請用此 Handle URI 來引用此文件:
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/77843
完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 吳益群(Yi-Chun Wu) | |
dc.contributor.author | Yen-Ling Chang | en |
dc.contributor.author | 張宴菱 | zh_TW |
dc.date.accessioned | 2021-07-11T14:35:52Z | - |
dc.date.available | 2022-09-04 | |
dc.date.copyright | 2017-09-04 | |
dc.date.issued | 2017 | |
dc.date.submitted | 2017-08-20 | |
dc.identifier.citation | Ahmadian, M., Abbott, M.J., Tang, T., Hudak, C.S., Kim, Y., Bruss, M., Hellerstein, M.K., Lee, H.-Y., Samuel, V.T., and Shulman, G.I. (2011). Desnutrin/ATGL is regulated by AMPK and is required for a brown adipose phenotype. Cell metabolism 13, 739-748.
Ashrafi, K. (2007). Obesity and the regulation of fat metabolism. Bartz, R., Li, W.-H., Venables, B., Zehmer, J.K., Roth, M.R., Welti, R., Anderson, R.G., Liu, P., and Chapman, K.D. (2007a). Lipidomics reveals that adiposomes store ether lipids and mediate phospholipid traffic. Journal of lipid research 48, 837-847. Bartz, R., Zehmer, J.K., Zhu, M., Chen, Y., Serrero, G., Zhao, Y., and Liu, P. (2007b). Dynamic activity of lipid droplets: protein phosphorylation and GTP-mediated protein translocation. Journal of proteome research 6, 3256-3265. Beller, M., Sztalryd, C., Southall, N., Bell, M., Jäckle, H., Auld, D.S., and Oliver, B. (2008). COPI complex is a regulator of lipid homeostasis. PLoS biology 6, e292. Bezaire, V., Mairal, A., Ribet, C., Lefort, C., Girousse, A., Jocken, J., Laurencikiene, J., Anesia, R., Rodriguez, A.-M., and Ryden, M. (2009). Contribution of adipose triglyceride lipase and hormone-sensitive lipase to lipolysis in hMADS adipocytes. Journal of Biological Chemistry 284, 18282-18291. Brooks, K.K., Liang, B., and Watts, J.L. (2009). The influence of bacterial diet on fat storage in C. elegans. PloS one 4, e7545. Chakrabarti, P., English, T., Karki, S., Qiang, L., Tao, R., Kim, J., Luo, Z., Farmer, S.R., and Kandror, K.V. (2011). SIRT1 controls lipolysis in adipocytes via FOXO1-mediated expression of ATGL. Journal of lipid research 52, 1693-1701. Chen, S., Whetstine, J.R., Ghosh, S., Hanover, J.A., Gali, R.R., Grosu, P., and Shi, Y. (2009). The conserved NAD(H)-dependent corepressor CTBP-1 regulates Caenorhabditis elegans life span. Proceedings of the National Academy of Sciences of the United States of America 106, 1496–1501. Cunningham, K.A., Bouagnon, A.D., Barros, A.G., Lin, L., Malard, L., Romano-Silva, M.A., and Ashrafi, K. (2014). Loss of a neural AMP-activated kinase mimics the effects of elevated serotonin on fat, movement, and hormonal secretions. PLoS genetics 10, e1004394. Daval, M., Diot-Dupuy, F., Bazin, R., Hainault, I., Viollet, B., Vaulont, S., Hajduch, E., Ferré, P., and Foufelle, F. (2005). Anti-lipolytic action of AMP-activated protein kinase in rodent adipocytes. Journal of Biological Chemistry 280, 25250-25257. Duncan, R.E., Wang, Y., Ahmadian, M., Lu, J., Sarkadi-Nagy, E., and Sul, H.S. (2010). Characterization of desnutrin functional domains: critical residues for triacylglycerol hydrolysis in cultured cells. Journal of lipid research 51, 309-317. Gaidhu, M.P., Fediuc, S., Anthony, N.M., So, M., Mirpourian, M., Perry, R.L., and Ceddia, R.B. (2009). Prolonged AICAR-induced AMP-kinase activation promotes energy dissipation in white adipocytes: novel mechanisms integrating HSL and ATGL. Journal of lipid research 50, 704-715. Gauthier, M.