Die besondere Herausforderung der medizinischen Wissenschaft besteht heutzutage darin, die zunehmend unüberschaubare Fülle weltweiter Forschungsergebnisse in für die Therapie verwertbare Botschaften umzumünzen. Diese Überlegung bildet das Fundament und den Antrieb aller in dieser Habilitationsschrift vorgelegten Arbeiten. Inhaltlich befassen sich die Arbeiten mit der Pharmakotherapie der akuten Depression und der Transgenerationalität des Suizidrisikos. Die Fragen nach der relativen Wirksamkeit von Antidepressiva gegenüber Placebo und nach dem optimalen Behandlungsvorgehen bei unzureichendem Ansprechen auf eine erste Therapie mit Antidepressiva zählen zu den klinisch wohl drängendsten Fragen in der Akutbehandlung der Depression. Vor diesem Hintergrund behandelt der Hauptteil der in der vorliegenden Arbeit präsentierten Studien pharmakotherapeutische Aspekte der Akutbehandlung affektiver Störungen. Im Zentrum der wissenschaftlichen Forschungen steht dabei die Behandlung der unipolaren Depression mit Antidepressiva in der Akutphase der Erkrankung. Gemeinsames Ziel der entsprechenden in der Habilitationsschrift zusammengefassten Studien ist es u.a. der Praxis wissenschaftlich abgesicherte Informationen über den optimalen Einsatz von Antidepressiva zur Verfügung zu stellen. Geforscht wurde u. a. nach statistisch belastbaren Anhaltspunkten, ob eine langfristige antidepressive Wirkung nicht allein auf den natürlichen Verlauf der Erkrankung, sondern auch auf eine pharmakologische Wirkung zurückzuführen ist. Weitere Forschungen behandeln die Fragen nach dem Verlauf des Ansprechens auf eine Pharmakotherapie, dem optimalen Zeitpunkt eines Therapiewechsels bei unzureichendem Ansprechen, sowie die Frage nach Wirksamkeit und Verträglichkeit der antidepressiven Kombinationstherapie. Als eigenständiger weiterer Forschungsschwerpunkt wird die Transgenerationalität affektiver Störungen am Beispiel der Suizidalität betrachtet. Hier ging es dem Verfasser und den weiteren Mitgliedern des Forschungsteams darum, das transgenerationale Suizidrisiko zu quantifizieren, sowie auf Basis der wissenschaftlichen Erkenntnisse zu Transmissionswegen und Einflussfaktoren ein Modell der familiären Weitergabe von Suizidalität zu entwerfen, anhand dessen Strategien zur Suizidprävention für die Praxis entwickelt werden können. Eine verbindende Klammer zwischen allen vorgestellten Studien ist die gewählte Forschungsmethode. So beruhen sämtliche in dieser Arbeit vorgestellten Ergebnisse auf der Methodik der Meta-Analyse. In diese spezifische Methode wird daher in einem einleitenden Kapitel gesondert eingeführt.
Weniger anzeigenZiel des Dissertationsprojektes ist eine Neubewertung des Einflusses des irischen Christentums auf dem Kontinent seit dem Frühmittelalter am Beispiel der Vita sancti Columbae Adamnani. Im Unterschied zu bisherigen Untersuchungen konzentriert sich das Projekt auf die Textzeugen der gekürzten Fassung. Die Leitfrage ist, welche Bearbeitungen diese in Abhängigkeit von Ort und Zeit erfahren haben. Voraus gehen Abwägungen zur Anwendung narratologischer Theorien auf mittelalterliche Erzählformen sowie die Entscheidung, dass Phänomene der hier sich darstellenden Erzählpraxis mit historisierten literaturtheoretischen Konzepten wie literarischer oder juristischer Fiktion und othering in Texten betrachtet werden. Die Arbeit geht davon aus, dass die jeweiligen genetischen Stufen der Überlieferung als „Modernisierung“ des Textes zu bewerten sind und dem Zweck der erleichterten Rezeption folgten. Die Studie verdeutlicht, dass die Erzählstrategie in ihrer Betonung des geografischen und sprachlichen Raumes sowie in der Integration folkloristischer Elemente von den Genreerwartungen abweicht. Sie stellt jedoch kein Sub-Genre der irischen Hagiografie dar, sondern die Leistung eines Autors. Der normative Anspruch der Vita zeigt sich in verschiedenen Episoden, die kanonisches Recht und irische Normen als Narrative verarbeiten und ein bestehendes Rechtsverständnis nicht innovieren, sondern be- bzw. verstätigten. Es wird gezeigt, wie gattungsinhärente Narrationen ein bestimmtes Handeln zur Norm erheben und wie weit der Autor geht, um Ethik durch glaubhafte Charaktere zu importieren. Das monastische Lesekonzept betont regionale Unterschiede und trägt zur Andersartigkeit des Textes innerhalb des Genres bei. In seiner Anlage war er durchlässig genug, um zur Identitätsbildung im monastischen Kontext beitragen zu können. Abschließend werden die gewonnenen Erkenntnisse weiter gefasst kontextualisiert. In der Summe wird herausgestellt, dass die Funktionen nicht immer zu allen Zeiten wirksam und deshalb Anpassungen notwendig waren. So kann im Zusammenspiel dargelegt werden, dass die Quelle Zeugnis zeitbezogener Religiosität einer Kommunität und Region ablegt und regionsbezogenes politisches Handeln dokumentiert.
Weniger anzeigenSensory attenuation (SA) describes the process by which self-initiated sensory input is perceived with reduced intensity compared to externally generated sensory input. Motor-based forward models constitute the dominant approaches to explain this phenomenon. According to this framework, action-planning involves the generation of efference copies in addition to motor commands. These efference copies allow predictions about sensory consequences, which are then compared to the actual sensory input. Subsequently, the amount of sensory discrepancy deriving from this comparison assists in forming judgements about our sense of agency (SoA) - the experience of control over self-initiated actions and their sensory consequences. However, recent studies have observed the influence of external mechanisms on SA, thereby challenging this explanatory approach. The theory of predictive processing proposes that all anticipated sensory stimuli, irrespective of their origin, can be subject to SA, potentially explaining the diverse range of observed results. In this dissertation, I describe both explanatory approaches and provide an overview on the impact of temporal predictability, identity prediction and SoA. I continue with summarizing the four dissertation studies, which all examined the influence of motor and non-motor cues on perceptual processing. At last, I will discuss the implications, both methodologically and explanatory, of the observed effects. In Study 1, we examined visual SA by comparing the intensities of virtually occluded stimuli to non-occluded stimuli in a Virtual Reality (VR) set-up. Participants were instructed to move their hands, which were not rendered (i.e., not visible) in VR, into their visual field. The hand movement triggered the appearance of the stimuli, which were either placed behind the participant’s hand or elsewhere. The results indicated that the location of the hand had a stronger impact on perceptual sensitivity than the hand movement itself. In Study 2, using a two-phase comparison to examine auditory SA online, we observed enhancement instead of attenuation for self-initiated auditory stimuli. Overall, these findings suggested the influence of certain external factors, namely accompanying sensory input, identity prediction and signal strength. Study 3 investigated the influence of supraliminal and subliminal prime stimuli on SoA while avoiding post-hoc subject selection. The findings indicated that primes influenced SoA solely when consciously processed. In Study 4, we aimed to gain more control over stimulus presentation by implementing a novel VR set-up to examine somatosensory SA. The results suggested that SA is adaptive and influenced by external factors like signal strength and temporal predictability.
