Mechanosensation is a process by which nerves encode physical stimuli such as cotton swab or pinprick into electrical signals that can be understood by the nervous system. In this way, organisms can gain crucial information about the environment by means of touch sensation and avoid harmful influences thanks to nociceptive pain. But what is the molecular basis of mechanosensation, allowing this process to occur? And what happens if its functioning is disrupted? I tackle those questions in my doctoral thesis, investigating a role of newly described mechanosensitive channel and discussing tactile phenotypes in autism spectrum disorders (ASDs). This work is mostly an electrophysiological study of cutaneous mechanoreceptors, studied with the use of ex vivo mouse skin-nerve preparation. Focus is on c-fibers, small diameter unmyelinated sensory neurons, involved in relying nociceptive cues. In the first part of my doctoral project I investigate the role of Elkin1 (TMEM87a) channel in the nociceptor physiology. Results show that Elkin1-/- knockout mice exhibit lowered mechanical sensitivity when tested in behavioral assays using a hindpaw stimulation. Electron microscopy showed no structural changes in the somatosensory system of mutant animals, albeit there are changes in the physiology of sensory afferents. Extracellular recordings from single nerve fibers, made during simultaneous mechanical stimulation of receptors located in the skin, showed a changed pattern of activity in response to mechanical stimulation with faster adaptation in fibers from Elkin1-/- animals, but only when a specific protocol of stimulation was used. Furthermore, I explore the relationship of Elkin1 with Piezo2 mechanosensitive channel by studying double knockout animals. Effect of deleting both protein seem to have greater effect on dampening response to mechanical stimuli than removing any one of them separately. On the other hand, introducing human point mutation into mouse genome slightly strengthen the response. Overall, Elkin1 is a novel mechanosensory protein presumably required mostly for light touch, as changes in functioning of c-fibres point toward minor involvement in nociception. Sense of touch is also critically important for proper development. It constitutes the most primal form of communication between an infant and a parent, building foundation for more advanced social skills. Tactile-related impairments observed in toddlers pose a strong predictor of core autistic symptoms later in life and sensory processing disturbances belong to the most replicable symptoms emerging early in the diagnosis of ASDs. Modified touch perception phenotype observed in human subjects is replicated in animal models. Global knockout of 4E-BP1, the downstream effector of mTOR signalling pathway affected in some ASDs forms, was shown to be a source of mechanical hypersensitivity with enhanced nociception in mice. However, my results on the specific involvement of this phenomenon in the peripheral sensory neurons did not show any positive results. My findings, both of electrophysiological study and behavioral assessment, indicate that mechanical hypersensitivity observed in the model of 4E-BP1 deletion ca not be explained by differences in the physiology of cutaneous nociceptors.
Weniger anzeigenTwo-dimensional (2D) materials exhibit unique physical and chemical properties that make them promising candidates for electronic, optoelectronic, and energy-related applications. However, the limited tunability of pristine 2D materials restricts their broader practical use. This work presents a series of computational studies focused on tailoring the structural, electronic, optical, magnetic, and catalytic properties of 2D materials through functionalization and engineering strategies, including defect engineering, doping, heterostructure formation, molecular modification, and strain or pressure. The results demonstrate that these approaches effectively modulate key material properties such as band structure, charge transfer, excitonic behavior, magnetic ordering, and catalytic performance. Overall, this study provides theoretical insight and design guidelines for the rational tuning of 2D materials toward advanced device and energy applications.
Weniger anzeigenThis thesis focuses on the exploration of the metabolomics approach as a guided tool in the field of anti-doping by defining a workflow based on the synergy between High-Resolution Mass Spectrometry and chemometric tools.
First, the optimization of a low-energy electron ionization source to maximize the formation of molecular ion and minimize the fragmentation degree of steroid pathways, preserving the specific fragmentation pathway of the steroids considered and increasing the m/z coverage range. To this end, the effects of electron energy, emission current and source temperature on steroid fragmentation pathways were studied by performing full factorial experimental designs, using steroid reference materials chosen to cover the entire urinary steroid profile.
Second, the development and validation of systematic metabolomics workflows to reduce the time and resources required to identify direct drug metabolites for GCHRMS. To do so, the administration of 7-keto-DHEA was studied as a Proof-of-Concept to highlight the strong synergy between high-resolution mass spectrometry and chemometric tools for early detection of drug metabolites in anti-doping. A comparison of the most significant features with the spectra library validated the proposed metabolomics approach, further supported by existing data in the literature.
Third, extension of the previously proposed workflow on GCHRMS data to LCHRMS data, development and validation. The primary differences between the two workflows lie in the method validation, sample analysis processes, including preparation and acquisition, as well as in the raw data preprocessing steps. This knowledge gives the opportunity to gain insight into all possible metabolic changes, regardless of whether it is the formation of new compounds or the reduction of compounds. In contrast, the metabolite-focused approach generally reduces the scope of investigation to the formation of metabolites from the parent molecule, thus losing the response that other endogenous compounds might have as a result of its intake.
Fourth, application of the developed workflow for the investigation of the physiological and post training effects of ecdisteroid supplementation on the human serum metabolome. These outcomes elucidates the effectiveness of a metabolomics-based approach in detecting specific trends related to the intake of performance-enhancing substances that would otherwise remain undetected through traditional analytical methods or be masked by physiological changes.
The results presented in this thesis are of relevance for a more depth understanding of the complex relationships between different steroids, which may not be apparent when examining individual steroids in isolation, and in the identification of patterns or combinations of steroids that may discover new biomarkers for disease diagnosis, prognosis, or monitoring. This is a step forward in the metabolic characterization of different physio-pathological conditions that allow for the personalization of treatment strategies and optimization of individual performance outcomes. This personalized treatment enhances the value of the proposed metabolomics approach, making it beneficial not only for improving sports performance, but also in the clinical setting, where targeted supplementation can promote better health and recovery.
