1,720,953 research outputs found
Miro1-Mediated Mitochondrial Positioning In The Development And Metastasis Of Breast Cancer
No full textBreast cancer remains a leading cause of cancer related mortality worldwide, with triple-negative breast cancer (TNBC) representing one of the most aggressive and therapeutically challenging subtypes. Mitochondrial positioning within cells has emerged as a critical determinant of cancer cell metabolism, signaling, and survival, yet the molecular mechanisms governing these spatial dynamics and their contribution to tumorigenesis are not well understood. Miro1 (mitochondrial Rho GTPase 1) is a protein embedded in the mitochondrial outer membrane. Miro1 is essential for coordinating mitochondrial trafficking along microtubules through its interactions with adaptor proteins such as TRAK1/2 and motor proteins. Beyond its canonical role in mitochondrial transport, Miro1 is also involved in calcium homeostasis, organelle contact site formation, and mitophagy. Importantly, published data indicate that breast cancer patients whose tumors express high levels of Miro1 have significantly poorer survival outcomes compared to those with low Miro1 expression, highlighting the importance of investigating its role in the molecular mechanisms that drive breast cancer progression.In recent years, Miro1 has been implicated in supporting cellular processes such as migration and proliferation in both normal and malignant cells, including breast cancer. To investigate the role of Miro1 in breast cancer tumorigenesis and metastasis, we generated MDA-MB-231 human breast cancer cells with stable knockdown of Miro1. Loss of Miro1 led to increased phosphorylation of ERK1/2, loss of DUSP6 translation, and increased 4EHP expression. In our functional assays, Miro1 knockdown was associated with reduced cell proliferation, migration, and invasion in vitro. In vivo, xenografts derived from Miro1 knockdown cells resulted in significantly reduced tumorigenesis compared to wild-type controls. To further assess the role of Miro1 in mammary tumor development in vivo, we generated a novel transgenic mouse model with inducible, tissue-specific deletion of Miro1 in mammary epithelial cells, in combination with polyomavirus middle T-antigen (PyVMT) oncogene activation. In this model, Miro1 wild-type mice developed tumors at all mammary gland sites and exhibited pulmonary metastases. In contrast, mice with complete Miro1 deletion failed to form tumors despite oncogene activation. Notably, heterozygous mice with only one intact Miro1 allele developed primary tumors but displayed a markedly reduced capacity for metastasis. Together, these findings demonstrate that Miro1 is not merely a regulator of mitochondrial positioning, but a key modulator of cellular behaviors that drive both the initiation and progression of breast tumors. Its loss impairs primary tumor formation, disrupts oncogenic signaling pathways, and diminishes the metastatic potential of breast cancer cells. The observed dose-dependent effects ranging from complete tumor suppression in Miro1-null mice to reduced metastasis in heterozygous models further emphasize the importance of Miro1 expression levels in determining tumor initiation. These data suggest that Miro1 may serve as a valuable biomarker for tumor status, reflecting both proliferative capacity and metastatic risk. Moreover, the findings highlight Miro1 as a promising therapeutic target, where modulation of mitochondrial positioning and associated signaling pathways could offer novel strategies for treating aggressive subtypes such as triple-negative breast cancer.Cellular, Molecular and Biomedical SciencesDoctor of Philosophy (PhD
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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