1,720,954 research outputs found
The fer tyrosine kinase contributes to aberrant androgen receptor signaling in prostate cancer
No full textProstate cancer (PCa) is the most common cancer in Canadian men and the third leading cause of cancer mortality. Despite castration resistance (CRPC) in advanced disease, the androgen receptor (AR) remains transcriptionally active in prostate tumor cells. Our lab has reported on the interleukin (IL)-6 activated tyrosine (Y) kinase (TK) Fer, which phosphorylates and forms nuclear complexes with key transcription factors (TFs) involved in CRPC: signal transducer and activator of transcription (STAT)3 (Y705) and AR (Y223). Recent AR chromatin immunoprecipitation data on PCa tissues from CRPC patients indicates aberrant AR binding to DNA motifs associated to STATs, Myc, and E2Fs. The central hypothesis was that nuclear Fer and possibly other TKs keep TFs activated to allow an integration of signals emanating from different pathways upregulated in advanced forms of human PCa. Accordingly, specific pY223AR and pY714Fer antibodies (Abs) generated in the host lab, along with Fer, AR, AR-V7 (constitutively active AR splice variant), STAT3, pSTAT3, c-Myc, E2F1, and pY Abs, were used as tools to characterize AR Y223 phosphorylation and the formation of complexes in PCa cell lines exposed to diverse stimuli. Our findings confirmed the activation of full-length AR by phosphorylation on Y223, mediated by IL-6 and R1881 (synthetic androgen) in LNCaP cells, whereas full-length AR and the AR-V7 variant are constitutively activated in the more aggressive 22RV1 PCa cell line. Further characterization of the interaction between activated pY223AR and pSTAT3 showed that it is mediated by the SH2 domain of STAT3 binding to the pY223 motif of AR. Of interest, the activation of STAT3 in 22RV1 cells and its interaction with activated AR-V7 are not constitutive but mediated by IL-6. The nuclear co-localization of AR was observed with activated STAT3, c-Myc, and E2F1. Furthermore, AR forms complexes with c-Myc upon exposure of LNCaP to IL-6, but not androgens. AR complexes with E2F1 were also observed under IL-6 or R1881. The pY223 motif of AR is required for these IL-6 mediated interactions, as shown in PC3 cells transfected with wild type vs mutant (Y223F) AR cDNAs. The possible Y-phosphorylation of both c-Myc and E2F1 was also observed in PC3 and LNCaP cells, especially in conditions favoring activation of TKs. Fer directly phosphorylates c-Myc, but not E2F1. Finally, we show clinical relevance of our findings in human prostate tumors, where high nuclear expression of STAT3 and c-Myc are predictive of biochemical recurrence. Taken together, AR activation by Y223 phosphorylation independently of androgens allows the integration of signals emanating from upregulated pathways in CRPC. Aberrant AR signaling reorienting genomic programs may alter cell phenotypes, thereby favoring PCa progression.Le cancer de la prostate (CaP) est le cancer le plus courant chez les hommes au Canada et la troisième cause de mortalité par cancer. Malgré la résistance à la castration (CRPC) dans la maladie avancée, le récepteur des androgènes (AR) reste actif sur le plan transcriptionnel dans les cellules tumorales. Notre laboratoire a étudié l'activation par l'interleukin (IL)-6 de la tyrosine (Y) kinase (TK) Fer qui phosphoryle et forme des complexes nucléaires avec deux facteurs de transcription (FTs) impliqués dans le CRPC: « signal transducer and activator of transcription » (STAT)3 (Y705) et AR (Y223). Une étude récente par immunoprécipitation du AR au niveau de la chromatine sur des tissus de prostate provenant de patients CRPC a indiqué une liaison aberrante du AR à des séquences de l'ADN associées aux FTs STATs, Myc et E2Fs. L'hypothèse centrale est que Fer nucléaire et d'autres TK maintiennent les FTs activés pour permettre une intégration de signaux émanant de différentes voies suractivées dans les formes avancées du CP humain. En conséquence, des anticorps pY223AR et pY714Fer spécifiques générés dans notre laboratoire, ainsi que des anticorps Fer, AR, AR-V7 (variant de AR constitutivement actif), STAT3, pSTAT3, c-Myc, E2F1 et pY ont été utilisés pour caractériser la phosphorylation du AR sur Y223 et la formation de complexes dans les lignées cellulaires du CaP exposées à diverses conditions. Nos résultats ont confirmé l'activation du AR par phosphorylation sur Y223, médiée par l'IL-6 et le R1881 (androgène synthétique) dans les cellules LNCaP, alors que le AR et le variant AR-V7 sont constitutivement activés dans les cellules 22RV1, aussi plus agressives. La caractérisation de l'interaction entre pY223AR activé et pSTAT3 a montré que ceci est médié par le domaine SH2 de STAT3 se liant au motif pY223 du AR. De plus, l'activation de STAT3 dans les 22RV1 et son interaction avec le AR-V7 activé ne sont pas constitutives, mais médiés par l'IL-6. La colocalisation nucléaire du AR a été observée avec STAT3 activé, c-Myc et E2F1. En outre, AR forme des complexes avec c-Myc dans les cellules LNCaP exposées à l'IL-6, mais pas aux androgènes. Des complexes AR avec E2F1 ont également été observés dans ces cellules sous l'IL-6 et le R1881. Dans les cellules PC3 transfectées avec l'ADNc du AR forme sauvage ou mutant (Y223F), on observe que le motif Y223 de AR est important pour ces interactions sous l'IL-6. Les FTs c-Myc et E2F1 peuvent également être phosphorylés sur Y dans les cellules PC3 et LNCaP, notamment dans des conditions favorisant l'activation des TK par le pervanadate. Fer phosphoryle directement c-Myc, mais pas E2F1. Enfin, nous montrons la connotation clinique de nos résultats dans des tumeurs de prostate humaine, la forte expression nucléaire de STAT3 et c-Myc étant prédictives de la récidive biochimique. Pris ensemble, l'activation du AR par la phosphorylation sur Y223 indépendamment des androgènes permet l'intégration de signaux émanant des voies suractivées dans le CRPC. La signalisation aberrante du AR réorientant les programmes génomiques peut altérer les phénotypes des cellules et ainsi favoriser la progression du CaP
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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