-kDa glial cell protein interacts with the AGGGAAGGGA domain of the JC virus early promoter only in the presence of the neighboring cis DNA elements. Virology 203: 116-124. Laing, K. J., T. Wang, J. Zou, J. Holland, S. Hong, N. Bols, I. Hirono, T. Aoki & C. J. Secombes, (2001) Cloning and expression analysis of rainbow trout Oncorhynchus mykiss tumour necrosis factor-alpha. European journal of biochemistry / FEBS 268: 1315-1322. Lambeth, L. S., Y. Yao, L. P. Smith, Y. Zhao & V. Nair, (2009) MicroRNAs 221 and 222 target p27Kip1 in Marek's disease virus-transformed tumour cell line MSB-1. J Gen Virol 90: 1164-1171. LaPatra, S. E., L. Barone, G. R. Jones & L. I. Zon, (2000) Effects of infectious hematopoietic necrosis virus and infectious pancreatic necrosis virus infection on hematopoietic precursors of the zebrafish. Blood cells, molecules & diseases 26: 445-452. Lawton, P., J. Nelson, R. Tizard & J. L. Browning, (1995) Characterization of the mouse lymphotoxin-beta gene. J Immunol 154: 239-246. Le, M. T., C. Teh, N. Shyh-Chang, H. Xie, B. Zhou, V. Korzh, H. F. Lodish & B. Lim, (2009) MicroRNA-125b is a novel negative regulator of p53. Genes Dev 23: 862-876. Lecellier, C. H., P. Dunoyer, K. Arar, J. Lehmann-Che, S. Eyquem, C. Himber, A. Saib & O. Voinnet, (2005) A cellular microRNA mediates antiviral defense in human cells. Science (New York, N.Y 308: 557-560. Lee, S. B., I. H. Bae, Y. S. Bae & H. D. Um, (2006) Link between mitochondria and NADPH oxidase 1 isozyme for the sustained production of reactive oxygen species and cell death. The Journal of biological chemistry 281: 36228-36235. Levitzki, A. & A. Gazit, (1995) Tyrosine kinase inhibition: an approach to drug development. Science (New York, N.Y 267: 1782-1788. Li, H., H. Zhu, C. J. Xu & J. Yuan, (1998) Cleavage of BID by caspase 8 mediates the mitochondrial damage in the Fas pathway of apoptosis. Cell 94: 491-501. Lin, Y., S. Choksi, H. M. Shen, Q. F. Yang, G. M. Hur, Y. S. Kim, J. H. Tran, S. A. Nedospasov & Z. G. Liu, (2004) Tumor necrosis factor-induced nonapoptotic cell death requires receptor-interacting protein-mediated cellular reactive oxygen species accumulation. The Journal of biological chemistry 279: 10822-10828. Liu, M. & V. N. Vakharia, (2006) Nonstructural protein of infectious bursal disease virus inhibits apoptosis at the early stage of virus infection. Journal of virology 80: 3369-3377. Locksley, R. M., N. Killeen & M. J. Lenardo, (2001) The TNF and TNF receptor superfamilies: integrating mammalian biology. Cell 104: 487-501. Luo, X., I. Budihardjo, H. Zou, C. Slaughter & X. Wang, (1998) Bid, a Bcl2 interacting protein, mediates cytochrome c release from mitochondria in response to activation of cell surface death receptors. Cell 94: 481-490. Macdonald, R. D., K. L. Roy, T. Yamamoto & N. Chang, (1977) Oligonucleotide fingerprints of the RNAs from infectious pancreatic necrosis virus. Arch Virol 54: 373-377. Madesh, M., B. Antonsson, S. M. Srinivasula, E. S. Alnemri & G. Hajnoczky, (2002) Rapid kinetics of tBid-induced cytochrome c and Smac/DIABLO release and mitochondrial depolarization. The Journal of biological chemistry 277: 5651-5659. Magyar, G. & P. Dobos, (1994) Evidence for the detection of the infectious pancreatic necrosis virus polyprotein and the 17-kDa polypeptide in infected cells and of the NS protease in purified virus. Virology 204: 580-589. Majno, G. & I. Joris, (1995) Apoptosis, oncosis, and necrosis. An overview of cell death. Am J Pathol 146: 3-15. Marzo, I., C. Brenner, N. Zamzami, J. M. Jurgensmeier, S. A. Susin, H. L. Vieira, M. C. Prevost, Z. Xie, S. Matsuyama, J. C. Reed & G. Kroemer, (1998) Bax and adenine nucleotide