-S., Miyoshi, H., Souza, S.C., Cacicedo, J.M., Saha, A.K., Greenberg, A.S., and Ruderman, N.B. (2008). AMP-activated protein kinase is activated as a consequence of lipolysis in the adipocyte potential mechanism and physiological relevance. Journal of Biological Chemistry 283, 16514-16524. Granneman, J.G., Moore, H.-P.H., Krishnamoorthy, R., and Rathod, M. (2009). Perilipin controls lipolysis by regulating the interactions of AB-hydrolase containing 5 (Abhd5) and adipose triglyceride lipase (Atgl). Journal of Biological Chemistry 284, 34538-34544. Guo, Y., Walther, T.C., Rao, M., Stuurman, N., Goshima, G., Terayama, K., Wong, J.S., Vale, R.D., Walter, P., and Farese Jr, R.V. (2008). Functional genomic screen reveals genes involved in lipid-droplet formation and utilization. Nature 453, 657. Haemmerle, G., Moustafa, T., Woelkart, G., Büttner, S., Schmidt, A., Van De Weijer, T., Hesselink, M., Jaeger, D., Kienesberger, P.C., and Zierler, K. (2011). ATGL-mediated fat catabolism regulates cardiac mitochondrial function via PPAR-[alpha] and PGC-1. Nature medicine 17, 1076-1085. Haynes, C.M., Petrova, K., Benedetti, C., Yang, Y., and Ron, D. (2007). ClpP mediates activation of a mitochondrial unfolded protein response in C. elegans. Developmental cell 13, 467-480. Jeong, P.Y., Kwon, M.S., Joo, H.J., and Paik, Y.K. (2009) Molecular Time-Course and the Metabolic Basis of Entry into Dauer in Caenorhabditis elegans. PloS one 4, e4162. Jo, H., Shim, J., Lee, J.H., Lee, J. and Kim, J.B. (2009) IRE-1 and HSP-4 contribute to energy homeostasis via fasting-induced lipases in C. elegans. Cell metabolism 9, 440–448. Jump, D.B., and Clarke, S.D. (1999). Regulation of gene expression by dietary fat. Annual review of nutrition 19, 63-90. Klapper, M., Ehmke, M., Palgunow, D., Böhme, M., Matthäus, C., Bergner, G., Dietzek, B., Popp, J., and Döring, F. (2011). Fluorescence-based fixative and vital staining of lipid droplets in Caenorhabditis elegans reveal fat stores using microscopy and flow cytometry approaches. Journal of lipid research 52, 1281-1293. Kraemer, F.B., and Shen, W.-J. (2002). Hormone-sensitive lipase control of intracellular tri-(di-) acylglycerol and cholesteryl ester hydrolysis. Journal of lipid research 43, 1585-1594. Lass, A., Zimmermann, R., Oberer, M., and Zechner, R. (2011). Lipolysis–a highly regulated multi-enzyme complex mediates the catabolism of cellular fat stores. Progress in lipid research 50, 14-27. Lee, J.H., Kong, J., Jang, J.Y., Han, J.S., Ji, Y., Lee, J., and Kim, J.B. (2014). Lipid droplet protein LID-1 mediates ATGL-1-dependent lipolysis during fasting in Caenorhabditis elegans. Molecular and cellular biology 34, 4165-4176. Liu, Z., Li, X., Ge, Q., Ding, M., and Huang, X. (2014). A lipid droplet-associated GFP reporter-based screen identifies new fat storage regulators in C. elegans. Journal of Genetics and Genomics 41, 305-313. MacNeil, L.T., Watson, E., Arda, H.E., Zhu, L.J., and Walhout, A.J. (2013). Diet-induced developmental acceleration independent of TOR and insulin in C. elegans. Cell 153, 240-252. McKay, R.M., McKay, J.P., Avery, L., and Graff, J.M. (2003). C. elegans: a model for exploring the genetics of fat storage. Developmental cell 4, 131-142. Mihaylova, M.M., and Shaw, R.J. (2011). The AMP-activated protein kinase (AMPK) signaling pathway coordinates cell growth, autophagy, & metabolism. Nature cell biology 13, 1016. Miyoshi, H., Perfield, J.W., Souza, S.C., Shen, W.