走在汽車革命的路上論文書籍站
國立陽明交通大學 跨領域神經科學國際研究生博士學位學程 王桂馨、李怡萱所指導 王李馨的 探討在神經退化性疾病中調控核醣核酸結合蛋白MBNL2表現之機轉 （2021），提出R 1250 RT關鍵因素是什麼，來自於核醣核酸結合蛋白MBNL2、蛋白分解酵素Calpain-2、神經興奮性毒性、肌強直型肌肉萎縮症、阿茲海默症、神經退化、核醣核酸剪接。
而第二篇論文慈濟大學 醫學系藥理暨毒理學碩士班 賴國筑、劉晉宏所指導 陳彥儒的 探討檳榔萃取物對肌肉分化及代謝之影響 （2021），提出因為有 檳榔子、檳榔萃取物、肌肉分化、肌肉萎縮的重點而找出了 R 1250 RT的解答。
R 1250 RT進入發燒排行的影片
2021 BMW Motorrad R 1250 RT 試駕｜搭載 ACC 自動跟車，劃時代科技休旅登場！
→https://www.mobile01.com/topicdetail.php?f=662&t=6345988
去年 10 月 2021 BMW Motorrad R 1250 RT 正式發表，最大驚喜就是帶來 ACC 主動式車距調節巡航系統（台灣為標配），以及新的 DCC 動態巡航控制系統，為長途騎乘帶來全新體驗，這回 R 1250 RT 還換上更俐落的車頭造型、全新 LED 智能轉向輔助頭燈、10.25" TFT 液晶儀錶板，為車系帶來更年輕、科技化的氣息，其它還包含音響系統、電動風鏡、加溫坐墊、帶中控鎖側箱、無線充電置物盒等，帶你盡情享受旅行的樂趣，可別看 RT 是個"大傢伙"，用「靈活的胖子」來形容可不是小編在膨風！
#BMW#Motorrad#R1250RT#ACC#Mobile01
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探討在神經退化性疾病中調控核醣核酸結合蛋白MBNL2表現之機轉
為了解決R 1250 RT 的問題，作者王李馨 這樣論述：
中文摘要 iAbstract iiContents iiiIntroduction 1Myotonic dystrophy type 1 (DM1) 1Cerebral involvement of adult-onset DM1 2Genetic basis of DM1 4Molecular mechanism in DM1 4Mouse models of DM1 with expression of CUG repeats 6RNA-binding protein: Muscleblind-like (MBNL) family
8MBNL1 and MBNL2 knockout mice 9Calcium-dependent cysteine protease: Calpain 11Calpain-1 and -2 11Calpain-1 and -2 deficient mice 12Calpain-1 and -2 in neurodegeneration 13Alzheimer’s disease (AD) 14Disease stages of AD 14Clinical presentations of AD 15Brain atrophy of AD
15Two pathological hallmarks of AD 16The aims of the study 20Materials and methods 211. Animals 212. Primary hippocampal neuron culture, drug treatment, virus infection and transfection 213. Cell culture and transient transfection 234. Total protein extraction and sub
cellular fractionation 245. Immunoprecipitation (IP) 256. Immunoblotting analysis 257. RNA preparation, RT-PCR and splicing analysis 268. Immunofluorescence staining and immunohistochemistry 279. Quantification of fluorescent images of brain sections 2910. Quantif
ication of fluorescent images of neurons 3011. Antibodies 3012. Plasmids 3113. Statistical analysis 31Results 331. Characterize the role of MBNL2 in neuronal maturation1.1. MBNL2 is expressed postnatally and increased as neuronal maturation 331.2. MBNL2 expression
is required for promoting adult pattern of RNA processingand neuronal differentiation 342. Determine how neurodegenerative conditions reduce MBNL2 expression2.1. Glutamate-induced excitotoxicity reduces MBNL2 protein expression viaNMDAR activation 352.2. NMDAR-mediated Calpain-2 acti
vation causes MBNL2 protein degradation 362.3. Calcium-dependent nuclear translocation of CAPN2 is associated with reducedMBNL2 expression 382.4. Dysregulated calcium homeostasis reduces MBNL2 expression 392.5. Enhanced nuclear translocation of CAPN2 occurs in the EpA960/CamKII-Cre
brain 402.6. Enhanced nuclear translocation of CAPN2 in neurodegeneration recapitulates thefetal developmental pattern 413. Explore the possibility of the reduced MBNL2 expression associated re-induced fetalpattern of RNA processing as a common feature among neurodegenerative disorders3.
