1,721,009 research outputs found

    Copper Chaperone-Dependent and -Independent Activation of Three Copper-Zinc Superoxide Dismutase Homologs Localized in Different Cellular Compartments in Arabidopsis

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    超氧歧化酶(Superoxide Dismutase;SOD),可將超氧分子轉變為過氧化氫及氧分子,具有解除氧化逆境的功能。對於銅鋅超氧歧化酶(CuZnSOD;CSD)的活化機制,目前已知有兩條路徑,一者是藉由銅鑲嵌輔助蛋白(Copper Chaperone of SOD1;CCS)的幫助,達到銅離子鑲嵌與形成內生性雙硫鍵的活化型態;另一者則是在人類及老鼠中發現,在沒有CCS情況下,CuZnSOD仍然具有少量的活性,只是其活化途徑與機制仍未明朗。本論文,將阿拉伯芥三個不同的CuZnSOD基因表現於酵母菌及阿拉伯芥原生質體中,我們證實阿拉伯芥不同CuZnSOD的活化具有不同的偏好:CSD1位在細胞質中,可藉由兩條活化機制達成活化,在無CCS的情況下,仍保有~36%的活性,類似人類的CuZnSOD;CSD2位在葉綠體中,只能經由CCS來達成活化,與酵母菌的CuZnSOD類似;CSD3位在過氧化體中,只經由非CCS的路徑來達成活化,類似線蟲的CuZnSOD。我們證實在AtCCS-knockout突變株中,此殘存的CuZnSOD活性量就足以提供正常生理功能之所需。最後,我們也證實了還原態的榖胱甘肽(Glutathione;GSH)參與在非CCS的活化CuZnSOD的路徑上,並且需有一未知功能的因子共同合作才能完成。我們綜合前人之研究及本實驗之證據,提出兩種不需經由CCS而達成活化的可能作用機制,以及提出CuZnSOD蛋白質之C端具有與未知因子交互作用,而達成促進活化的功用。綜上而言,我們的研究提出植物體之複雜精密的抗氧化途徑,是在其他物種中從所未見的,而其詳細的機制,則仍有待後續的研究加以釐清。Superoxide dismutases (SODs) are enzymes that protect cells from oxidative damage. The major pathway for CuZnSOD activation involves the function of a Copper Chaperone for SOD (CCS), whereas an additional, minor CCS-independent pathway that has been observed in mammals. Through overexpression of three Arabidopsis CuZnSOD genes (CSDs) in yeast and Arabidopsis protoplasts, we demonstrate the existence of a CCS-independent activation pathway in Arabidopsis thaliana. Interestingly, the three Arabidopsis CSDs show strongly different preference for the two activation pathways: the main activation pathway for CSD1 in the cytoplasm involved a CCS-dependent and -independent pathway, which was similar to that for human CSD. Activation of CSD2 in chloroplasts depended totally on CCS similar to yeast (Saccharomyces cerevisiae) CSD. Peroxisome-localized CSD3 via a CCS-independent pathway was similar to nematode (Caenorhabditis elegans) CSD in retaining activity in the absence of CCS. The residual SOD activity detected in AtCCS knockout plants is sufficient for seed germination and root growth, confirming that this alternative pathway is physiologically functional. Through a series of glutathione manipulation experiments, we further confirmed that glutathione plays a role in CCS-independnet pathway but must cooperate with an unknown factor for SOD activation. According to previous publications and our finding, two models of the CCS-independent mechanism are proposed. We also suggest that the CSD protein conformation at C-terminal is important in providing a docking site for unknown factor to interact with. Our findings reveal a complex system underlying CSD activation which ensures a highly specific and sophisticated regulation of antioxidant pathways in plants and has not been reported in other organisms. However, the clear and definite mechanism needs further investigation

    Dynamic Relations Between VADO Index, Stock Returns and Turnover Ratio from the Taiwan Stock Market:Based on Firm Characteristics

