China und die Corona-Pandemie in der Wahrnehmung der deutschen Öffentlichkeit : Analyse der Berichterstattung in der deutschsprachigen Presse

Seit dem Ausbruch der Corona-Pandemie in Wuhan sind insbesondere im ersten Halbjahr viele Beiträge über China in den deutschen Medien erschienen, allmählich haben sie im Laufe der Zeit ihr Interesse an China bezüglich der Pandemie verloren. In dieser Dissertation wurde das Chinabild während der Corona-Pandemie in fünf deutschen Leitmedien, nämlich der FAZ, der SZ, der ZEIT, dem Spiegel und der Bild-Zeitung, untersucht. Und der Untersuchungszeitraum beginnt mit dem Ausbruch in Wuhan im Januar 2020 und endet mit den Olympischen Winterspiele in Peking im Februar 2022. Um das Chinabild in diesen Medien herauszuarbeiten, wurden zwei Fragen auf der Grundlage der Interkulturellen Hermeneutik und der diskursanalytischen Theorien untersucht: Warum und wie Menschen kulturelle, soziale und andere Gegebenheiten anderer Länder lernen und reflektieren, und wie die deutschen Diskursstrukturen und Argumentationsmuster durch die Analyse der China-Berichterstattung in den deutschen Medien herausgearbeitet werden können. Im Kontext der deutschen China-Berichterstattung wurden auch erläutert, dass Medien die Rezipienten beeinflussen können. Anschließend wurden zwei Analysen jeweils auf der Makro- und Mikroebene durchgeführt: In der quantitativen Analyse wurden zuerst die Beiträge mit Chinabezug in der China-Berichterstattung identifiziert, und durch tabellarische und grafische Darstellungen wurde ein statistischer Überblick über die Interessen- und Schwerpunkteverteilung, sowie die statistische Entwicklung der China-Berichterstattung sowohl in jedem einzelnen Medium als auch in allen Leitmedien herausgearbeitet und verglichen. In der qualitativen Analyse, dem Hauptteil der Dissertation, wurden die durch die quantitative Analyse identifizierten 3248 Beiträge mit Chinabezug ausführlich analysiert. Die Positionen und Argumentationen deutscher Medien gegenüber China wurden anhand wichtiger Themenfelder durch 31 Diskursstränge detailliert präsentiert, welche darauf basieren, dass die fünf Leitmedien verschiedene Meinungen gegenüber einem gleichen Thema vertreten, und selbst das gleiche Medium oft keine einheitliche Meinung zu dem gleichen Thema vertritt. Zum Schluss wurden die problematischen Aspekte diskutiert

Cellular and molecular defence mechanisms against Legionella infection

The two most prevalent causes of Legionnaires’ disease are L. pneumophila and L. longbeachae. The rising incidence of the Legionnaires’ disease over the past two decades together with the increasing prevalence of L. longbeachae in the Northern hemisphere highlights the necessity to gain a more detailed insight into the L. longbeachae-induced immune response. The aim of this thesis was to investigate the cellular and molecular mechanisms required for protection, focussing on immune cell responses and intracellular host-bacterial interactions. By combining a murine mouse model, a novel fluorescent reporter to track L. longbeachae, and cell depletion experiments, I uncovered the differential contribution of tissue-resident alveolar macrophages (AM) and infiltrating neutrophils to the defence against L. longbeachae. Early during infection, AM contained most of the bacteria. AM numbers sharply decreased during infection, which was accompanied by a large influx of neutrophils that also internalized bacteria. Comparative analysis of bacterial viability revealed that neutrophils were more efficient at killing and clearing of L. longbeachae than AM. In contrast, the results presented here indicated that lung-resident AM promoted infection, most likely by serving as a replicative niche. Defence against L. pneumophila is known to require IFN-gamma but not IL-18, a strong IFN-gamma inducer. However, Il18r1–/– mice were less able to clear L. longbeachae and had significantly impaired IFN-gamma levels in the lung. Furthermore, IL-18R signalling was critical for the efficient bacterial killing by neutrophils via production of reactive oxygen species. Previous bone marrow chimera experiments in our laboratory suggested that IL-18R expression in epithelial cells was necessary and sufficient for protection against L. longbeachae. However, genetic in vivo experiments using the Cre-lox-system revealed that IL-18R+ NK cells and T cells were central players in the IL-18-dependent anti-L. longbeachae defence via IFN-gamma secretion, whereas IL-18R expression by ciliated bronchiolar epithelial cells did not confer protection. Finally, our results highlighted key mechanisms by which Legionella subverts host macrophages to form an intracellular endoplasmic reticulum (ER)-like vacuole as its intracellular replicative niche. Establishment of the Legionella-containing vacuole (LCV) by recruitment of ER-derived vesicles induces ER stress. Although the relevance of ER stress in this process is unclear, effector proteins secreted by L. pneumophila are known to inhibit onset of the ER stress response. Using the pharmacological ER stress inducer thapsigargin, we showed that ER stress induces a protective host response promoting the secretion of pro-inflammatory cytokines, limiting intracellular L. pneumophila replication, and improving host survival. Mechanistically, ER stress induced a novel non-canonical activation of the transcription factor STAT1 via the IRE1 kinase driving transcription of the IFN-gamma-induced chemokine CXCL10. These results highlighted a potential role of the host ER stress response in the initiation of a protective cellular immune response towards L. pneumophila

