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Rolle von IFN-γ bei der Immunität und Kontrolle gastrointestinaler Nematodeninfektionen
No full textInfections by gastrointestinal nematodes mandate an effective type 2 response for the parasite clearance. In line with the cross-regulatory nature of Th1 lineage specifying factors on the differentiation of Th2 cells seen at the molecular level, strong type 1 activity resulted by inflammation associated with senescence, specific genetic predisposition and co-infections with intracellular pathogens exacerbate the Th2 responses resulting in poor resistance in nematode infections. Despite reported cross-regulation, the Th1 and Th2 pathways are not mutually exclusive as polarization with IFN-g, IL-12 and IL-4 results in the generation of T-bet and GATA-3 co-expressing Th2/1 cells in vitro. Th2/1 cells are also induced naturally in nematode infections (Affinass et al., 2018; Bock et al., 2017; Peine et al., 2013).
In the current study we demonstrate that the IFN-g competence progressively rises with the age of uninfected BALB/c mice displaying high resistance to nematode infection. The elevated type 1 bias in 5-10 months old compared to 2-3 months old mice resulted in poor parasite control manifested by higher female fecundity in the mature cohort infected with H. polygyrus. The poor resistance was accompanied by stronger generation and mucosal accumulation of Th2/1 hybrid cells and elevated proportions of parasite specific IFN-g producing cells.
Substantiating the above findings, restriction of IFN-g availability in the priming phase of nematode infection led to improved resistance coinciding with sharp reduction in systemic and mucosal Th2/1 cells and a near complete absence of parasite specific IFN-g producing cells. Conversely, supplementation of early IFN-g availability led to impaired parasite control associated with robust expansion of Th2/1 cells and a significant rise in IFN-g producing cells in parasite specific T cell pool. Importantly, elevated IFN-g availability did not inhibit classical Th2 cells in the long run and rather promoted an accumulation of systemic GATA-3+ Teff cells in IFN-g treated BALB/c mice. The increased parasite egg production upon IFN-g treatment was traced back to the increased fitness of the L4 larvae maturating in the gut of IFN-g treated mice.
In line with the findings in differently aged mice, C57BL/6 mice genetically predisposed to higher susceptibility in H. polygyrus infection more rapidly accumulate Th1 cells at steady state compared to resistant BALB/c mice. The elevated type 1 activity in C57BL/6 mice translated to greater accumulation of small intestinal Th2/1 cells post infection and poor resistance compared to BALB/c mice. However, the stark differences seen between the strains at younger age leveled out in older mice due to increased IFN-g competence and increased bias in favor of Th2/1 cells in mature BALB/c mice. Restricting IFN-g availability in C57BL/6 mice led to increased resistance thereby substantiating the significance of IFN-g in differential susceptibility across inbred lines. Overall, our findings report an age-dependent reduction in anti-nematode type 2 immunity resulted by steady state accumulation of IFN-g competent effector cells in the vertebrate host.Infektionen durch Magen-Darm-Nematoden erfordern eine effektive Typ-2 Immunantwort für die Beseitigung des Parasiten. Entsprechend der Kreuzregulation der THelferzelldifferenzierung durch molekulare Faktoren, welche die Th1-Differenzierung unterstützen, kann eine starke Typ-1-Immunaktivität als Ergebnis von Immunseneszenz, spezifischer genetischer Prädisposition oder der Ko-Infektionen mit intrazellulären Pathogenen die Ausbildung von Th2-Antworten behindern, was zu einer geringen Resistenz gegen Nematodeninfektionen führen kann. Vorherige in vitro und in vivo Studien haben gezeigt, dass sich die Differenzierungswege in Th2- beziehungsweise Th1- Zellen nicht gegenseitig ausschließen, da T-Helferzellen unter gleichzeitiger Einwirkung der Th1-beziehungsweise Th2-polarisierenden Zytokine IFN-g/IL-12 und IL-4 einen Th2/1-Hybridphänotyp annehmen. Dieser Differenzierungsstatus ist durch die Koexpression von GATA-3 und T-bet gekennzeichnet und vorherige Arbeiten haben gezeigt, dass die Differenzierung von Th2/1-Hybridzellen auch als natürliche Reaktion auf Infektionen mit Darmnematoden vorkommt (Affinass et al., 2018; Bock et al., 2017; Peine et al., 2013).
