24 research outputs found

    CagI Is an Essential Component of the Helicobacter pylori Cag Type IV Secretion System and Forms a Complex with CagL

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    Helicobacter pylori, the causative agent of type B gastritis, peptic ulcers, gastric adenocarcinoma and MALT lymphoma, uses the Cag type IV secretion system to induce a strong proinflammatory response in the gastric mucosa and to inject its effector protein CagA into gastric cells. CagA translocation results in altered host cell gene expression profiles and cytoskeletal rearrangements, and it is considered as a major bacterial virulence trait. Recently, it has been shown that binding of the type IV secretion apparatus to integrin receptors on target cells is a crucial step in the translocation process. Several bacterial proteins, including the Cag-specific components CagL and CagI, have been involved in this interaction. Here, we have examined the localization and interactions of CagI in the bacterial cell. Since the cagI gene overlaps and is co-transcribed with the cagL gene, the role of CagI for type IV secretion system function has been difficult to assess, and conflicting results have been reported regarding its involvement in the proinflammatory response. Using a marker-free gene deletion approach and genetic complementation, we show now that CagI is an essential component of the Cag type IV secretion apparatus for both CagA translocation and interleukin-8 induction. CagI is distributed over soluble and membrane-associated pools and seems to be partly surface-exposed. Deletion of several genes encoding essential Cag components has an impact on protein levels of CagI and CagL, suggesting that both proteins require partial assembly of the secretion apparatus. Finally, we show by co-immunoprecipitation that CagI and CagL interact with each other. Taken together, our results indicate that CagI and CagL form a functional complex which is formed at a late stage of secretion apparatus assembly

    Helicobacter pylori cag-Pathogenicity Island-Dependent Early Immunological Response Triggers Later Precancerous Gastric Changes in Mongolian Gerbils

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    Infection with Helicobacter pylori, carrying a functional cag type IV secretion system (cag-T4SS) to inject the Cytotoxin associated antigen (CagA) into gastric cells, is associated with an increased risk for severe gastric diseases in humans. Here we studied the pathomechanism of H. pylori and the role of the cag-pathogenicity island (cag-PAI) for the induction of gastric ulcer and precancerous conditions over time (2–64 weeks) using the Mongolian gerbil model. Animals were challenged with H. pylori B128 (WT), or an isogenic B128ΔcagY mutant-strain that produces CagA, but is unable to translocate it into gastric cells. H. pylori colonization density was quantified in antrum and corpus mucosa separately. Paraffin sections were graded for inflammation and histological changes verified by immunohistochemistry. Physiological and inflammatory markers were quantitated by RIA and RT-PCR, respectively. An early cag-T4SS-dependent inflammation of the corpus mucosa (4–8 weeks) occurred only in WT-infected animals, resulting in a severe active and chronic gastritis with a significant increase of proinflammatory cytokines, mucous gland metaplasia, and atrophy of the parietal cells. At late time points only WT-infected animals developed hypochlorhydria and hypergastrinemia in parallel to gastric ulcers, gastritis cystica profunda, and focal dysplasia. The early cag-PAI-dependent immunological response triggers later physiological and histopathological alterations towards gastric malignancies

    The Helicobacter pylori Genome Project : insights into H. pylori population structure from analysis of a worldwide collection of complete genomes

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    Helicobacter pylori, a dominant member of the gastric microbiota, shares co-evolutionary history with humans. This has led to the development of genetically distinct H. pylori subpopulations associated with the geographic origin of the host and with differential gastric disease risk. Here, we provide insights into H. pylori population structure as a part of the Helicobacter pylori Genome Project (HpGP), a multi-disciplinary initiative aimed at elucidating H. pylori pathogenesis and identifying new therapeutic targets. We collected 1011 well-characterized clinical strains from 50 countries and generated high-quality genome sequences. We analysed core genome diversity and population structure of the HpGP dataset and 255 worldwide reference genomes to outline the ancestral contribution to Eurasian, African, and American populations. We found evidence of substantial contribution of population hpNorthAsia and subpopulation hspUral in Northern European H. pylori. The genomes of H. pylori isolated from northern and southern Indigenous Americans differed in that bacteria isolated in northern Indigenous communities were more similar to North Asian H. pylori while the southern had higher relatedness to hpEastAsia. Notably, we also found a highly clonal yet geographically dispersed North American subpopulation, which is negative for the cag pathogenicity island, and present in 7% of sequenced US genomes. We expect the HpGP dataset and the corresponding strains to become a major asset for H. pylori genomics

