1,720,953 research outputs found
Non-coding RNAs in psoriasis : insights into epidermal dysregulation and inflammation
Plaque psoriasis is a common chronic inflammatory skin disorder characterised by pruritic and scaly focal skin lesions. Characteristic skin changes include abnormal keratinocyte proliferation, dysregulated epidermal differentiation, activation of inflammatory pathways, and infiltration of immune cells into the skin. The inflammatory axis of the cytokines interleukin-23 (IL-23) and IL-17A is recognised as a central signalling pathway in the development of psoriasis and serves as an effective therapeutic target.Non-coding RNAs have received increased attention over the past three decades as essential regulators of gene expression and translation in development, homeostasis, and disease. While some previous research has characterised the roles of various non-coding RNAs in psoriasis, their functions remain poorly understood. Therefore, this thesis investigates long non-coding RNAs and microRNAs and their role in psoriasis inflammatory signalling and keratinocyte dysfunction. Our work utilised bulk and single-cell RNA sequencing to profile the non-coding transcriptome, and we validated our findings through in vitro keratinocyte culture in monolayer and 3D epidermal models, in vivo mouse models of psoriasis skin inflammation, RT-qPCR and RNA in situ hybridisation.Study I characterised miR-378a, a miRNA upregulated in psoriasis and regulated by IL17A that activates NF-KB signalling by repressing NFKBIA. Delivery of miR-378a lead to exacerbated skin inflammation in the imiquimod mouse model and potentiated the inflammatory effects of IL-17A in cell culture through a positive feedback mechanism, emphasising its pathogenic role in psoriasis.Study II investigated the evolutionarily conserved role of miR-149 as an intrinsic suppressor of skin inflammation by repressing the TWEAK receptor. In psoriasis, miR-149 is downregulated, and epidermal deletion of miR-149 in mice leads to increased production of inflammatory mediators by keratinocytes, even in the absence of inflammatory stimuli, with no apparent phenotype resulting from its deletion in mice. In the imiquimod and Il-23 models of skin inflammation, epidermal miR-149 deletion exacerbated skin inflammation, increased immune cell infiltration, and production of inflammatory mediators. Single-cell RNA sequencing of the Il-23 model of skin inflammation identified mast cell infiltration as a notable cellular change caused by miR-149 epidermal depletion; pharmaceutical induction of mast cell apoptosis reduced imiquimod-induced skin inflammation in mice. These findings emphasise the importance of miR-149 in suppressing TWEAK/TWEAKR signalling to prevent skin inflammation, suggesting that restoring epidermal miR-149 could be a potential future treatment option for psoriasis.Study III systematically describes the landscape of long non-coding RNAs in epidermal keratinocytes within psoriasis lesions and healthy skin. The skin-enriched lncRNA RP11-295G20.2 is found to be upregulated in psoriasis, regulated by IL-17A and early epidermal differentiation, and is demonstrated to suppress late-stage keratinocyte differentiation. Based on our findings, we renamed it cytoplasmic differentiation-associated epidermal RNA CYDAER.Study IV created a single cell atlas of long non-coding RNAs in keratinocytes and immune cells in psoriasis and healthy epidermis, identifying distinct non-coding signatures of psoriasis cell states. LINC01137 is identified as a long non-coding RNA specifically overexpressed in psoriasis activated keratinocyte subtypes and regulated by IL-17A. LINC00892 is specifically expressed in Th1 and Th17 helper T cell subsets and proliferative cytotoxic T cells, possibly indicating T cell activation in psoriasis.Collectively, the four constituent studies of this thesis elucidate the critical roles of differentially expressed non-coding RNAs in the pathogenesis of psoriasis, including amplifying inflammatory signalling, disrupting keratinocyte differentiation, and modulating immune cells. The findings contribute to an improved understanding of psoriasis pathogenesis and provide potential therapeutic targets and disease biomarkers.List of scientific papersI. miR-378a regulates keratinocyte responsiveness to interleukin-17A in psoriasis. Ping Xia, Lorenzo Pasquali, Chenying Gao, Ankit Srivastava, Nupur Khera, Jan Cedric Freisenhausen, Longlong Luo, Einar Rosen, Anke van Lierop, Bernhard Homey, Andor Pivarcsi, Eniko Sonkoly. British Journal of Dermatology, 2022 Aug;187(2):211-222. https://doi.org/10.1111/bjd.21232II. Loss of epidermal microRNA-149 sensitizes to skin inflammation. Longlong Luo, Hao Yuan, Ankit Srivastava, Karl Annusver, Nupur Khera, Piyal Saha, Roxane Prieux, Kunal Das Mahapatra, Evelyn Kelemen, Menil Dholakia, Jan C Freisenhausen, Milena Petkova, Taija Mäkinen, Gunnar Pejler, Maria Kasper, Andor Pivarcsi, Eniko Sonkoly. [Manuscript]III. RNA Sequencing Reveals the Long Non-Coding RNA Signature in Psoriasis Keratinocytes and Identifies CYDAER as a Long Non-Coding RNA Regulating Epidermal Differentiation. Jan Cedric Freisenhausen*, Longlong Luo*, Evelyn Kelemen, Jonathan Elton, Viktor Skoog, Andor Pivarcsi, Eniko Sonkoly. Experimental Dermatology, 2025 Feb;34(2):e70054. https://doi.org/10.1111/exd.70054IV. Single-cell transcriptomic analysis uncovers keratinocyte- and immune-specific long non-coding RNAs in psoriasis epidermis. Jan Cedric Freisenhausen*, Longlong Luo*, Huaitao Cheng, Martin Enge, Andor Pivarcsi, Enikö Sonkoly. [Manuscript]* equal contribution.</p
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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