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Lysophospholipids Induce Matrix Metalloproteinases Expression in Human Endothelial Cells
No full text摘要
Lysophosphatidic acid (LPA)與 sphingosine-1-phosphate (S1P)是形態與構造十分簡單的小分子水解磷酸脂(lysophopholipid, LPLs)，經由釵h不同種類細胞分泌，具有一些與蛋白質生長因子十分相似的作用，對細胞的生存、複製、增生及分化都扮演很重要的角色。LPA和S1P會經由和細胞表面特異接受器之接合來達成對細胞的作用，目前已有八個水解磷酸脂的接受器在人類基因中被發現，均屬於內皮細胞分化基因(Endothelial differentiation gene)的G蛋白接合型的接受器(G protein-coupled receptor)，進而活化各種中下游之細胞基質，達到傳遞訊息的目的。Matrix metalloproteinases (MMPs)是一群zinc-dependent的蛋白質水解酵素，可分解釵h細胞外基質(extracellular matrix)，在釵h的研究中已發現MMPs參與在組織重建、胚胎發育、傷口修復和血管新生等，也會增加癌細胞侵入(invation)的能力，其中MMP-2不但廣泛表達而且是參與在這些過程的重要成員。在本研究中，使用RT-PCR，西方墨點法和gelatin zymographic analysis等實驗方法，探討LPA與S1P對人類內皮細胞MMP-2表現的調控。發現MMP-2在包括mRNA、蛋白質和酵素活性等各個不同層次的表現皆受到誘導而增加，且生成量的多寡，與處理時間以及濃度皆呈現正相關。又以一些特異訊息傳導路徑化學抑制物質，找出包括MEK/ERK-，NF-κB-，和鈣離子流動所造成的訊息傳遞都參與在這個調控過程中。之後為了更進一步了解LPA和S1P對內皮細胞在生理弁鄋瑤梇情A我們進行細胞侵入能力的實驗，證實了LPA和S1P明顯地增強內皮細胞的侵入能力，而且此作用會被MMP的抑制物所抑制。同時也觀察到在mRNA的層次，S1P能增加MMP的天然抑制物，Tissue inhibitor of metalloproteinases (TIMPs)的表現，包括TIMP-2和TIMP-3。由此推論水解磷酸脂可藉由對MMP-2活性的調控，以增加細胞遷移或侵入的能力，而對MMP活性的調節也可能經由其抑制物來達成。Abstract
Lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P) are both low molecular weight lysophopholipid (LPLs), which can promote cell proliferation, migration, and invasion via interaction with the endothelial differentiation gene (Edg) family of specific G protein-coupled receptors. Matrix metalloproteinases (MMPs) are a family of zinc-dependent proteolytic enzymes, which are involved in degradation of extracellular matrix, and play critical roles in endothelial cell migration and matrix remodeling during the angiogenesis. Among these MMPs, MMP-2 is an important molecule that is known to trigger the invasion of tumor cells. On the other hand, the nature inhibitors of MMPs, tissue inhibitor of metalloproteinases (TIMPs), are key physiological regulators of MMPs. In our present study, we examine the effects of LPA and S1P on MMPs, especially MMP-2 expression of human endothelial cell. By using RT-PCR, Western blotting, and gelatin zymographic analysis, we showed that LPA and S1P enhanced MMP-2 expression in mRNA, protein levels and also enzymatic activity. The enhancement effects are in a concentration- and time-dependent manner. Next, we evaluated the signal transduction pathway relevant to the MMP-2 expression stimulated by LPLs. Several chemical inhibitors were used including pertussis toxin (Gi blocker), PD98059 (MEK/ERK blocker), U73122 (PLC blocker), LY294002 (PI3 kinase blocker), PDTC (NF-κB blocker), PP2 (Src family kinase blocker), and SKF 96365 (receptor mediate calcium influx blocker). By real-time PCR analysis, the results indicated that these effects are involved in MEK/ERK-, NF-κB-, or calcium influx mediate signaling-dependent pathways. Furthermore, we used chemotaxis chamber to investigate LPL’s effects on cell invasion. Our results showed that endothelial cell invasion was potently increased by LPLs, and the induction can be prevented by preincubation with GM6001, a chemically synthesized MMP inhibitor. Interestingly, we find that S1P also regulated TIMPs expression, including TIMP-2 and TIMP-3. These observations suggest that LPA and S1P may play important roles in endothelial cell invasion by regulating the expression of MMP-2 and may be also MMPs inhibitors.Contents
Abstract................................................I
Introduction............................................1
LPA and S1P.............................................1
Endothelial cell migration..............................3
Mrtix metalloproteinases (MMPs).........................3
Tissue inhibitor of metalloproteinases (TIMPs)..........6
Angiogenesis............................................8
Atherosclerosis.........................................8
MMPs and Cancer........................................10
Material and Methods...................................13
Reagents...............................................13
Cell culture...........................................13
LPLs stimulation.......................................14
RNA extraction and RT-PCR..............................14
Quantitative Real-time PCR.............................15
Western boltting.......................................16
Gelatin zymograghy.....................................18
Invasion assay.........................................19
Chemical inhibition....................................20
Statistical analysis...................................20
Results................................................21
1. Edg receptors expression profile of EAhy926 cells...21
2. LPA and S1P enhance MMP-2 mRNA levels in human endothelial cells......................................21
3. LPA and S1P enhance MMP-2 protein levels in human endothelial cells......................................22
4. LPA and S1P enhance MMP-2 enzymatic activity in human endothelial cells......................................23
5. The LPLs effects on MMP-2 mRNA expression were involved in MEK/ERK-, NF-κB-dependent and calcium influx-pathways...............................................25
6. Enhancement of MMP-2 gelatinolytic activity by LPLs treatments is partially suppressed by these chemical inhibitors.............................................26
7. LPA and S1P induced MMP-dependent endothelial cell invasion...............................................26
8. S1P enhanced TIMP-2 and TIMP-3 mRNA levels in EAhy926 cells..................................................27
Discussion.............................................29
References.............................................38
Tables.................................................50
Figures................................................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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