請用此 Handle URI 來引用此文件:
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/90817
完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 陳為堅 | zh_TW |
dc.contributor.advisor | Wei J. Chen | en |
dc.contributor.author | 黃嘉宏 | zh_TW |
dc.contributor.author | Chia-Hung Huang | en |
dc.date.accessioned | 2023-10-03T17:45:17Z | - |
dc.date.available | 2023-11-10 | - |
dc.date.copyright | 2023-10-03 | - |
dc.date.issued | 2023 | - |
dc.date.submitted | 2023-08-07 | - |
dc.identifier.citation | Chapter 6. References
1. Picard M, McEwen BS: Mitochondria impact brain function and cognition. Proceedings of the National Academy of Sciences 2014, 111:7. 2. Brenner C, Kroemer G: Mitochondria-the death signal integrators. Science 2000, 289:1150-1151. 3. Chinnery PF, Schon EA: Mitochondria. Journal of Neurology, Neurosurgery & Psychiatry 2003, 74:1188-1199. 4. Wallace DC: Genetics: Mitochondrial DNA in evolution and disease. Nature 2016, 535:498-500. 5. Barshad G, Marom S, Cohen T, Mishmar D: Mitochondrial DNA Transcription and Its Regulation: An Evolutionary Perspective. Trends Genet 2018, 34:682-692. 6. Stimpfel M, Jancar N, Virant-Klun I: New Challenge: Mitochondrial Epigenetics? Stem Cell Rev Rep 2018, 14:13-26. 7. Lister R, Mukamel EA, Nery JR, Urich M, Puddifoot CA, Johnson ND, Lucero J, Huang Y, Dwork AJ, Schultz MD, et al: Global epigenomic reconfiguration during mammalian brain development. Science 2013, 341. 8. Markunas CA, Semick SA, Quach BC, Tao R, Deep-Soboslay A, Carnes MU, Bierut LJ, Hyde TM, Kleinman JE, Johnson EO, et al: Genome-wide DNA methylation differences in nucleus accumbens of smokers vs. nonsmokers. Neuropsychopharmacology 2021, 46:554-560. 9. Desplats P, Dumaop W, Cronin P, Gianella S, Woods S, Letendre S, Smith D, Masliah E, Grant I: Epigenetic alterations in the brain associated with HIV-1 infection and methamphetamine dependence. PLoS One 2014, 9:e102555. 10. Rizzardi LF, Hickey PF, Rodriguez DiBlasi V, Tryggvadóttir R, Callahan CM, Idrizi A, Hansen KD, Feinberg AP: Neuronal brain-region-specific DNA methylation and chromatin accessibility are associated with neuropsychiatric trait heritability. Nat Neurosci 2019, 22:307-316. 11. Horvath S: DNA methylation age of human tissues and cell types. Genome Biology 2013, 14:3156. 12. Benayoun BA, Pollina EA, Brunet A: Epigenetic regulation of ageing: linking environmental inputs to genomic stability. Nat Rev Mol Cell Biol 2015, 16:593-610. 13. Shireby GL, Davies JP, Francis PT, Burrage J, Walker EM, Neilson GWA, Dahir A, Thomas AJ, Love S, Smith RG, et al: Recalibrating the epigenetic clock: implications for assessing biological age in the human cortex. Brain 2020, 143:3763-3775. 14. Kozlenkov A, Jaffe AE, Timashpolsky A, Apontes P, Rudchenko S, Barbu M, Byne W, Hurd YL, Horvath S, Dracheva S: DNA Methylation Profiling of Human Prefrontal Cortex Neurons in Heroin Users Shows Significant Difference between Genomic Contexts of Hyper- and Hypomethylation and a Younger Epigenetic Age. Genes 2017, 8:152. 15. Zillich L, Poisel E, Frank J, Foo JC, Friske MM, Streit F, Sirignano L, Heilmann-Heimbach S, Heimbach A, Hoffmann P, et al: Multi-omics signatures of alcohol use disorder in the dorsal and ventral striatum. Transl Psychiatry 2022, 12:190. 16. Zillich L, Frank J, Streit F, Friske MM, Foo JC, Sirignano L, Heilmann-Heimbach S, Dukal H, Degenhardt F, Hoffmann P, et al: Epigenome-wide association study of alcohol use disorder in five brain regions. Neuropsychopharmacology 2022, 47:832-839. 