TY - JOUR A1 - Tibken, Catharina A1 - Richter, Tobias A1 - Linden, Nicole von der A1 - Schmiedeler, Sandra A1 - Schneider, Wolfgang T1 - The role of metacognitive competences in the development of school achievement among gifted adolescents JF - Child Development N2 - Gifted underachievers perform worse in school than would be expected based on their high intelligence. Possible causes for underachievement are low motivational dispositions (need for cognition) and metacognitive competences. This study tested the interplay of these variables longitudinally with gifted and non-gifted students from Germany (N = 341, 137 females) in Grades 6 (M = 12.02 years at t1) and 8 (M = 14.07 years). Declarative and procedural metacognitive competences were assessed in the domain of reading comprehension. Path analyses showed incremental effects of procedural metacognition over and above intelligence on the development of school achievement in gifted students (β = .139). Moreover, declarative metacognition and need for cognition interactively predicted procedural metacognition (β = .169), which mediated their effect on school achievement. KW - metacognitive competences KW - high intelligence KW - school Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-258376 VL - 93 IS - 1 ER - TY - JOUR A1 - Tegtmeyer, Nicole A1 - Moodley, Yoshan A1 - Yamaoka, Yoshio A1 - Pernitzsch, Sandy Ramona A1 - Schmidt, Vanessa A1 - Traverso, Francisco Rivas A1 - Schmidt, Thomas P. A1 - Rad, Roland A1 - Yeoh, Khay Guan A1 - Bow, Ho A1 - Torres, Javier A1 - Gerhard, Markus A1 - Schneider, Gisbert A1 - Wessler, Silja A1 - Backert, Steffen T1 - Characterisation of worldwide Helicobacter pylori strains reveals genetic conservation and essentiality of serine protease HtrA JF - Molecular Microbiology N2 - HtrA proteases and chaperones exhibit important roles in periplasmic protein quality control and stress responses. The genetic inactivation of htrA has been described for many bacterial pathogens. However, in some cases such as the gastric pathogen Helicobacter pylori, HtrA is secreted where it cleaves the tumour-suppressor E-cadherin interfering with gastric disease development, but the generation of htrA mutants is still lacking. Here, we show that the htrA gene locus is highly conserved in worldwide strains. HtrA presence was confirmed in 992 H.pylori isolates in gastric biopsy material from infected patients. Differential RNA-sequencing (dRNA-seq) indicated that htrA is encoded in an operon with two subsequent genes, HP1020 and HP1021. Genetic mutagenesis and complementation studies revealed that HP1020 and HP1021, but not htrA, can be mutated. In addition, we demonstrate that suppression of HtrA proteolytic activity with a newly developed inhibitor is sufficient to effectively kill H.pylori, but not other bacteria. We show that Helicobacter htrA is an essential bifunctional gene with crucial intracellular and extracellular functions. Thus, we describe here the first microbe in which htrA is an indispensable gene, a situation unique in the bacterial kingdom. HtrA can therefore be considered a promising new target for anti-bacterial therapy. KW - Helicobacter pylori KW - cag pathogenicity island KW - Differential RNA-sequencing KW - epithelial cells KW - campylobacter jejuni infection Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-190774 VL - 99 IS - 5 ER - TY - JOUR A1 - Gil-Pulido, Jesus A1 - Cochain, Clement A1 - Lippert, Malte A. A1 - Schneider, Nicole A1 - Butt, Elke A1 - Amézaga, Núria A1 - Zernecke, Alma T1 - Deletion of Batf3-dependent antigen-presenting cells does not affect atherosclerotic lesion formation in mice JF - PLoS ONE N2 - Atherosclerosis is the main underlying cause for cardiovascular events such as myocardial infarction and stroke and its development might be influenced by immune cells. Dendritic cells (DCs) bridge innate and adaptive immune responses by presenting antigens to T cells and releasing a variety of cytokines. Several subsets of DCs can be discriminated that engage specific transcriptional pathways for their development. Basic leucine zipper transcription factor ATF-like 3 (Batf3) is required for the development of classical CD8α\(^{+}\) and CD103\(^{+}\) DCs. By crossing mice deficient in Batf3 with atherosclerosis-prone low density lipoprotein receptor (Ldlr\(^{−/-}\))-deficient mice we here aimed to further address the contribution of Batf3-dependent CD8α\(^{+}\) and CD103\(^{+}\) antigen-presenting cells to atherosclerosis. We demonstrate that deficiency in Batf3 entailed mild effects on the immune response in the spleen but did not alter atherosclerotic lesion formation in the aorta or aortic root, nor affected plaque phenotype in low density lipoprotein receptor-deficient mice fed a high fat diet. We thus provide evidence that Batf3-dependent antigen-presenting cells do not have a prominent role in atherosclerosis. KW - atherosclerosis KW - dendritic cells KW - Batf3 KW - deficiency Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170535 VL - 12 IS - 8 ER - TY - THES A1 - Schneider, Nicole T1 - Untersuchung der Expression von SET7 und anderer epigenetischer Enzyme in vitro und vivo im Modell der Atherosklerose T1 - Analysis of the expression of SET7 and other epigenetic enzymes in vitro and vivo in a model of atherosclerosis N2 - Bei der Atherosklerose handelt es sich um eine chronische inflammatorische Erkrankung, die sich an der arteriellen Gefäßinnenwand abspielt. Ihre Haupt-Manifestationsformen Schlaganfall und Herzinfarkt zählen zu den häufigsten