Weniger anzeigenThis dissertation has explored the development and application of black phosphorus (BP) nanomaterials through sustainable synthesis methods, aiming to unlock their potential in biomedicine and environmental remediation. The research focused on three interconnected goals: covalent functionalization of BP nanoflakes for biomedical applications, enhancement of mechanochemical synthesis for sustainable BP production, and application of mechanochemically derived BP-polyglycerol (BP-PG) nanomaterials in environmental remediation. In the first project of the thesis, a one-pot covalent functionalization method was successfully developed for exfoliated BP nanoflakes using an anionic ring-opening polymerization of glycidol. This innovative approach resulted in the formation of a BP-PG nanohybrid with high amphiphilicity, significantly enhancing its aqueous dispersibility and biocompatibility. The functionalized BP-PG demonstrated efficacy in near-infrared-responsive drug delivery against A549 lung carcinoma, MCF-7 breast cancer, and HeLa cervical cancer cell lines. These findings showcase the potential of BP-PG as a promising candidate for a broad range of biomedical applications, particularly in targeted drug delivery systems where hydrophilicity and biocompatibility are crucial. The second project addressed the challenges associated with the practical application of BP by optimizing mechanochemical synthesis methods. By modifying the ball-milling medium to enhance mass transfer and kinetic energy distribution, the research introduced a novel design that improved the efficiency of mechanosynthesis. This advancement not only reduced production costs and time but also significantly improved product quality due to the enhanced transfer of mass and reagents within the ball-mill chambers. The mechanochemical approach circumvented the need for high temperatures, toxic solvents, and complex purification steps, aligning with global sustainability efforts and providing a scalable method for producing high-quality BP essential for real-world applications. In the third project of the thesis, the mechanochemically synthesized covalently functionalized BP-PG nanomaterials were applied to environmental remediation, specifically in the recovery of precious metals like gold from simulated electronic waste leachate. This work marked the first successful mechanochemical polymerization of glycidol into polyglycerol via a "grafting-from" technique. The resulting BP-PG nanomaterial exhibited a uniform amorphous structure with a high surface area, advantageous for interfacial reactions such as gold-ion reduction. Remarkably, BP-PG achieved gold recovery capacities exceeding three times its own weight and efficiently converted gold ions into polymer-stabilized gold nanoparticles. This highlights the significant impact of nanohybrid architecture on interfacial properties and underscores the potential of mechanochemically derived BP-PG in environmental applications. Collectively, this dissertation contributes to expanding the understanding and utility of BP nanomaterials by developing sustainable and environmentally friendly synthesis methods that facilitate large-scale production. By enhancing the functional properties of BP through covalent functionalization, the research has led to improved biocompatibility and aqueous dispersibility, critical for biomedical applications. Demonstrating the versatility of BP-PG nanohybrids in targeted drug delivery and efficient recovery of precious metals showcases their potential in diverse fields ranging from medicine to environmental science. Furthermore, the pioneering of new mechanochemical techniques that can be applied to other materials and processes promotes innovation in green chemistry. This work paves the way for future advancements in sustainable material science, emphasizing the importance of designing synthesis strategies that are not only efficient but also environmentally responsible. In conclusion, the advancements presented in this dissertation lay a solid foundation for the practical application of polyglycerol functionalized BP nanomaterials. By addressing key challenges in synthesis and functionalization, and by demonstrating significant applications in biomedicine and environmental remediation, this research contributes valuable insights to the field of nanotechnology. Future work can build upon these findings to explore additional applications, optimize material properties, and further integrate BP nanomaterials into commercial technologies.
Weniger anzeigenThe presented work depicts an in-depth approach on how to reach confident mass spectrometric analysis of metabolites of metandienone by gas chromatography. Metandienone is an anabolic androgenic steroid and a commonly used doping substance. Therefore, anti-doping testing strives to uncover its illicit intake by the detection of metandienone and its metabolites in athletes’ samples. In the following, the focus is mainly set on a reliable identification of the A-ring reduced metabolite structures 17ξ-methyl-5ξ-androstane-3ξ,17ξ-diol, 17ξ-hydroxymethyl-17ξ-methyl-18-nor-5ξ-androst-13-en-3ξ-ol and 17α-hydroxymethyl-17β-methyl-18-nor-5β-androst-1,13-dien-3α-ol in human urine samples in parallel. First of all, the synthesis of reference material and its structural characterization built the basis of these investigations. It found application in a study of mass spectrometric fragmentation of 17α-methyl-5ξ-androstane-3ξ,17β-diol and various isotopologues and enabled fundamental understanding on underlying fragment ion formation in electron ionization mass spectrometry. Further assessment of the analytical method was supported by the latter investigations and allowed developing a method for confident identification of the targeted analytes. Therefore, only chromatographic separation of inter alia diastereomeric molecule structures made it possible to overcome the encountered challenges of indistinguishable mass spectrometric signals. In the end, proof of concept was provided by the application of this method to an administration study with metandienone. Not only did it lead to the confident identification of known and unknown excreted metabolite structures but also gave a deeper insight into the human metabolism of anabolic androgenic steroids. Concluding, besides the support to maintain confidence in anti-doping analysis of metandienone this work generally contributes to the field of bioanalytics by highlighting the importance of integral understanding of the analytical conditions. In general, chemosynthetic knowhow was used to obtain reported reference material and corresponding isotopologues. Applied analytical techniques consist of nuclear magnetic resonance experiments, gas chromatography coupled to unit mass spectrometry, high-resolution mass spectrometry, and tandem mass spectrometry.
Weniger anzeigenAwareness of escalating sustainability crises, including climate change, species extinction, and growing social injustice, evokes a wide range of emotions, often negative, in a growing number of people. Worry, anxiety, sadness, frustration, and anger are frequently reported, especially by young people. Consequently, the high relevance of emotions for effective sustainability education has long been acknowledged. At the same time, emotional competencies have received too little attention in prevailing competence models. Studies from educational practice also indicate that teachers often feel unqualified to deal with emotions. The frequent suppression of emotions that results from this can demonstrably contribute to learners feeling overwhelmed by sustainability issues and avoiding them. Against this background, this dissertation examines how human emotions, sustainability crises, and education interrelate. Specifically, it examines the questions of why emotion-sensitive sustainability education is necessary and how it could be realized. In order to answer these questions, it is first necessary to examine how emotions are addressed in the German education system. The current state of research indicates that emotions are in fact too strongly neglected, despite their high relevance for all forms of learning. A mixed-methods analysis of 422 German curricula confirms this hypothesis and shows that emotional competence (with the facets of emotion knowledge, emotion recognition, emotion expression, emotion regulation, and empathy) is insufficiently structurally anchored in the German school system (Study 1). At the same time, a latent class analysis of 3,000 young people and teachers shows how widespread feelings of hopelessness are among both educators and students (Study 2). This hopelessness, along with increasingly widespread worries, fears, and frustrations, can affect mental health. Using the same sample, multiple regression analysis shows that sustainability-related emotions are significantly stronger predictors of behavior than knowledge and attitudes and thus could be central drivers of the sustainability transformation (Study 3). A systematic review then examines the role of emotions in transformative sustainability learning and derives implications for educational practice and science. The review (n = 20) reveals that widespread negative emotions (e.g., frustration, sadness, guilt) are found particularly at the beginning of transformative learning processes. In contrast, predominantly positive emotions are found during social interactions (e.g., gratitude, fun) and when trying out new actions (e.g., satisfaction, pride). This suggests how learners’ emotionality may differ substantially depending on their learning phase and the didactics chosen (Study 4). The results of the four studies and the findings of the respective strands of research highlight an asymmetry: emotions are highly relevant when people engage with sustainability issues, but at the same time the German education system in general, and sustainability education in particular, still pays too little attention to emotions. For this reason, emotional competence is proposed as a competence concept for sustainability education. Using five competence facets and concrete examples, the usefulness of the concept for sustainability education is illustrated and general recommendations for science and practice are derived.