-J., Zhang, H.-H., Stancheva, Z.S., Kraemer, F.B., Obin, M.S., and Greenberg, A.S. (2007). Control of adipose triglyceride lipase action by serine 517 of perilipin A globally regulates protein kinase A-stimulated lipolysis in adipocytes. Journal of Biological Chemistry 282, 996-1002. Moreno-Arriola, E., Hafidi, M.E., Ortega-Cuéllar, D., and Carvajal, K. (2016). AMP-Activated Protein Kinase Regulates Oxidative Metabolism in Caenorhabditis elegans through the NHR-49 and MDT-15 Transcriptional Regulators. PloS one 11, e0148089. Mullaney, B.C., and Ashrafi, K. (2009). C. elegans fat storage and metabolic regulation. Biochimica et Biophysica Acta (BBA)-Molecular and Cell Biology of Lipids 1791, 474-478. Narbonne, P., and Roy, R. (2009). Caenorhabditis elegans dauers need LKB1/AMPK to ration lipid reserves and ensure long-term survival. Nature 457, 210. O'Rourke, E.J., Soukas, A.A., Carr, C.E., and Ruvkun, G. (2009). C. elegans major fats are stored in vesicles distinct from lysosome-related organelles. Cell metabolism 10, 430-435. Ong, K.T., Mashek, M.T., Bu, S.Y., Greenberg, A.S., and Mashek, D.G. (2011). Adipose triglyceride lipase is a major hepatic lipase that regulates triacylglycerol turnover and fatty acid signaling and partitioning. Hepatology 53, 116-126. Perez, C.L., and Van Gilst, M.R. (2008). A 13 C isotope labeling strategy reveals the influence of insulin signaling on lipogenesis in C. elegans. Cell metabolism 8, 266-274. Rambold, A.S., Cohen, S., and Lippincott-Schwartz, J. (2015). Fatty acid trafficking in starved cells: regulation by lipid droplet lipolysis, autophagy, and mitochondrial fusion dynamics. Developmental cell 32, 678-692. Rydel, T.J., Williams, J.M., Krieger, E., Moshiri, F., Stallings, W.C., Brown, S.M., Pershing, J.C., Purcell, J.P., and Alibhai, M.F. (2003). The crystal structure, mutagenesis, and activity studies reveal that patatin is a lipid acyl hydrolase with a Ser-Asp catalytic dyad. Biochemistry 42, 6696-6708. Sathyanarayan, A., Mashek, M.T., and Mashek, D.G. (2017). ATGL promotes autophagy/lipophagy via SIRT1 to control hepatic lipid droplet catabolism. Cell reports 19, 1-9. Schweiger, M., Schoiswohl, G., Lass, A., Radner, F.P., Haemmerle, G., Malli, R., Graier, W., Cornaciu, I., Oberer, M., and Salvayre, R. (2008). The C-terminal region of human adipose triglyceride lipase affects enzyme activity and lipid droplet binding. Journal of Biological Chemistry 283, 17211-17220. Schweiger, M., Schreiber, R., Haemmerle, G., Lass, A., Fledelius, C., Jacobsen, P., Tornqvist, H., Zechner, R., and Zimmermann, R. (2006). Adipose triglyceride lipase and hormone-sensitive lipase are the major enzymes in adipose tissue triacylglycerol catabolism. Journal of Biological Chemistry 281, 40236-40241. Singh, R., and Cuervo, A.M. (2012). Lipophagy: connecting autophagy and lipid metabolism. International journal of cell biology 2012. Soni, K.G., Mardones, G.A., Sougrat, R., Smirnova, E., Jackson, C.L., and Bonifacino, J.S. (2009). Coatomer-dependent protein delivery to lipid droplets. Journal of cell science 122, 1834-1841. STEIN, S.C., WOODS, A., JONES, N.A., DAVISON, M.D., and CARLING, D. (2000). The regulation of AMP-activated protein kinase by phosphorylation. Biochemical Journal 345, 437-443. Thiam, A.R., Farese Jr, R.V., and Walther, T.C. (2013). The biophysics and cell biology of lipid droplets. Nature reviews Molecular cell biology 14, 775. Wang, M.C., O’Rourke, E.J., and