translocator cooperate in the mitochondrial control of apoptosis. Science (New York, N.Y 281: 2027-2031. Meeker, N. D. & N. S. Trede, (2008) Immunology and zebrafish: spawning new models of human disease. Developmental and comparative immunology 32: 745-757. Meurer, R. & D. E. MacIntyre, (1989) Lack of effect of pertussis toxin on TNF-alpha-induced formation of reactive oxygen intermediates by human neutrophils. Biochemical and biophysical research communications 159: 763-769. Morgan, M. J., Y. S. Kim & Z. G. Liu, (2008) TNFalpha and reactive oxygen species in necrotic cell death. Cell Res 18: 343-349. Motsch, N., T. Pfuhl, J. Mrazek, S. Barth & F. A. Grasser, (2007) Epstein-Barr virus-encoded latent membrane protein 1 (LMP1) induces the expression of the cellular microRNA miR-146a. RNA Biol 4: 131-137. Nahid, M. A., K. M. Pauley, M. Satoh & E. K. Chan, (2009) miR-146a is critical for endotoxin-induced tolerance: IMPLICATION IN INNATE IMMUNITY. The Journal of biological chemistry 284: 34590-34599. Nicholson, B. L. & J. Dunn, (1974) Homologous viral interference in trout and Atlantic salmon cell cultures infected with infectious pancreatic necrosis virus. Journal of virology 14: 180-182. Novogrodsky, A., A. Vanichkin, M. Patya, A. Gazit, N. Osherov & A. Levitzki, (1994) Prevention of lipopolysaccharide-induced lethal toxicity by tyrosine kinase inhibitors. Science (New York, N.Y 264: 1319-1322. Olsen, P. H. & V. Ambros, (1999) The lin-4 regulatory RNA controls developmental timing in Caenorhabditis elegans by blocking LIN-14 protein synthesis after the initiation of translation. Dev Biol 216: 671-680. Oltvai, Z. N., C. L. Milliman & S. J. Korsmeyer, (1993) Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell 74: 609-619. Otsuka, M., Q. Jing, P. Georgel, L. New, J. Chen, J. Mols, Y. J. Kang, Z. Jiang, X. Du, R. Cook, S. C. Das, A. K. Pattnaik, B. Beutler & J. Han, (2007) Hypersusceptibility to vesicular stomatitis virus infection in Dicer1-deficient mice is due to impaired miR24 and miR93 expression. Immunity 27: 123-134. Pedersen, I. M., G. Cheng, S. Wieland, S. Volinia, C. M. Croce, F. V. Chisari & M. David, (2007) Interferon modulation of cellular microRNAs as an antiviral mechanism. Nature 449: 919-922. Pfeffer, S., M. Zavolan, F. A. Grasser, M. Chien, J. J. Russo, J. Ju, B. John, A. J. Enright, D. Marks, C. Sander & T. Tuschl, (2004) Identification of virus-encoded microRNAs. Science (New York, N.Y 304: 734-736. Praveen, K., D. L. Evans & L. Jaso-Friedmann, (2006) Constitutive expression of tumor necrosis factor-alpha in cytotoxic cells of teleosts and its role in regulation of cell-mediated cytotoxicity. Molecular immunology 43: 279-291. Rager, K. J., J. O. Langland, B. L. Jacobs, D. Proud, D. G. Marsh & F. Imani, (1998) Activation of antiviral protein kinase leads to immunoglobulin E class switching in human B cells. Journal of virology 72: 1171-1176. Rahman, M. M. & G. McFadden, (2006) Modulation of tumor necrosis factor by microbial pathogens. PLoS pathogens 2: e4. Reinhart, B. J., F. J. Slack, M. Basson, A. E. Pasquinelli, J. C. Bettinger, A. E. Rougvie, H. R. Horvitz & G. Ruvkun, (2000) The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans. Nature 403: 901-906. Robertsen, B., V. Bergan, T. Rokenes, R. Larsen & A. Albuquerque, (2003) Atlantic salmon interferon genes: cloning, sequence analysis, expression, and biological activity. J Interferon Cytokine Res 23: 601-612. Roca, F. J., I. Mulero, A. Lopez-Munoz, M. P. Sepulcre, S. A. Renshaw, J. Meseguer & V. Mulero, (2008) Evolution of the inflammatory response in vertebrates: fish TNF-alpha is a powerful activator of endothelial cells but hardly