1,720,959 research outputs found
Dissecting the role of mitochondrial Ca2+ signaling in cancer cell migration and progression
Le metastasi rappresentano la principale causa di mortalità correlata al cancro. Si evidenzia dunque l’importanza di identificare i processi biologici e le componenti molecolari chiave per prevenire e controllarne la progressione.
Il segnale calcio (Ca2+) gioca un ruolo fondamentale nel modulare diverse funzioni cellulari come contrazione muscolare, mobilità cellulare, fertilità, proliferazione e apoptosi. La deregolazione dell’omeostasi di questo ione è correlata a diverse patologie tra cui il cancro. La migrazione cellulare rappresenta un aspetto cruciale del processo metastatico in quanto permette alle cellule tumorali di diffondersi dalla sede del tumore primario e colonizzare sedi più o meno distanti da esso. Durante la migrazione cellulare, l’organizzazione spazio-temporale del Ca2+ intracellulare garantisce una rapida ed effettiva attivazione delle componenti di segnalazione che giocano un ruolo centrale nella motilità cellulare. Infatti, mentre il ruolo del Ca2+ citosolico nella migrazione è ben noto, il ruolo funzionale del calcio mitocondriale e le sue dinamiche sono emerse solo recentemente.
Pertanto, l’ipotesi di questo studio sostiene che MCU e la segnalazione del Ca2+ mitocondriale siano fondamentali per il movimento cellulare e abbiano un ruolo decisivo nelle fasi iniziali del processo metastatico. A questo scopo, abbiamo sviluppato un modello sperimentale di imaging cellulare in vitro che ha permesso di monitorare simultaneamente i livelli di Ca2+ mitocondriale e la migrazione cellulare per analizzare le variazioni di Ca2+ nelle cellule tumorali metastatiche e non. Abbiamo osservato che le cellule tumorali che migrano attivamente richiedono un robusto assorbimento di Ca2+ mitocondriale e un elevato potenziale di membrana mitocondriale per poter migrare efficientemente. Notevoli variazioni nei livelli di Ca2+ mitocondriale basale sono state rilevate tra le cellule tumorali migranti e non. In particolare, il silenziamento di MCU ha portato a una significativa diminuzione dell’assorbimento di Ca2+ mitocondriale compromettendo notevolmente la capacità di migrazione delle cellule di carcinoma polmonare NCI-H460.
Tali approcci evidenziano il ruolo fondamentale del Ca2+ mitocondriale nella migrazione cellulare. Pertanto, avere come target la segnalazione alterata del calcio nel corso della tumorigenesi potrebbe essere un approccio terapeutico promettente per limitare o bloccare le metastasi.Tumor metastasis represent the primary cause of cancer morbidity and mortality thus highlighting the importance to find new therapeutic strategies to eradicate this process. Calcium (Ca2+) is one of the crucial signalings that modulate various cellular functions. The dysregulation of Ca2+ homeostasis has been suggested as a significant event in driving the expression of malignant phenotypes. Cell migration is a prerequisite for tumor metastasis enabling cancer cells to disseminate from their original site. During cell migration, the spatio-temporally organization of intracellular Ca2+ provides a rapid and robust way for the activation of signaling components that play a central role in cytoskeletal reorganization, traction force generation, and focal adhesion dynamics. However, while the role of cytosolic Ca2+ in cell migration is well established, the functional role of mitochondrial Ca2+ and dynamics has only emerged recently. Thanks to the identification of the genetic component of the mitochondrial Ca2+ uniporter (MCU), the role of mitochondrial Ca2+ homeostasis in cell migration can be directly examined. In this study, we address the hypothesis that MCU and mitochondrial Ca2+ signaling are pivotal for cell movement and have a decisive role in the initial steps of the metastatic process. For this purpose, we have developed an in vitro model of single-cell imaging that allowed us to simultaneously monitor mitochondrial Ca2+ levels and cell migration in order to analyze Ca2+ variations in metastatic and in non-metastatic cancer cells. We observed that actively migrating cancer cells require a robust transient mitochondrial Ca2+ uptake and high mitochondrial membrane potential in order to migrate. Moreover, remarkable variations in basal mitochondrial Ca2+ levels have been detected between migrating and non-migrating cancer cells. Notably, MCU silencing led to a significant decrease in mitochondrial Ca2+ uptake and markedly impaired the migration ability of NCI-H460 lung cancer cells.
In conclusion, these approaches highlight the fundamental role of mitochondrial Ca2+ homeostasis in cell migration, thus targeting altered calcium signaling during the course of tumorigenesis could be a promising therapeutic approach to limit or block metastasis
Going Beyond Counting First Authors in Author Co-citation Analysis
The 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
“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
We 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
We 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
We 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.
Author-wise bibliometric analysis based on entropy.</p
Author Under Sail The Imagination of Jack London, 1893-1902
In 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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