17. Wang F, Xu H, Zhao H, Gelernter J, Zhang H: DNA co-methylation modules in postmortem prefrontal cortex tissues of European Australians with alcohol use disorders. Sci Rep 2016, 6:19430. 18. Hagerty SL, Bidwell LC, Harlaar N, Hutchison KE: An Exploratory Association Study of Alcohol Use Disorder and DNA Methylation. Alcohol Clin Exp Res 2016, 40:1633-1640. 19. Ponomarev I, Wang S, Zhang L, Harris RA, Mayfield RD: Gene coexpression networks in human brain identify epigenetic modifications in alcohol dependence. J Neurosci 2012, 32:1884-1897. 20. Manzardo AM, Henkhaus RS, Butler MG: Global DNA promoter methylation in frontal cortex of alcoholics and controls. Gene 2012, 498:5-12. 21. Koller G, Zill P, Soyka M, Adorjan K, Weiss C, Kern A, Nguyen-Thien M-L, Kamp F, Proebstl L, Krause D, et al: Short-term changes in global methylation and hydroxymethylation during alcohol detoxification. European Neuropsychopharmacology 2019, 29:897-903. 22. Devine MJ, Kittler JT: Mitochondria at the neuronal presynapse in health and disease. Nat Rev Neurosci 2018, 19:63-80. 23. Hazkani-Covo E, Zeller RM, Martin W: Molecular poltergeists: mitochondrial DNA copies (numts) in sequenced nuclear genomes. PLoS Genet 2010, 6:e1000834. 24. Liu B, Du Q, Chen L, Fu G, Li S, Fu L, Zhang X, Ma C, Bin C: CpG methylation patterns of human mitochondrial DNA. Scientific Reports 2016, 6:23421. 25. Mawlood SK, Dennany L, Watson N, Dempster J, Pickard BS: Quantification of global mitochondrial DNA methylation levels and inverse correlation with age at two CpG sites. Aging (Albany NY) 2016, 8:636-641. 26. Mechta M, Ingerslev LR, Fabre O, Picard M, Barrès R: Evidence Suggesting Absence of Mitochondrial DNA Methylation. Frontiers in genetics 2017, 8:166-166. 27. Wolters JEJ, van Breda SGJ, Caiment F, Claessen SM, de Kok T, Kleinjans JCS: Nuclear and Mitochondrial DNA Methylation Patterns Induced by Valproic Acid in Human Hepatocytes. Chem Res Toxicol 2017, 30:1847-1854. 28. Dou X, Boyd-Kirkup JD, McDermott J, Zhang X, Li F, Rong B, Zhang R, Miao B, Chen P, Cheng H, et al: The strand-biased mitochondrial DNA methylome and its regulation by DNMT3A. Genome Res 2019, 29:1622-1634. 29. Mechta M, Ingerslev LR, Barrès R: Methodology for Accurate Detection of Mitochondrial DNA Methylation. Journal of visualized experiments : JoVE 2018:57772. 30. Guitton R, Dölle C, Alves G, Ole-Bjørn T, Nido GS, Tzoulis C: Ultra-deep whole genome bisulfite sequencing reveals a single methylation hotspot in human brain mitochondrial DNA. Epigenetics 2022:1-16. 31. Patil V, Cuenin C, Chung F, Aguilera JR R, Fernandez-Jimenez N, Romero-Garmendia I, Bilbao JR, Cahais V, Rothwell J, Herceg Z: Human mitochondrial DNA is extensively methylated in a non-CpG context. Nucleic Acids Research 2019, 47:10072-10085. 32. Patil V, Ward RL, Hesson LB: The evidence for functional non-CpG methylation in mammalian cells. Epigenetics 2014, 9:823-828. 33. Devall M, Smith RG, Jeffries A, Hannon E, Davies MN, Schalkwyk L, Mill J, Weedon M, Lunnon K: Regional differences in mitochondrial DNA methylation in human post-mortem brain tissue. Clin Epigenetics 2017, 9:47. 34. Amigo I, Traba J, Rueda Diez CB: Isolating Brain Mitochondria by Differential Centrifugation. Bio-protocol 2016, 6:e1810. 35. Krueger F: Trim Galore 0.5.0. vol. 2018, 0.5.0 edition. UK: Babraham Bioinformatics; 2018. 36. Krueger F, Andrews SR: Bismark: a flexible aligner and methylation caller for Bisulfite-Seq applications. Bioinformatics 2011, 27:1571-1572. 37. Li H, Handsaker B, Wysoker A, Fennell T, Ruan J, Homer N, Marth G, Abecasis G, Durbin R: The Sequence Alignment/Map format and SAMtools. Bioinformatics 2009, 25:2078-2079. 