Die vorliegende Arbeit zeigt, dass es in gesunden Labormäusen der gegen Nematodeninfektionen hoch resistenten BALB/c-Linie mit steigendem Alter zu einer Zunahme der IFN-g-Kompetenz kommt. Als Konsequenz dieses Th1-Bias ist die Kontrolle einer Nematodeninfektionen beeinträchtigt, wenn BALB/c-Mäuse im Alter von 5-10 Monaten anstatt von 2-3 Monaten mit H. polygyrus infiziert werden, was aus der erhöhten Eiproduktion der Würmer in älteren Mäusen ersichtlich wird. Die verminderte Resistenz der geht einher mit der Anreicherung von Th2/1-Hybridzellen in der Mukosa und mit einem erhöhten Anteil von IFN-g produzierenden, parasiten-spezifischen T-Helferzellen.
Dieser Zusammenhang konnte durch die Blockade von IFN-g in der frühen Phase der Immunantwort weiter belegt werden. Dieser Ansatz führte zu einer drastischen Reduktion von systemischen und mukosalen Th2/1-Hybridantworten und dem nahezu vollständigen Ausbleiben der IFN-g Produktion durch parasiten-spezifische T-Zellen, wodurch die Resistenz erhöhte wurde. Wurde jedoch die Verfügbarkeit von IFN-g in der frühen Infektionsphase durch Gabe des Zytokins erhöht, so resultierte dies in der starken Expansion von Th2/1 Hybridzellen, einer signifikanten Zunahme von IFN-g produzierenden Zellen in der parasiten-spezifischen T-Zellpopulation und der verminderten Kontrolle der Parasiteninfektion. Zudem zeigte sich, dass die erhöhte Verfügbarkeit von IFN-g die Differenzierung von klassischen GATA-3+ Th2-Zellen langfristig nicht inhibiert, sondern dass es nach IFN-g-Behandlung von BALB/c Mäusen zu einer gesteigerten systemischen Akkumulation von GATA-3+ Zellen kommt. Weiter konnte die nach IFN-g Gabe erhöhte Eiproduktion durch die Parasiten mit einer erhöhten Fitness des sich im Darm entwickelnden vierten Larvenstadiums nach IFN-g Gabe in Zusammenhang gebracht werden.
Abweichend von der verzögerten, altersbedingten Zunahme der IFN-g-Kompetenz von BALB/c Mäusen zeigten Mäuse der C57BL/6-Linie mit einer genetisch veranlagten hohen Empfänglichkeit für die H. polygyrus-Infektion bereits als junge Tiere eine Anreicherung von Th1-Zellen in Abwesenheit von Infektionen. Nach Wurminfektion resultierte die stärkere Typ-1 Aktivität der C57BL/6 Linie in der stärkeren Anreicherung von Th2/1-Zellen im infizierten Dünndarm und in der geringeren Resistenz im Vergleich zur BALB/c Linie. Diese deutlichen Unterschiede zwischen den beiden Mauslinien zeigten sich insbesondere bei jungen Tieren. In älteren Tieren glichen sich jedoch die Reaktionen auf die Infektion durch die Zunahme der IFN-g Kompetenz und die verstärkte Bildung von Th2/1 Zellen in älteren BALB/c Mäusen an. Die Beschränkung der IFN-g Verfügbarkeit in C57BL/6 Mäusen führte zu einer erhöhten Resistenz, was die Bedeutung von IFN-g für die unterschiedliche Empfänglichkeit von Mauslinien unterstreicht.
Zusammenfassend zeigt diese Studie also eine altersabhängige Abnahme der Typ-2 abhängigen Immunität gegenüber Nematodeninfektionen durch die spontane Zunahme von IFN-g kompetenten Zellen
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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