Ruvkun, G. (2008). Fat Metabolism Links Germline Stem Cells and Longevity in C. elegans. Science (New York, N.Y.) 322, 957–960. Witham, E., Comunian, C., Ratanpal, H., Skora, S., Zimmer, M., and Srinivasan, S. (2016). C. elegans body cavity neurons are homeostatic sensors that integrate fluctuations in oxygen availability and internal nutrient reserves. Cell reports 14, 1641-1654. Xie, M., and Roy, R. (2015). AMP-Activated kinase regulates lipid droplet localization and stability of adipose triglyceride lipase in C. Elegans dauer larvae. PloS one 10, e0130480. Yin, W., Mu, J., and Birnbaum, M.J. (2003). Role of AMP-activated protein kinase in cyclic AMP-dependent lipolysis In 3T3-L1 adipocytes. Journal of Biological Chemistry 278, 43074-43080. Zechner, R., Zimmermann, R., Eichmann, T.O., Kohlwein, S.D., Haemmerle, G., Lass, A., and Madeo, F. (2012). FAT SIGNALS-lipases and lipolysis in lipid metabolism and signaling. Cell metabolism 15, 279-291. Zhang, P., Na, H., Liu, Z., Zhang, S., Xue, P., Chen, Y., Pu, J., Peng, G., Huang, X., and Yang, F. (2012). Proteomic study and marker protein identification of Caenorhabditis elegans lipid droplets. Molecular & Cellular Proteomics 11, 317-328. Zhang, S.O., Box, A.C., Xu, N., Le Men, J., Yu, J., Guo, F., Trimble, R., and Mak, H.Y. (2010a). Genetic and dietary regulation of lipid droplet expansion in Caenorhabditis elegans. Proceedings of the National Academy of Sciences 107, 4640-4645. Zhang, S.O., Trimble, R., Guo, F., and Mak, H.Y. (2010b). Lipid droplets as ubiquitous fat storage organelles in C. elegans. BMC cell biology 11, 96. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/77843 | - |
dc.description.abstract | 在生物體中,能量的調節對於發育各個時期是相當關鍵的。能量的累積與消耗經由脂肪代謝過程來進行,而脂肪代謝受到錯綜複雜的基因調控。這些調控脂肪的基因對於不同的營養素攝入如何反應目前尚未完全了解。油滴作為脂肪儲存的胞器存在於線蟲的腸道及表皮組織當中,油滴裡的中性脂肪(三酸甘油酯)透過脂肪分解作用(lipolysis)被降解。脂肪分解作用的第一步驟是由酵素三酸甘油酯酶(adipose triglyceride lipase; ATGL)催化釋放出一條脂肪酸鏈。在本研究裡,利用線蟲解析脂肪分解作用(lipolysis)在飲食改變體內的脂肪恆定 (lipid homeostasis)過程及現象中所扮演的角色。不同的細菌飲食已知造成線蟲當中的脂肪含量變化。我們首先建立BODIPY 493/503活體染色法以及DHS-3螢光蛋白標定線蟲為飲食研究中可用的脂肪分析工具,發現Comamonas DA1877餵食下的線蟲相比於標準食物Escherichia coli OP50餵食下的線蟲能觀察到腸道與表皮組織裡皆具有數量較少且尺寸較小的油滴。值得注意的是,atgl-1突變時造成DA1877飲食下的油滴明顯變大,OP50飲食下油滴則稍微變大,顯示atgl-1對於不同飲食的線蟲具有不同的貢獻,而此差異造成了不同飲食下線蟲體內脂肪含量變化的原因。我們進一步了解飲食如何造成ATGL-1有不同的貢獻,經由轉錄報導品種及定量反轉錄聚合酶鏈式反應(quantitative RT-PCR)證實atgl-1的基因轉錄表現在兩種食物餵食下是相同的。然而,根據西方墨點法的分析,ATGL-1蛋白表現量在DA1877餵食下的線蟲比起OP50餵食下較低,這可能是ATGL-1因應兩種飲食下的油滴大小所造成的效應。此外,因為ATGL-1坐落於油滴的表面,經由顯微鏡觀察發現在OP50和DA1877飲食中ATGL-1表現量的差異並非來自於蛋白坐落形式的不同。抑制蛋白酶體(proteasome)的實驗也說明不是ATGL-1降解速率(turnover rate)改變所造成。另一方面,AMPK被證實在DA1877飲食下會抑制ATGL-1蛋白表現。有趣的是,我們發現ATGL-1對於飲食轉換快速產生反應,推測其控制的脂肪分解能幫助生物因應飲食差異以達到新的脂肪動態平衡。此外,經由脂肪分解作用釋放的脂肪酸及其用途也被證明受到飲食的調控。本研究為飲食如何經由控管良好的脂肪分解作用進一步影響體內脂肪含量變化提供新的見解。 | zh_TW |
dc.description.abstract | Energy regulation is crucial for developmental processes in the organisms. Accumulation and exploitation of energy through fat metabolism involves an intricate network of genes. How these fat-regulatory genes respond to different nutrients remains unclear. Lipid droplets as fat storage organelles are found in the intestine and hypodermis of C. elegans. Neutral lipids, mainly triacylglycerols, constitute lipid droplets which are decomposed by lipolysis. The initial rate limiting step of lipolysis is catalyzed by the enzyme adipose triglyceride lipase (ATGL) to release a single free fatty acid from substrate. In this study, we proposed that different