1,720,954 research outputs found
Unveiling the Role of BORA in Ovarian Cancer Dissemination: a new potential targeted therapeutic strategy
No full textEl càncer d'ovari (CO) és la neoplàsia ginecològica més letal en països desenvolupats, amb una supervivència als 5 anys menor al 30%. Aquest mal pronòstic s'explica, principalment, perquè la majoria de les pacients són diagnosticades en estadis avançats, quan el càncer ja ha disseminat per la cavitat peritoneal i on les opcions terapèutiques són limitades.
BORA és el principal cofactor de PLK1, una quinasa amb múltiples rols en mitosis, entre els quals destaca el seu paper en la transició G2/M. A més, PLK1 també té diferents funcions fora del cicle cel·lular, entre les quals hi ha promoure la transició epiteli-mesènquima (EMT). La EMT és un procés clau en la disseminació del càncer degut a que confereix a les cèl·lules més motilitat, propietats de cèl·lules mare, resistència a la mort per anoikis, i major resistència a la quimioteràpia. Tant BORA com PLK1 s'han trobat sobreexpressades en diferents neoplàsies, incloent el CO, on se'ls hi han atribuït propietats oncogèniques. Considerant això, en aquesta tesis hem avaluat el paper de BORA en la disseminació del CO, en concret, la seva capacitat de promoure la EMT de forma PLK1-dependent.
En aquest projecte hem demostrat que la sobreexpressió ectòpica de BORA promou la EMT, augmentant el potencial de migrar i envair de les cèl·lules tumorals in vitro, i incrementant la formació de metàstasis in vivo. A més, hem demostrat que les cèl·lules amb nivells endògens de BORA alts migren més que la població parental, el que ens fa postular que alta expressió endògena de BORA confereix a les cèl·lules canceroses més flexibilitat per iniciar la EMT, un estat cel·lular conegut com a "metastable". D'altra banda, els nostres resultats també indiquen que nivells ectòpics elevats de BORA afavoreixen la angiogènesis, un procés necessari pel creixement tant del tumor primari com del secundari. Finalment, també hem testat la inhibició de BORA utilitzant siRNAs contra BORA conjugats amb un tipus de nanopartícules anomenades Quatsomes. Amb aquesta estratègia, hem demostrat que silenciar BORA redueix la viabilitat de les cèl·lules de CO, disminueix la seva capacitat de migrar i que, quan es combina amb els fàrmacs que s'utilitzen actualment contra el CO en la clínica, augmenta el seu benefici terapèutic.
En resum, els nostres resultats suggereixen que BORA contribueix a la disseminació del CO a través de promoure la EMT. Per tant, la inhibició de BORA podria bloquejar aquest procés i així reduir la capacitat del CO de disseminar, així com també disminuiria la viabilitat de les cèl·lules. Per tant, els nostres resultats descriuen una nova potencial estratègia terapèutica per tractar les pacients amb CO avançat.El cáncer de ovario (CO) es la neoplasia ginecológica más letal en los países desarrollados, con una supervivencia a los 5 años menor al 30%. Este mal pronóstico se explica, principalmente, debido a que la mayoría de las pacientes son diagnosticadas en estadios avanzados de la enfermedad, cuando el cáncer ya ha diseminado por la cavidad peritoneal y donde las opciones terapéuticas son limitadas.
BORA es el principal cofactor de PLK1, una quinasa con múltiples funciones en la mitosis, destacando su papel en la transición G2/M. Además, PLK1 también tiene funciones fuera del ciclo celular, entre las cuales está promover la transición epitelio-mesénquima (EMT). La EMT se considera un proceso clave en la diseminación del cáncer debido a que confiere a las células mayor motilidad, propiedades de células madre, resistencia a la muerte por anoikis, y mayor resistencia a los fármacos quimioterapéuticos. Tanto BORA como PLK1 se han visto sobreexpresadas en diferentes neoplasias, incluyendo el CO, donde se les han atribuido propiedades oncogénicas. Considerando esto, en esta tesis hemos evaluado el papel de BORA en la diseminación del CO, en concreto, su capacidad de promover la EMT de forma PLK1-dependiente.
Hemos demostrado que la sobreexpresión ectópica de BORA promueve la EMT, aumentando el potencial de migrar e invadir de las células tumorales in vitro, e incrementando la formación de metástasis in vivo. Además, hemos demostrado que aquellas células con niveles endógenos altos de BORA migran más que la población parental, lo que nos hace postular que una alta expresión endógena de BORA confiere a las células cancerosas más flexibilidad para iniciar la EMT, un estado celular conocido como "metastable". Por otro lado, nuestros resultados indican que niveles ectópicos elevados de BORA favorecen la angiogénesis, un proceso necesario para el crecimiento tanto del tumor primario como del secundario. Finalmente, hemos testado la inhibición de BORA mediante siRNAs contra BORA conjugados con un tipo de nanopartículas llamadas Quatsomes. Con esta aproximación hemos demostrado que silenciar BORA reduce la viabilidad de las células de CO, disminuye su capacidad de migrar y que, al combinarse con los fármacos utilizados actualmente contra el CO en la clínica, aumenta su beneficio terapéutico.
En resumen, nuestros resultados sugieren que BORA contribuye a la diseminación del CO a través de promover la EMT. Por lo tanto, la inhibición de BORA podría bloquear este proceso y así reducir la capacidad del CO de diseminar, así como también disminuiría la viabilidad de las células. Por lo tanto, nuestros resultados describen una nueva potencial estrategia terapéutica para tratar a las pacientes con CO avanzado.Ovarian cancer (OC) accounts for the most lethal gynecologic malignancy in developed countries, with a five-year survival of less than 30%. This poor outcome is mainly explained because the majority of OC cases are diagnosed at advanced stages, when the disease has already spread into the peritoneal cavity and the therapeutic options available are limited.
BORA is the main cofactor of PLK1, a kinase with key roles in multiple steps of mitosis, highlighting its implication in G2/M transition. Furthermore, PLK1 has also several functions beyond cell cycle, among which there is the triggering of the epithelial-mesenchymal transition (EMT). EMT is a key event for cancer dissemination, which gives to cancer cells increased motility, stem cell properties, resistance to anoikis, and increased chemoresistance. Both PLK1 and BORA have been found overexpressed in several malignancies, including OC, where have been associated with oncogenic functions. Considering this, in this thesis we have evaluated the role of BORA in OC dissemination, particularly its capacity to promote EMT in a PLK1-dependent manner.
We have demonstrated that ectopic BORA overexpression induces EMT, which gives OC cells increased migration and invasion capabilities in vitro, resulting in increased metastasis formation in vivo. Furthermore, we have proven that cells with high endogenous BORA expression migrate more than the average, hence we postulate that high endogenous BORA levels might confer to cancer cells increased flexibility to undergo EMT, a cell state referred to as "metastable". Additionally, we have shown that high ectopic BORA expression promotes angiogenesis, a process required for the outgrowth of both the primary and the secondary tumors. Finally, we have tested BORA inhibition using siRNAs against BORA delivered via a type of nanoparticles named Quatsomes. We have demonstrated that BORA silencing decreases OC cells viability, reduces their migration potential, and enhances the therapeutic benefit when combined with the standard of care.
In summary, our findings indicate that BORA contributes to OC dissemination by triggering EMT. Therefore, BORA inhibition might block this process and thus it might reduce the disseminative potential of OC, while also decreasing OC cells viability. Altogether, our results point out a new potential therapeutic strategy to treat advanced OC patients.Universitat Autònoma de Barcelona. Programa de Doctorat en Bioquímica, Biologia Molecular i Biomedicin
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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