Weniger anzeigenO presente trabalho percorre o cenário de desenvolvimento de ideias que viriam a convergir em torno da arte e da poesia neoconcretas, a partir da elaboração da Teoria do não-objeto de Ferreira Gullar. De sua origem em um contexto de periferia com relação às tradições histórico-artísticas as quais se vinculava, às aspirações de renovação que ultrapassavam os limites impostos pelos seus antecedentes críticos e institucionais. Uma série de artigos, distribuídos ao longo de três capítulos consolidados por enfoques distintos, na qual se pretende oferecer uma visão em perspectiva dos elementos estruturantes daquela vanguarda anunciada, seus condicionantes epistemológicos e dos embates institucionais nos quais a crítica serviria como atualização permanente das posições ocupadas pelos agentes daquelas disputas. Um sobrevôo às grandes configurações sistêmicas, sociais e epistemológicas, indicadas em termos como arte, cultura, vanguarda e tradição, e que encontra no não-objeto um lugar privilegiado para organizar esta narrativa que tem a história da arte e a literatura como pano de fundo.
Weniger anzeigenThe oxidoreductase Retinol Saturase (RetSat), known to catalyse the reaction of all-trans-retinol to all-trans-13,14-dihydroretinol, is highly expressed in metabolically active tissues and differentially regulated in metabolic disorders such as insulin resistance and type 2 diabetes. To date, RetSat has been shown to be involved in adipocyte differentiation, to act as an upstream regulator of hepatic glucose and lipid metabolism, to alter macrophage function, to affect avian vision and to be associated with the generation of reactive oxygen species (ROS). These effects appear to be independent of the originally described saturation reaction, suggesting alternative enzymatic reactions that may lead to the observed effects. RetSat is highly expressed in the metabolically active kidneys, which regulate the filtration, reabsorption and excretion of metabolites. The function of RetSat in the mouse kidney is completely unknown and its role in the development of metabolic diseases remains to be elucidated. The aim of this study was to generate and characterize a mouse model with kidney-specific deletion of RetSat to investigate its function in the kidney. Loss of RetSat in adult male and female C57BL/6J mice resulted in profound proteinuria with additional hyperphosphaturia. Using a label-free quantification (LFQ) proteomics approach, we identified increased excretion of a number of proteins in 24 h urine, including RBP4 and FXYD5. Middle-aged RetSat-deficient mice fed normal chow (NC) showed an increase in body weight that was independent of food intake, with no change in body composition or metabolic profile. Middle-aged male mice lacking RetSat showed hypercalciuria without the development of nephrocalcinosis and an unexpected hypophosphaturia. In addition, RNA-sequencing analysis revealed upregulation of the vitamin D receptor (Vdr) and differential mRNA expression of its target genes in whole kidney tissue. Subsequent Gene Ontology (GO) analysis revealed involvement in the biological process of cell junction assembly. XII RetSat-deficient mice fed with a high-fat diet (HFD) showed an increase in body weight that was independent of food intake, with a relative increase in fat mass, a decrease in lean mass, and impaired glucose clearance. In RetSat-deficient mice, relative energy expenditure (EE) changed without changes in respiratory exchange rate (RER), locomotor activity, or drinking volume. Interestingly, there was a reduction in absolute and relative kidney weight in RetSat-deficient mice in the fed state and less accumulation of fat droplets in the renal cortex. In conclusion, we have successfully generated, validated and metabolically characterized a new mouse model with kidney-specific deletion of RetSat. In this thesis, we have identified a previously unknown link between the renal loss of RetSat and the upregulation of renal Vdr.
Weniger anzeigenNew Delhi metallo-β-lactamase-1 (NDM-1) was first reported in 2009 from a patient who had traveled to India from Sweden and has been rapidly spread worldwide until today. Resistance by NDM-1 is commonly identified in strains of Enterobacteriaceae, Pseudomonas aeruginosa, Acinetobacter baumannii, and some other Gram-negative strains. Enterobacteriaceae are the largest family of clinically important bacteria, infections caused by them related to many diseases, e.g., gastroenteritis, hemorrhagic colitis, bacteremia, neonatal meningitis, urinary tract infections, intraabdominal infections, and pneumonia. With a broad substrate spectrum and improved stability for zinc ion starvation conditions compared with other B1 metallo-β-lactamases (MBLs), NDM-1 is currently one of the most challenging resistance factors threatening the efficacy of carbapenems, the last resort of β-lactam antibiotics. Synergistic usages of inhibitors for β-lactamases with β-lactam antibiotics have become a promising way for keeping the efficacy of carbapenems as well as other essential β-lactam antibiotics. However, until now no effective inhibitors for NDM-1-expressing pathogens are available for clinical treatment, thus there is an urgent requirement for the development of inhibitors targeting NDM-1. In this work, derivatives of DPA (dipicolinic acid or pyridine-2,6-dicarboxylic acid) and quinoline scaffold derivatives were developed as inhibitors for NDM-1 based on the initial fragment screening and supported by docking studies. The modified derivatives had improved inhibitory activity and binding affinity relative to the fragment hits, especially the substituted 8-sulfonamide derivatives such as compounds 94(YJh182), 95(YJh196) and 83(YJh174) with IC50 values ranging from 0.2 µM to 0.3 µM. The interaction modes of the top active and some other representative compounds with NDM-1 were studied by bio-layer interferometry (BLI), isothermal titration calorimetry (ITC), native protein mass spectrometry, thermal shift assay (TSA), circular dichroism (CD) and zinc restoration assays. The top active compounds 94(YJh182) and 95(YJh196) with the 4- or 5-phenyl groups were more specific for the active pocket of NDM-1 compared with compound 83(YJh174) according to docking studies and interacted with NDM-1 mainly by forming stable binding complexes of holo-NDM-1 with the inhibitors which was identified by native protein mass spectrometry. Compounds 94(YJh182), 95(YJh196) and 83(YJh174) all bound the protein reversibly under the BLI assay conditions, and the trend of the Kd values obtained from BLI assays correlated with the trend of the inhibitory activity of the inhibitors. The ITC assays showed binding of ligands to protein and