Weniger anzeigenNeurons are highly polarized cells characterized by specific structural and functional regions. The soma, or cell body, serves as a primary site for protein synthesis, while synaptic terminals located at the ends of axons are responsible for synaptic transmission. The precise transport of presynaptic proteins from the soma to these terminals is vital for the development, maturation, and maintenance of synapses. Presynaptic precursor biogenesis is a fundamental process for synaptic function and plasticity; however, its molecular mechanisms remain incompletely understood. Our research identifies Rab2 and its effector RUND1 as key regulators of presynaptic precursor vesicle (PV) formation at the trans-Golgi network (TGN). Rab2, a small GTPase, coordinates the biogenesis, sorting, and maturation of vesicles carrying presynaptic proteins essential for synaptic vesicle (SV) recycling and active zone (AZ) organization. Loss of Rab2 results in the accumulation of synaptic material— including scaffold proteins, SV proteins, and lysosomal markers—within motoneuronal cell bodies in Drosophila larval ventral nerve cords (VNCs). This mislocalization depletes presynaptic protein levels at synaptic terminals, leading to impaired neurotransmission. Electron microscopy revealed that these aggregates likely correspond to Golgi-derived transport vesicles, suggesting that Rab2 is crucial for efficient precursor export. Our RNAi-mediated screen identified RUND1 as a critical Rab2 effector that regulates presynaptic protein sorting, maturation, and trafficking. The RUN domain of RUND1 facilitates interactions with Rab2 and other regulatory proteins, including ICA69, Trabuco, and Golgin104. ICA69, a Rab2 effector, participates in secretory vesicle biogenesis and synaptic organization, while Golgin104 (CCDC186) is implicated in vesicle tethering at the TGN. Notably, the loss of RUND1produces a phenotype reminiscent of Rab2 mutants, supporting its role in the same pathway of presynaptic precursors biogenesis. Interestingly, ultrastructural analysis of vesicles in rund1−/−mutant backgrounds revealed a striking increase in elongated and tubular structures. These vesicles exhibited two distinct populations: clear and dense-core vesicles, potentially indicating a disruption in fusion or maturation processes. The presence of these heterogeneous vesicle populations suggests that RUND1 is essential for the proper segregation and functional refinement of vesicles before their transport to synaptic terminals. Overall, our findings highlight the intricate regulation of presynaptic precursor trafficking by Rab2 and RUND1, reinforcing the importance of Golgi-associated sorting mechanisms in synaptic development and function. Disruptions in this pathway impair synaptic protein localization and neurotransmission, with potential implications for understanding synaptic disorders.
Weniger anzeigenDeciphering the intricate cellular interactions within the bone marrow (BM) is crucial for understanding a wide range of multifactorial diseases in immunology, regenerative medicine, and BM biology. The intricate BM microenvironment, characterized by dynamic cell trafficking, production of immune cells and self-organized remodeling, constantly shapes osteoimmunological cell functions and their metabolic adaptations. This specific microenvironment is challenging to replicate in vitro or in silico. Current intravital optical imaging techniques can investigate cells within the complex BM microenvironment but are invasive or limited in observation time, depth, hindering long term investigation of bone regeneration or specific cellular niches. This dissertation presents three novel optical imaging technologies to satisfy the critical need for long-term, minimally invasive intravital microscopy of the BM: 1) a high-energy, high-repetition-rate 3-photon (3P) laser, enabling intravital visualization of plasma cell (PC) dynamics and antibody production capacity; 2) Limbostomy, a modular microendoscope for longitudinal in vivo imaging of deep femoral BM, facilitating quantification of cellular self-organization during bone healing; and 3) FLIMB, integrating microendoscopy with NAD(P)H-dependent fluorescence lifetime imaging (FLIM), enabling label-free metabolic imaging of myeloid cells in the living BM. These methods revealed an antiproportional correlation between PC motility and antibody production capacity; the chronicity of rapid vessel sprouting and subsequent reorganization into a confined network accompanied by myeloid interactions after bone injury; and metabolic heterogeneity among myeloid cells, indicating specific metabolic patterns linked to the activation of oxidative burst and phagocytic function. These innovations provide researchers with powerful tools to study complex cellular interactions in living bone marrow, develop therapeutic strategies and monitor drug responses, for example to improve bone regeneration, combat PC dysfunction and cancer, and fundamentally understand the interplay of cellular behaviour, microenvironment and disease progression in bone marrow.
Weniger anzeigenAddressing open-ended questions, the dissertation undertakes a transdisciplinary mixed-method experiment to reconstruct historical LGBT epistemic frameworks in state-socialist East Central Europe. Its aim is twofold. First, it develops new methods—combining quantitative and qualitative, evidence-based research grounded in primary sources and the critical reinterpretation of secondary sources—to recover the operations of the socialist state through an imparative (non-comparative) analytical approach. Second, it demonstrates how such decolonized perspectives enable new interpretations of queer cultural artefacts situated within socialist social, cultural, and political fields. This approach makes it possible to identify a distinctive category of LGBT artefacts within state socialism: works that were non-political, non-identitarian, and non-activist, yet profoundly queer in their epistemic and aesthetic operations. Using the uniquely transparent queer oeuvre of Soviet-Hungarian transgender artist El Kazovszkij (1948, Leningrad – 2008, Budapest) as its point of departure, the project moves between micro- and macro-levels of inquiry. Zooming in on Kazovszkij’s corpus and zooming out to the broader social and political discourses that framed and integrated it, ranging from historical political, legal and social analysis to critical hermeneutics. Grounded in art-historical inquiry, the dissertation challenges dominant Western-centric narratives of global queer history by foregrounding the specificity and complexity of state-socialist queer epistemes. It enriches non-Western histories of twentieth-century LGBT cultures and contributes to post-socialist and post-colonial studies. Through its rigorous empirical methodological experimentation, the dissertation proposes a new model for conducting research in non-Western contexts on historically ambiguous subjects - particularly in cases where empirical evidence and primary sources are opaque, uncatalogued, or difficult to access.