activates phagocytes. J Immunol 181: 5071-5081. Santi, N., A. Sandtro, H. Sindre, H. Song, J. R. Hong, B. Thu, J. L. Wu, V. N. Vakharia & O. Evensen, (2005) Infectious pancreatic necrosis virus induces apoptosis in vitro and in vivo independent of VP5 expression. Virology 342: 13-25. Santi, N., V. N. Vakharia & O. Evensen, (2004) Identification of putative motifs involved in the virulence of infectious pancreatic necrosis virus. Virology 322: 31-40. Sato, A., A. Hiramoto, Y. Uchikubo, E. Miyazaki, A. Satake, T. Naito, O. Hiraoka, T. Miyake, H. S. Kim & Y. Wataya, (2008) Gene expression profiles of necrosis and apoptosis induced by 5-fluoro-2'-deoxyuridine. Genomics 92: 9-17. Scheurich, P., B. Thoma, U. Ucer & K. Pfizenmaier, (1987) Immunoregulatory activity of recombinant human tumor necrosis factor (TNF)-alpha: induction of TNF receptors on human T cells and TNF-alpha-mediated enhancement of T cell responses. J Immunol 138: 1786-1790. Schultz, J., R. R. Copley, T. Doerks, C. P. Ponting & P. Bork, (2000) SMART: a web-based tool for the study of genetically mobile domains. Nucleic Acids Res 28: 231-234. Schweichel, J. U. & H. J. Merker, (1973) The morphology of various types of cell death in prenatal tissues. Teratology 7: 253-266. Seet, B. T., J. B. Johnston, C. R. Brunetti, J. W. Barrett, H. Everett, C. Cameron, J. Sypula, S. H. Nazarian, A. Lucas & G. McFadden, (2003) Poxviruses and immune evasion. Annu Rev Immunol 21: 377-423. Shakibaei, M., G. Schulze-Tanzil, Y. Takada & B. B. Aggarwal, (2005) Redox regulation of apoptosis by members of the TNF superfamily. Antioxid Redox Signal 7: 482-496. Shen, H. M. & S. Pervaiz, (2006) TNF receptor superfamily-induced cell death: redox-dependent execution. FASEB J 20: 1589-1598. Shi, X. B., L. Xue, A. H. Ma, C. G. Tepper, H. J. Kung & R. W. White, (2011) miR-125b promotes growth of prostate cancer xenograft tumor through targeting pro-apoptotic genes. Prostate 71: 538-549. Spriggs, D. R., S. Deutsch & D. W. Kufe, (1992) Genomic structure, induction, and production of TNF-alpha. Immunol Ser 56: 3-34. Sullivan, C. & C. H. Kim, (2008) Zebrafish as a model for infectious disease and immune function. Fish & shellfish immunology 25: 341-350. Taganov, K. D., M. P. Boldin, K. J. Chang & D. Baltimore, (2006) NF-kappaB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses. Proceedings of the National Academy of Sciences of the United States of America 103: 12481-12486. Tili, E., J. J. Michaille, A. Cimino, S. Costinean, C. D. Dumitru, B. Adair, M. Fabbri, H. Alder, C. G. Liu, G. A. Calin & C. M. Croce, (2007) Modulation of miR-155 and miR-125b levels following lipopolysaccharide/TNF-alpha stimulation and their possible roles in regulating the response to endotoxin shock. J Immunol 179: 5082-5089. Ting, A. T., F. X. Pimentel-Muinos & B. Seed, (1996) RIP mediates tumor necrosis factor receptor 1 activation of NF-kappaB but not Fas/APO-1-initiated apoptosis. EMBO J 15: 6189-6196. Tomita, M., Y. Tanaka & N. Mori, (2009) MicroRNA miR-146a is induced by HTLV-1 tax and increases the growth of HTLV-1-infected T-cells. Int J Cancer. Traver, D., P. Herbomel, E. E. Patton, R. D. Murphey, J. A. Yoder, G. W. Litman, A. Catic, C. T. Amemiya, L. I. Zon & N. S. Trede, (2003) The zebrafish as a model organism to study development of the immune system. Adv Immunol 81: 253-330. van der Sar, A. M., B. J. Appelmelk, C. M. Vandenbroucke-Grauls & W. Bitter, (2004) A star with stripes: zebrafish as an infection model. Trends in microbiology 12: 451-457. Vanden Berghe, T., W. Declercq & P. Vandenabeele, (2007) NADPH oxidases: new players in TNF-induced necrotic cell death. Mol Cell 26: 769-771. Vandenabeele, P., W. Declercq & T. Vanden Berghe, (2008) Necrotic cell death and 'necrostatins': now we can control cellular explosion. Trends Biochem Sci 33: 352-355. Vandenabeele, P., W. Declercq, F. Van Herreweghe & T. Vanden Berghe, (2010) The role of the kinases RIP1 and RIP3 in TNF-induced necrosis. Sci Signal 3: re4. Wang, C. Y., M. W. Mayo, R. G. Korneluk, D. V. Goeddel & A. S. Baldwin, Jr., (1998) NF-kappaB antiapoptosis: induction of TRAF1 and TRAF2 and c-IAP1 and c-IAP2 to suppress caspase-8 activation. Science (New York, N.Y 281: 1680-1683. Wang, E., W. J. Ma, C. Aghajanian & D. R. Spriggs, (1997) Posttranscriptional regulation of protein expression in human epithelial carcinoma cells by adenine-uridine-rich elements in the 3'-untranslated region of tumor necrosis factor-alpha messenger RNA. Cancer Res 57: 5426-5433. Wang, L., F. Du & X. Wang, (2008) TNF-alpha induces two distinct caspase-8 activation pathways. Cell 133: 693-703. Wang, W. L., J. R. Hong, G. H. Lin, W. Liu, H. Y. Gong, M. W. Lu, C. C. Lin & J. L. Wu, (2011a) Stage-specific expression of TNFalpha regulates bad/bid-mediated apoptosis and RIP1/ROS-mediated secondary necrosis in Birnavirus-infected fish cells. PLoS One 6: e16740. Wang, W. L., W. Liu, H. Y. Gong, J. R. Hong, C. C. Lin & J. L. Wu, (2011b) Activation of cytokine expression occurs through the TNFalpha/NF-kappaB-mediated pathway in birnavirus-infected cells. Fish & shellfish immunology 31: 10-21. Wang, X., L. Ye, W. Hou, Y. Zhou, Y. J. Wang, D. S. Metzger & W. Z. Ho, (2009) Cellular microRNA expression correlates with susceptibility of monocytes/macrophages to HIV-1 infection. Blood 113: 671-674. Wolf, K. & J. A. Mann, (1980) Poikilotherm vertebrate cell lines and viruses: a current listing for fishes. In Vitro 16: 168-179. Wolf, K., S. F. Snieszko, C. E. Dunbar & E. Pyle, (1960) Virus nature of infectious pancreatic necrosis in trout. Proc Soc Exp Biol Med 104: 105-108. Wyllie, A. H., J. F. Kerr & A. R. Currie, (1980) Cell death: the significance of apoptosis. International review of cytology 68: 251-306. Yamaoka, S., G. Courtois, C. Bessia, S. T. Whiteside, R. Weil, F. Agou, H. E. Kirk, R. J. Kay & A. Israel, (1998) Complementation cloning of NEMO, a component of the IkappaB kinase complex essential for NF-kappaB activation. Cell 93: 1231-1240. Yang, E., J. Zha, J. Jockel, L. H. Boise, C. B. Thompson & S. J. Korsmeyer, (1995) Bad, a heterodimeric partner for Bcl-XL and Bcl-2, displaces Bax and promotes cell death. Cell 80: 285-291. Yeung, M. L., Y. Bennasser, T. G. Myers, G. Jiang, M. Benkirane & K. T. Jeang, (2005) Changes in microRNA expression profiles in HIV-1-transfected human cells. Retrovirology 2: 81. Yoshida, M., (2001) Multiple viral strategies of HTLV-1 for dysregulation of cell growth control. Annu Rev Immunol 19: 475-496. Zamzami, N. & G. Kroemer, (2001) The mitochondrion in apoptosis: how Pandora's box opens. Nat Rev Mol Cell Biol 2: 67-71. Zhang, D. W., J. Shao, J. Lin, N. Zhang, B. J. Lu, S. C. Lin, M. Q. Dong & J. Han, (2009) RIP3, an energy metabolism regulator that switches TNF-induced cell death from apoptosis to necrosis. Science (New York, N.Y 325: 332-336. Zeng, Y., R. Yi & B. R. Cullen, (2003) MicroRNAs and small interfering RNAs can inhibit mRNA expression by similar mechanisms. Proceedings of the National Academy of Sciences of the United States of America 100: 9779-9784. Zheng, L., N. Bidere, D. Staudt, A. Cubre, J. Orenstein, F. K. Chan & M. Lenardo, (2006) Competitive control of independent programs of tumor necrosis factor receptor-induced cell death by TRADD and RIP1. Mol Cell Biol 26: 3505-3513. Zhou, M., Z. Liu, Y. Zhao, Y. Ding, H. Liu, Y. Xi, W. Xiong, G. Li, J. Lu, O. Fodstad, A. I. Riker & M. Tan, (2010a) MicroRNA-125b confers the resistance of breast cancer cells to paclitaxel through suppression of pro-apoptotic Bcl-2 antagonist killer 1 (Bak1) expression. The Journal of biological chemistry 285: 21496-21507. Zhou, R., G. Hu, A. Y. Gong & X. M. Chen, (2010b) Binding of NF-kappaB p65 subunit to the promoter elements is involved in LPS-induced transactivation of miRNA genes in human biliary epithelial cells. Nucleic Acids Res 38: 3222-3232. Zhou, R., G. Hu, J. Liu, A. Y. Gong, K. M. Drescher & X. M. Chen, (2009) NF-kappaB p65-dependent transactivation of miRNA genes following Cryptosporidium parvum infection stimulates epithelial cell immune responses. PLoS pathogens 5: e1000681. Ziegelbauer, J. M., C. S. Sullivan & D. Ganem, (2009) Tandem array-based expression screens identify host mRNA targets of virus-encoded microRNAs. Nat Genet 41: 130-134. Zou, J., C. J. Secombes, S. Long, N. Miller, L. W. Clem & V. G. Chinchar, (2003) Molecular identification and expression analysis of tumor necrosis factor in channel catfish (Ictalurus punctatus). Developmental and comparative immunology 27: 845-858. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/30896 | - |
dc.description.abstract | 感染性胰臟壞死病毒(Infectious Pancreatic Necrosis Virus, IPNV)為兩段雙股核醣核酸病毒科(Birnaviridae)的魚類病毒,對漁撈及水產養殖上皆造成重大損失。過去研究發現,IPNV在感染魚類細胞後,可造成宿主細胞發生細胞凋亡(apoptosis)與細胞壞死(necrosis)的現象,此外抗細胞凋亡基因Mcl-1表現量下降而促細胞凋亡基因Bad表現量增加,並經由tyrosine kinase調控途徑活化下游的caspase-8與caspase-3,使被感染細胞走向細胞凋亡,但IPNV藉由何種機制調控並決定被感染宿主細胞走向細胞凋亡或細胞壞死的機制仍然並不清楚。
以斑馬魚微矩陣晶片組(oligo microarray)分析在斑馬魚胚胎細胞(ZF4)被IPNV感染6、12與24小時後,在免疫與細胞凋亡上轉錄表現改變的相關基因組,結果顯示腫瘤壞死因子α (TNFα)與多數促細胞凋亡(pro-apoptotic)的Bcl-2家族基因表現量在病毒感染初期即開始增加,進一步以腫瘤壞死因子α專一性的小片段干擾核醣核酸(siRNA)或其抑制劑tyrphostin AG-126處理細胞再感染病毒後,宿主細胞的死亡率與細胞凋亡的情形皆明顯下降,同時Bcl-2家族促細胞凋亡基因Bad與Bid的表現量以及caspase-3, -8與-9的活化情形都受到明顯的抑制。此外以腫瘤壞死因子α或促細胞壞死基因RIP-1專一性的siRNA及其抑制劑tyrphostin AG-126處理後,宿主細胞壞死比例與活性氧化物(ROS)的生成量也有明顯的下降情形。因此由研究結果可知,魚類細胞株在遭受感染性胰臟壞死病毒感染時,藉由活化腫瘤壞死因子α之途徑啟動細胞凋亡與壞死之機制以抵抗病毒之有效入侵。 以定量反轉錄聚合酶連鎖反應(quantitative real-time PCR)分析在IPNV感染後的斑馬魚胚胎細胞,在免疫反應及相關調節因子轉錄表現量上的改變,結果顯示包括ifna, ifng, mx, irf1, irf2, irf4, tnfa, tnfb, il-1b, il-15, il-26, ccl4與mmp家族基因被誘導表現,此外免疫調節因子cebpb, junb, nfkb, stat1, stat4與stat5表現量亦增加。進一步以軟體(Pathway Studio software)分析發現,腫瘤壞死因子α影響多數下游免疫與細胞素基因在IPNV感染後的表現量,將被感染細胞以腫瘤壞死因子α的siRNA或其專一性抑制劑tyrphostin AG-126處理後,轉錄因子NF-κB的表現量受到抑制,進一步研究發現干擾素與部份細胞間素的表現受到腫瘤壞死因子α與轉錄因子NF-κB連鎖途徑調控。 我們以斑馬魚微小核醣核酸微矩陣晶片組(microRNA microarray)與定量PCR分析IPNV所感染宿主細胞的microRNA表現量後發現,miR-132、miR-146a與miR-155的轉錄表現量增加,而miR-125b的表現量則在感染後下降。過去的研究發現miR-125b可藉由攻擊腫瘤壞死因子α的3端未轉譯區域 (3’-UTR) 降低其表現量。研究結果指出魚類細胞以miR-125 mimic處理後再感染病毒,腫瘤壞死因子α的表現量較未處理之細胞低,此外被感染後的宿主細胞凋亡與壞死的比例亦較未處理細胞為低。以miR-125b mimic處理後的細胞感染IPNV後,caspase的活化情形與活性氧化物的累積也受到抑制。因此我們的結果顯示miR-125b在病毒感染的宿主細胞中可作為腫瘤壞死因子α途徑引發細胞凋亡與壞死的負向調控者。 感染性胰臟壞死病毒之致病機制上,腫瘤壞死因子α的角色與功能至為重要,除了可調控宿主細胞的細胞凋亡與壞死之外,亦可藉由調控下游轉錄因子NF-κB增加免疫相關細胞間素或干擾素的表現,可在雙股RNA病毒的研究與防治上可提供更為有效的策略與應用。 | zh_TW |
dc.description.abstract | The infectious pancreatic necrosis virus (IPNV) belongs to the Birnaviridae family of viruses and causes acute contagious diseases in a number of economically important freshwater and marine fish. Previous studies have shown that IPNV induces both atypical apoptosis and secondary necrosis in fish cells. The expression of the survival factor Mcl-1 has been shown to be down-regulated and that of the pro-apoptotic bcl-2 family gene Bad has been shown to be up-regulated by IPNV. IPNV infection can trigger the tyrosine kinase-mediated death pathway and cause the activation of caspase-8 and -3 in virus-infected cells. IPNV can induce Bad-mediated apoptosis followed by secondary necrosis in fish cells, but it is not known how these two types of cell death are regulated by IPNV.