binding of zinc ions to ligands. No or less significant changes for the secondary structures of NDM-1 treated with low excess of the inhibitors were detected by CD measurements, and some changes of the CD signals for NDM-1 treated with high excess of the inhibitors especially compounds 95(YJh196) and 83(YJh174) might be contributed by ligand binding. The inhibition by compounds 94(YJh182), 95(YJh196) and 83(YJh174) for NDM-1 can be partially restored by zinc ions, the different entropic changes observed in the ITC measurements could be contributed by conformational changes at the active site about the amino acid residues and the coordinated Zn(II) ions, and binding with the inhibitors reduced the thermal stability of NDM-1 which was identified via TSA studies. Furthermore, the activity of some representative compounds was also tested toward other clinically relevant B1 MBLs including IMP-1, VIM-2 and GIM-1, and all the tested compounds were potent inhibitors, which suggested that the developed inhibitors are broad-spectrum candidates for B1 MBLs. Activity tests by other metalloenzymes such as hCAII, HDAC-1 and MMP-2 showed that the tested inhibitors all had high selectivity for NDM 1 and had no inhibitory activity for hCAII and HDAC 1 at all. The selected substituted 8-sulfonamide inhibitors all could significantly reduce the MICs of meropenem for the bacteria recombinantly expressing blaNDM‑1 and clinical resistant isolates co-expressing blaNDM‑1 to susceptible levels with lower combined concentrations and had no or little effects on the proliferation and viability of HEK293 cells, which demonstrated that the substituted 8-sulfonamide inhibitors developed in this work are potent and non-toxic or weakly toxic Zn(II)-binding inhibitors targeting NDM 1 restoring the carbapenem susceptibility of multidrug-resistant clinical isolates. Above all, the best active inhibitors developed in this work for NDM 1 had improved specificity and inhibitory activity especially at the cell-level compared to most previously published Zn(II)-chelating or Zn(II)-binding inhibitors such as the AMA-type inhibitors, DPA derivatives and thiol-based structures. The interaction mode of forming protein-inhibitor complexes and reducing the thermal stability of NDM 1 is a more promising mode of action for drug-like candidates than other more toxic mechanisms such as the Zn(II) ion depriving function of EDTA or AMA-type inhibitors and the covalent binding mechanism which is generally limited to the cysteine or lysine residues at the active site.
Weniger anzeigenProteins represent the main target class of bioactive compounds.1 The identification of a drug’s protein target is crucial to understand drug function on a molecular level. Major progress has been achieved in both the construction of large scale screening libraries of structures with drug-like properties as well as in high-throughput methods to screen the bioactivity of those substances against a phenotype of interest. Such phenotypic screens allow to identify hit compounds that alter the disease phenotype in a desired manner.2,3 However, the following deconvolution of the mode of action (MoA) and identification of corresponding protein targets remains a key challenge in drug discovery.2,4 Here we developed a novel target identification (target-ID) approach, which combines the power of photoaffinity labeling (PAL) and quantitative affinity purification mass spectrometry (qAP-MS). This compound interaction screen on a photoactivatable cellulose membrane (CISCM) allows us to probe the interaction of many proteins with multiple compounds in parallel without compound derivatization or structure-activity relationship (SAR) studies being required. To achieve this, we equipped cellulose membranes with a diazirine PAL-probe and photoimmobilized a selection of wellstudied bioactive compounds with ultraviolet (UV) light. The resulting photocrosslinked compound cellulose array was then incubated with protein extract and specific targets were identified via quantitative affinity purification mass spectrometry. For the natural structure analogues cyclosporine A (CsA), tacrolimus (FK506) and sirolimus (rapamycin) this reliably identified known protein interactors, while the known targets of small fragment-like compounds, such as (S)-thalidomide, lenalidomide, methotrexate and metformin, could not be detected. As another limitation, the target tubulin beta (TUBB) could not be identified as a specific interactor of the pharmaceuticals vinblastine and paclitaxel. The observed results were nearly unaffected by the increase of the spacer-arm length, separating the diazirine from the cellulose surface, and by photocrosslinking the compounds isolated from the cellulose membranes with subsequent immobilization of resulting photocrosslinking products. Physisorbed CsA on diazirine-modified non-UV irradiated cellulose membranes could identify the known interactors Peptidyl-prolyl cis-trans isomerases A and F (PPIA, PPIF), whereas physisorbed CsA, sirolimus and FK506 on non-functionalized cellulose membranes could not identify any of their known protein interactors. In summary, we developed a novel compound interaction screen that can rapidly screen for drug targets in a parallel fashion without prior derivatization of the drugs. CISCM reliably identifies the targets of natural products and current limitations of our method are due to the known limitations of diazirine-based photocrosslinking strategies and affinity purification mass spectrometry.
Weniger anzeigenDem griechischen Roman und insbesondere dem frühneuzeitlichen Abenteuerroman haftet das Bild einer idealisierenden Gattung an, deren schöne und vorbildliche Heldinnen und Helden durch exotische Welten reisen und nach vielen Irrwegen ihren Liebestraum glücklich erfüllen. Die Untersuchung der spanischen 'novelas bizantinas', die an Heliodor und Achilleus Tatios modelliert sind, relativiert dieses eskapistische Genrebild. Viele der Texte spielen in einer vertrauten europäischen bis iberischen Geografie und verweisen auf die zeitgenössische Realität, in der allerdings nicht das Märchenhafte der 'romance', sondern eine Atmosphäre der Unsicherheit und Prekarität des menschlichen Schicksals herrscht: eine trostlose Wirklichkeit. Zentral für diese Neudefinition des Musters war Lope de Vegas bislang wenig beachteter Roman 'El peregrino en su patria', der zwischen Einhaltung und Herausforderung des Wahrscheinlichkeitsgebots neoaristotelischer Wirkungspoetiken den Akzent auf die Destitution des Helden legt, der unterhaltsamen Handlungsführung der 'Aithiopika' eine eigenartige Dimension ethischer Reflexion verleiht und damit das Profil einer 'novela helenizante de peregrinación' auf den Punkt bringt.