Weniger anzeigenThe nuclear periphery including the nuclear lamina is one of the main nuclear sub-compartments that facilitate the complex yet dynamic chromatin organization in eukaryotes. The concept of plant lamina is relatively recent, as true lamin homologs are absent in plants, a thorough understanding of its functionality is not fully delved into. In Arabidopsis thaliana it has been shown previously that PWO1, an interactor of Polycomb repressive complex 2 (PRC2), collaborates with the nuclear lamina protein CRWN1 to mediate gene regulation. This study has demonstrated that the SWI/SNF chromatin remodeler subunit AtBAF60 interacts with PWO1 and CRWN1 by employing protein-protein interaction studies, gene expression analysis, and nuclear phenotype measurements using confocal microscopy. Transcriptome and genome-wide analyses coupled with immunocytochemical-high resolution microscopy studies have revealed the functional interplay between the interacting partners suggesting their role in stress responses and heterochromatin organization. In a nutshell, the present study discovered a novel interrelationship between SWI/SNF chromatin remodeler complex subunit AtBAF60 with the nuclear periphery and PWO1, thereby interconnecting three major players of gene regulation and chromatin organization in A. thaliana
Weniger anzeigenDespite their seemingly simple chemical composition, many molecular liquids exhibit complex behaviors arising from their intermolecular structure: while they seem disordered on the macroscale, they feature locally ordered environments on the microscopic scale. At interfaces with other substances, the liquid's organization is altered due to chemical interactions with the opposing substance and the interfacial geometry. The local interfacial structure of liquids determines key physicochemical properties, such as wettability and surface reactivity. When a liquid is further constrained by confining it to a nanoscopic space, they undergo additional structural perturbations, leading to the emergence of unique and exotic behaviors.
Characterizing the microscopic structure of molecular liquids and relating it to their macroscopic properties stands as a central challenge in chemical physics. Among the various experimental techniques employed to study the microscopic structure of liquids, spectroscopic methods sensitive to intra- and intermolecular vibrations of molecules have proven especially successful. However, interpreting experimental spectroscopic data in terms of molecular motion and structure is still not fully understood, as the high degree of collectivity in the dynamics of molecular liquids complicates the identification of spectral features with simple molecular mechanisms.
The present thesis contributes to this field by employing molecular modeling techniques that resolve the local liquid structure and dynamics, while establishing relations between modeling results and experimental observables through concepts from statistical mechanics. We focus on liquid water, whose hydrogen bond network is paradigmatic for the complex intermolecular structure of molecular liquids, and perfluorinated hydrocarbons, a synthetic organic liquid of industrial significance, and analyze how external constraints, in the form of single interfaces and nanoconfinement, alter their molecular structure. In the bulk phase, we illustrate how signatures of the highly collective vibrational behavior in the linear absorption spectrum of perfluorinated hydrocarbons can be interpreted with the help of different molecular modeling methods and establish a method to uncover the influence of varying conformational dynamics on vibrational line shapes. We then discuss the structure of water at the interface to air and fluorinated surfaces. There, anisotropic orientation of water molecules gives rise to local electric fields and specific vibrational signatures, which we contextualize with the available experimental data. Finally, we analyze the influence of geometric confinement on the hydrogen bond network of liquid water. We propose a decomposition of linear absorption spectra to distinguish between bulk, interfacial, and confinement effects, allowing us to identify signatures of long-range collectivity in the vibrations of nanoconfined water.
Weniger anzeigenAuf gesellschaftlicher Ebene spielt Bildung in Deutschland eine wichtige Rolle bei der Reproduktion kultureller Normen und Werte. Aber auch auf individueller Ebene fördert sie die soziale Teilhabe und die Identitätsentwicklung. Trotz des Prinzips der Chancengleichheit bleibt der Bildungserfolg in Deutschland nach wie vor stark von der sozialen Herkunft und somit vom familiären Kontext abhängig. In dieser Dissertation wird das Zusammenspiel verschiedener Aspekte des familiären Zusammenlebens und ihr Einfl uss auf die Bildung von Kindern untersucht. Die Analysen basieren auf Daten der Startkohorte 3 (SC3) des Nationalen Bildungspanels (NEPS) sowie des Beziehungs- und Familienpanels (pairfam). Im Fokus stehen Kinder, die mindestens die vierte und höchstens die zehnte Klasse besuchen. Die Ergebnisse zeigen, dass die Qualität der innerfamiliären Beziehungen eine Rolle für die Bildung dieser Kinder spielt. In der deutschen Forschung fand dieses Thema bislang wenig Beachtung, ebenso wie die Einbeziehung der Wahrnehmung und Perspektive der Kinder auf die Familie. Untersucht wird insbesondere, wie Veränderungen innerhalb der Familie - sowohl hinsichtlich ihrer Form als auch der Beziehungsqualität - die Mathematikleistungen und Bildungsaspirationen von Kindern beeinflussen. Ein besonderer Fokus liegt dabei auf dem Vergleich zwischen Kindern, die mit beiden leiblichen Elternteilen in einem Haushalt aufwachsen, und solchen, die dies nicht tun. Die Erkenntnisse dieser Dissertation unterstreichen die zentrale Bedeutung familiärer Beziehungsdynamiken für Bildungsprozesse und betonen, wie wichtig es ist, die Perspektiven und Bedürfnisse der Kinder stärker in den Mittelpunkt zu stellen. Es zeigt sich, dass eine umfassende Förderung, die sowohl emotionale als auch materielle Unterstützung umfasst, unerlässlich ist, um negative Einflüsse auf schulische Leistungen, insbesondere in instabilen Familienverhältnissen, zu vermeiden. Die Ergebnisse bieten wertvolle Impulse für die Familien- und Bildungspolitik und verdeutlichen die Notwendigkeit ganzheitlicher Unterstützungsangebote, die allen Kindern gleiche Bildungs- und Entwicklungschancen ermöglichen, unabhängig von ihrer familiären Situation. Dabei ist es von zentraler Bedeutung, Programme zu entwickeln, die die emotionalen, sozialen und akademischen Bedürfnisse der Kinder gleichermaßen berücksichtigen.
Weniger anzeigenThe overall objectives of this thesis were (1) to evaluate different methods of serum collection for the detection of FTPI via refractometry in neonatal calves, (2) to evaluate a pyroelectric infrared monitoring system assessing movement of preweaned calves, and (3) to assess temperature preferences for heated calf hutches during winter in newborn dairy calves.
