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Study on calcium-induced proteolytic cleavage of DNA topoisomerases
No full text時間與空間上的嚴格控制對鈣蛋白酶來調控它的蛋白質水解活性功能是很重要的。這裡，我們證實位於細胞質中的鈣蛋白酶2可以切割水解位於細胞核的人類拓樸異構酶1（hTOP1）及拓樸異構酶2 beta (hTOP2 beta)，而拓樸異構酶2 alpha (hTOP2 alpha)並不會被水解切割,此現象可能透過Ca2+所誘導的鈣蛋白酶2進入細胞核而發生。此由以下的證據支持：(一)細胞處理Ca2+或Ca2+離子載體(ionophores)會造成在細胞核內的hTOP1及hTOP2 beta蛋白質被快速切割水解。 （二）兩種Ca2+螯合物都能有效地阻止ionomycin (一種Ca2 +離子載體)所引起的hTOP1及hTOP2 beta的蛋白質切割；而且添加Ca2+可以直接活化細胞萃取物中蛋白酶切割hTOP1與hTOP2 beta的現象；都支持細胞內的鈣離子濃度[Ca2 +]i對於hTOP1與hTOP2 beta蛋白質的切割是必要的。（三）進一步，我們利用重組蛋白質，實驗顯示鈣蛋白酶2 比鈣蛋白酶 1具有更高的效率去切割hTOP1蛋白質。(四)與以上概念一致，我們推論鈣蛋白酶2可能是主要Ca2 +活化切割hTOP1的蛋白酶之一，因為在降低鈣蛋白酶2表現(si-Capn2)的細胞中hTOP1對於ionomycin 誘導的蛋白質切割有高的抗性。(五)另外，我們的實驗也發現hTOP2 beta與hTOP1均是鈣蛋白酶2的新受質，且hTOP2 beta似乎較hTOP1更容易在相同濃度的ionomycin處理下被切割。(六)鈣蛋白酶2所切割hTOP1蛋白質的位置位於hTOP1的N端(N-terminus)第158及183個胺基酸賴胺酸(K158 and K183)上，而切割後的大片斷hTOP1(hTOP1tr)蛋白質則具有更強解螺旋 (relaxation)的能力。（七）此外，hTOP1tr蛋白質依然保有可以和DNA及喜樹鹼(camptothesin，CPT)形成可切割複合體（TOP1 cleavable complex，TOP1cc），並具有與核仁蛋白質nucleolin的蛋白交互作用能力。（八）細胞處理ionomycin後，鈣蛋白酶 2的活化似乎可以保護細胞免於CPT所引起的細胞毒殺害作用。總結,我們的結果為細胞質中的鈣蛋白酶2如何切割細胞核內蛋白質提供了良好的說明與實驗證據支持：在被Ca2+活化後的鈣蛋白酶2會藉由細胞質-核穿梭運輸，讓鈣蛋白酶 2 從細胞質到細胞核從而接觸到並切割其核內受質。Crucial to calpain function is the tight regulation of its proteolytic activity, which is temporally and spatially controlled. Here, we demonstrated that the cytoplasm-located calpain 2 cleaves human nuclear topoisomerases I (hTOP1) and II beta (hTOP2 beta) but not II alpha (hTOP2 alpha) possibly through the Ca2+-induced nuclear translocation of active proteases. This is supported by the followings: (I) Treatments of cells with Ca2+ or Ca2+ ionophores caused a rapid proteolytic cleavage of hTOP1 and 2 beta in the nucleus. (II) Elevated intracelluar [Ca2+] is responsible for this hTOP1 and 2 beta proteolysis event as suggested by the observations that two Ca2+ chelators could both effectively block the ionomycin-induced cleavage of hTOP1 and 2 beta and addition of Ca2+ in the in vitro protease activation assay caused hTOP1 and 2 beta proteolysis. (III) Using recombinant proteins, our in vitro experiments showed that calpain 2 cleaved hTOP1 more efficient than calpain 1 did.(IV) Consistent with above notion that calpain 2 as a main protease responsible for Ca2+-activated proteolysis of hTOP1, hTOP1 proteins in calpain 2-knockdown (si-Capn2) cells were resistant to the ionomycin-induced proteolysis. (V) Similar to hTOP1, hTOP2 beta has also been identified as a novel substrate for calpain 2. In addition, Ca2+-activated calpain 2 appeared to cleave hTOP2 beta more completed than hTOP1 in the same dose of ionomycin treatment. (VI) The calpain 2 cleavage sites of hTOP1 were mapped at its N’-terminus K158 and K183 and the resulting hTOP1tr exhibited an enhanced relaxation activity. (VII) In addition, the hTOP1tr proteins remained the abilities to form the hTOP1-DNA-camptothecin (CPT) cleavable complex (hTOP1cc) and to interact with nucleolin proteins. (VIII) Ionomycin treatment caused a calpain 2-dependent protection of cells from cytotoxic killing by CPT. In sum, our results provided a good support for the regulation of calpain in the proteolytic cleavage of nuclear proteins via a cytoplasmic-to-nuclear trafficking of calpain 2
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
Get PDF“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
Get PDFWe 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
Get PDFWe 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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