Die Integration von Multiskalen- und Multi-Omik-Daten zur Erforschung von Wirt-Pathogen-Interaktionen am Beispiel von pathogenen Pilzen

The ongoing development and improvement of novel measurement techniques for scientific research result in a huge amount of available data coming from hetero- geneous sources. Amongst others, these sources comprise diverse temporal and spatial scales including different omics levels. The integration of such multiscale and multi-omics data enables a comprehensive understanding of the complexity and dynamics of biological systems and their processes. However, due to the biologically and methodically induced data heterogeneity, the integration process is a well-known challenge in nowadays life science. Applying several computational integration approaches, the present doctoral thesis aimed at gaining new insights into the field of infection biology regarding host- pathogen interactions. In this context, the focus was on fungal pathogens causing a variety of local and systemic infections. Based on current examples of research, on the one hand, several well-established approaches for the analysis of multiscale and multi- omics data have been presented. On the other hand, the novel ModuleDiscoverer approach was introduced to identify regulatory modules in protein-protein interac- tion networks. It has been shown that ModuleDiscoverer effectively supports the integration of multi-omics data and, in addition, allows the detection of potential key factors that cannot be detected by other classical approaches. This thesis provides deeper insights into the complex relationships and dynamics of biological systems and, thus, represents an important contribution to the investigation of host-pathogen interactions. Due to the interactions complexity and the limitations of the currently available knowledge databases as well as the bioinformatic tools, further research is necessary to gain a comprehensive understanding of the complexity of biological systems

Umsetzung der Energiestrategie 2050: Herausforderungen und Chancen für Staat und Wirtschaft

Sammelband der Reihe "Energy Governance Working Paper" Nr. 1 bis 7Die Energiestrategie 2050 des Bundes definiert anspruchsvolle Ziele. Für deren Erreichung hat der Bundesrat daher unter anderem den Aktionsplan Energieforschung ins Leben gerufen. Dazu wurden acht sogenannte SCCERs, Swiss Competence Center for Energy Research, initiiert, in denen hochschulübergreifend angewandte Energie-Forschung betrieben wird. Die Zürcher Hochschule für Angewandte Wissenschaften (ZHAW) ist an vier dieser acht SCCERs aktiv beteiligt. Die ZHAW hat diese Aufgabe zum Anlass genommen, Energieforschung zum strategischen Schwerpunkt der gesamten Fachhochschule zu erklären und in allen Departementen Kompetenzaufbauprojekte zu starten. Der vorliegende Sammelband präsentiert die ersten Ergebnisse dieser Kompetenzaufbauprojekte an der School of Management and Law, wobei zwei dieser Projekte in Zusammenarbeit mit Forschern aus den Departementen Angewandte Linguistik und School of Engineering erfolgten. Dabei wurden die Herausforderungen und Chancen, die sich für Staat und Wirtschaft aus der Umsetzung der Energiestrategie 2050 ableiten, auf verschiedenen Ebenen betrachtet: die Schweiz im internationalen Vergleich, Besonderheiten der Führung von EVUs, rechtliche und ökonomische Rahmenbedingungen und die Gestaltung der Energie-Zukunft in Schweizer Städten

Учебная программа по учебной дисциплине Иностранный язык (французский)

Учебная программа "Иностранный язык (французский)" кафедры "Белорусский и иностранные языки" для дневной и заочной форм получения образования: общее количество часов - 320 ч., трудоемкость учебной дисциплины - 8 з.е., форма контроля знаний - зачет, экзамен, тестирование

Facing the challenges of multiscale modelling of bacterial and fungal pathogen-host interactions

Recent and rapidly evolving progress on high-throughput measurement techniques and computational performance has led to the emergence of new disciplines, such as systems medicine and translational systems biology. At the core of these disciplines lies the desire to produce multiscale models: mathematical models that integrate multiple scales of biological organization, ranging from molecular, cellular and tissue models to organ, whole-organism and population scale models. Using such models, hypotheses can systematically be tested. In this review, we present state-of-the-art multiscale modelling of bacterial and fungal infections, considering both the pathogen and host as well as their interaction. Multiscale modelling of the interactions of bacteria, especially Mycobacterium tuberculosis, with the human host is quite advanced. In contrast, models for fungal infections are still in their infancy, in particular regarding infections with the most important human pathogenic fungi, Candida albicans and Aspergillus fumigatus. We reflect on the current availability of computational approaches for multiscale modelling of host-pathogen interactions and point out current challenges. Finally, we provide an outlook for future requirements of multiscale modelling

ModuleDiscoverer: Identification of regulatory modules in protein-protein interaction networks

The identification of disease-associated modules based on protein-protein interaction networks (PPINs) and gene expression data has provided new insights into the mechanistic nature of diverse diseases. However, their identification is hampered by the detection of protein communities within large-scale, whole-genome PPINs. A presented successful strategy detects a PPINs community structure based on the maximal clique enumeration problem (MCE), which is a non-deterministic polynomial time-hard problem. This renders the approach computationally challenging for large PPINs implying the need for new strategies. We present ModuleDiscoverer, a novel approach for the identification of regulatory modules from PPINs and gene expression data. Following the MCE-based approach, ModuleDiscoverer uses a randomization heuristic-based approximation of the community structure. Given a PPIN of Rattus norvegicus and public gene expression data, we identify the regulatory module underlying a rodent model of non-alcoholic steatohepatitis (NASH), a severe form of non-alcoholic fatty liver disease (NAFLD). The module is validated using single-nucleotide polymorphism (SNP) data from independent genome-wide association studies and gene enrichment tests. Based on gene enrichment tests, we find that ModuleDiscoverer performs comparably to three existing module-detecting algorithms. However, only our NASH-module is significantly enriched with genes linked to NAFLD-associated SNPs. ModuleDiscoverer is available at http://www.hki-jene.de/index.php/0/2/490 (Others/ModuleDiscoverer).Funding Agencies|Jena School for Microbial Communication (JSMC); Interdisciplinary Center for Clinical Research - IZKF Jena [J50]; DFG [Transregio 124]</p