The on-farm monitoring of FTPI to optimize colostrum management is an integral part of heifer rearing. Therefore, the objective of the first study was to compare 4 different methods of serum collection to assess failed transfer of passive immunity (FTPI) in dairy calves. We hypothesized that centrifuged serum, filtered serum and clotted serum at room temperature, and clotted serum at refrigerator temperature measured with Brix refractometry would highly correlate with IgG concentration assessed by radial immunodiffusion (RID; gold standard) in centrifuged serum. Blood samples were collected from 321 newborn dairy calves. In centrifuged serum, serum clotted at room temperature, serum clotted at refrigerator temperature, and filtered serum, total solids (TS) in % Brix, and IgG concentrations measured with RID were highly correlated. Regarding the refractometry results among the different serum types, the TS of clotted and filtered serum showed high correlation coefficients compared with the TS results of centrifuged serum. Filtered serum was slightly less accurate. All serum types are valid methods to detect an FTPI in dairy calves, if the specific Brix thresholds for each serum type are considered. Nevertheless, serum clotted at refrigerator temperature should not be the preferred method to avoid the risk of hemolysis.
Sensor technology is becoming more and more popular in calf rearing, and could provide important information about health and performance in the future. The objective of this study was to correlate movement assessed by a pyroelectric infrared sensor system (IMS) in preweaned dairy calves with lying and standing time assessed by a 3D accelerometer considering the temperature-humidity index (THI). A total of 35 dairy calves (1–7 d of age) were enrolled in the study and 20 calves were included in the final analyses. Number of movements per hour measured by the IMS was compared with data obtained with a validated 3D accelerometer. The Pearson correlation coefficient between both standing and lying time and the number of movements was r = 0.85 and r = −0.85, respectively. The Pearson correlation coefficients were only slightly influenced by THI. Our data show that the number of movements of dairy calves measured by IMS were highly correlated with the chosen gold standard reference method. High THI slightly affects the measurement accuracy of IMS. Newborn calves face challenges adapting from the warm uterine environment to cold ambient temperatures, often experiencing cold stress. Therefore, the objective of the third study was to assess the preferred inside hutch temperature of dairy calves in their first week after birth during Central European winter and to compare lying behavior in heated and non-heated hutches. Calves spent 90% of their time inside a hutch, irrespective of the number of heat lamps switched on. No preference for a specific inside hutch temperature existed. There was, however, a tendency for the location of the hutches closest to the control calf. Lying behavior did not differ between preference and control phase, but decreased marginally with increasing age. These findings could indicate that there is a need of shelter for calves in winter, but without a preference for a certain inside hutch temperature under the prevailing conditions of deep straw bedding, highly sufficient milk supply and an ambient temperature of 5.4 ± 3.3°C.
Overall, the results of this thesis show that (1) there are different valuable methods to harvest serum for the detection of FTPI in newborn dairy calves, even without centrifugation, (2) there is a high correlation between the assessment of movement with an IMS and the lying and standing times assessed with a 3D accelerometer data logger, and (3) there is no preference for a certain inside hutch temperature in mild winters, but a preference for social contact. All three studies provide results that can contribute to concrete decision-making and practical application for good calf health monitoring
Weniger anzeigenThis dissertation consists of four independent chapters that contribute to the literature of labor and public economics. Institutions influence the labor market outcomes and redistribution of incomes, ultimately shaping the income distributions we observe today. The first chapter focuses on the legal framework for migrants on the German labor market and highlights the differences between two groups of foreign workers: citizens of EU member states and citizens of third countries. Germany’s institutions favor EU citizens in terms of mobility, leading to higher wages and higher unemployment. The second and third chapter take a broader perspective on the entire German population and how the earnings dynamics and income inequalities differ between birth cohorts – including welfare implications. The final chapter examines the German tax and transfer system and its implicit welfare weights along the income distribution. Chapter 1 examines the difference in mobility on the German labor market for citizens of EU member states and third countries and its consequences. Immigrants from non-EU countries face considerably higher barriers. I develop a wage posting model to illustrate the underlying mechanisms and provide reduced-form evidence of the causal effects of EU citizenship on labor market outcomes. I exploit the 2004 enlargement of the European Union, which granted EU status to immigrants from ten Eastern European countries residing in Germany. Using a difference-in-differences framework as well as an event-study and rich administrative data from the Sample of Integrated Labour Market Biographies (SIAB), I compare the labor market trajectories of this group before and after enlargement with those of non-EU immigrants who did not benefit from such a change in legal status. The results show that EU citizenship increases wages while unemployment rates increase. These effects are persistent over time. Chapter 2 puts a spotlight on the earnings dynamics of different birth cohorts in Germany. Women born later experience greater earnings growth volatility at given ages than older cohorts. This implies a welfare loss due to increased earnings risk. However, German registry data for the years 2001-2016 reveal a moderation in higher-order earnings risk: Men and women born later face higher skewness in earnings changes, indicating fewer large decreases than increases, and lower kurtosis at younger ages, implying fewer large earnings changes. These trends point at a welfare increase and remain true for 5-year earnings changes, which are more reflective of persistent changes. During the Great Recession, males' skewness dropped sharply; younger women were unaffected. Chapter 3 examines the welfare effects of changes in real income distributions between German birth cohorts. We calculate the relative income increase at every income level of the cohort born earlier necessary to make a person behind the veil of ignorance indifferent between being born into either cohort. With relatively low risk aversion, individuals born in the 1970s are on average better off with respect to labor earnings than those born in the 1960s and individuals born in the 1980s enjoy higher welfare than those born in the 1970s. At higher levels of risk aversion, the welfare gain diminishes, implying that increased earnings inequality offset much of the gain of increased average earnings. However, redistribution through households and the welfare state cushioned much of the increase in inequality. Focusing on post-government household income instead of individual labor earnings, for both women and men, the proportional income increase for the earlier cohort for someone to be indifferent between being born in the earlier or the later cohort is substantially larger, especially at higher degrees of relative risk aversion. Chapter 4 investigates the question: How much does society value redistribution? The common method to derive inverse-optimum welfare weights is by inverting an optimal-tax model. Our alternative imposes fewer restrictions on labor supply and enables comparisons across household types. We use a structural labor supply model to calculate the marginal value of public funds for various small tax reductions, directly linked to welfare weights. An application to Germany finds: i) The tax-transfer system is optimal if society values one additional Euro for the bottom decile three times as much as for the median. ii) At low-medium incomes, weights for couples exceed those for singles substantially.