Weniger anzeigenSome degree of income concentration is necessary in well-functioning market economies as it financially incentivizes individuals to work harder or take the risks of entrepreneurship. But if in- equality becomes too high, it is not only morally concerning and poses a risk to social cohesion and democratic cooperation, but carries real economic consequences. It can lead to economic instability, hinder economic growth, and jeopardize labor market functionality if the belief in up- ward mobility through work is lost. In recent decades, empirical evidence has shown a steep rise in income inequality for many industrialized countries including Germany (e.g., Chancel and Piketty 2021), elevating this topic to be among the major issues of our time.
The goal of this dissertation is to contribute to a more comprehensive understanding of labor market inequality and mobility in Germany. In particular, it is guided by the following research questions: Using different measurement approaches, how has labor market inequality and mobility evolved within generations? How has it evolved across generations? And how do current trends in inequality and mobility compare to historical trends?
Chapters 1 and 2 measure earnings growth and inequality predominantly within the same generation, a common and important way to measure labor market inequality. However, another important puzzle piece in understanding the secular evolution of inequality and its drivers is to compare work and living standards across generations. Individuals often assess their own eco- nomic progress by comparing their earnings to their parents (e.g., Goldthorpe 1987; Hochschild 2016). While the vast majority of these studies focus on relative intergenerational mobility (e.g., Chetty et al. 2014; Bratberg et al. 2017), measuring how children’s outcomes depend on parental income ranks, research has shown that people tend to think in absolute rather than in relative terms (Amiel and Cowell 1999; Ravallion et al. 2018). Therefore, Chapter 3 uses a relatively novel measure to assess intergenerational mobility: absolute income mobility. It measures the fraction of children who earn weakly more than their parents did. Chapter 4 provides a comprehensive picture of the evolution of earnings growth, inequality, and absolute mobility since 1882. This broad scope enables the historical contextualization of the other chapters’ findings.
Weniger anzeigenDie Sarkopenie, das zentrale Thema dieser Arbeit, bezeichnet einen fortschreitenden und generalisierten Prozess eines zunehmenden Verlustes an Muskelmasse, Muskelkraft und muskulärer Funktion, welcher ab einem bestimmten Ausmaß auch zu negativen Folgen wie erhöhter Sturzhäufigkeit und funktionellen Einbußen führen kann. Die Sarkopenie gilt als wesentlich mit dem Alterungsprozess und den damit einhergehenden Veränderungen in der Muskulatur assoziiert. Der Schwerpunkt dieser Arbeit lag auf der Bestimmung der Prävalenz der Sarkopenie gemäß den zum Zeitpunkt der Untersuchungen empfohlenen diagnostischen Kriterien und der Analyse von Zusammenhängen zwischen Sarkopenie einerseits und möglichen Ursachen sowie auch Folgen der Sarkopenie andererseits. Ergänzt wurde dieser Schwerpunkt durch methodische Fragestellungen in Hinblick auf die diagnostischen Kriterien und Überlegungen hinsichtlich möglicher therapeutischer Optionen. In den vorgestellten Originalarbeiten konnte gezeigt werden, dass auch bei noch vergleichsweise gesunden älteren Menschen eine als relevant hoch einzuschätzende Prävalenz der Sarkopenie vorliegen kann. Es zeigte sich dabei auch, dass methodische Aspekte wie die Verwendung unterschiedlicher Parameter der Muskelmasse die Erhebung der Sarkopenieprävalenz stark beeinflussen können. Ferner waren signifikante Unterschiede zwischen zwei dieser untersuchten Parameter zu beobachten was deren Assoziation zu Pre-Frailty/Frailty und zu selbstberichteten Limitationen der physischen Performance und damit potentiellen Folgen der Sarkopenie angeht. In weiteren Analysen konnte gezeigt werden, dass ein Diabetes mellitus Typ 2 mit Sarkopenie assoziiert ist und eine niedrige Muskelmasse mit einer ausgeprägteren Insulinresistenz einherzugehen scheint, wobei hier die Kausalität aufgrund der Limitation querschnittlicher Analysen vorerst unklar bleibt. In weiteren Analysen ergaben sich zudem Hinweise, dass Störungen der thyreoidalen Funktion eine Sarkopenie begünstigen könnten. Dieser mögliche Effekt scheint sich jedoch insbesondere in Hinblick auf eine hypothyreote Stoffwechsellage in höherem Alter abzuschwächen. Ein positiver Zusammenhang zwischen der Einnahme von Angiotensin Converting Enzyme (ACE) – Hemmern und mehreren Parametern der Sarkopenie, hypothetisch möglich aufgrund potentieller protektiver Effekte von ACE-Hemmern auf die Skelettmuskulatur, fand sich nicht.
Weniger anzeigenCollective states with their fascinating optical properties occur through the coupling of dipole moments. The coupling of the dipoles leads to an overall optical response that varies strongly from the monomer. Dipole coupled systems are manifold systems with optical properties that are interesting for a variety of optoelectronic applications, solar cells, and catalytic reactions. The lattices range from atomic and molecular lattices up to plasmonic structures and can vary in their dimensionality. Depending on the approach, dipole coupled systems can easily be adapted to the relevant requirements, such as excitation energy. The first part of this work investigates collective states in one- and two-dimensional molecular lattices. These states are highly emissive, have narrow line widths as well as short radiative life times. With a microscopic real space dipole model, I show that excitations of two-dimensional molecular monolayers are robust against various forms of disorder. I realize the growth of two-dimensional monolayers with a perylene derivate and show that the collective states also exist on materials that provide a large radiative decay channel. Then I explore collective states in one-dimensional molecular aggregates, namely in molecule chains encapsulated in boron nitride nanotubes. I verify that the collective exitonic states of single- and multi-file chains show an enormous shift to lower energies that is not captured by the model of a chain of interacting dipoles. The last part of my work focuses on a different kind of dipole coupled system, namely bimetallic nanoparticle supercrystals for photocatalytic experiments. Small platinum particles that are placed in the hotspots of a gold supercrystal show an increased production of hydrogen. I investigate the layer dependent optical response of the crystal and calculate the electric fields in the hotspots which I compare with wavelength dependent catalytic experiments. In photocatalytic experiments the binary crystal shows a higher hydrogen generation rate than other top performers for formic acid dehydrogenation.