Human Neutrophils Produce Antifungal Extracellular Vesicles against Aspergillus fumigatus

Invasive fungal infections caused by the mold Aspergillus fumigatus are a growing concern in the clinic due to the increasing use of immunosuppressive therapies and increasing antifungal drug resistance. These infections result in high rates of mortality, as treatment and diagnostic options remain limited. In healthy individuals, neutrophilic granulocytes are critical for elimination of A. fumigatus from the host; however, the exact extracellular mechanism of neutrophil-mediated antifungal activity remains unresolved. Here, we present a mode of antifungal defense employed by human neutrophils against A. fumigatus not previously described. We found that extracellular vesicles produced by neutrophils in response to A. fumigatus infection are able to associate with the fungus, limit growth, and elicit cell damage by delivering antifungal cargo. In the end, antifungal extracellular vesicle biology provides a significant step forward in our understanding of A. fumigatus host pathogenesis and opens up novel diagnostic and therapeutic possibilities.Polymorphonuclear granulocytes (PMNs) are indispensable for controlling life-threatening fungal infections. In addition to various effector mechanisms, PMNs also produce extracellular vesicles (EVs). Their contribution to antifungal defense has remained unexplored. We reveal that the clinically important human-pathogenic fungus Aspergillus fumigatus triggers PMNs to release a distinct set of antifungal EVs (afEVs). Proteome analyses indicated that afEVs are enriched in antimicrobial proteins. The cargo and the release kinetics of EVs are modulated by the fungal strain confronted. Tracking of afEVs indicated that they associated with fungal cells and even entered fungal hyphae, resulting in alterations in the morphology of the fungal cell wall and dose-dependent antifungal effects. To assess as a proof of concept whether the antimicrobial proteins found in afEVs might contribute to growth inhibition of hyphae when present in the fungal cytoplasm, two human proteins enriched in afEVs, cathepsin G and azurocidin, were heterologously expressed in fungal hyphae. This led to reduced fungal growth relative to that of a control strain producing the human retinol binding protein 7. In conclusion, extracellular vesicles produced by neutrophils in response to A. fumigatus infection are able to associate with the fungus, limit growth, and elicit cell damage by delivering antifungal cargo. This finding offers an intriguing, previously overlooked mechanism of antifungal defense against A. fumigatus

Post-anaesthesia pulmonary complications after use of muscle relaxants (POPULAR): a multicentre, prospective observational study

Background Results from retrospective studies suggest that use of neuromuscular blocking agents during general anaesthesia might be linked to postoperative pulmonary complications. We therefore aimed to assess whether the use of neuromuscular blocking agents is associated with postoperative pulmonary complications. Methods We did a multicentre, prospective observational cohort study. Patients were recruited from 211 hospitals in 28 European countries. We included patients (aged ≥18 years) who received general anaesthesia for any in-hospital procedure except cardiac surgery. Patient characteristics, surgical and anaesthetic details, and chart review at discharge were prospectively collected over 2 weeks. Additionally, each patient underwent postoperative physical examination within 3 days of surgery to check for adverse pulmonary events. The study outcome was the incidence of postoperative pulmonary complications from the end of surgery up to postoperative day 28. Logistic regression analyses were adjusted for surgical factors and patients’ preoperative physical status, providing adjusted odds ratios (ORadj) and adjusted absolute risk reduction (ARRadj). This study is registered with ClinicalTrials.gov, number NCT01865513. Findings Between June 16, 2014, and April 29, 2015, data from 22803 patients were collected. The use of neuromuscular blocking agents was associated with an increased incidence of postoperative pulmonary complications in patients who had undergone general anaesthesia (1658 [7·6%] of 21694); ORadj 1·86, 95% CI 1·53–2·26; ARRadj –4·4%, 95% CI –5·5 to –3·2). Only 2·3% of high-risk surgical patients and those with adverse respiratory profiles were anaesthetised without neuromuscular blocking agents. The use of neuromuscular monitoring (ORadj 1·31, 95% CI 1·15–1·49; ARRadj –2·6%, 95% CI –3·9 to –1·4) and the administration of reversal agents (1·23, 1·07–1·41; –1·9%, –3·2 to –0·7) were not associated with a decreased risk of postoperative pulmonary complications. Neither the choice of sugammadex instead of neostigmine for reversal (ORadj 1·03, 95% CI 0·85–1·25; ARRadj –0·3%, 95% CI –2·4 to 1·5) nor extubation at a train-of-four ratio of 0·9 or more (1·03, 0·82–1·31; –0·4%, –3·5 to 2·2) was associated with better pulmonary outcomes. Interpretation We showed that the use of neuromuscular blocking drugs in general anaesthesia is associated with an increased risk of postoperative pulmonary complications. Anaesthetists must balance the potential benefits of neuromuscular blockade against the increased risk of postoperative pulmonary complications