38. Robinson JT, Thorvaldsdóttir H, Winckler W, Guttman M, Lander ES, Getz G, Mesirov JP: Integrative genomics viewer. Nature Biotechnology 2011, 29:24-26. 39. Akalin A, Kormaksson M, Li S, Garrett-Bakelman FE, Figueroa ME, Melnick A, Mason CE: methylKit: a comprehensive R package for the analysis of genome-wide DNA methylation profiles. Genome Biology 2012, 13:R87. 40. R Development Core Team: R: A language and environment for statistical computing. Vienna, Austria R Foundation for Statistical Computing; 2020. 41. Sun X, Han Y, Zhou L, Chen E, Lu B, Liu Y, Pan X, Cowley AW, Jr, Liang M, Wu Q, et al: A comprehensive evaluation of alignment software for reduced representation bisulfite sequencing data. Bioinformatics 2018, 34:2715-2723. 42. Daunay A, Baudrin LG, Deleuze JF, How-Kit A: Evaluation of six blood-based age prediction models using DNA methylation analysis by pyrosequencing. Sci Rep 2019, 9:8862. 43. Sadakierska-Chudy A, Frankowska M, Filip M: Mitoepigenetics and drug addiction. Pharmacol Ther 2014, 144:226-233. 44. Stoccoro A, Coppede F: Mitochondrial DNA Methylation and Human Diseases. Int J Mol Sci 2021, 22. 45. Sanchez-Mut JV, Heyn H, Vidal E, Moran S, Sayols S, Delgado-Morales R, Schultz MD, Ansoleaga B, Garcia-Esparcia P, Pons-Espinal M, et al: Human DNA methylomes of neurodegenerative diseases show common epigenomic patterns. Transl Psychiatry 2016, 6:e718. 46. Byun H-M, Panni T, Motta V, Hou L, Nordio F, Apostoli P, Bertazzi PA, Baccarelli AA: Effects of airborne pollutants on mitochondrial DNA Methylation. Particle and Fibre Toxicology 2013, 10:18. 47. D'Aquila P, Giordano M, Montesanto A, De Rango F, Passarino G, Bellizzi D: Age-and gender-related pattern of methylation in the MT-RNR1 gene. Epigenomics 2015, 7:707-716. 48. Bayliak MM, Lushchak VI: Pleiotropic effects of alpha-ketoglutarate as a potential anti-ageing agent. Ageing Research Reviews 2021, 66:101237. 49. Martínez-Reyes I, Chandel NS: Mitochondrial TCA cycle metabolites control physiology and disease. Nature Communications 2020, 11:102. 50. Curran HV, Morgan C: Cognitive, dissociative and psychotogenic effects of ketamine in recreational users on the night of drug use and 3 days later. Addiction 2000, 95:575-590. 51. Pan WH, Wu KC, Chen CY, Chu YR, Wu SC, Jou S, Lu TP, Tung YC, Hsu J, Chen WJ: First-time offenders for recreational ketamine use under a new penalty system in Taiwan: incidence, recidivism and mortality in national cohorts from 2009 to 2017. Addiction 2021, 116:1770-1781. 52. Chuang SM, Lu JH, Lin KL, Long CY, Lee YC, Hsiao HP, Tsai CC, Wu WJ, Yang HJ, Juan YS: Epigenetic regulation of COX‑2 expression by DNA hypomethylation via NF‑κB activation in ketamine‑induced ulcerative cystitis. Int J Mol Med 2019, 44:797-812. 53. Choi M, Lee SH, Wang SE, Ko SY, Song M, Choi J-S, Kim Y-S, Duman RS, Son H: Ketamine produces antidepressant-like effects through phosphorylation-dependent nuclear export of histone deacetylase 5 (HDAC5) in rats. Proceedings of the National Academy of Sciences 2015, 112:15755. 54. Nakama H, Chang L, Fein G, Shimotsu R, Jiang CS, Ernst T: Methamphetamine users show greater than normal age-related cortical gray matter loss. Addiction (Abingdon, England) 2011, 106:1474-1483. 55. Cederbaum AI: Alcohol metabolism. Clin Liver Dis 2012, 16:667-685. 56. Verlinden I, Güiza F, Derese I, Wouters PJ, Joosten K, Verbruggen SC, Van den Berghe G, Vanhorebeek I: Time course of altered DNA methylation evoked by critical illness and by early administration of parenteral nutrition in the paediatric ICU. Clinical Epigenetics 2020, 12:155. 