1,720,976 research outputs found
REGULATION OF THE HEMATOPOIETIC SELF-RENEWAL AND LINEAGE CHOICE: ROLE OF PBX1 AND MICRO-RNAS
Get PDFHematopoiesis is a highly regulated process (Orkin and Zon, 2008). For a constant supply of short-lived terminally differentiated blood cells, and for rapid response to hematopoietic stresses, HSCs are endowed with the ability to continuously provide more mature progenitors while properly maintaining their pool size, without exhaustion, throughout life. This equilibrium is finely maintained on one hand by precisely balancing self-renewal and differentiation in HSCs, and on the other hand by regulating proliferation and differentiation also of their downstream progenitors, including lineage choice. Thus, understanding mechanisms of regulation of self-renewal versus differentiation of HSCs and downstream progenitors is a central issue in stem cell field, since tiny alteration of these mechanisms may lead to hematopoietic failure and disease.
Pbx1 is a transcription factor that positively regulates post-natal HSC quiescence. Its absence in HSCs causes an excessive proliferation that leads to their exhaustion, indicating a profound self-renewal defect, and premature myeloid differentiation at the expenses of lymphoid differentiation (Ficara et al., 2008). However, the precise molecular mechanisms through which Pbx1 exerts its function in HSCs and its role in progenitor biology are two still unexplored issues. In particular, it is not known whether Pbx1 function is also mediated by micro-RNAs, crucial new players in the regulation of proliferation and differentiation in several tissues, including the hematopoietic system.
Taking advantage of Pbx1 conditional KO mice, in this study, we demonstrate that Pbx1 functions as a brake on cell differentiation not only in HSCs but also in multi-potent and myeloid-restricted progenitors, to maintain progenitor reservoirs and lymphoid potential. In absence of Pbx1, both myeloid and lymphoid progenitors are able to differentiate into mature progeny but with higher efficiency and premature kinetic for the myeloid lineage and a decreased efficiency in the lymphoid (and erythroid) lineage. Pbx1 acts also upstream to lineage restricted progenitors, affecting lineage choice of multipotent progenitors (MPPs) by restraining myeloid differentiation and allowing lymphoid differentiation.
Moreover, we show that in the absence of Pbx1 HSCs display an altered micro-RNA profile, which resembles the normal MPP profile, suggesting a role for miRNAs in maintaining HSC identity.
Pbx1-null HSCs and MPPs show specific lists of DE miRNAs, with substantial overlaps with the normal HSC-to-MPP transition. Combining miRNA data with transcriptional profile data of the same populations (Ficara et al., 2008) allowed searching for miRNA predicted targets whose change in expression inversely correlates with those of mRNAs. This analysis, coupled with extensive bioinformatics studies (promoter analysis, co-targeting and GSEA) allowed selection of very few candidate miRNAs to be further studied for their specific role in maintaining HSC self-renewal, and their possible regulation by Pbx1. In addition to a list of Pbx1-dependent miRNAs in HSCs and MPPs, we also analyzes for the first time miRNAs characteristic of the normal transition from HSCs to the first MPP stage, which represent an important finding for understanding miRNAs physiologically involved at the apex of hematopoietic system. Overall, this analysis set the basis for the discovery of miRNAs involved in the regulation of self-renewal versus differentiation of HSCs
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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