1,720,977 research outputs found
Study of TRAIL apoptosis signaling regulated by Helicobacter pylori in activation of mitochondria pathway
No full textTRAIL (又稱為Apo2 ligand) 屬於腫瘤壞死因子家族的一員，可透過與其死亡受體結合引起細胞凋亡。TRAIL具有引發多種轉型細胞株進行細胞凋亡的能力，但是對於大部分的正常細胞則不具細胞毒殺性。在我們實驗室過去的研究中發現，人類胃上皮細胞對TRAIL具有抗性，然而胃幽門螺旋桿菌可以改變人類胃上皮細胞對TRAIL的抗性。我們認為此增加的細胞凋亡現象，是由於胃幽門螺旋桿菌經由活化caspase-8下游途徑進而造成粒線體訊息傳遞路徑活化而打破對細胞凋亡的抗性。而幽門螺旋桿菌所調控的位置是位於胃上皮細胞株內caspase-8的上游及Bid活化的下游。
在本研究中，我們的結果顯示出只有在胃幽門螺旋桿菌存在的情況下，人類胃上皮細胞株在加入TRAIL作用可以活化caspase-2。而加入caspase-2的抑制劑可以抑制幽門螺旋桿菌所引起的細胞凋亡。這樣的結果指出caspase-2在幽門螺旋桿菌所引起TRAIL的細胞凋亡途徑中是被需要的。
爲了進一步探討在TRAIL所調控的細胞凋亡當中caspase-2的作用機制，我們利用加入caspase-2的抑制劑來觀察Bid活化的情形。我們的結果顯示出，只有在幽門螺旋桿菌存在的情況下，TRAIL會引起胃上皮細胞株的Bid被切開和t-Bid產生。這樣的現象可以在加入caspase-2抑制劑所抑制。因此，在幽門螺旋桿菌所引起TRAIL細胞凋亡途徑中，caspase-2可以作用在切開Bid的上游。此外，加入caspase-8的抑制劑可以抑制caspase-2活化而加入caspase-2抑制劑卻不影響caspase-8活化。由這些結果我們認為在幽門螺旋桿菌所引起TRAIL細胞凋亡途徑中caspase-2是位於caspase-8的下游途徑。另外，我們也觀察到只有在幽門螺旋桿菌存在的情況下，TRAIL會引起Bax的轉位，暗示在幽門螺旋桿菌所引起TRAIL細胞凋亡途徑中，t-Bid可能會透過活化Bax來造成粒腺體釋放出cytochrome c。綜合以上結果顯示在幽門螺旋桿菌所引起TRAIL細胞凋亡途徑中，caspase-2可以在切開Bid上扮演調控的角色並透過Bax轉位來活化粒線體途徑。Tumor necrosis factor-related apoptosis-inducing ligand or Apo 2 ligand (TRAIL/Apo2L) is a member of the tumor necrosis factor (TNF) family of ligands capable of initiating apoptosis through engagement of its death receptors. TRAIL selectively induces apoptosis of a variety of tumor cells and transformed cells, but not most normal cells. Previous studies in our laboratory have demonstrated that human gastric epithelial cells are resistant to TRAIL. However, Helicobacter pylori can confer human gastric epithelium cells to TRAIL sensitivity. The enhanced TRAIL sensitivity by H. pylori is via activation of caspase-8 downstream pathway to activate mitochondria signaling pathway, leading to breaking apoptosis resistance. The alteration of H. pylori-sensitized TRAIL sensitivity is at the level of caspase-8 downstream pathway and upstream of Bid cleavage.
In this study, our results demonstrated that caspase-2 was activated by TRAIL in human gastric epithelial cells only in the presence of H. pylori. Pre-treatment with caspase-2 inhibitor, z-VDVAD-fmk, could block H. pylori-sensitized TRAIL-mediated apoptosis in human gastric epithelium cells. This suggested that caspase-2 is required for H pylori- induced TRAIL apoptosis signaling.
