1,721,035 research outputs found
The immune system is part of a whole-organism regulatory network
No full textEditoriale per introdurre gli articoli dello Special Issue di Research in Veterinary Science intitolato "Periparturient Immune Function and the Acute Phase Response in Dairy Animals. An immunological approach to production diseases of high-yielding dairy cows". Di questo special issue, Gianfranco Gabai è il curatore principale (Guest Editor)
Toll-like receptors in domestic animals
Full text linkToll-like receptors are pattern recognition receptors with which hosts recognize pathogen-associated molecular patterns (PAMP). This recognition process is translated rapidly into a meaningful defense reaction. This form of innate host defense is preserved in the animal kingdom: invertebrates heavily depend on it; higher vertebrates also have an adaptive immune system. Both adaptive and innate immune systems are intertwined in that the former also depends on an intact innate recognition and response system. Members of the TLR system cover recognition of parasitic, bacterial or viral germs. Due to the constraints imposed by the necessity to recognize PAMP and to interact with downstream signaling molecules, the TLR system is relatively conserved in evolution. Nevertheless, subtle species differences have been reported for several mammalian TLR members. Examples of this will be given. In all mammalian species investigated, part of the coding sequence is available for the most important TLR members, thus allowing study of expression of these TLR members in various tissues by reverse-transcription polymerase chain reaction in its classical (RT-PCR) and quantitative real time RT-PCR (qRT-PCR) form. In some species, the whole coding sequences of the most important or even all TLR members are known. This allows construction of cDNA and transfection of common host cells, thus permitting functional studies. Extensive investigations were devoted to the study of non-synonymous single nucleotide polymorphisms. In a few cases, expression of a given amino acid in the extracellular (ligand-binding) portion of TLR members could be associated with infectious diseases. This will be discussed below
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe 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
Full text link“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
Full text linkWe 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
Full text linkWe 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
Molekulare Mechanismen der Wirtszelltransformation und Arzneimittelresistenz von Theileria annulata
No full textIn tropical theileriosis of cattle, the major driver of pathology is the transformation of host macrophagesby the intracellular apicomplexan parasite Theileria annulata. In Theileria-transformed leukocytes, several oncogene-associated signaling pathways including Activator Protein 1 (AP-1) and NF-κB, are constitutively activated in a parasite-dependent manner. These pathways are essential for proliferation, dissemination and resistance to apoptosis in infected cells. The exact mechanisms employed by Theileria to constitutively activate these pathways is not fully known. Taking other Apicomplexans such as Toxoplasma gondii and Plasmodium falciparum as models, Theileria might achieve this via secretion of effector proteins. Here we studied the contribution of a secreted T. annulata effector protein Ta9 to the transcriptional de-regulation of bovine macrophage genes by performing RNA-seq on macrophages that stably expressed Ta9. Ta9 was previously shown to be capable of stimulating AP-1-driven transcription when introduced into human HEK cells in luciferase reporter assays. RNA-seq analysis revealed that Ta9 affected the expression of 560 (400 upregulated and 160 downregulated) bovine genes that included oncogenes, tumor suppressor genes and inflammation-associated genes previously known or hypothesized to be involved in the pathogenesis of tropical theileriosis. Example genes include FRA1, IL-6, TGFß1, TNFɑ, MMP2 and the proto-oncogene haematopoetic cell kinase (HCK). We further characterized the contribution of HCK to the Theileria-induced leukocyte transformation by using a selective HCK inhibitor (A419219) in cell proliferation and transformation (soft agar colony formation) assays. HCK belongs to the SRC family of non-receptor tyrosine kinases that is constitutively active in T. parvatransformed B cells and contributes to AP-1-driven transcription (similar to Ta9). This raised the possibility that Ta9 might do so by augmenting HCK signaling. Indeed, Ta9-mediated upregulation of hck (as detected first by RNA-seq) was confirmed by qRT-PCR and the increase in protein levels by immunofluorescence (IF). Furthermore, Ta9-expressing cells grew membrane protrusions and microspikes. These results were consistent with Ta9 potentially augmenting HCK activity in the cells and treatment of T. annulata-infected macrophages with A419219 negatively impacted on the parasite-dependent transformed phenotype. A419219 could also block proliferation of sheep leukocytes transformed by another acutely pathogenic Theileria species, T. lestoquardi.