Using DNA microarray and quantitative RT-PCR analyses, two major subsets of differentially expressed genes were characterized, including the innate immune response gene TNFα and the pro-apoptotic genes Bad and Bid. In the early replication stage, we observed that the pro-inflammatory cytokine TNFα underwent a rapid six-fold induction. Then during the early-middle replication stages, the TNFα level was eight-fold higher, and the pro-apoptotic Bcl-2 family members Bad and Bid were also up-regulated. Specific inhibitors of TNFα expression (AG-126 or TNFα-specific siRNA) were used to block apoptotic and necrotic death signaling during the early or early-middle stages of IPNV infection. Inhibition of TNFα expression dramatically reduced the activity of the Bad/Bid-mediated apoptotic and Rip1/ROS-mediated necrotic cell death pathways and rescued host cell viability. The Rip1/ROS-mediated secondary necrotic pathway appeared to be reduced in IPNV-infected fish cells during the middle-late stage of infection. We also infected zebrafish embryonic (ZF4) cells with IPNV and analyzed the gene expression patterns of normal and infected cells using quantitative real-time PCR. We identified a number of immune response genes, including ifna, ifng, mx, irf1, irf2, irf4, tnfa, tnfb, il-1b, il-15, il-26, ccl4 and mmp family genes, that are induced after viral infection. Transcriptional regulators, including cebpb, junb, nfkb and stat1, stat4 and stat5, were also up-regulated in IPNV-infected cells. In addition, we used Pathway Studio software to identify TNFα as the factor with the greatest downstream influence among these altered genes. Treating virus-infected cells with an siRNA targeting TNFα inhibited NF-κB expression. To further interrupt the TNFα/NF-κB-mediated pathway, the expression levels of cytokines and metalloproteinases were inhibited in IPNV-infected cells. Using microRNA array and real-time quantitative PCR assays, the expression patterns of microRNAs in IPNV-infected fish cells were characterized during different replication stages of IPNV. We found that the gene transcription levels of miR-132, miR-146a and miR-155 were up-regulated, and miR-125b was down-regulated. Previous studies have shown that the 3’-untranslated regions of TNFα transcripts can be targeted by miR-125b. A miR-125b mimic or a TNFα-specific siRNA was able to down-regulate the expression of TNFα in IPNV-infected cells. Following miR-125b mimic treatment, the viability of IPNV-infected cells was increased. The percentages of apoptotic and necrotic IPNV-infected ZF4 cells that were pretreated with a miR-125b mimic or a TNFα-specific siRNA were decreased, as shown by fluorescence images of Annexin V-fluorescein and PI staining. The activation of caspase-3, -8, and -9 and the formation of ROS were inhibited following miR-125b mimic or TNFα-specific siRNA treatment of ZF4 cells infected with IPNV. Therefore, this work indicates that miR-125b is suppressed in response to IPNV and acts as a negative regulator of TNFα-mediated apoptosis and secondary necrosis induced by IPNV. Taken together, our results indicate that IPNV triggers two death pathways via upstream induction of the pro-inflammatory cytokine TNFα and that the expression of cytokines and metalloproteinases might be initiated through the TNFα/NF-κB-mediated pathway. TNFα plays important roles in cell death and immune responses during IPNV infection. These results may provide new insights into the pathogenesis of RNA viruses. | en |