1. Enhanced nuclear translocation of CAPN2, reduced MBNL2 expression and associated aberrant MBNL2-regulated alternative splicing in the degenerative brains of AD 41Discussion 44Perspective 48References 49List of figuresFigure 1. MBNL2 is expressed postnatally and increased with bra
in maturation 64Figure 2. MBNL2 is expressed in the more differentiated cells during hippocampusmaturation 65Figure 3. MBNL2 is expressed ubiquitously in the adult mouse brain 66Figure 4. MBNL2 is expressed in the neurons, oligodendrocytes and astrocytes 67Figure 5. The knockdown
efficiency of MBNL2 shRNAs in cultured neurons 68Figure 6. The alternative splicing and polyadenylation of MBNL2 targets show a fetal to adult transition during neuronal differentiation 70Figure 7. MBNL2 depletion disrupts the developmental RNA processing transition in cultured neurons
71Figure 8. MBNL2 depletion impairs dendrite maturation in cultured neurons 72Figure 9. Glutamate treatment induces excitotoxicity in mature cultured neurons showing condensed nucleus 74Figure 10. Glutamate-induced excitotoxicity reduces MBNL2 protein level in mature cultured neurons 75
Figure 11. Glutamate reduces MBNL2 level via NMDAR activation in cultured neurons 77Figure 12. NMDAR-mediated MBNL2 reduction is calcium dependent 78Figure 13. The alternative splicing and polyadenylation of MBNL2 targets are disrupted in neurons treated with glutamate or NMDA 79Figure 14.
MBNL2 mRNA level is unchanged in cultured neurons treated with glutamate or NMDA 81Figure 15. MBNL2 protein is stable in the neurons 82Figure 16. NMDAR signaling-mediated MBNL2 reduction requires calpain activity incultured neurons 83Figure 17. Protein expression of CAPN1 and CAPN2 are alte
red in NMDA-treatedneurons 84Figure 18. MBNL2 binds to both CAPN1 and CAPN22 in HEK293 cells 85Figure 19. Knockdown efficiency of CAPN1 or CAPN2 shRNAs in neurons 86Figure 20. NMDAR-mediated calpain-2 activation causes MBNL2 degradation inneurons 87Figure 21. Depletion of CAPN2 preserves
MBNL2-regulated alternative splicing andpolyadenylation in neurons upon NMDA treatment 88Figure 22. CAPN2 is predominantly expressed in the cytoplasm of mature neurons 90Figure 23. NMDA treatment induces the nuclear translocation of CAPN2 in neurons 91Figure 24. NMDAR-mediated MBNL2 reduct
ion requires calpain-2 expression in thenucleus and cytoplasm of neurons 92Figure 25. NMDA-induced nuclear translocation of CAPN2 requires calcium 93Figure 26. Nuclear translocation of CAPN2 involves in MBNL2 degradation 94Figure 27. Dysregulated calcium homeostasis induces the nuclear tran
slocation of CAPN2 and reduced MBNL2 expression in neurons 95Figure 28. CAPN2 depletion preserves MBNL2 expression in the neurons with dysregulated calcium homeostasis 96Figure 29. Effect of CAPN2 depletion on the RNA processing pattern of MBNL2 targets in A23187-treated neurons 97Figure 30
. CAPN2 nuclear translocation is occurred in the EpA960/CaMKII-Cre mouse brains 98Figure 31. Nuclear-to-cytoplasmic distribution of CAPN2 during neuronal differentiation 99Figure 32. Nuclear translocation of CAPN2 occurs in the APP/PS1 and THY-Tau22brains 100Figure 33. Reduced MBNL2 express
ion in the APP/PS1 and THY-Tau22 brains 101Figure 34. Aberrant MBNL2-regulated alternative splicing in the APP/PS1 and THY-Tau22 brains 102
探討檳榔萃取物對肌肉分化及代謝之影響
為了解決R 1250 RT 的問題，作者陳彥儒 這樣論述：
檳榔使用相當普遍，全球約有6億人有使用檳榔的習慣。檳榔已知會抑制胚胎發育、具有細胞毒性及致癌性。此外，長期暴露檳榔會出現肌肉萎縮的現象，但是檳榔對於肌肉細胞影響尚未明確。因此，本研究利用小鼠C2C12肌肉細胞體外模式，觀察檳榔萃取物 (areca nut extract, ANE) 對肌母細胞及分化的肌管細胞是否有影響。利用免疫螢光染色觀察分化過程中細胞形態。並以即時聚合酶連鎖反應與西方墨點法，分析分化相關生物指標，如myoblast determination protein (Myod1) 、myogenin (Myog) 和myosins heave chain 4 (Myh4) 表現
。結果發現，40 μg/mL ANE無細胞毒性，但會抑制肌母細胞分化。相似地，ANE也會造成肌管細胞肌肉萎縮。ANE藉由顯著降低Myod1、Myog和Myh4抑制肌母細胞分化。ANE並不影響蛋白質生成及降解路徑。最後以LC-MS/MS進行代謝體分析，分析ANE是否會影響肌管細胞的代謝。胺基酸的分析中，發現glutamine (p-value = 0.03) 顯著減少。醣類代謝的部分，糖解作用的中間產物2-phosphoglyceric acid (2PG) (p-value = 0.003) 、phosphoenolpyruvate (PEP) (p-value = 0.007) 顯著增加。這
些結果證實ANE會抑制肌肉細胞分化及代謝，未來需要更多的研究坦探討其分子機轉。