Todesursachen weltweit. Eine chronische Endothelbelastung und -funktionsstörung, beeinflusst durch Risikofaktoren wie Diabetes, arterieller Bluthochdruck, Rauchen und Entzündungszustände, führen zur Permeabilitätserhöhung des Endothels, zur Zelleinwanderung, subendothelialen Lipidanreicherung, Migration glatter Muskelzellen und der Ausbildung atherosklerotischer Läsionen. Es kommt zu Aktivierung des Immunsystems und fortschreitender Entzündungsreaktion, schließlich zur Ausbildung eines nekrotischen Kerns und zunehmender Vulnerabilität des Plaques. Epigenetische Veränderungen betreffen klassischerweise das Chromatingerüst. Durch DNA-Methylierung und -Demethylierung sowie verschiedene Modifikationen der Histon-Proteine kann die DNA in ihrer Zugänglichkeit verändert werden. So kann die Transkription eines bestimmten Genes direkt und potenziell längerfristig beeinflusst werden, ohne dass Alterationen der DNA-Basenfolge selbst stattfinden. Das Enzym SET7 nimmt hierbei eine Sonderrolle ein, da es neben einer Methylierung von Histon 3 auch verschiedene zelluläre Zielstrukturen posttranslational direkt methylieren kann. Epigenetische Veränderungen im Kontext der Atherosklerose sind bereits vereinzelt beschrieben. Auch sind sie relevant in der Reaktion auf Umwelteinflüsse und bei inflammatorischen Vorgängen. Der Frage, ob epigenetische Mechanismen im atherosklerotischen Geschehen eine Rolle spielen, sollte in dieser Arbeit nachgegangen werden. Dazu wurde in Zellkulturversuchen für Makrophagen und glatte Muskelzellen geprüft, ob die einzelnen pro-atherosklerotischen Stimuli oxLDL, IL-1β, TNFα und LPS bereits zu relevanten Veränderungen epigenetischer Enzyme führen. Dies erfolgte über Vergleich der entsprechenden mRNA mittels qPCR. Zur Untersuchung der genaueren Dynamik wurde für die Enzyme SET7 und DNMT1 der zeitliche Ablauf dieser Reaktion auf TNFα-Stimulation in Makrophagen genauer betrachtet. Unter gleichen Versuchsbedingungen wurde außerdem die Änderung der mRNA-Expression einiger Matrixmetalloproteasen, TIMP-Enzyme, Zytokine und Transkriptionsfaktoren analysiert,um zukünftig kausale Zusammenhänge weiter aufdecken zu können. Auch die Frage nach Veränderungen epigenetischer Enzyme in der Ldlr-/--Maus nach fettreicher Diät im Vergleich zu Ldlr-/--Mäusen ohne Diät sollte hier beantwortet werden. Dazu wurde die mRNA der Zellsuspensionen aus Milz, Aortenwurzel und gesamter Aorta der Tiere mithilfe der qPCR verglichen. Schließlich sollte ein effizienter Weg für einen individuellen und flexiblen SET7 knock-out etabliert werden, um weitere Studien dieses Enzyms zu ermöglichen. Hierzu wurde die Methode des CRISPR/Cas9 Systems gewählt und abschließend die Funktionalität des Systems überprüft. N2 - Atherosclerosis is a chronic inflammatory disease which occurs at the inner layer of the artery wall. Its two main manifestations are stroke and myocardial infarction, which are two of the most common causes of death worldwide. Chronical endothelial stress and endothelial dysfunction, affected by different risk factors such as hypertension, diabetes mellitus, smoking, and an inflammatory state, lead to an increased permeability, cell accumulation, subendothelial lipid accumulation and migration of smooth muscle cells, causing immune system activation, a subsequent inflammatory reaction, and the formation of atherosclerotic lesions. Finally, the development of a necrotic core occurs, accompanied by a progressive plaque vulnerability. Epigenetic mechanisms affect the chromatin structure. Therefore, the accessibility of the DNA can be altered by DNA methylation, -demethylation and different modifications of histone proteins. This can directly affect the transcription of a certain gene in a potentially long-lasting way without altering the DNA base sequence itself. The enzyme SET7 is noteworthy because of its ability of direct methylation of different cellular targets in addition to its function as a histone 3 methyltransferase. Some epigenetic alterations in the context of atherosclerosis have already been described. Epigenetic changes also play a role in the reaction to environmental signals and in processes caused by inflammation. The aim of this study was to clarify whether epigenetic mechanisms play a role in atherosclerosis. Therefore, epigenetic alterations in macrophages and smooth muscle cells after pro-atherosclerotic stimulation with oxLDL, IL-1β, TNFα and LPS were tested in cell culture experiments and their mRNA expression was compared via qPCR. Regarding the dynamics, the temporal SET7 and DNMT1 expression after stimulation was investigated for macrophages in detail. Furthermore, changes of mRNA expression for certain matrix-metalloproteases, TIMP-enzymes, cytokines, and transcription factors could be detected under constant experimental conditions. By this, the detection of causal dependencies between individual changes could be facilitated in the future. To answer the question of relevant changes in epigenetic enzyme expression in Ldlr-/--mice after high-fat diet compared to mice without any diet, mRNA expression of cell suspension gained from the mice spleen, aortic sinus and total aorta were compared by using qPCR. Finally, an efficient way of knocking down SET7 was established by the usage of the CRISPR/Cas9 method, and functionality of this approach was demonstrated in this study. KW - Arteriosklerose KW - Epigenetik KW - Atherogenese KW - Atherosklerose KW - Atherosclerosis KW - epigenetics KW - SET7 Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-328952 ER -