Weniger anzeigenThe dissertation deals with the memory of the Syrian revolution that began in 2011 in the context of the Arab Spring. It examines how leftist actors have used digital media to make visible an anarchist dimension of the revolution that has often been lost in the common narrative of a ‘complicated civil war’. At the centre of this left-wing appropriation of the Syrian revolution are the local councils, hundreds of which have sprung up across the country from the late 2011 onwards. They were conceptualized in 2011/2012 by the Syrian intellectual Omar Aziz from an anarchist perspective as forms of local self-organization against the state and political parties. The aim of the study is to reconstruct digital memory work in social media (Facebook, Twitter) and blogs in such a way that the interplay of actors, practices (archiving, circulating, claiming) and technology for the emergence of memory becomes clear. Drawing on research in the fields of social movements, cultural memory and digital media, the study contributes to theory building, differentiates existing concepts and tests new methodological approaches. The manually collected data (posts, tweets, articles from blogs and other platforms) were coded and qualitatively analyzed according each platform in order to identify different aspects of memory work: temporal dynamics, different roles of actors, interactions between platforms in the circulation and archiving of memory, etc. A backlink analysis of blogs and a qualitative content analysis of the most relevant blog articles deepen the analysis of how memory is circulated and claimed. As a result, the roles of actors were differentiated according to their skills, degree of commitment and existing (offline) networks. The findings provide a nuanced picture of how the technological ‘affordances’ of a medium play out and depend on actors and practices. The importance of blogs as temporary archives or resting points in the initial phase of memory work is emphasized, while Twitter and Facebook functioned more as circular hubs and pacemakers of a memory rhythm over nearly ten years. Alongside the question of how memory was created and cultivated, there is the question of the object of memory itself. Previous studies of the local councils have not adequately grasped how the councils functioned and have failed to recognize the links between the Syrian councils and a (left-wing) council tradition and hence their potential as an alternative to representative, statist democracy. Omar Aziz explicitly pointed to this connection by placing the Syrian revolution in the tradition of the Paris Commune of 1871, which has an iconic significance in all communist and anarchist movements and is seen as an early realization of council democracy. The analysis of claiming showed that the left reception of the Syrian revolution has also had difficulties in spelling out how the Syrian councils are related to the left council tradition. The main arguments proposed by the memory workers have relied on the ‘anarchist’ personality of Aziz, who functions as a guarantor of the anarchist credentials of the councils; on ‘mnemonic chains’ that refer to the Paris Commune; and on the emphasis on the anti-state and grassroots-democratic character of the councils. The dissertation therefore reconstructs in detail how the actual existing local councils came about and functioned while also examining the reasons for their failure. Methodically, the analysis is based on three pillars: On expert interviews, on the analysis of a website of the local council in Darayya and on studies by international NGOs. In dialogue with previous theoretical reflections on councils and drawing on key principles of anarchism, the local councils are reconstructed along four dimensions: as social sites of agency and self-organisation; as institutions of anti-state democracy; in their capacity to anticipate a new order; and as manifestations of a cooperative order. The research shows that the councils initiated a de-professionalisation of politics in favour of an expansion of agency and learning processes; that they reorganised the separation of powers in different ways; that a major achievement was the preservation of order and the restoration of everyday life; and that they promoted to some extent a new cooperative ethic. The councils’ failure to build up a ‘structural solidarity’ to ensure the provision of basic goods is identified as the major weakness which made them vulnerable to other actors’ agendas (Islamists, international NGOs, opposition in exile) and substantially undermined their independence. These findings suggest to re-consider more classical materialist objections to the assumption that councils could consolidate themselves in the long term in a purely civil or political sphere while refraining from socialization of private property. Omar Aziz’s Papers, that were written in 2011/12 from a pragmatic point of view during the turmoil of the revolution, are for the first time thoroughly analyzed, and the question is raised as to how they can be placed paradigmatically within the theory of the councils. The hitherto unrecognised theoretical potential of Aziz’s texts is revealed by reconstructing his intellectual background. Ideas such as the different everyday logics ‘authority’s time versus revolutionary time’, the ‘desire for life’ and councils as social spaces for learning and joyful experiences are identified as essential contributions to the further development of council theory.
Weniger anzeigenBasierend auf dem in dem sechsbändigen Wörterbuch Derleme Dergisi und dem zwölfbändigen Wörterbuch Derleme Sözlüğü versammelten Dialektmaterial untersucht diese Arbeit den Sprachgebrauch und Wortbestand türkeitürkischer Dialekte am Beispiel von Pflanzen- und Tierbezeichnungen in Mundarten auf dem Gebiet der Republik Türkei. Die Wortbestände der beiden Werke wurden im zweiten Viertel des 20. Jahrhunderts gesammelt und erlauben eine Untersuchung auf Basis von synchronischen Daten. Die untersuchten Pflanzen- und Tierbezeichnungen haben sich mehrheitlich als Typen, die im Oghusischen bereits vor der Sesshaftmachung der Stämme in Kleinasien verwendet wurden, als Onomatopoesie und als Lehnwörter aus Sprachen außerhalb der Türksprachen erwiesen. Die Verteilung der verschiedenen Lehnwörter liefert in diversen Fällen Hinweise auf Siedlungsräume von Sprechern dieser Sprachen oder deren Nachfahren und lässt dabei Rückschlüsse auf die historische Demografie Kleinasiens zu. In den Ergebnissen dieser Arbeit überwiegen Lehnwörter armenischen, griechischen und persischen Ursprungs. Dieses Fazit ist für sich allein nicht überraschend, nachdem diese Bevölkerungsgruppen früh mit den türkischen Stämmen Kontakt hatten. Persische Entlehnungen ins Oghusische sind bereits im 11. Jahrhundert, bevor die Besiedlung Kleinasiens durch die türkischen Stämme, belegt. Kleinasien war zu der Zeit bereits seit Jahrtausenden von griechischen und armenischen Bevölkerungen besiedelt. Diese Lehnwörter stellen frühe Entlehnungen dar. Später introduzierte Pflanzen, wie die Tomate und die Kartoffel, können sich naturgemäß allein als spätere Bildungen und Entlehnungen erweisen. Eine Übereinstimmung zwischen frühen Klassifikationsversuchen und den Verteilungen der in dieser Arbeit untersuchten Pflanzen- und Tierbezeichnungen konnte nur in wenigen Fällen nachgewiesen werden. Bei der Verteilung einiger Bezeichnungen finden wir weithin Übereinstimmungen mit Gruppen von CAFEROĞLU (1959), BANGUOĞLU ([1959] 1998) und KARAHAN (1996). Ein signifikanter Teil der untersuchten Typen von Pflanzen- und Tierbezeichnungen dokumentiert gleichwohl eine weite Verteilung über die Gruppierungen der verschiedenen Klassifikationen hinweg. Der Vergleich zwischen der Verteilung der Pflanzen- und Tierbezeichnungen und den Siedlungsräumen der neun Oghusenstämme, die als besonders bedeutsam für die Bildung der Dialekte Kleinasiens erachtet werden, kann bei der Schärfentiefe dieser Arbeit lediglich ein interpretationsfähiges Ergebnis liefern. Die breite Verstreuung der Oghusenstämme und ihre geografisch gemeinsame Präsenz in Kleinasien verbildlichen ohnehin die Schwierigkeit, Zusammenhänge zwischen ihnen und der Verteilung der Mundarten Kleinasiens herzustellen.