57. Levine B, Smith ML, Smialek JE, Caplan YH: Interpretation of low postmortem concentrations of ethanol. J Forensic Sci 1993, 38:663-667. 58. Kugelberg FC, Jones AW: Interpreting results of ethanol analysis in postmortem specimens: a review of the literature. Forensic Sci Int 2007, 165:10-29. 59. Crider KS, Yang TP, Berry RJ, Bailey LB: Folate and DNA methylation: a review of molecular mechanisms and the evidence for folate's role. Adv Nutr 2012, 3:21-38. 60. Gatta E, Auta J, Gavin DP, Bhaumik DK, Grayson DR, Pandey SC, Guidotti A: Emerging Role of One-Carbon Metabolism and DNA Methylation Enrichment on delta-Containing GABAA Receptor Expression in the Cerebellum of Subjects with Alcohol Use Disorders (AUD). Int J Neuropsychopharmacol 2017, 20:1013-1026. 61. Nutt D, King LA, Saulsbury W, Blakemore C: Development of a rational scale to assess the harm of drugs of potential misuse. Lancet 2007, 369:1047-1053. 62. Shock LS, Thakkar PV, Peterson EJ, Moran RG, Taylor SM: DNA methyltransferase 1, cytosine methylation, and cytosine hydroxymethylation in mammalian mitochondria. Proc Natl Acad Sci U S A 2011, 108:3630-3635. 63. Yue Y, Ren L, Zhang C, Miao K, Tan K, Yang Q, Hu Y, Xi G, Luo G, Yang M, et al: Mitochondrial genome undergoes de novo DNA methylation that protects mtDNA against oxidative damage during the peri-implantation window. Proc Natl Acad Sci U S A 2022, 119:e2201168119. 64. Lee SR, Han J: Mitochondrial Nucleoid: Shield and Switch of the Mitochondrial Genome. Oxid Med Cell Longev 2017, 2017:8060949. 65. Dostal V, Churchill MEA: Cytosine methylation of mitochondrial DNA at CpG sequences impacts transcription factor A DNA binding and transcription. Biochim Biophys Acta Gene Regul Mech 2019, 1862:598-607. 66. Lou S, Lee HM, Qin H, Li JW, Gao Z, Liu X, Chan LL, Kl Lam V, So WY, Wang Y, et al: Whole-genome bisulfite sequencing of multiple individuals reveals complementary roles of promoter and gene body methylation in transcriptional regulation. Genome Biol 2014, 15:408. 67. Adam-Vizi V, Chinopoulos C: Bioenergetics and the formation of mitochondrial reactive oxygen species. Trends Pharmacol Sci 2006, 27:639-645. 68. Bobba A, Amadoro G, Valenti D, Corsetti V, Lassandro R, Atlante A: Mitochondrial respiratory chain Complexes I and IV are impaired by β-amyloid via direct interaction and through Complex I-dependent ROS production, respectively. Mitochondrion 2013, 13:298-311. 69. Giorgi C, Marchi S, Simoes ICM, Ren Z, Morciano G, Perrone M, Patalas-Krawczyk P, Borchard S, Jędrak P, Pierzynowska K, et al: Chapter Six - Mitochondria and Reactive Oxygen Species in Aging and Age-Related Diseases. In International Review of Cell and Molecular Biology. Volume 340. Edited by López-Otín C, Galluzzi L: Academic Press; 2018: 209-344 70. Wu D, Cederbaum AI: Alcohol, oxidative stress, and free radical damage. Alcohol Res Health 2003, 27:277-284. 71. Miozzo F, Arnould H, de Thonel A, Schang AL, Sabéran-Djoneidi D, Baudry A, Schneider B, Mezger V: Alcohol exposure promotes DNA methyltransferase DNMT3A upregulation through reactive oxygen species-dependent mechanisms. Cell Stress Chaperones 2018, 23:115-126. 72. Viola TW, Orso R, Florian LF, Garcia MG, Gomes MGS, Mardini EM, Niederauer JPO, Zaparte A, Grassi-Oliveira R: Effects of substance use disorder on oxidative and antioxidative stress markers: A systematic review and meta-analysis. Addiction Biology 2023, 28:e13254. | - |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/90817 | - |