bacterial diet may regulate fat storage through ATGL-1 dependent lipolysis in C. elegans. We first established BODIPY 493/503 staining protocol and ensured DHS-3::GFP labeling worms are suitable for dietary studies. By using these approaches, the results revealed that Comamonas DA1877-fed worms showed decreased lipid droplets in size and number in both of intestine and hypodermis compared to standard E. coli OP50-fed worms. Notably, atgl-1 mutation enlarged lipid droplets clearly on DA1877 but slightly on OP50, indicating that atgl-1 contributes differerently to diets-mediated lipid storage change. To understand how diets resulted in different ATGL-1 activities, we found the transcriptional level of atgl-1 is identical in both diets by reporter strain and quantitative RT-PCR analysis. Surprisingly, by microscopic observation, we demonstrated that ATGL-1 protein level is reduced in the worms fed DA1877 compared to OP50 while ATGL-1 localization patterns on lipid droplets were very similar between two diets-fed animals. These results which were also supported by Western blotting suggested that the ATGL-1 expression is adjusted to correlate with lipid droplet size regardless of the diets. We further demonstrated that the difference of ATGL-1 expression level on OP50 and DA1877 was not caused from changes of ATGL-1 turnover rate by proteasome inhibition experiments. The protein degradation pathway other than proteasome, such as lysosomal proteolysis could explain the differences. On the other hand, AMPK was identified to inhibit ATGL-1 expression in DA1877 diet. Moreover, we found that ATGL-1 is rapidly responsive to dietary switch for new lipid homeostasis achievement. Furthermore, in a pulse-chase experiment, the release of lipid droplets-derived fatty acids and subsequent location were demonstrated to be modulated by diets. The study here would provide new insights into how nutrient options affect lipid content alteration through well-regulated lipolysis. | en |
dc.description.provenance | Made available in DSpace on 2021-07-11T14:35:52Z (GMT). No. of bitstreams: 1 ntu-106-R04b43017-1.pdf: 3656302 bytes, checksum: 432a0a7d05ba8d7681fbea590a9d41fd (MD5) Previous issue date: 2017 | en |
dc.description.tableofcontents | 誌謝 i
摘要 ii Abstract iv Introduction 1 Materials and Methods 9 Worm strains and culture 9 Worm synchronization 9 Oil Red O staining and quantification 10 BODIPY staining and visualization 11 Microscopy and quantification 12 RNA isolation and quantitative RT-PCR 13 Western blotting 14 Gateway and microinjection 15 MG132 treatment 16 Dietary switch assay 16 Results 18 BODIPY 493/503 staining detects neutral lipids within the lipid droplets in the intestine and hypodermis 18 DHS-3::GFP is a suitable lipid droplet marker and not affected by dietary bacteria 19 DA1877-fed worms showed decreased lipid droplets in size and number in both intestine and hypodermis compared to OP50-fed ones 20 ATGL-1 contributes to the diet-mediated lipid storage changes 21 ATGL-1 overexpression in OP50-fed animals reduced fat content to the level similar to DA1877-fed wildtype animals 22 DA1877-mediated lipid reduction is less likely through hosl-1-dependent lipolysis 23 The transcriptional level of atgl-1 is similar in OP50 and DA1877-fed worms 24 ATGL-1::GFP level is lower in DA1877-fed worms but the localization pattern is similar in different diets-fed animals 25 The turnover rate of ATGL-1 is