Buparvaquone is currently the only drug in the market to treat T. annulata, T. lestoquardi and T. parva infections, however resistance is spreading worldwide and the need to for a drug to replace buparvaquone is rising. Due to the therapeutic effect that HCK inhibition showed against T.annulata- and T. lestoquardi-transformed leukocytes in our hands, as a parallel part of this project we generated buparvaquone-resistant T. annulata parasites and tested whether A419219 could block the proliferation of macrophages that harbored resistant parasites. As expected, A419219 was equally effective against macrophages containing buparvaquone-resistant parasites. Past studies have reported susceptibility of T. parva transformed leukocytes to Src kinase inhibitors and herein we have extended that reports to T. annulata and T. lestoquardi infections and to buparvaquone-resistant T. annulata parasites. Therefore, the ensemble highlights the importance of Src kinases as potential targets for the consideration in the development of the next generation of therapies against theileriosis.In der tropischen Theileriose des Rindes ist der Haupttreiber der Pathologie die Transformation von Wirtsmakrophagen durch den intrazellulären Apicomplexa-Parasiten Theileria annulata. In Theileriatransformierten Leukozyten werden mehrere mit Onkogenen assoziierte Signalwege, darunter der Activator Protein 1 (AP-1) und NF-kB-Wege, parasitenabhängigen konstitutiv aktiviert. Diese Signalwege sind essenziell für die Proliferation, Dissemination und Apoptoseresistenz der infizierten Zellen. Die genauen Mechanismen, mit denen Theileria diese Signalwege dauerhaft aktiviert, sind nicht vollständig geklärt. Unter Berücksichtigung anderer Apicomplexa wie Toxoplasma gondii und Plasmodium falciparum könnte Theileria dies durch die Sekretion von Effektorproteinen bewirken. In der vorliegenden Studie untersuchten wir den Beitrag eines sekretorischen T. annulata-Effektorproteins, Ta9, zur transkriptionellen Deregulation boviner Makrophagengene, indem wir RNA-Seq an Makrophagen durchführten, die stabil Ta9 exprimierten. Frühere Luziferase-Reporter-Assays zeigten, dass Ta9 die AP-1-gesteuerte Transkription humane HEK-Zellen stimuliert.
Die RNA-Seq-Analyse identifizierte 560 differenziell exprimierte bovine Gene (400 hoch-, 160 herunterreguliert), darunter Onkogene, Tumorsuppressorgene und entzündungsassoziierte Gene, die bereits als potenziell an der Pathogenese der tropischen Theileriose beteiligt identifiziert oder vermutet wurden. Beispiele hierfür sind FRA1, IL-6, TGFß, TNFɑ, MMP2 und das Proto-Onkogen haematopoietic cell kinase (HCK). Wir untersuchten weiter den Beitrag von HCK zur Theileria-induzierten Leukozytentransformation durch den Einsatz eines selektiven HCK-Inhibitors (A419219) in Zellproliferations- und Transformationstests (Soft-Agar-Koloniebildung). HCK gehört zur SRC-Familie der nicht-rezeptorassoziierten Tyrosinkinasen, die in T. parva-transformierten B-Zellen konstitutiv aktiv ist und zur AP-1-gesteuerten Transkription beiträgt (ähnlich wie Ta9). Dies legte die Möglichkeit nahe, dass Ta9 HCK-Signalwege verstärken könnte. Tatsächlich bestätigten wir die durch RNA-Seq detektierte Ta9-vermittelte Hochregulation von hck durch qRT-PCR sowie den Anstieg der Proteinspiegel mittels Immunfluoreszenz (IF). Darüber hinaus bildeten Ta9-exprimierende Zellen Membranprotrusionen und Mikrospikes aus. Diese Ergebnisse deuten darauf hin, dass Ta9 die HCK-Aktivität in den Zellen potenziell verstärken könnte. Die Behandlung von T. annulata-infizierten Makrophagen mit A419219 beeinträchtigte zudem den parasitenabhängigen transformierten Phänotyp. A419219 blockierte auch die Proliferation von Schafsleukozyten, die durch eine weitere akut pathogene Theileria-Spezies, T. lestoquardi, transformiert wurden. Derzeit ist Buparvaquone das einzige verfügbare Medikament zur Behandlung von Infektionen mit T. annulata, T. lestoquardi und T. parva. Allerdings breiten sich Resistenzen weltweit aus, was die Notwendigkeit für ein alternatives Medikament verstärkt. Aufgrund der therapeutischen Wirkung von HCK-Inhibitoren gegen T. annulata- und T. lestoquardi-transformierte Leukozyten haben wir in einem parallelen Projekt Buparvaquone-resistente T. annulata-Parasiten erzeugt und getestet, ob A419219 die Proliferation von Makrophagen, die resistente Parasiten enthalten, blockieren kann. Wie erwartet, war A419219 auch gegen Makrophagen mit Buparvaquone-resistenten Parasiten wirksam. Frühere Studien berichteten über die Empfindlichkeit T. parva-transformierter Leukozyten gegenüber Src-Kinase-Inhibitoren. Unsere Ergebnisse erweitern diese Beobachtungen auf T. annulata und T. lestoquardi sowie auf Buparvaquon-resistente T. annulata-Parasiten. Diese Erkenntnisse unterstreichen die Bedeutung von Src-Kinasen als potenzielle Ziele für die Entwicklung neuer Therapien gegen Theileriose
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
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