Weniger anzeigenRift Valley fever (RVF) is an emerging mosquito-borne zoonotic disease caused by the Rift Valley Fever virus (RVFV). It heavily impacts human and animal health and the economies of countries where it occurs, especially in Africa, by causing large epizootics, resulting in high morbidity and mortality among livestock and humans. In March 2016, Uganda reported an outbreak of RVF for the first time since 1968 when human cases were recorded in the central region. Since 2016, Uganda has experienced repeated outbreaks of RVF. The disease can cause mass abortions and high calf mortality in animals and flu-like symptoms in humans, occasionally developing into deadly haemorrhagic fever or inflammation of the brain. Humans are likely infected when handling infected livestock or via bites of infected mosquitos. RVF has socio-economic consequences such as bans on international animal trade, disruption of food security, and economic losses for livestock keepers as well as for governments. The design and implementation of control strategies for RVF in Uganda are currently hampered by various limitations, including limited knowledge on the distribution of RVFV and the associated risk factors, gaps in understanding of the local community knowledge on RVF identification, risk factors for disease occurrence, and pathways for RVFV introduction, exposure, and outbreak consequences in humans and animals. While previous seroprevalence studies that have been implemented in Uganda have illustrated the burden and risk factors for RVF in various locations, there is a need to map the distribution of the disease risk across the country. In addition, in Uganda, during RVF outbreaks, control measures have mainly revolved around limited surveillance and preparing situational reports with diminutive inclusion of local community knowledge on predisposing risk factors and disease identification.
To better understand the distribution of RVFV in livestock and the associated risk factors and to develop a risk map, we collected blood samples from cattle, sheep, and goats in a national cross-sectional survey. Secondary data used included information on RVF outbreaks in livestock and humans between 2016-2021 that were obtained from Ugandan Health authorities, and data on climate and other environmental factors that facilitate mosquito breeding from various online databases. Screening of animal samples for exposure to RVFV provided data for generating a RVFV prevalence map. Data obtained were analysed using a Bayesian model which investigated animal-level factors (age, sex, species) and multiple environmental data including meteorological factors, soil types, and altitude. The overall RVFV seroprevalence was 11.3% (95% confidence interval: 10.2–12.3%). Analysis showed that antibodies were more often detected in older animals compared to the young, and more in cattle compared to sheep and goats. The presence of antibodies was also more pronounced in areas with lower precipitation seasonality, haplic planosols (soil types), and lower cattle density. The risk map generated shows that RVF is endemic in several regions including those in northeastern Uganda where outbreaks have not yet been reported. Considering that a district is the smallest administrative unit that has the mandate to design and administer public and animal health interventions at the sub-national level, districts were classified into one of the three RVF risk levels: high, moderate, and low.
To assess pastoralists’ and agropastoralists’ knowledge of RVF, participatory epidemiological studies using various PE techniques were conducted with livestock keepers and key informants in Napak, Lyantonde, Isingiro, and Butebo districts, located in the Ugandan cattle corridor. Napak and Lyantonde districts were classified as pastoralists while Isingiro and Butebo as agropastoralists. Results of semi-structured interviews revealed that livestock keepers in all four districts possessed knowledge of RVF, local names or descriptions for it, and epidemiological risk factors such as the presence of infected mosquitoes, living in flood-prone areas, and excessive rainfall. Pastoralists called RVF Lonyang, which symbolized a disease associated with jaundice, high fever, abortions in pregnant cows, and sudden death in calves. In Butebo, Lyantonde, and Isingiro, participants likened RVF to an Ebola-like disease, referring to haemorrhaging symptoms such as vomiting, blood, bloody stool, and gum bleeding in humans, and abortion in livestock. RVF was ranked among the top ten most important cattle diseases.
Three risk pathways for RVF introduction, exposure, and consequence were assessed by key informants who included animal health and public health workers. For RVFV introduction in an area, infected domestic animals were considered the most important, followed by livestock movement and trade, while infected wild animals were considered the least important. The findings of the practices that promote human exposure to RVF virus were via drinking raw animal blood and milk, handling of infected animal tissues and fluids at parturition, handling of infected meat and fluids at slaughter, and contact with infected domestic animals in the herd. Drinking raw blood and milk was perceived as the highest exposure pathway. The likelihood of consequences ranked highest were high treatment costs, abortions, reduced production, and morbidity.
The findings of this study suggest low-level endemic circulation of RVFV among livestock across Uganda notwithstanding the absence of clinical cases, with cattle as the species with highest exposure. The study further suggests that the risk of RVF is higher in areas with stable precipitation patterns, as this can maintain critical mosquito population levels by replenishing breeding sites. Coupled with precipitation seasonality, the study suggests that RVF risk is higher in areas with planosols, a type of soil with clayey properties that are prone to flooding when inundated, a critical factor in the sustenance of mosquito breeding sites. Further, as RVF is zoonotic, increased numbers of animal exposure could present an increased risk of spillover infection to humans over time.
Practical implications of these findings include targeted RVF surveillance as well as implementation of risk-based control measures. The RVF risk map would guide the Ugandan authorities in the identification of RVF hotspots as well as design and implement appropriate interventions. For instance, it can guide a vaccination strategy to minimize the burden of the disease in livestock and pre-empty zoonotic spillover to humans by implementing periodic and reactive vaccination in high and medium-risk areas respectively. Further, the findings indicate that veterinary authorities need to be vigilant in their surveillance as some of the clinical cases in some areas may have been underreported or not at all. A stronger collaboration between sectors, guided by the One Health framework, would enhance the detection of any new cases especially if data from human and animal surveillance activities are integrated and analysed jointly. The results of the PE study could be integrated into an early warning system and strategies for veterinary and public health service delivery in Uganda.
Weniger anzeigenCLCA4 ist ein Mitglied der CLCA-Genfamilie, das einer tierartspezifischen Genduplikation unterliegt und vorwiegend im Darmtrakt exprimiert wird. CLCA4 scheint eine bislang unbekannte Rolle bei entzündlichen Darmerkrankungen des Menschen wie UC oder CD und bei kolorektalen Tumoren zu spielen. Diese Erkrankungen zeigen in westlichen Gesellschaften eine steigende Prävalenz und verlaufen häufig tödlich. Die Entwicklung diagnostischer und therapeutischer Ansätze zur Behandlung dieser Krankheiten ist ein zentrales Ziel der Forschung. Die Maus, welche ein wichtiges Modelltier für die Erkrankungen darstellt, hat im Gegensatz zum Menschen zwei funktionelle Clca4 Homologe. Die speziesspezifischen Unterschiede in der Genexpression sowohl im gesunden Darm wie auch im pathologisch veränderten Darm sind noch weitegehend unbekannt.
Ziel dieser Arbeit war die Erstellung eines detaillierten Expressionsprofils der murinen und humanen CLCA4-Homologe im Darmtrakt mittels RT-qPCR und ISH. Dabei wurde zunächst die Expression der murinen Vertreter in verschiedenen Abschnitten des Darms sowie entlang der Zotten-Krypten-Achse unter gesunden Bedingungen untersucht. Zusätzlich wurde eine Expressionsanalyse der beiden murinen Vertreter während der frühen postnatalen Entwicklung durchgeführt. Weiterhin wurde deren Expression im Darm eines DSS-Kolitismodells und AOM/DSS-induzierten Darmtumormodells untersucht. Vergleichend wurde die zelluläre Expression des humanen Homologen in gesunden Darmabschnitten und in CRC untersucht.