Weniger anzeigenInfections of the lower respiratory tract represent the fifth most common cause of death worldwide. This study describes a mechanism that influences the course of pneumococcal pneumonia based on genetic determinants as well as environmental factors. Previous experiments have shown that animals deficient in IL-33 or its receptor ST2 exhibit an enhanced bacterial defense against Streptococcus pneumoniae. Initially, associations between the susceptibility to human pneumococcal pneumonia and single nucleotide polymorphisms (SNPs) in the genes coding for IL-33 and ST2 were demonstrated. Furthermore, IL-33-deficient animals were shown to produce increased amounts of IL-22, and experiments using Il33-/- Il22-/- animals as well as recombinant IL-22 revealed that enhanced IL-22 production was responsible for the increased resistance of Il33-/- mice to Streptococcus pneumoniae. Classical type 2 immune responses driven by type 2 innate lymphoid cells (ILC2s) or IL-4/IL-13 signaling cascades were not involved in the IL-33-dependent regulation, while ST2-negative ILCs, most likely representing ILC3s, were identified as the main differential producers of IL-22. Additionally, an association between bacterial defense and animal housing conditions was revealed. The IL-33-dependent negative regulation of pneumococcal pneumonia could only be reproduced in facilities with specific individual hygiene conditions. This effect was accompanied by differences in the composition of the intestinal microbiota of the animals, where increased abundance of Lactobacillus spp. correlated with a protective phenotype in Il33-/- mice. Finally, microbiota depletion and co-housing experiments resulted in equilibration of bacterial burden, while a fecal microbiota transplant was able to rescue the observed phenotype in microbiota-depleted animals. Taken together it was demonstrated, that the intestinal microbiota influences pneumococcal pneumonia. The results presented in this study enhance our understanding of the bidirectional communication between microbiota and the immune system and demonstrate that genetic as well as environmental factors infl uence the defense against Streptococcus pneumoniae.
Weniger anzeigenThis dissertation examines the production and transformation of knowledge in early modern Ottoman Arabia. It proposes a new historical narrative of seventeenth-century Medina by closely perusing the biography and works of Ibrahim al-Kurani (d. 1690), the most prominent Kurdish theologian, Sufi, and hadith scholar during the eleventh Islamic century, or the seventeenth century, situating this figure within broader cultural, intellectual, and political milieus in the global configuration of Islamic thought in the early modern period. This dissertation investi-gates particular routes of knowledge transmissions that took place in the post-Timurid and post-Mamluk intellectual spheres, which became the multifaceted settings of the Ottoman scholarly tradition. It argues that Kurani’s pursuit of multiple genealogies from both intellectual traditions enabled him to balance between the rational and traditional sciences, which strengthened his authority in Medina where the production, circulation, transmission, and transformation of his writings occurred through trans-imperial and transregional connections.
To examine this phenomenon, this dissertation uses a corpus of manuscripts produced and written in Arabian, Maghrebi, Indian, Ottoman, and Southeast Asian cultural contexts. It reveals the sites of connection and contestation in order to explore how Kurani’s scholarly and religious authority was formed, circulated, and contested through the views of his proponents and opponents in different geographical locations. This study demonstrates that Medinan intellectual culture in the seventeenth century was shaped by the confluence among various streams of knowledge that underpinned Ibrahim al-Kurani’s intellectual persona among Muslim elites and scholars throughout the Islamic empires. It also emphasizes the importance of textual produc-tion and transmission in comparative and transregional settings, explains the inevitability of engaging with unexplored and understudied sources from multiple cultural ecologies, and explicates an ideal case of extensive networks in the Islamicate Republic of Letters in the early modern time.
Weniger anzeigenIn mammals, female cells achieve dosage compensation between the sexes randomly chosing and transcriptionally silencing one of the two X chromosomes through a process known as X-chromosome inactivation (XCI). This process is initiated during early development through up-regulation of the long non-coding RNA Xist, which mediates chromosome-wide gene silencing of the future inactive chromosome (Xi) in cis. Upon completion of the XCI process Xi will maintain its silenced state in all daughter cells, which results in the genetic mosaicism of female organisms. Cell differentiation, Xist up-regulation and gene silencing are thought to be coupled at multiple levels to ensure inactivation of exactly one out of two X chromosomes.
In this thesis I performed an integrated analysis of all three processes through the analysis of allele-specific single-cell RNA-sequencing data. Specifically, I investigated the endogenous random XCI process in hybrid mouse embryonic stem cells at different time points throughout cellular differentiation developing dedicated analysis approaches that rely on the high number of polymorphisms between the two parental strains.
Putative Xist regulators were identified exploiting the inter-cellular heterogeneity of XCI onset. A large fraction of cells transiently expressed Xist on both X chromosomes which resulted in biallelic gene silencing right before being resolved to a monoallelic state, confirming a prediction of the stochastic model of XCI. The two X chromosomes showed different gene silencing dynamics, and a number of strain-specific escapees (namely, genes that escape transcriptional silencing) were identified and experimentally validated. These results suggest that genetic variation modulates the XCI process at multiple levels, providing a potential explanation for the long-known X-controlling element (Xce) effect, which leads to preferential inactivation of a specific X chromosome in inter-strain crosses.
Overall, this work provides a detailed picture of the different levels of regulation that govern both Xist up-regulation and the initiation of XCI.