Biosynthesis and biotechnological application of the glycine-glucolipid from the marine bacterium <em>Alcanivorax borkumensis</em>

(noch nicht zugänglich / not yet accessible

Analysis of the cAMP-regulated metabolome of skeletal muscle and adipose tissue

(noch nicht zugänglich / not yet accessible

Immune activation by DNA sensors in ANCA associated vasculitis

Anti-neutrophilic cytoplasmatic antibody (ANCA) associated vasculitis (AAV) is a group of rare inflammatory autoimmune diseases primarily affecting the small vessels of kidney and lung. Current treatment options mainly involve broad immunosuppressive therapy, which is associated with severe side effects, including susceptibility to infection. A deeper understanding of the complex pathophysiology is needed to improve targeted therapy for patients. Neutrophils have been implicated in disease pathology, as they damage tissues. In AAV, neutrophils undergo NETosis, a process that releases DNA bound to antimicrobial peptides such as myeloperoxidase (MPO). ANCAs specifically bind to proteins like MPO, which is bound to the DNA released by neutrophils. This thesis provides insights how nucleic acids by activating DNA sensors propagate signals and drive disease progression in AAV. By utilizing a murine model of pulmonary vasculitis, extensive release of nucleic acids could be detected upon induction of vasculitis. The released DNA was able to bind the nucleic acid sensor cGAS and induce the production of second messenger cGAMP. Accordingly, AAV patients displayed elevated levels of cGAMP compared to healthy donors. Complexation of MPO with DNA in vitro showed that MPO partially protected DNA from digestion. Moreover, addition of MPO antibodies significantly facilitated uptake of MPO bound to DNA in murine bone marrow derived dendritic cells (BMDCs). Stimulation of BMDCs with complexes of plasmid DNA, MPO and MPO antibodies resulted in upregulation of CD40, CD86 and release of pro- inflammatory cytokines. Data obtained from knockout BMDCs revealed that complexes shuttled to the endosomes where they were sensed through TLR9. Lastly, co-culture experiments with BMDCs and neutrophils showed that addition of MPO antibodies facilitate immune activation of BMDCs by neutrophil-derived DNA via TLR9. In summary, the data shows that in vivo, induction of pulmonary vasculitis triggers DNA release, which can activate the cGAS pathway. The in vitro data demonstrates how MPO antibodies protect DNA from degradation and facilitate their uptake and trafficking in AAV. These mechanisms lead to recognition of DNA by TLR9 and contribute to inflammatory responses and disease progression