    Georg Hansen / Norbert Wenning: Schulpolitik für andere Ethnien in Deutschland. Zwischen Autonomie und Unterdrückung. Münster, New York, München, Berlin: Waxmann 2003 (233 S.) [Rezension]

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    Rezension von: Georg Hansen / Norbert Wenning: Schulpolitik für andere Ethnien in Deutschland. Zwischen Autonomie und Unterdrückung. Münster, New York, München, Berlin: Waxmann 2003 (233 S.; ISBN 3-8309-1122-X; 19,50 EUR)

    Ingrid Gogolin/Ursula Neumann/Lutz Reuter (Hrsg.): Schulbildung für Kinder aus Minderheiten in Deutschland 1989-1999. Schulrecht, Schulorganisation, curriculare Fragen, sprachliche Bildung. Münster, New York, München, Berlin: Waxmann 2001 (474 S.) [Rezension]

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    Rezension von: Ingrid Gogolin/Ursula Neumann/Lutz Reuter (Hrsg.): Schulbildung für Kinder aus Minderheiten in Deutschland 1989-1999. Schulrecht, Schulorganisation, curriculare Fragen, sprachliche Bildung. Münster, New York, München, Berlin: Waxmann 2001 (474 S.; ISBN 3-89325-993-7)

    Acquisition of pedagogical knowledge during the first phase of teacher education: Are there differences between students of different cohorts and in different teacher-education programs?

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    Der Beitrag untersucht, ob sich Studierende verschiedener Lehrämter am Ende der ersten Ausbildungsphase in ihrem pädagogischen Wissen unterscheiden und ob sich Unterschiede im Verlauf des Studiums zeigen. Ausgegangen wird von der Annahme, dass Studierende in Ausbildungsgängen, die stark pädagogisch ausgerichtet sind, besser abschneiden als Studierende des Gymnasiallehramts, in dem traditionell die Fachwissenschaften dominieren. Die Untersuchung basiert auf einer Stichprobe von Studierenden der Universität zu Köln, die sich zum Zeitpunkt der Befragung in unterschiedlichen Lehrämtern (GHR, Sonderpädagogik, Gymnasium) und Ausbildungsstadien befanden (Grundstudium, Hauptstudium, Examensphase). Als Instrument wird der TEDS-M-Test zur Erfassung pädagogischen Wissens eingesetzt. Am Ende der universitären Phase zeigen sich Leistungsunterschiede zwischen den Studierenden unterschiedlicher Lehrämter in der erwarteten Richtung. Quasi-längsschnittliche Analysen legen zudem die Vermutung eines Wissenszuwachses im Verlauf des Studiums bei Studierenden der Lehrämter GHR und Sonderpädagogik nahe, nicht aber bei Studierenden des Gymnasiallehramtes. Die Ergebnisse werden im Hinblick auf mögliche Konsequenzen für die Gestaltung der Lehrerausbildung diskutiert. (DIPF/Orig.)The report investigates whether university students in different teacher-education programs differ in their pedagogical knowledge at the end of their university training and whether differences exist in the course of this first phase of German teacher education. [The authors] assume that students in programs with a pedagogical focus show better test results than students pursuing the teaching career for the Gymnasium which traditionally has a strong subject-related focus. The study is based on a sample of students at the University of Cologne including three teacher-education programs (elementary and lower secondary schools, special education, Gymnasium) and three cohorts (beginning students, advanced students, exam candidates). The TEDS-M test instrument measuring pedagogical knowledge was applied. As expected, at the end of their university training future Gymnasium teachers were significantly outperformed by the two other groups. Based on quasi-longitudinal analyses the two latter groups show significant gains in their pedagogical knowledge as well in contrast to students pursuing a teaching career for the Gymnasium. Consequences for teacher education are discussed. (DIPF/Orig.
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