Die Expression der murinen Clca4 Vertreter zeigte einige Unterschiede. Während Clca4a in Enterozyten des gesamten Darmtraktes exprimiert war, fand sich Clca4b nur in Enterozyten des Dünndarms. Clca4a wurde ausschließlich in den luminalen Bereichen der Schleimhaut nachgewiesen, wohingegen die Expression von Clca4b tiefer reichte. Die in der Literatur beschriebene Expression von humanem CLCA4 im luminalen Epithel des Dickdarms konnte bestätigt werden. Es fand sich aber keine Expression in Enterozyten des Dünndarms. Die murinen und der humane CLCA4 Vertreter zeigten somit zum Teil ein überlappendes, zum Teil unterschiedliches Expressionsmuster.
Die postnatale Expressionsanalyse zeigte, dass Clca4b vor allem in sich noch entwickelnden Mausdärmen exprimiert war, während Clca4a seine höchsten Expressionswerte erst bei adulten Tieren erreichte.
Im DSS-Kolitismodell zeigte sich eine im Vergleich zu Kontrolltieren erhöhte Expression von Clca4a in distalen, erkrankten Dickdarmabschnitten sowie eine extrem starke de-novo-Expression von Clca4b im gesamten entzündeten Kolon. Beide Homologe wiesen besonders starke Signale in der unmittelbaren Nähe von Ulzerationen. Das unterschiedliche Expressionsmuster im gesunden Mausdarm könnte auf verschiedene Funktionen der beiden murinen Clca4 hindeuten. Das Expressionsprofil insbesondere von Clca4b wäre mit der Rolle eines intestinalen Differenzierungsproteins vereinbar.
Im murinen intestinalen Tumormodell wurden beide murinen Clca4 zwar fast gar nicht in den neoplastisch veränderten Darmzellen nachgewiesen, aber massiv in angrenzenden, nicht tumorösen Enterozyten. Dieses Expressionsprofil zeigte auch das CLCA4 in Proben von humanem CRC. Ein solches Expressionsmuster wäre auch mit einer Funktion als Differenzierungsprotein im Darm vereinbar.
Auch wenn sich einige Aspekte der murinen intestinalen Clca4-Expression in der Expression des humanen CLCA4 widerspiegeln, müssen insbesondere die Unterschiede in den Expressionsmustern bei der Interpretation der Ergebnisse aus der translationalen Forschung berücksichtigt und kritisch hinterfragt werden. Die Entdeckung solcher Unterschiede stellt einen zentralen Aspekt dar, die Übertragbarkeit der Ergebnisse vom Tier auf den Menschen besser einzuschätzen und mögliche Limitationen zu erkennen.
Weniger anzeigenAntibiotic resistance is a highly relevant issue today. In the environmental context, chicken manure can serve as a significant source of antibiotic resistance genes, as well as ESBL‑producing and fluoroquinolone-resistant E. coli. Anaerobic digestion, meanwhile, is a promising technology for biogas production and represents an alternative energy source. In this study, antibiotic resistance was monitored during the anaerobic digestion of chicken manure.
In the first study, we monitored the concentration of total E. coli, including ESBL-producing and fluoroquinolone resistant E. coli, during anaerobic digestion in the mesophilic temperature range, both with and without the addition of sawdust as a carbon source. Temperature had a major impact on E. coli concentrations, as well as on the overall anaerobic digestion process and biogas production. While optimizing the C/N ratio by adding sawdust had no significant effect on E. coli concentrations, it did influence nitrogen content during digestion and affected biogas content.
In the second study, we investigated the presence and abundance of antibiotic resistance genes during mesophilic anaerobic digestion of chicken manure. Neither temperature nor the addition of sawdust had a significant impact on ARG abundance.
Additionally, in both studies, chicken manure was analyzed for AMR E. coli and antibiotic resistance genes, confirming that manure is a potential source for the spread of antibiotic resistance in the environment.
To improve the reduction of antibiotic-resistant E. coli during anaerobic digestion, pretreatment methods and co-digestion with sewage sludge have been suggested. While no effective approach was identified for significantly reducing antibiotic resistance genes, pre‑treatment and co-digestion with sewage sludge may still have a positive impact. The persistence of ARGs is likely related to the microbial community composition, which may help maintain ARG levels.
We conclude that anaerobic digestion is an effective process for reducing AMR E. coli; however, our experimental batch setup was not effective for reducing ARGs, indicating the need for further optimization and modification of the process.
Weniger anzeigenKinetose stellt ein ernst zu nehmendes Problem in der heutigen Zeit dar insbesondere im Hinblick auf autonomes Fahren. Daher müssen die Ursachen von Kinetose zur Vermeidung und für mögliche Therapieansätze ergründet werden. In dieser Arbeit werden zwei Möglichkeiten zur Entstehung von Kinetose experimentell untersucht: die Theorie der Otolithenorganasymmetrie, die aufgrund ungleich verteilter Massen zu Kinetose führen soll, und als neuartiger Ansatz die Hypothese eines Zusammenhangs zwischen intestinalem Mikrobiom und Kinetose im Zusammenhang mit der Darm-Hirn-Achse. Die Messungen für die Berechnung der Otolithenorganasymmetrie beinhalteten VEMP-Messungen, unilaterale Rotation, SVV, OOR-Bestimmung und SVMT. Für den SVMT wurde zusätzlich eine Abfrage des Kinetosezustands auf einer Skala von 1 bis 10 erfragt (MISC). Zur Berechnung der Alpha- und Beta-Diversität sowie zur Prüfung eines Zusammenhangs zwischen Darmflora und Abbruchzeit beim SVMT wurden Stuhlproben der Probanden an die Firma BIOMES geschickt und mittels NGS analysiert. Die Gesamtkohorte umfasste 125 Probanden (51 Frauen und 36 Männer), von denen 87 Datensätze in die Auswertung eingeflossen sind. Anhand der Abbruchzeit des SVMT wurden die Gruppen in sensibel (< 8 Minuten), medium (8 – 16 Minuten) und unsensibel (> 16 Minuten) eingeteilt. Bei höherer Asymmetrie im Sacculus bzw. Utriculus zeigten sich verkürzte Abbruchzeiten, insbesondere bei Frauen. In der Mikrobiomanalyse zeigten sich größtenteils negative Korrelationen zwischen der Anzahl an Mikroben (gemessen in OTU) und der Abbruchzeit. Das heißt, ein geringes Vorkommen führt zu späteren Abbrüchen. Die Untersuchungen zur Otolithenorganasymmetrie lassen weiterhin Fragen offen. Ob die Asymmetrie aufgrund von Massenveränderungen an den Calcit-Kristallen zustande kommt oder der Einfluss von kurzkettigen Fettsäuren und Transmittern die Ursache für die asymmetrische Signalweiterleitung ist, muss in weiterführenden Studien geklärt werden. Mit den Untersuchungen zum Zusammenhang zwischen Mikrobiom und Kinetose ist ein neues Forschungsfeld eröffnet. Die Ergebnisse lassen einen Zusammenhang vermuten, der in weiteren Forschungsarbeiten diskutiert werden sollte.
