1,720,957 research outputs found
Mechanistic and functional analysis of Slit-Robo proteins
Get PDFSlits are large secreted proteins which mediate their functions by binding to single pass transmembrane receptors called Robo. This signalling axis was first identified as a pivotal guidance mechanism in the development of the nervous system. A repulsive activity of Slit proteins controls the projection and movement of Robo expressing neurons in Drosophila and vertebrates. Slit and Robo expression is not limited to the nervous system or development only, they were found to be expressed in many different tissues both in embryo and adult organism. Correspondingly, the Slit-Robo signalling axis now is implicated in many other biological and pathological processes such as angiogenesis, cancer and tissue remodelling. This study sought to investigate two different aspects of the Slit-Robo signalling system: Robo1 transmembrane signalling mechanism and possible Slit-Robo roles within the immune system.
Robos and other type I transmembrane receptors are unable to transmit signal across the membrane within a single molecule because a single transmembrane α-helix restricts propagation of conformational changes between extracellular and intracellular parts of the protein. Therefore, the type I receptors usually act as homo- or heterooligomers, formation or dissociation of which is controlled by ligand binding. Based on indirect evidence a similar transmembrane signalling mechanism was suggested for Robo receptors. It was hypothesized that Slit binding induces changes in oligomeric state of Robo which in turn initiates downstream signalling events. In order to test this hypothesis and determine details of the transmembrane signalling mechanism, the oligomeric state of Robo1 receptor was assessed in live cells using two different fluorescence resonance energy transfer (FRET) based methods. A strong FRET signal was observed between differently tagged Robo1 proteins, indicating that the receptor forms oligomers in the resting state. However, contrary to the initial hypothesis, the addition of Slit2 protein did not have an observable effect on the FRET signal and thus on receptor oligomeric state. Moreover, Robo1 proteins were found to form higher density domains within the cell membrane. This property could be abolished by removing the intracellular part of the protein indicating constant Robo1 association with intracellular structures. These data show that the Robo1 transmembrane signalling mechanism might be more complicated than initially expected and likely involves structural changes within the Robo1 oligomer or Robo1 complexes with other proteins.
The Slit-Robo signalling axis was linked to the immune system when it was demonstrated that Slit2 is able to inhibit chemotactic leukocyte migration and reduce inflammatory responses in mice. However, the precise role of these proteins remained unknown. In order to gain further insight into possible Slit-Robo functions within the immune system promoter analysis was performed with the aim to identify transcription factors responsible for the control of these proteins. Among many putative transcription factors discovered, Foxn1 was the most prominent as its binding site was identified both in Slit2 and Slit3 promoters. Development and functions of thymus, a primary lymphoid organ responsible for T cell development, is regulated by Foxn1 and since thymic activity includes active and abundant leukocyte movement into, out-of and within the organ, a hypothesis was suggested that Slits contribute to regulation of these processes. Quantitative Slit2-Slit3 expression studies and assessment of embryonic thymus cellular composition in Slit2 knockout mouse were employed to test this hypothesis. Quantitative PCR revealed that both Slit2 and Slit3 are downregulated four-fold in thymic epithelial cells starting embryonic stage E13, however no differences in cellular composition of embryonic thymi were detected between wild type and Slit2 knockout animals using flow cytometry. Possible Slit2 and Slit3 redundancy might be the reason for the lack of observable effects, unfortunately a Slit3 knockout model was unavailable for these studies. Interestingly, flow cytometry also revealed that in addition to thymic epithelial cells, Slit2 is expressed by pericyte type cells surrounding the thymic vasculature. It seems that Slit proteins have intricate and regulated expression patterns within the thymus, however their precise role remains an open question.
In summary, data collected during this study illuminates two different aspects of the Slit-Robo signalling system. Both of them, despite Slits being secreted proteins, hint at short-range, possibly even juxtacrine, ligand – receptor interactions. Given Robo receptor evolutionary connections to cell adhesion molecules and Slit affinity to heparan sulphate it is not a completely unexpected finding
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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