Weniger anzeigenBats worldwide are experiencing severe declines, and a concerning percentage of bat species are considered endangered, with inadequate data for many others. This makes the application of meaningful conservation efforts challenging, as a comprehensive understanding of the behavior and habitat use of endangered species is crucial for successful conservation. The nocturnal and flying nature of bats additionally complicates observational studies. However, bats hold great potential for non-invasive acoustic monitoring as they are highly vocal and constantly emit high-frequency echolocation calls for orientation in their predominantly dark environment. While species discrimination via echolocation calls became more and more reliable over the years, similar calls evolved in some species based on habitat and prey preferences, complicating identification via echolocation calls. This is especially true within the genus Myotis. Besides calls for orientation, most species also employ a variety of social calls for communication. Social calls are far less studied than echolocation calls, especially when produced on the wing. As those calls are known to contain information about individual identity, sex, or age of the sender they should at the very least be species-specific, thus also holding great potential to be used for species identification. I aimed to study bats’ behavior and social calls during autumn swarming at a large hibernaculum in Northern Germany, the Kalkberg Cave in Bad Segeberg, whose main inhabitants are Daubenton’s bats (Myotis daubentonii) and Natterer’s bats (Myotis nattereri). Prior to hibernation, temperate zone bats gather in front of underground hibernacula (winter roosts) and participate in a behavior known as swarming. Swarming is characterized by intense flight activity and is accompanied by large amounts of both echolocation calls and social calls. Different functions of swarming are suggested, incorporating information transfer, mating, and the facilitation of gene flow between otherwise isolated colonies. The small differences between the echolocation calls of the two predominant Myotis species become further attenuated in this swarming context. To tackle that problem, in Chapter One, I tested the possibility of species identification from overlapping echolocation call sequences recorded in a crowded swarming situation. With a combination of Linear Frequency Cepstral Coefficients (LFCCs) and classic acoustic parameters, I analyzed the “soundscape” rather than single echolocation calls. This combination enabled me to detect the predominant species at the time of recording. The method has great potential to facilitate species identification and long-term monitoring in situations with more than one individual calling, e.g. on so far understudied swarming sites. By gathering information on species assemblage during autumn swarming conclusions about winter populations in hibernacula can be drawn, reducing the necessity of disruptive winter controls. Chapter Two was dedicated to further investigations of social call repertoire and function in a swarming context. I identified ten distinct call types based on differences in their spectro-temporal structure and confirmed the grouping via a discriminant function analysis. An additional analysis of the surrounding echolocation calls (as developed in Chapter One) revealed that both species potentially present at the swarming site employed social calls with large structural similarities. However, a subsequent analysis of classic acoustic parameters revealed subtle but significant differences in the structure of such calls. For a better understanding of the call function, I conducted playback experiments in the vicinity of the swarming site. I broadcasted three different call types for each species and observed an increase in bat activity (approximated as echolocation call rates) during and after the playback in three out of six scenarios, indicating that bats inspected or approached the playback site. By simultaneously taking photographs with a camera trap, I sometimes managed to identify approaching bats to species level. The results suggest that one call type is used to maintain group cohesion within the same species, while another type is used for communication between different species. The results are in line with what we already knew about the autumn swarming phenomenon and further enhance our understanding of it. The results from Chapter Two underlined the function of swarming sites for communication and in this situation, it could be possible to introduce a cue to the bats, which is subsequently connected to a suitable hibernaculum. Thus, for Chapter Three, I installed hollow hemispheres as strong echo-reflective cues at the swarming site, where bats first encountered them during swarming. Those cues are known to provide an equally strong echo over a broad range of angles which should be highly conspicuous to passing bats. To investigate whether bats subsequently prefer roosts with hollow hemispheres I installed 60 boxes (30 with and 30 without hollow hemispheres) across three study sites. To non-invasively measure bat activity I constructed a light beam system that recorded activity at boxes, and indeed, bat activity exhibited significant variation. However, I found that prior familiarity with bat boxes played a bigger role in roost occupation than the advanced echo-reflective properties did. Additionally, I developed an effective monitoring system for tracking activity rates at bat boxes. This system revealed activity at boxes weeks to months before bats or feces were detectable via traditional visual inspections. To not interfere with the animals’ natural behavior and not disturb them in their environment all investigations were made as non-invasive as possible. A reasonable combination of monitoring techniques has the potential to gain comprehensive overviews of species-specific behavior, thereby laying the basis for informed conservation decisions for endangered species. Consequently, this study enhances our understanding of bat behavior and establishes a foundation for comprehensive monitoring in the future: By integrating both soundscape analysis and social call monitoring we potentially will gain deeper insights into bat populations, including habitat usage, species assemblage, phenology, and seasonal variations.
Weniger anzeigenThe present study investigated the effect of a preceding, short cold treatment (4 °C, 24 h) on the resistance of Arabidopsis thaliana against hemibiotrophic Pseudomonas syringae pv. tomato (Pst) and necrotrophic Botrytis cinerea. For this aim, two different experimental cold setups were compared. In the first setup (cold pre-treatment; CT), the pathogen infection occurred directly after the cold treatment. The second experimental setup (cold priming; CP) included a memory phase between the cold treatment and the infection, whereby the impact of a priming memory on the resistance against pathogens was investigated. Arabidopsis benefited from the cold treatment and exhibited significantly increased resistance against Pst and B. cinerea. For plant defense against Pst, cold priming and cold pre-treatment led to increased resistance, while against B. cinerea only cold pretreatment resulted in transient resistance increase. To identify the immune signaling pathways responsible for the increased resistance, transcript analyses and pathogen growth experiments were conducted with Arabidopsis (Accession: Col-0) and selected mutant lines. The experiments demonstrated that cold priming-mediated resistance in Arabidopsis against virulent Pst is independent of the plant immune regulator Enhanced Disease Susceptibility 1 (EDS1) and does not alter transcript levels of pathogen-triggered Pathogenesis-related 1 (PR1), Isochorismate Synthase 1 (ICS1), FLG22-induced receptor-like Kinase 1 (FRK1), and NDR1/HIN1-like 10 (NHL10). These results, but also the observation that cold priming does not confer resistance against avirulent Pst avrRPS4 and Pst avrRPM1, indicated that cold-mediated resistance against Pst is mainly independent from effector-triggered immunity (ETI), hypersensitive response (HR), PAMPs-triggered immunity (PTI) and salicylic acid (SA) signaling. Cold pretreatment-mediated resistance against B. cinerea was also without cold signatures on the transcript levels of Pathogenesis-related 1 (PR1), Pathogenesis-related 4 (PR4), Plant Defensin 1.2a (PDF1.2a) and Phytoalexin Deficient 3 (PAD3). This suggested that cold exposure-mediated resistance against B. cinerea is independent of SA signaling, jasmonic acid (JA) signaling, and camalexin biosynthesis. Increased accumulation of reactive oxygen species (ROS) was observed in Arabidopsis leaves after the cold pre-treatment and subsequent B. cinerea infection indicating a central function of ROS in the crosstalk between the prior cold and pathogen infection. Besides other functions, ROS contribute to lignin and callose formation. Enhanced callose formation and lignification could be detected immediately after the cold exposure. In contrast, B. cinerea did not alter plant lignin amounts and pathogen-triggered callose deposition was not further affected by prior cold treatment. We extended our analyses by investigating the impact of cold-pre-treatments on the establishment of systemic aquired resistance (SAR). The induction of SAR in cold-pretreated plants was successful, but the prior cold treatments did not provide additional benefits for SAR against Pst. Interestingly, a syringe infiltration with the mock solution instead of the SAR-triggering primary Pst inoculation enhanced the susceptibility of Arabidopsis after a cold pre-treatment against Pst. The most pivotal finding of this work demonstrated that the chloroplast-localized ROS-scavenging enzymes stromal ascorbate peroxidase (sAPX) and thylakoid ascorbate peroxidase (tAPX) are essential for the wildtype-like enhanced resistance against Pst and B. cinerea after prior cold treatments. CP-mediated resistance was also confirmed in the immunocompromised null mutant enhanced disease susceptibility 1 (eds1-2) crossed with stroma ascorbate peroxidase knockout (eds1 sapx). This work, furthermore, showed that sAPX is essential for cold-induced callose formation and dispensable for pathogen-induced callose. Finally, sapx, but not thylakoid ascorbate peroxidase knockout (tapx), showed a different ROS generation pattern, with significantly more ROS being generated than in cold-treated sapx or compared to wildtype plants without cold pre-treatment. These results highlight the relevance of the chloroplast antioxidant system in cold sensing and its impact on the plant immune system.