dc.description.abstract | 研究背景:大腦運作仰賴粒線體提供大量的能量,然而目前表觀遺傳學的研究多針對細胞核染色體,僅少部分研究探討粒線體染色體之DNA甲基化情形。我們針對大腦伏核及前額葉皮質部分,分析粒線體DNA甲基化之特徵與1.該二腦區、2.老化程度、3.非法藥物及酒精使用之關聯性。
方法與結果: 我們自53位死者腦部收集伏核及前額葉檢體,以全粒線體基因體亞硫酸定序法分析甲基化程度。依血液是否檢出藥物分為無藥物組(n = 39)及藥物組(n = 14),發現無藥物組兩腦區之甲基化達顯著差異(P = 3.89 × 10-9),這些可能與腦部特殊功能相關的甲基化差異,則因施用藥物而縮小;其次,我們發現甲基化程度與年齡呈正相關(R2 為0.34於伏核,0.37於前額葉),施用非法藥物會加速老化,且以施用愷他命最為明顯;最後,我們篩選與用藥相關之甲基化點位,這些點位可以有效區分藥物組與對照組之差異(AUC達0.88於伏核,AUC達0.94於前額葉)。此外,我們改以血液是否檢出酒精及酒精來源將此53位死者重新分組至無酒精組(n = 34)、飲酒組(n = 9)及死後發酵組(n = 10),發現飲酒組的甲基化情形與無酒精組及死後發酵組均達顯著差異(AUC達0.89於伏核,AUC達0.94於前額葉),兩腦區對長期飲酒之敏感程度不同,且長期飲酒可能造成伏核粒線體的甲基化程度整體降低。 結論: 粒線體於不同腦區之間有不同的甲基化情形,且甲基化程度隨年齡增長而逐漸增加,並受非法藥物及酒精所影響。我們認為這是首件的研究報導指出人腦之粒線體DNA甲基化之重要性。 | zh_TW |
dc.description.abstract | Background:
Despite the brain’s high demand for energy, research on its epigenetics focuses on nuclear methylation, and much of the mitochondrial DNA methylation remains seldom investigated. With a focus on the nucleus accumbens (NAcc) and the prefrontal cortex (PFC), we aimed to identify the mitochondrial methylation signatures for 1) distinguishing the two brain areas, 2) correlating with aging, 3) reflecting the influence of illicit drugs and alcohol on the brain. Result: We collected the brain tissue in the NAcc and the PFC from the deceased individuals without (n = 39) and with (n = 14) drug use, and used whole genome bisulfite sequencing to cover cytosine sites in the mitochondrial genome. We first detected differential methylations between the NAcc and the PFC in the non-users group (P = 3.89 × 10-9). These function-related methylation differences diminished in the drug-positive due to the selective alteration in the NAcc. Next, we found the correlation between the methylation levels and the legal ages in the non-users group (R2 = 0.34 in the NAcc and 0.37 in the PFC). The epigenetic clocks in illicit drug users, especially in the ketamine users, were accelerated in both brain regions by comparison with the non-users. Then, we summarized the effect of the illicit drugs on the methylation, which could significantly differentiate the drug users from the non-users (AUC = 0.88 in the NAcc, AUC = 0.94 in the PFC). In order to capture the alcohol effect on the mitochondrial DNA methylation, we reassigned the 53 deceased individuals into the BAC-negative group (with undetected blood alcohol concentration, n = 34), the Alcohol group (with ante-mortem alcohol use, n = 10) and the Fermentation group (with the detected blood alcohol from bacterial fermentation, n = 9). Finally, we summarized the transient effect of alcohol use on the methylation, which could significantly differentiate the ante-mortem alcohol users from the non-users (AUC = 0.89 in the NAcc, AUC = 0.94 in the PFC). The mitochondrial global hypomethylation, reflecting the chronic effect of the alcohol use, was selectively observed in the NAcc due to the different resiliencies of the two brain areas. Conclusion: The mitochondrial methylations were different between different brain areas, generally accumulated with aging, and sensitive to the effects of illicit drugs and alcohol. We believed this is the first report to elucidate comprehensively the importance of mitochondrial DNA methylation in human brain. | en |
dc.description.provenance | Submitted by admin ntu (admin@lib.ntu.edu.tw) on 2023-10-03T17:45:17Z No. of bitstreams: 0 | en |
dc.description.provenance | Made available in DSpace on 2023-10-03T17:45:17Z (GMT). No. of bitstreams: 0 | en |
dc.description.tableofcontents | Table of Contents