Characterization and Optimization of Spray Freeze Drying Processes

(noch nicht zugänglich / not yet accessible

Revisiting the innate immune response using systems immunology

(noch nicht zugänglich / not yet accessible

The Role of High-Salt Diet on Melanoma Growth

Cutaneous melanoma is one of the most aggressive cancer types in Western countries with a rising incidence over the last decades. Treatment of early-diagnosed melanoma constitutes a good survival rate and recovery. However, melanoma is a multifaceted disease with high mutational burden that hinders novel therapeutic strategies. Another risk factor in developed countries is the excessive consumption of processed food, the so-called Western diet. This diet is characterized by high content of fat, sugar, proteins, and salt. It is widely believed that a high-salt diet (HSD) leads to sodium accumulation in the skin and modulates the immune system towards a pro-inflammatory state. The main goal of the thesis was to investigate the influence of a HSD on cutaneous cancer growth and to identify cellular and molecular mechanisms for potential therapeutic strategies. Mice fed with HSD showed significantly less tumor volume compared to mice under a control diet. Furthermore, metastasis formation in the lung tissue was also reduced in mice under HSD. Analysis of the tumor microenvironment revealed a similar abundance of immune cells in both investigated groups. Furthermore, the distribution of immune cells in the tumor-draining lymph nodes was not altered by the increased salt intake so the role of the immune system was excluded in the HSD-mediated tumor reduction Instead, HSD tremendously affects tumor metabolism by reducing glycolysis and oxidative phosphorylation activity. Transcriptomic analysis revealed downregulation of cell cycle and metabolism-associated pathways, and metabolomic profiling of tumor tissue confirmed downregulation of glycolysis and fatty acid metabolism. Analyzing glycolytic enzymes showed downregulation of mRNA levels in melanoma cells under HSD, strengthening the theory that excessive salt intake impairs glycolysis. Furthermore, melanoma cells after HSD showed significant upregulation of modulators involved in the melanogenesis pathway. This activity may rather promote melanoma toward cell differentiation and result in the inhibition of cell proliferation. In conclusion, the thesis revealed new insights into how HSD influences melanoma growth. The direct effect of HSD affects tumor metabolism and could be considered in future therapeutic approaches. Furthermore, the presented data indicate changes in melanogenesis activity in melanoma cells exposed to HSD and may explain the salt-mediated tumor reduction

Dynamics of vaginal immunity during HSV-2 and murine filariasis co-infection

(noch nicht zugänglich / not yet accessible

Genetic Analyses to Identify Causative Germline Variants and Molecular Subtypes in Colorectal Polyposis Syndromes

Colorectal polyposis syndromes are rare and genetically heterogeneous precancerous conditions with an increased risk to develop colorectal cancer. In a substantial fraction of patients, no genetic cause can be identified during routine diagnostics. As part of the European Solve-RD project, a multi-layered genomic approach was applied to a multi-center cohort of 219 patients with unexplained polyposis to identify novel causal germline variants and characterize early steps of polyp formation. The systematic reanalysis of existing leukocyte exome sequencing data using updated bioinformatic pipelines and variant interpretation guidelines was able to resolve 3% of the cohort with a definitive genetic diagnosis. Furthermore, candidate variants were identified in another 4%. Building on these findings, a comprehensive molecular profiling was conducted. Exome sequencing was performed for 299 colorectal tumors (273 polyps, 26 carcinomas) from the same cohort. Key differences were identified between adenomas and serrated polyps in somatic driver gene events. Furthermore, the etiology in 19% of cases could be resolved through detection of APC mutational mosaicism. In 9% of serrated polyps, a CIMP-high methylation status was detected. Mutational signature analysis indicated that serrated polyps are molecularly more similar to normal colon tissue than adenomas. In addition, leukocyte genome sequencing was performed in a separate cohort of 98 patients with unexplained ultra-rare tumor syndromes. Thereby, 7% of cases could be clarified and several non-coding candidate variants were identified that may contribute to disease. The study demonstrates the value of a systematic combined analysis of both leukocyte and tumor exome data to solve unexplained polyposis cases. Molecular tumor profiling of the largest collection of both adenomatous and serrated polyps from patients with unexplained polyposis provided clues on the tumorigenic processes involved. Follow-up projects should extend these analyses beyond predefined gene lists and apply innovative technologies to discover novel candidates and gain further insights in tumorigenesis