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    本論文在探討台灣股票市場操作在投資界普遍所參考的指標之一為籌碼集中度分析,藉由數量累積散佈擺盪 (volume accumulation/distribution oscillator, VADO) 指標來衡量股票籌碼集中度,同時以市場上的高/週轉率、大/小公司規模和高/低股價淨值比 (成長型/價值型) 公司之特徵的投資組合來進行探討股票籌碼集中度指標與股價及交易活動之間的互動關係的研究。本文將蒐集2003年初到2013年底之股票的每日交易資料來進行分析,同時並以單根檢定、Granger因果關係分析、向量自我迴歸模型 (VAR)和衝擊反應分析等計量方法進行驗證。最後,再經由實證後獲得主要知結論: 首先,平均報酬率由高至低依序為成長型、低週轉率、大公司、高週轉率、加權指數、小公司及價值型的投資組合。這個結果大致於上與市場法人或投資人所偏好投資標的之股票的公司特徵是一致的,市場上投資人喜愛高成長型的股票,而法人則偏愛ETF 50成份股等大公司股票。其次,也發現在低週轉率、大公司規模和價值型等特徵的公司,則股票籌碼集中度指標對於股價報酬率是具有參考價值和意義的,所以認為投資人可藉由觀察籌碼面的變化,在這些特徵的類股中來研判股價的變化是可行的。另外,除了大公司以外,其他特徵公司之投資組合的籌碼集中度指標對於股票的交易活動也是具有參考價值。 最後,由於並非所有的特徵公司之股票籌碼集中度指標與股價報酬率或週轉率是不具有解釋關係,所以認為籌碼集中度指標並不完全可適用於股票市場所有的股票,本研究的結果可供台灣股市投資人參考。This paper discusses one of the commonly used investment indicator in the stock market of Taiwan–chip concentration analysis. It uses volume accumulation/distribution oscillator (VADO) to measure the stock chip concentration. Meanwhile the investment combinations of different company characteristics, such as turnover rate, firm size, and price-book ratio, are used to discuss the interaction among the chip concentration index, stock price, and trading activities. This paper collects the daily trading information of stock from early 2003 to the end of 2013. The data are verified using unit root test, Granger causality test, Vector Autoregression (VAR), and impulse response analysis. The conclusions are reached based on the validation. First, the average rate of return, in the descending order is: growth type, low turnover rate, large firm, high turnover rate, weighted index, small firm, and value type. This finding is consistent with the preferred company characteristics of institutional and individual investors. Individual investors prefer high growth stocks, while institutional investors prefer ETF 50 stocks. Moreover, for companies with characteristics of low turnover rate, large firm size, and value type, the chip concentration indicator has reference value and significance to rate of return. Hence, it is feasible that investors can observe the changes of chip value values to determine the changes of stock prices. Moreover, besides large companies, the chip concentration indicator of investment combinations of other company characteristics has reference value to stock trading activities. Lastly, not all chip concentration indicators have no explanatory relationship with the stock returns of turnover ratio, it is inferred that the chip concentration indicator cannot be applied to all stocks in the stock market. Hence, the findings of this paper can provide references to stock investors in Taiwan.口試委員會審定書……………………………………………… i 誌謝……………………………………………………………… ii 中文摘要……………………………………………..………… iii Abstract………………………………………………………… iv 目錄…….........……………………………………...…... v 圖目錄……………………………………………...…...... vii 表目錄………………………………………………......... viii 第一章 緒論……………………………….………………….. 1 第一節 研究動機………………………............………… 1 第二節 研究目的……………………………....……………… 2 第三節 研究內容架構與流程………………………………….. 3 第二章 相關理論及文獻回顧………………………………... 6 第一節 相關理論………………………………….……………. 6 第二節 相關文獻回顧……………………………….…………. 7 第三章 研究資料說明及方法設計……………………….... 12 第一節 籌碼集中度指標的計算方式與資料說………………. 12 第二節 序列之單根檢定……………………………………... 15 第三節 Granger因果關係檢定………………………………… 17 第四節 動態關係的解釋模型:向量自我迴歸模型…………. 20 第五節 衝擊反應分析………………………………………… 21 第四章 實證結果分析……………………………………….. 23 第一節 基本敘述統計與單根檢定……………………………. 23 第二節 配對Granger因果關係分析…………………………. 34 第三節 動態關係的解釋模型:向量自我迴歸模型…….…. 41 第四節 衝擊反應分析…………......................… 60 第五章 研究結論及建議…………………………………….. 73 參考文獻………………………………………………….……. 8

    Study of hexosamine derivatives on osteogenic differentiation of dental pulp stem cells