dc.description.provenance | Made available in DSpace on 2021-06-13T02:19:59Z (GMT). No. of bitstreams: 1 ntu-100-D91243001-1.pdf: 2050935 bytes, checksum: 76bf7b43610ad6f31492f1162d063cc9 (MD5) Previous issue date: 2011 | en |
dc.description.tableofcontents | Contents ………………………………………………… i
List of Tables ………………………………………………… viii List of Figures ………………………………………………… ix List of Appendix ………………………………………………… xiv Abstract ………………………………………………… xv Chapter 1. Introduction………………………………………………...... 1 1.1 Infectious pancreatic necrosis virus……………………. 1 1.1.1 Biophysical and biochemical characteristics of IPNV………………………………………………. 1 1.1.2 Function of viral proteins…………………………. 1 1.1.3 Atypical apoptosis and secondary necrosis induced by IPNV………………………………… 2 1.1.4 Zebrafish as a infectious model animal of IPNV... 4 1.2 Mechanism of apoptosis and necrosis………………….. 4 1.2.1 Mechanism of apoptosis…………………………... 5 1.2.2 Mechanism of necrosis……………………………. 6 1.3 Tumor Necrosis Fector (TNF)…………………………. 7 1.3.1 Tumor Necrosis Factor Receptor 1 (TNFR1)......... 7 1.3.2 TNFα-mediated anti-microbial responses……….. 8 1.4 microRNA………………………………………………... 10 1.4.1 Cellular microRNAs and viruses…………………. 11 1.4.2 Virus-encoded microRNAs...................................... 12 1.5 Objectives and specific aims……………………………. 12 1.5.1 Stage-specific expression of TNFα regulates Bad/Bid-mediated apoptosis and RIP1/ROS- mediated secondary necrosis in birnavirus- infected fish cells…................................................ 12 1.5.2 Suppression of microRNA-125b in response to IPNV infection leads to TNFα-mediated apoptosis…………………………………………... 13 1.5.3 Activation of cytokine expression occurs through the TNFα/NF-κB-mediated pathway in birnavirus-infected cells………………………….. 14 Chapter 2. Materials and methods……………………………………... 15 2.1 Cells and viruses………………………………………… 15 2.2 Reagents………………………………………………….. 15 2.3 Cell viability assays ……………………………………... 16 2.4 Western blot……………………………………………... 16 2.5 Annexin V-FITC and PI labeling………………………. 17 2.6 RNA preparation………………………………………... 18 2.7 Microarray preparation………………………………… 18 2.8 Microarray hybridization………………………………. 19 2.9 Microarray data analyses ……………............................ 20 2.10 Quantitative real-time PCR of mRNA………………... 20 2.11 Knockdown of TNFα and RIP1 by RNA interference.. 21 2.12 Caspase activity assays………………………………… 22 2.13 Intracellular ROS detection…………………………… 22 2.14 Small RNA extraction…………………………………. 23 2.15 MicroRNA microarray hybridization………………... 23 2.16 MicroRNA microarray data analyses………………… 24 2.17 Quantitative real-time PCR for microRNA………….. 24 2.18 Treatment with miR-125b mimic or inhibitor……….. 25 2.19 Real-time cell proliferation analysis………………….. 25 2.20 Treatment with the TNFα-specific inhibitor tyrphostin AG-126…………………………………... 26 2.21 Treatment with the TNFα inducer lipopolysaccharide 26 2.22 Treatment with the NF-κB-specific inhibitor panepoxydone…………………………………………. 27 2.23 Statistical analyses……………………………………... 27 Chapter 3. Results………………………………………………………... 28 3.1 Stage-specific expression of TNFα regulates Bad/Bid-mediated apoptosis and RIP1/ROS- mediated secondary necrosis in birnavirus-infected fish cells…………………………………………………. 28 3.1.1 IPNV-induced gene expression profiles in zebrafish embryonic cells……………………….. 28 3.1.2 Blockade of TNFα-mediated death signals enhances host cell viability……………………… 30 3.1.3 Recognition of a TNFα-mediated death signal may regulate the expression of the pro-apoptotic genes bad and bid………………... 31 3.1.4 A TNFα-mediated death signal may induce apoptosis and activate caspases………………… 32 3.1.5 A TNFα-mediated death signal may regulate the apoptotic and secondary necrotic death pathway during the middle stage of replication…………... 