口試委員會審定書 i 誌謝 ii 中文摘要 iii Abstract iv Table of Contents vi List of Figures viii List of Tables ix Chapter 1. Introduction 1 1.1. Background 1 1.2. Specific aims 3 1.3. Publication arising from this thesis 4 Chapter 2. Methods 5 2.1. Sample collection 5 2.2. Toxicological analysis for the forensic toxicology report 6 2.3. Group assignments 6 2.3.1. For the analyses of brain areas, aging, and drug use 7 2.3.2. For the analysis of alcohol use 8 2.4. Isolation of mitochondrion 9 2.5. Whole mitochondrial genome bisulfite sequencing 9 2.6. Read quality check and alignment 10 2.7. Availability of data and materials 12 2.8. Statistical analysis 12 2.8.1. Comparisons of groups 12 2.8.2. Construction of indices 13 Chapter 3. Results 15 3.1. Modest levels of mitochondrial methylation in both the PFC and the NAcc 15 3.2. Methylation differences between the PFC and the NAcc 16 3.3. The link between legal age and mitochondrial genome methylation levels 16 3.4. Generic effects of drug usage on mitochondrial cytosine methylation 18 3.5. The influence of ante-mortem alcohol use on cytosine methylation in the mitochondrial genome 18 3.6. The alcohol drinking history with the global mitochondrial DNA methylation and the ALC_index 19 3.7. Common methylation sites among indices 20 3.8. Sensitivity analysis 20 Chapter 4. Discussion 22 4.1. The CpG methylation and the non-CpG methylation in the NAcc and the PFC 22 4.2. The methylation differences regarding to the cerebral areas, aging, and drug usage 23 4.3. The methylation differences regarding to the alcohol usage 25 4.4. The influenced cytosine sites and the severity of harmful substances 26 4.5. The potential biological roles of mitochondrial DNA methylation in the promoters and the gene bodies 26 4.6. Limitations 27 Chapter 5. Conclusion 29 Chapter 6. References 30 Appendix 78 Appendix 1. The certificate of approval from the IRB of Antai Medical Care Corporation, Antai Tian-Sheng Memorial Hospital, Taiwan. 78 Appendix 2. The quality control data 79 Appendix 2.1. The log data of quality trimming of the 106 samples from the TrimGalore. 79 Appendix 2.2. The log data of sequence alignment of the 106 samples from the Biskmark. 107 Appendix 2.3. The M-bias plots of the 106 samples from the Biskmark. 135 Appendix 2.4. The sequence coverage of the 105 samples from the IGV 150 Appendix 2.5. The summary table of the quality control of the 105 samples 154 | - |
dc.language.iso | en | - |
dc.title | 前額葉皮質及伏核之粒線體DNA甲基化情形與年齡增長、非法藥物及酒精使用之關聯 | zh_TW |
dc.title | Mitochondrial DNA Methylation Profiling of the Human Prefrontal Cortex and the Nucleus Accumbens: Correlations with Aging, Drug Use, and Alcohol Intake | en |
dc.type | Thesis | - |
dc.date.schoolyear | 111-2 | - |
dc.description.degree | 博士 | - |
dc.contributor.oralexamcommittee | 謝松蒼;俞松良;蕭朱杏;盧子彬 | zh_TW |
dc.contributor.oralexamcommittee | Sung-Tsang Hsieh;Sung-Liang Yu;Chuhsing Kate Hsiao;Tzu-Pin Lu | en |
dc.subject.keyword | 表觀遺傳學,全粒線體基因體亞硫酸定序法,老化,非法藥物,酒精,伏核,前額葉皮質, | zh_TW |
dc.subject.keyword | epigenetic,whole-mitochondrial-genome bisulfite sequencing,aging,illicit drug,alcohol,nucleus accumbens,prefrontal cortex, | en |
dc.relation.page | 156 | - |
dc.identifier.doi | 10.6342/NTU202301330 | - |
dc.rights.note | 未授權 | - |
dc.date.accepted | 2023-08-07 | - |
dc.contributor.author-college | 公共衛生學院 | - |
dc.contributor.author-dept | 流行病學與預防醫學研究所 | - |
顯示於系所單位: | 流行病學與預防醫學研究所 |
文件中的檔案:
檔案 | 大小 | 格式 | |
---|---|---|---|
ntu-111-2.pdf 目前未授權公開取用 | 18.35 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。