not altered when worms fed different diets 26 AMPK regulated ATGL-1 differentially in the intestine of different diets-fed animals 27 A basal level of AMPK promotes lipid storage in the intestine under well-fed condition 28 ATGL-1 is rapidly up-regulated in response to dietary switch from OP50 to DA1877 29 Lipid droplet-derived fatty acids are mobilized in different pace and may be transported to distinct destination in the worms fed different diets 30 Discussion 32 The relationship between fat content and lipid droplets size 32 The complicated regulation of ATGL-1 expression 33 The cooperation between lipolysis and lipophagy for lipid degradation 34 The role of AMPK in regulating of ATGL-1 and lipid metabolism 34 Hydrolyzed fatty acids as a role in signaling pathways 36 Figures 38 Figure 1. DA1877-fed worms showed reduced BODIPY 493/503-staining which coincides with PLIN-1-labeled lipid droplets in the intestine and hypodermis compared to OP50-fed worms by vital dye feeding approach. 39 Figure 2. DA1877-fed worms revealed less and smaller lipid droplets compared to OP50-fed worms using dhs-3::gfp lipid droplet marker strain. 40 Figure 3. ATGL-1 is required for DA1877 diet mediated lipid reduction. 42 Figure 4. ATGL-1 overexpression in OP50 diet-fed worms reduced fat stores level to the one in DA1877-fed worms by Oil Red O staining. 43 Figure 5. hosl-1 mutation increased fat storage level in both diets-fed worms but lipid level remained low in DA1877-fed hosl-1 mutants and wildtype. 44 Figure 6. atgl-1 transcriptional level is similar on both diets. 46 Figure 7. The localization pattern of ATGL-1::GFP is similar in different diets-fed animals, but the protein level is lower in DA1877-fed worms. 48 Figure 8. The ATGL-1::GFP expression level induced by MG132 treatment is similar in different diets-fed animals. 49 Figure 9. aak-2 regulated the expression of ATGL-1::GFP differently in the worms fed different diets. 51 Figure 10. AMPK deficiency resulted in low fat content in the intestine of worms fed different diets. 53 Figure 11. ATGL-1 is rapidly up-regulated in response to dietary switch from OP50 to DA1877. 54 Figure 12. Lipid droplets- derived fatty acids are mobilized at a different pace in the animals fed different diets. 57 Figure 13. The model of diet-mediated ATGL-1 function in C. elegans. 58 Figure 14. The comparison of various methods for lipid detection on different diets. 59 Supplementary figure 60 Figure S1. Quantification of lipid droplets in the intestine of wildtype and atgl-1 animals fed on both diets. 63 References 64 | |
dc.language.iso | en | |
dc.title | 線蟲飲食轉換調節之三酸甘油酯酶的脂肪分解作用 | zh_TW |
dc.title | ATGL-1-Dependent Lipolysis during Dietary Change in C. elegans | en |
dc.type | Thesis | |
dc.date.schoolyear | 105-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 潘俊良(Chun-Liang Pan),王昭雯(Chao-Wen Wang) | |
dc.subject.keyword | DA1877,脂肪代謝,脂肪分解作用,三酸甘油酯?, | zh_TW |
dc.subject.keyword | DA1877,fat metabolism,lipolysis,adipose triglyceride lipase (ATGL), | en |
dc.relation.page | 68 | |
dc.identifier.doi | 10.6342/NTU201703885 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2017-08-20 | |
dc.contributor.author-college | 生命科學院 | zh_TW |
dc.contributor.author-dept | 分子與細胞生物學研究所 | zh_TW |
顯示於系所單位: | 分子與細胞生物學研究所 |
文件中的檔案:
檔案 | 大小 | 格式 | |
---|---|---|---|
ntu-106-R04b43017-1.pdf 目前未授權公開取用 | 3.57 MB | Adobe PDF |
系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。