Weniger anzeigenThis thesis explores how LGBTQ+ identities, discourses, and forms of activism are negotiated on social media in Hungary’s increasingly illiberal political environment. As the Hungarian government promotes anti-gender ideology and frames LGBTQ+ existence as a threat to national values, queer lives become sites of ideological contestation. Social media platforms, while implicated in the reproduction of dominant ideologies, also offer alternative spaces for expression, connection, and resistance. The three empirical studies look at the relationship between social media and the socio-politics of Hungary in the experiences of LGBTQ+ youth. Study 1 examines how public discourse on Facebook reflects and reinforces broader ideological tensions around LGBTQ+ issues. By analysing comment sections of online news articles discussing the children’s book Fairyland is for Everyone, the study shows how users draw on discourses of heteronormative familialism, neocolonialism, and diversity and inclusion to either legitimise or delegitimise queerness. The findings highlight how Facebook becomes a contested space where political rhetoric and cultural narratives are both reproduced and challenged in everyday discourse. Study 2 focuses on the identity negotiation processes of LGBTQ+ youth in Hungary and examines how social media affordances shape their experiences. Drawing on interviews with 16 young LGBTQ+ individuals, the study identifies five key social media affordances: anonymity, audience curation, content curation, visibility, and connectivity. These affordances help self-expression and community building in an unsupportive offline environment. However, they also expose users to surveillance and anti-LGBTQ+ content, requiring young users to develop strategies for managing risks and navigating platform dynamics. Study 3 explores how LGBTQ+ activism takes shape on TikTok, a platform that blends personal branding, entertainment, and political commentary. Through a critical technocultural discourse analysis of content from four prominent Hungarian LGBTQ+ creators, the study identifies four creator roles: the Influencer, the Activist, the Influencer- Activist, and the Casual Creator. These roles reflect different strategies for balancing visibility, advocacy, and platform risk within a restrictive political and media landscape. Together, the studies show that LGBTQ+ digital participation in Hungary is a form of adaptive resistance, shaped by platform dynamics and broader ideological pressures. The thesis positions queer engagement with social media as a site of negotiation, conflict, and resilience in the face of illiberal governance.
Weniger anzeigenThe intestinal microbiome has a central role in the host's health. In pig production, newborn and weaned piglets are particularly affected by diarrheal diseases of multifactorial origin, which can often only be controlled with antibiotics. However, in line with the “One Health” approach, the aim is to reduce the use of antibiotics in animal husbandry. Targeted modulation of the intestinal microbiome could enable new preventive measures, with the mother sow playing a key role in the initial microbial colonization of newborn piglets and intestinal colonization up to weaning. This approach was investigated by the “OptiBiom” project by analyzing comprehensive microbiome and farm data and combined with targeted microbiome modulation and vaccines to develop new anti-infection strategies. For this purpose, fecal samples were collected from sows before and after birth and their piglets before and after weaning from 20 commercial farms. This thesis analyzes data on the fecal microbiome, antibiotic resistance genes, and bacterial virulence factors. In addition, the use of antibiotics in the corresponding production cycles was documented and evaluated for each farm. The hypothesis that the fecal microbiota composition and the occurrence of resistance and virulence genes differ significantly between the farms and age groups of the animals was investigated. In addition, correlations were examined between farm differences and the sow-piglet relationship, as well as between antibiotic use and the occurrence of bacterial genes. In the first publication, 802 DNA extracts from fecal samples were sequenced using Illumina NextSeq and analyzed for diversity and microbial composition. Detected genera were compared between the different age groups of the animals, and the differences could be visualized using non-metric multidimensional scaling and hierarchical clustering. Data from sows and their piglets were pooled to investigate the family effect on farm differences. In the second publication, quantitative real-time PCR was used to detect resistance genes of relevant antibiotics (sulfonamides, trimethoprim, colistin, cefotaxime) and an integron responsible for spreading resistance genes (Int1). In addition, the samples were examined for relevant pathogens associated with diarrhea in piglets (Clostridioides difficile, Clostridium perfringens, Salmonella, Escherichia/Shigella/Hafnia, Escherichia coli). The farms were analyzed for cluster formation based on their antibiotic use. Latent class analysis was then used to identify the genes relevant for cluster formation in each animal group. Adapted regression models were used to test correlations with the antibiotics administered. The phyla Bacillota (formerly Firmucutes) and Bacteroidota (formerly Bacteroidetes) dominate all samples with varying relative abundances depending on the production phase. Parturition (sows) and weaning (piglets) led to significant changes in the fecal microbiota composition. After birth, the relative abundance of non-dominant genera, in particular, decreased significantly, while previously dominant genera continued to predominate. In piglets, on the other hand, originally non-dominant genera became predominant after weaning, while previously dominant genera from the suckling phase decreased. The microbiome of suckling piglets was the most uniform and showed the least diversity. Combining the microbiome data of sows and their piglets revealed a distinctive cluster formation for two farms. The use of antibiotics on each farm led to different clusters for sows, suckling piglets, and weaners. The greatest diversity of antibiotics used was found in weaned piglets, including amoxicillin, lincomycin and enrofloxacin, which were associated with antibiotic resistance genes (mcr1, dfrA1, blaCTX-M). However, direct effects of a particular antibiotic on the associated resistance gene were rare, similarly between antibiotics and virulence genes. However, enrofloxacin and florfenicol favored the occurrence of C. difficile in sows. The Int1 gene was ubiquitously present and could be associated with the prevalence of F4 fimbriae in E. coli, while other E. coli fimbrial genes were not shown to be affected by antibiotics. The vertical transmission of the microbiota from sows to their offspring could be an important factor in the microbial individuality of farms and provide an approach for individual intervention strategies to get piglets through the vulnerable weaning phase in good health. Nevertheless, future studies must include other influencing factors such as the farm environment, detailed health data, and feeding. Extensive databases and integrating artificial intelligence and machine learning can be helpful here. The long-term goal should be indicators for defining a target microbiota that enables the highest possible disease resilience and productivity. It is essential to develop modulation strategies without the use of antibiotics.
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