1,720,957 research outputs found
Evaluation of the effect of lipid metabolism on the Hippo pathway through a novel extracellular matrix complex
Full text linkThe Hippo signalling pathway tightly governs tissue growth. Activation of the Hippo signalling pathway leads to phosphorylation and inactivation of transcriptional coactivators YAP and TAZ and their cytoplasmic retention, whereas inactivation of the Hippo signalling
pathway leads to dephosphorylation and hyperactivation of YAP/TAZ and translocation into the nucleus to modulate a diverse range of cellular functions such as cell proliferation,migration differentiation and apoptosis. YAP/TAZ can act as a central hub relaying multiple
signals and integrating diverse functions. The extracellular matrix (ECM) plays an important role in the regulation of the Hippo signalling pathway as do YAP/TAZ which can themselves be affected by cellular metabolism. Free fatty acids have been shown to regulate the
transcriptional activity of YAP/TAZ. However, a link between the ECM, Hippo signalling pathway and lipids has not been previously descibed. This project shows a direct relationship between the Hippo signalling pathway, the ECM and exogenously supplied lipids. Furthermore, the project provides an understanding of how novel ECM components
are involved in this regulation.
The Hippo signalling pathway effector YAP was shown to interact with ECM proteins; Talin, CD2AP, PDLIM7 and Ezrin by Co-immunoprecipitation leading to the characterisation of a
novel protein complex coupling the Hippo signalling pathway, the ECM and lipids in a CaCo2 and Hep-G2 cell culture model system. Scratch assays were used to observe the effect of complex member proteins on cellular migration. Knockdown of YAP and Talin was shown
to slow down the migration rate of CaCo-2 cells. Immunofluorescence (IF) imaging was used to describe the effect of the various complex member proteins on the stabilisation of YAP following siRNA knockdown of CD2AP/Talin/Ezrin to show that translocation of YAP
between nucleus and cytoplasm was affected.Depletion of talin resulted in inactivation of YAP by inducing its translocation from nucleus to cytoplasm in both CaCo-2 and Hep-G2 cells whereas depletion of CD2AP and Ezrin had no effect.
The availability of oleic acid (OA) and palmitic acid (PA), the most abundant fatty acids, on the Hippo signalling effector YAP and the novel components of the Hippo/ECM complex was described. The results obtained indicated that lipids leads to inhibition of YAP activity
by significantly increasing the p-YAP levels. CaCo-2 cells treated with lipids showed a marked decrease in cellular migration. Oleic acid was shown to disrupt the interaction of YAP with CD2AP and the interaction of Talin with CD2AP. Addition of OA was shown to affect the localization of proteins of the identified complex by mmunofluorescence microscopy. Upon OA treatment, nuclear YAP was decreased in both CaCo-2 and Hep-G2 cells. The levels of lipid droplet formation following addition of OA in conjunction with the
depletion of proteins within the complex was also evaluated in CaCo-2 and Hep-G2 cells. This provided a new insight into the relationship of lipid metabolism with the ECM and Hippo signalling pathway. Planarians have been used as a model organism in order to assess
the effect of lipid metabolism in a physiological relevant system. The results gathered with OA in-vivo are consistent with the results obtained in the tested mammalian cell lines.
Finally, the novel protein interactions and expression of specific genes with the Hippo signalling pathway upon addition of fatty acids was analysed by mass spectroscopy (MS)
and RNA-Sequencing. Numerous YAP-interactors were obtained by MS analysis and most importantly, OA was shown to abolish the interaction of Ezrin and Radixin with YAP. Thedata obtained from RNA-Sequencing revealed that, expression of downstream target genes
of YAP (MYC and ANKRD1) were downregulated whereas key upstream components of the Hippo signalling pathway (FRMD6 and TAOK-1) were upregulated upon addition of oleic acid.
The data obtained therefore indicates that fatty acids in part interact/manipulate the Hippo signalling pathway to regulate its activation state through the newly described ECM comple
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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