Weniger anzeigenThis work aims to develop superhydrophobic surfaces from supramolecular xerogels with low molecular weight gelators (LMWGs). LMWGs are small organic compounds that have a strong preference to form gels in a suitable solvent. To achieve a xerogel coating, one can drop-cast the gel onto substrates such as glass cover slips, allowing it to dry under ambient condition. The LMWGs used in this work are based on a trans-1,2-diamidocyclohexane core, equipped with two equilateral perfluorinated side chains (CFn, where n represents the number of the carbon atoms on each chain). The amide groups on the core facilitate strong intermolecular hydrogen bondings and lead the way to supramolecular self-assembly, while the perfluorinated side chains contribute to the intrinsic low surface energy of the materials. Both parts are essential for the formation of the superhydrophobic xerogel coating.
The first part of this work focuses on investigating the effect of the side-chain length on the resulting xerogel coating. Eight LMWGs, from CF3 to CF10, are included in the investigation. The xerogel coatings were examined from three different scales. In the nanoscale, surface x-ray diffraction (sXRD) reveals the difference in the structural properties of the resulting supramolecular aggregates. Scanning electron microscopy (SEM) and optical microscopy were used to reveal the morphologies of the aggregates in the microscale. As for the macroscopic scale, the coatings were tested for their hydrophobicity and durability towards water flushing. In addition to the standard contact angle measurements and gravimetric studies, an image processing script coined Morphology evolution analysis (MEA) was devised to investigate the change of the coating after intensive flushing. This method evaluates the durability by assessing the change in the relative thickness of the coating through pixel intensity. The first part of this work concludes that the length of the perfluorinated side chains has a significant impact on the resulting xerogel, as certain LMWGs provide xerogel coatings with better properties in terms of both hydrophobicity and durability.
To broaden the applicability of the xerogel coating, it is crucial to overcome the intrinsic mechanical fragility of the xerogels. Therefore, the second part of this work focuses on the preparation of the more mechanically-durable hydrophobic coatings from the combination of supramolecular xerogels and polymers. CF7 was selected as the concept LMWG, while two monomers, methyl methacrylate (MMA) and trifluoroethyl methacrylate (TFEMA), were chosen as the candidates for the polymer component. Extensive screening was done to find the optimised fabrication condition for a robust hydrophobic supramolecular-polymer co-assembly. The co-assemblies were investigated with SEM and Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS) for the structure of the aggregates and the uniformity of the coating, respectively. The iterability and durability of the co-assemblies are again tested with water flushing. A sclerometer was employed in addition to test the scratch resistance of the co-assemblies. Practical implementations including metal corrosion protection and oil-repellency were also carried out. In conclusion, xerogel-based hydrophobic and oleophobic coatings with significantly improved scratch-resistance are achieved by fixating the supramolecular network with a polymer matrix.
Weniger anzeigenT. gondii is a zoonotic protozoon that can infect virtually all warm-blooded species on all continents. The parasite has a complex population structure, including countries and continents dominated by only a few clonal lineages, while T. gondii populations in South America are highly diverse. The genetic diversity described in Central and South America is associated with higher virulence and more severe cases of toxoplasmosis in humans, making it important to detect the introduction of such genotypes into Europe. This work focused on genotyping of T. gondii in Europe where the clonal lineage type II is predominant. The predominance of T. gondii type II in Europe was described in the past as part of global studies on population genetics of T. gondii, but there were no studies that focused exclusively on Europe. Therefore, the available genotyping information on European T. gondii was summarized in a review and the distribution of circulating strains in Europe was mapped, revealing that there was little or no information available for some countries. Moreover, it was recognized that the application of genotyping methods was not consistent between different laboratories. A frequently used genotyping method for T. gondii is based on MS markers. It represents the current reference standard for genotyping and fingerprinting. To reach consistency in T. gondii MS typing, a ring trial among five European laboratories was organized and the results were published together with guidelines for a harmonized application of MS typing. On this basis, MS typing results may become more comparable in the future, which is necessary to combine larger data sets on T. gondii genotypes originating from different studies. Guidelines for MS typing may also encourage more laboratories in Europe to use the MS method, which may help to fill the identified gaps in genotyping data. MS typing and WGS analysis revealed genetic variability within T. gondii type II. To explore this further, an NGS-based typing method with a high typing resolution among T. gondii type II strains was established. This new Ion AmpliSeq method appears to be suitable to improve the understanding of transmission pathways of T. gondii, to trace infection sources in outbreaks or to detect recombination and the introduction of genotypes to new areas. Furthermore, the harmonized MS method was applied in a study for genotyping of T. gondii DNA extracted from tissue samples of red squirrels (Sciurus vulgaris) found dead in the Netherlands. This study identified genetic clusters based on the MS typing results, but without obvious regional association. In future studies, cluster analyses can be performed with large, combined datasets using the harmonized MS typing method or Ion AmpliSeq typing to obtain further insights into the population structure of T. gondii in Europe.
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