33 3.2 Suppression of microRNA-125b in response to IPNV infection leads to TNFα-mediated apoptosis…………... 35 3.2.1 Expression profiles of microRNAs after IPNV infection or LPS treatment………………………. 35 3.2.2 Expression patterns of immune response-related microRNAs after IPNV infection………………... 37 3.2.3 The expression of TNFα is inhibited by a miR-125b mimic…………………………………. 38 3.2.4 The miR-125b mimic down-regulates TNFα during IPNV infection……………………………. 39 3.2.5 miR-125b mimic enhances host cell viability following IPNV infection…………………………. 39 3.2.6 miR-125b inhibits apoptotic and secondary necrotic cell death………………………………… 40 3.2.7 miR-125b decreases caspase activation and ROS formation………………………………………….. 41 3.3 Activation of cytokine expression occurs through the TNFα/NF-κB-mediated pathway in birnavirus -infected cells…………………………………………… 42 3.3.1 Zebrafish embryonic cells infected by IPNV……. 42 3.3.2 Upregulation of immune response genes in IPNV-infected cells………………………………... 42 3.3.3 Upregulation of cytokines and metalloproteinases after IPNV infection in zebrafish cells…………... 43 3.3.4 Transcriptional regulators were upregulated or downregulated after IPNV infection…………….. 44 3.3.5 TNFα is effectively suppressed by TNFα-specific siRNA or tyrphostin AG-126…………………….. 44 3.3.6 TNFα is crucial to the activation of NF-κB in IPNV-infected cells………………………………... 45 3.3.7 Cytokine activation occurs through the TNFα/NF-κB pathway…………………………... 46 Chapter 4. Discussion…………………………………………………… 48 4.1 Stage-specific expression of TNFα regulates Bad/Bid-mediated apoptosis and RIP1/ROS- mediated secondary necrosis in birnavirus-infected fish cells………………………………………………... 48 4.1.1 The zebrafish as a model animal system to examine pathogen-induced transcriptomes…….. 48 4.1.2 Multiple pro-apoptotic death genes are involved in cell death………………………………………... 49 4.1.3 Up-regulation of Bcl-xL following infection with a pathogen………………………………………….. 50 4.1.4 TNFα-mediated apoptosis and necrosis pathway.. 51 4.2 Suppression of microRNA-125b in response to IPNV infection leads to TNFα-mediated apoptosis…………... 54 4.2.1 IPNV-induced apoptosis and secondary necrosis suppressed by miR-125b mimic………………….. 54 4.2.2 Cellular microRNAs serve as regulators in pathogen infection……………………………….. 56 4.2.3 miR-125b acts as a negative regulator of TNFα-mediated cell death………………………... 57 4.3 Activation of cytokine expression occurs through the TNFα/NF-κB-mediated pathway in birnavirus -infected cells…………………………………………….. 58 4.3.1 Innate immune response and cytokine activation activated in IPNV-infected cells………………….. 59 4.3.2 TNFα plays an important role in the pathogenesis of virus or bacteria………………………………... 60 4.3.3 The feedback mechanism between TNFα and NF-κB……………………………………………… 61 Chapter 5. Future perspectives………………………………………….. 63 5.1 Conclusions………………………………………………. 63 5.2 Perspectives……………………………………………… 65 Chapter 6. Reference…………………………………………………….. 68 | |
dc.language.iso | en | |
dc.title | 雙股RNA病毒經由腫瘤壞死因子α (TNFα) 調控宿主細胞表現細胞素與細胞凋亡之途徑 | zh_TW |
dc.title | Tumor Necrosis Factor α regulates cell apoptosis and cytokine expression in the pathogenesis of birnavirus | en |
dc.type | Thesis | |
dc.date.schoolyear | 99-2 | |
dc.description.degree | 博士 | |
dc.contributor.oralexamcommittee | 趙裕展,陳士隆,洪健睿,陳志毅,陳俊任,邱品文 | |
dc.subject.keyword | 感染性胰臟壞死病毒,斑馬魚,腫瘤壞死因子α,細胞凋亡,細胞壞死,微小核醣核酸, | zh_TW |
dc.subject.keyword | IPNV,zebrafish,TNFα,apoptosis,necrosis,microRNA, | en |
dc.relation.page | 188 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2011-08-01 | |
dc.contributor.author-college | 生命科學院 | zh_TW |
dc.contributor.author-dept | 漁業科學研究所 | zh_TW |
顯示於系所單位: | 漁業科學研究所 |
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