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    成體幹細胞是一群未分化完全的細胞,同時具有分裂及自我增生、分化成為具多種特定功能體細胞的特性。人類間葉幹細胞已知是目前用途最廣的多分化性細胞,大部份具有間葉細胞特性的細胞群,包含骨細胞、肌細胞、軟骨細胞、脂肪細胞等等,都可以由間葉幹細胞的分化而來。此外,間葉幹細胞也已經被證實富含於各組織中,包括肌肉、脂肪、臍帶、肝、肺、關節腔滑膜及牙髓組織等,都已經有報告指出可以分離出間葉幹細胞。 牙髓幹細胞具有很好的形成細胞群落、分裂及自我增生、及多重分化的能力,因此在硬組織再生工程中,是非常理想的細胞來源。在本篇研究的第一部份,由第三大臼齒的牙髓組織所分離培養的牙髓細胞,在經過數次的繼代培養後,經由流式細胞儀,分選出帶有及不帶有Stro-1及CD146表面抗原的細胞群。本研究中,帶有Stro-1及CD146表面抗原的細胞群定義為牙髓幹細胞 (DPSCs);而不帶有的則定義為牙髓細胞 (DPCs)。值得注意的是,牙髓幹細胞表現出較牙髓細胞更好的形成群落特性及成骨分化的能力。而這些特性的差異,則與牙髓幹細胞內N-乙醯葡萄醣胺轉移酶-5 (N-acetylglucosaminyltransferase V, GnT-V)的表現較高有關。 進一步探討後可以發現,在系統存在不同的小分子量醣胺類衍生物時,例如葡萄醣胺(glucosamine)、N-乙醯葡萄醣胺(N-acetyl-d-glucosamine)、甘露醣胺(d-mannosamine)、與N-乙醯甘露醣胺(N-acetyl-d-mannosamine)等,牙髓幹細胞中的N-乙醯葡萄醣胺轉移酶-5可以催化N-端連結醣鏈(N-glycan)形成第一型轉化生長因子接受器 (transforming growth factor-β receptor type I)的產生,且增加的第一型轉化生長因子接受器可以進一步的活化其下游Smads的信號。且實驗結果發現,在0.005 mg/ml的濃度中,細胞的早期成骨分化會有明顯的提升。藉由調控N-乙醯葡萄醣胺轉移酶-5催化N-端連結醣鍊(N-glycan)形成第一型轉化生長因子接受器與其下游的Smads信號,被葡萄醣胺/N-乙醯葡萄醣胺、甘露醣胺/N-乙醯甘露醣胺刺激的牙髓幹細胞會進一步的提高成骨特異性轉錄因子(Runx2/Cbfa1)的磷酸化表現,及後期與成骨分化相關的基因表現,如: 鹼性磷酸酵素(ALP)及骨鈣蛋白(osteocalcin)等等。再者,小分子醣胺類衍生物所引起的牙髓幹細胞早期成骨分化,在幫助誘導成骨分化的補充劑存在下,能夠刺激細胞產生更多的礦物基質沉積。 總結本篇的研究的結果,牙髓幹細胞具有較佳的形成細胞群落與分裂及自我增生的能力,而此現象與N-乙醯葡萄醣胺轉移酶-5 (N-acetylglucosaminyltransferase V, GnT-V) 的表現較高有關。在外加的低分子量葡萄醣胺/N-乙醯葡萄醣胺、甘露醣胺/N-乙醯甘露醣胺刺激時,O-端連結的蛋白質醣基化表現並不明顯。相對地,N-乙醯葡萄醣胺轉移酶可進一步增加N-端連結醣鏈形成的第一型轉化生長因子接受器的表現,且經由Smads的信號傳遞下,達到調控牙髓幹細胞成骨分化的效果。Adult stem cells are undifferentiated cells, which have the abilities to divide or self-renew indefinitely and generate most cell lineages. Human mesenchymal stem cells (MSCs) are known to be most useful multipotent cells capable of differentiating into various mesenchymal phenotypes, including osteogenic, myogenic, chrondogenic, and adipogenic lineages. Furthermore, MSCs have also been verified that they abound in various tissues and are able to be isolated from skeletal muscle, adipose tissue, umbilical cord, liver, lung, synovium as well as dental pulp. Dental pulp stem cells (DPSCs) are ideal cell source for hard tissue regeneration due to their well clonogenic, self-renewing, and multi-potential capability. In the part I of this study, primary cell cultures were obtained from human dental pulp tissue of developing third molars, and flow cytometry was used to sort the subpopulation of DPSCs with STRO-1 and CD146 double-positive expression (denoted “DPSCs”). It was noted that DPSCs exhibited superior colonogenic potential and osteogenic differentiation capability to the dental pulp cell subpopulation with STRO-1 and CD146 double-negative expression (denoted DPCs). Besides, our recent study first revealed that the higher level of N-acetylglucosaminyltransferase V (GnT-V) resulted in the superior colonogenic and self-renewal potential of DPSCs. Furthermore, the GnT-V catalyzed the production of N-glycan-branching transforming growth factor-β receptor (TGFβr) type I, which subsequently activated Smads signals in DPSCs with various hexosamine derivatives, e.g. glucosamine (GlcN), N-acetyl-d-glucosamine (GlcNAc), d-mannosamine (ManN) and acetyl-d-mannosamine (ManNAc). A low concentration (0.005 mg/ml) of exogenous hexosamine derivatives was effective in promoting the early osteogenic differentiation of DPSCs. By modulating the GnT-V catalyzed N-glycan forming TGF-βr type I and subsequently Smads signal pathways, GlcN/GlcNAc and ManN/ManNAc treated DPSCs phosphorylated the Runt-related transcription factor 2/Core-binding factor alpha1 (Runx2/Cbfa1) and upregulated mRNA levels of Runx2/Cbfa1, alkaline phosphatase (ALP) and osteocalcin (OCN). In the presence of osteogenic supplements, hexosamine-treated DPSCs produced more mineralized-matrix deposition than did the untreated groups. In summary, this study demonstrated that DPSCs exhibited high level of Gnt-V, which resulted in the superior colonogenic and self-renewal potential of DPSCs. The exogenous hexosamine with low molecular weight, such as GlcN/GlcNAc and ManN/ManNAc, facilitated GnT-V catalyzed N-glycan branching glycoprotein on surface, e.g. TGFβr type I, rather than O-linked glycosylation; and increase level of TGFβr type I further regulated the osteogenic differentiation of human DPSCs through Smads signal pathway

