1,720,985 research outputs found
Long non-coding RNAs in the epigenetic regulation of oligodendrocyte differentiation
No full textLong non-coding RNAs (lncRNAs) constitute a heterogeneous class of RNAs with limited coding potential, united by an arbitrarily placed cut off of >200 ntd. The past decade has seen the emergence of lncRNAs as versatile regulators of gene expression, amidst skepticism regarding the biological usefulness of pervasive genomic transcription and its non-coding RNA products prevalent in most eukaryotes. A significant portion of lncRNAs operate in the development and functioning of the mammalian CNS. Oligodendrocytes (OLs) are the myelinating cells of the CNS that are essential for efficient saltatory conduction and axonal survival. They are derived from OL precursors (OPCs) and progress into transcriptomically heterogeneous OL sub-populations along the differentiation pathway to produce mature OLs, capable of myelination. These epigenetic transitions between different OL subpopulations are carefully regulated, spatially and temporally, by a network of transcription factors, chromatin modulators and lncRNAs. In demyelinating diseases like multiple sclerosis (MS), patients suffer immune mediated attacks against myelin. Eventually, remyelination strategies fail due to deficits in OPC migration and OL differentiation at the site of lesions. Thus, understanding molecular mechanisms governing OL differentiation and myelination is crucial not only for understanding OL function in health but also in disease, in order to develop suitable therapeutic interventions.The investigations presented in this thesis explore the role of lncRNAs and RNA-binding proteins in neurodevelopment, particularly in embryonic stem cells (ESCs) and cells of the OL lineage. Article 1 provides a resource for the protein interactome of a key pioneering transcription factor, Sox2, in different nuclear fractions of mouse ESCs. We found Sox2 to be a multifaceted regulator forming interactions with HP1 family of proteins, whose members perform as both activators and repressors in a context dependent manner. In addition to interacting with RBPs involved in post-transcriptional processes, Sox2 also interacted with Rn7sk, a well-known ncRNA involved in the regulation of transcriptional elongation at promoters and enhancers. Although they did not influence each other‘s recruitment to the chromatin, this interaction opens up the possibility for ncRNA mediated modulation of ES transcriptional programs dependent on Sox2.Article 2 draws important insights regarding lncRNAs from a broad transcriptomic resource established from single cell- as well as bulk RNA- sequencing of OL lineage cells from different developmental stages. From a subset of lncRNAs which were found to be specific for certain OL subpopulations, we investigated the role of 2610035D17Rik in modulating the expression of its neighboring gene, Sox9, a transcription factor essential for OPC specification. We decoupled the role of lncRNA transcript from its genomic locus using various loss-of-function strategies and found that the regulation of Sox9 was dependent on the regulatory elements and/or ongoing transcription at the 2610035D17Rik locus, rather than the transcript itself. In Article 4, we investigated a hitherto unexplored RNA-binding function of myelin gene expression factor 2 (Myef2), a known transcriptional repressor of myelin basic protein (MBP). To this end, we uncovered the RNA interactome of Myef2 in a mouse oligodendroglial cell line with individual nucleotide resolution CLIP (iCLIP) followed by sequencing. We show that Myef2 interacts with CUG motifs located within introns and 3‘UTRs of protein-coding genes, a finding which implicates Myef2 in post-transcriptional processes like splicing and RNA stability.Finally, in Article 3 we have identified disease specific transcriptomic profiles of OL lineage cells through single-cell RNA sequencing of OPCs and OLs derived from experimental autoimmune encephalomyelitis (EAE) mice, a model that recapitulates several aspects of MS. EAE specific OPC and OL clusters were enriched for genes involved in antigen processing and presentation (MHC class I/II). We could demonstrate that OPCs can phagocytose myelin debris and MHC-II-expressing OPCs can activate memory and effector CD4-positive T cells. These findings show OL lineage cells as active participants in MS pathology than passive targets. Further, the findings of Article 2 implicate 2610035D17Rik as a regulator of immunomodulatory properties of oligodendroglia, as 2610035D17Rik KO cells showed reduced expression of IFNγ responsive genes and elevated expression of those involved in antigen presentation, compared to the controls, following IFNγ stimulation.List of scientific papersI. Interaction of Sox2 with RNA binding proteins in mouse embryonic stem cells. Samudyata, Paulo P. Amaral, Pär G. Engström, Samuel C. Robson, Michael L. Nielsen, Tony Kouzarides, Gonçalo Castelo-Branco. Experimental Cell Research. 2019 Aug 1;381(1):129-138. https://doi.org/10.1016/j.yexcr.2019.05.006 II. Role of long non-coding RNAs Pcdh17IT and 2610035D17Rik in oligodendrocyte lineage progression. Samudyata*, Marek Bartosovic*, David Van Bruggen, Sueli Marques, Darya Vanichkina, Bastienne Zaremba, Simone Codeluppi, Sten Linnarsson, Gonçalo Castelo-Branco. [Manuscript]III. Disease-specific oligodendrocyte lineage cells arise in multiple sclerosis. Ana Mendanha Falcão, David van Bruggen, Sueli Marques, Mandy Meijer, Sarah Jäkel, Eneritz Agirre, Samudyata, Elisa M. Floriddia, Darya P. Vanichkina, Charles ffrench-Constant, Anna Williams, André Ortlieb Guerreiro-Cacais and Gonçalo Castelo-Branco. Nature Medicine. 2018 Dec;24(12):1837-1844. https://doi.org/10.1038/s41591-018-0236-y IV. Myef2 interacts with RNAs with CUG motifs in oligodendrocytes. Samudyata, Eneritz Agirre, Ana Falcao, Roman Zubarev, Gonçalo Castelo-Branco. [Manuscript]* Authors contributed equally.</p
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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