To further explore the regulatory mechanism of caspase-2 in TRAIL-mediated apoptosis, we investigated Bid cleavage by pretreatment with z-VDVAD-fmk. Our results showed that in the presence of H. pylori, TRAIL induced Bid cleavage and truncated Bid (t-Bid) formation in gastric epithelial cells. This phenomenon was blocked by z-VDVAD-fmk. Therefore, caspase-2 could function upstream of Bid cleavage in H. pylori-induced TRAIL apoptosis signaling. Moreover, pretreatment with caspase-8 inhibitor, z-IETD-fmk, inhibit caspase-2 processing but pretreatment with caspase-2 inhibitor, z-VDVAD-fmk have no effect on caspase-8 processing. These results suggest that caspase-2 is in the downstream pathway of caspase-8 in TRAIL apoptosis signaling. In addition, TRAIL induced Bax translocation in the presence of H. pylori, indicating that t-Bid activated Bax to promote cytochrome c release from mitochondria during H pylori-induced TRAIL apoptosis signaling. Taken together, these results show that caspase-2 can play a regulatory role on Bid cleavage and activation of mitochondria pathway via BAX translocation in H. pylori-induced TRAIL apoptosis signaling.Chapter I. Introduction
Part 1. TRAIL and its receptors 1
Part 2. TRAIL-induced apoptosis signaling 2
Part 3. TRAIL sensitivity and resistance 5
Part 4. Helicobacter pylori 8
Part 5. Aims of the study 8
Chapter II. Materials and Methods
Part 1. Experimental Materials 11
Part 2. Experimental Procedures 19
1. Recombinant His-TRAIL 19
2. Measurement of apoptosis 20
3. Isolation of subcellular fractions 21
4. Western Blot 23
Chapter III. Results
Part 1. H. pylori induce activation of caspase-2 in TRAIL apoptosis signaling 24
Part 2. H. pylori-induced TRAIL sensitivity could be blocked by caspase-2 inhibitor, z-VDVAD-fmk 25
Part 3. Cleavage of Bid could be blocked by caspase-2 inhibitor, z-VDVAD- fmk 26
Part 4 .Caspase-2 can function downstream of caspase-8 27
Part 5 . H. pylori induce Bax translocation in AGS cells after TRAIL engagement 28
Chapter IV. Discussion
Part 1. H. pylori modulate TRAIL sensitivity via Caspase-2 31
Part 2. Caspase-2 can function upstream of Bid cleavage and downstream of caspase-8 32
Part 3. Role of Bcl-2 family in TRAIL mediated apoptosis 34
Part 4. Conclusion 36
Reference 37
Figures 46
Figure1. TRAIL apoptosis signaling pathway 46
Figure2. H. pylori induce caspase-2 activation after TRAIL engagement in AGS cells 47
Figure3. H. pylori-induced TRAIL sensitivity could be blocked by caspase-2 inhibitor, z-VDVAD-fmk 48
Figure4. H. pylori-induced Bid cleavage after TRAIL engagement could be inhibited by pretreatment of caspase-2 inhibitor, z-VDVAD-fmk 50
Figure5. Pretreatment with caspase-2 inhibitor, z-VDVAD-fmk, has no significant influence on caspase-8 processing 51
Figure6. Caspase-2 processing was inhibited by pretreatment with caspase-8 inhibitor, z-IETD-fmk 52
Figure7. BAX translocation in TRAIL-induced apoptosis in AGS cells by H. pylori 53
Figure8. Bcl-2, Bcl-xL, and Mcl-1 expression in the presence or absence of H. pylori during TRAIL engagement 54
Figure9. TRAIL signaling pathway regulated by H. pylori in AGS cells 5
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
Author Under Sail The Imagination of Jack London, 1893-1902
No full textIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Intro -- Title Page -- Copyright Page -- Dedication -- Contents -- Acknowledgments -- Introduction -- 1. Spirit Truth -- 2. From Absorption to Theatricality and Back Again -- 3. "I Will Build a New Present" -- 4. Sons as Authors -- 5. Fathers as Publishers -- 6. The Daughter as Author -- 7. Lovers as Authors -- 8. At Sea with the Family -- 9. Yellow News, Yellow Stories -- 10. The Return Home -- Notes -- Bibliography -- Index -- About Jay WilliamsIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Description based on publisher supplied metadata and other sources.Electronic reproduction. Ann Arbor, Michigan : ProQuest Ebook Central, YYYY. Available via World Wide Web. Access may be limited to ProQuest Ebook Central affiliated libraries
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