    Fig. 1 in Lactobacillus suantsaii sp. nov., isolated from suan-tsai, a traditional Taiwanese fermented mustard green

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    Fig. 1. Phylogenetic tree based on 16S rRNA gene sequences showing the relationship of Lactobacillus suantsaii sp. nov. L88T with strains of closely related species. The tree was reconstructed by the maximum-likelihood method on the basis of a comparison of approximately 1419 bp, and Leuconostoc mesenteroides subsp. mesenteroides ATCC 8293T was used as an outgroup. Bootstrap values (>60 %) based on 1000 replicates are shown at branch nodes. Bar, 2 % sequence divergence.Published as part of Liou, Jong-Shian, Huang, Chien-Hsun, Wang, Chun-Lin, Lee, Ai-Yun, Mori, Koji, Tamura, Tomohiko, Watanabe, Mizuki, Blom, Jochen, Huang, Lina & Watanabe, Koichi, 2019, Lactobacillus suantsaii sp. nov., isolated from suan-tsai, a traditional Taiwanese fermented mustard green, pp. 1484-1489 in International Journal of Systematic and Evolutionary Microbiology 69 (5) on page 1485, DOI: 10.1099/ijsem.0.003346, http://zenodo.org/record/622387

    Fig. 2 in Lactobacillus suantsaii sp. nov., isolated from suan-tsai, a traditional Taiwanese fermented mustard green

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    Fig. 2. Phylogenetic tree based on the concatenated housekeeping gene sequences (pheS and rpoA) showing the relationship of Lactobacillus suantsaii sp. nov. L88T with strains of closely related species. The tree was reconstructed by the neighbour-joining method on the basis of a comparison of 1138 bp, and Leuconostoc mesenteroides subsp. mesenteroides ATCC 8293T was used as an outgroup. Bootstrap values based on 1000 replicates are shown at branch nodes for neighbour-joining, maximum-likelihood and minimum-evolution methods, respectively. Bar, 5 % sequence divergence.Published as part of Liou, Jong-Shian, Huang, Chien-Hsun, Wang, Chun-Lin, Lee, Ai-Yun, Mori, Koji, Tamura, Tomohiko, Watanabe, Mizuki, Blom, Jochen, Huang, Lina & Watanabe, Koichi, 2019, Lactobacillus suantsaii sp. nov., isolated from suan-tsai, a traditional Taiwanese fermented mustard green, pp. 1484-1489 in International Journal of Systematic and Evolutionary Microbiology 69 (5) on page 1486, DOI: 10.1099/ijsem.0.003346, http://zenodo.org/record/622387

    The Practicalities of Terminally Ill Patients Signing Their Own Dnr Orders - a Study in Taiwan

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    Objectives: To investigate the current situation of completing the informed consent for do-not-resuscitate (DNR) orders among the competent patients with terminal illness and the ethical dilemmas related to it. Participants: This study enrolled 152 competent patients with terminal cancer, who were involved in the initial consultations for hospice care. Analysis: Comparisons of means, analyses of variance, Student's t test, chi(2) test and multiple logistic regression models. Results: After the consultations, 117 (77 .0%) of the 152 patients provided informed consent for hospice care and DNR orders. These included 21 patients (17. 9%) who signed the consent by themselves, and 96 (82.1%) whose consent sheet was signed only by family members. The reasons why patients were not involved in the discussions toward the consent (n = 82) included poor physical or psychological condition (44.9%), concerns of the consultant hospice team ( 37.2%), and the family's refusal (28.2%). On a multivariate analysis, patients' awareness of their poor prognosis (odds ratio = 4.07, 95% confidence interval = 2.05 to 8.07) and their understanding of hospice care (2.27, 1. 33 to 3.89) were two independent factors (p < 0.01) that influenced their participation in the discussions or their personal signature in the informed consent. Conclusion: The family-oriented culture in Asian countries may violate the principles of the Patient Self- Determination Act and the requirements of the Hospice Care Law in Taiwan, which inevitably poses an ethical dilemma. Earlier truth-telling and continuing education of the public by hospice care workers will be helpful in solving such ethical dilemmas
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