Mentalizing and Perspective Taking in Autistic Adults – Probing Speech Intonation, Eye Gaze and Free Indirect Discourse

Autistic adults with average intelligence show difficulties in mentalizing and perspective taking, particularly in tasks relying on nonverbal cues or in implicit tasks. This dissertation aims to refine our understanding of these difficulties by identifying perceptual communicative abilities that may be preserved. Two experimental paradigms were employed: (i) Studies 1a–c investigated the use of nonverbal prominence cues (gaze duration towards an object and intonation of an utterance denoting the respective object) in inferring the importance of objects to a virtual character; (ii) Study 2 examined the perception of Free Indirect Discourse (FID) in short written stories, a phenomenon assumed to involve implicit perspective taking. Studies 1a–c revealed that both autistic and non-autistic participants rated objects as more important to the virtual character when associated with longer gaze duration or higher pitch accent. Three subgroups with different response strategies were identified: “Lookers” (primarily influenced by the gaze cue), “Listeners” (primarily influenced by the intonation cue), and “Neithers” (not influenced by either cue). Compared to the non-autistic group, the autistic group took gaze duration into account to a greater extent than intonation. Study 2 found that both groups rated the target sentences similarly in terms of naturalness. Specifically, (i) sentences including FID were rated as less natural than those without FID, and (ii) FID sentences anchored to the less prominent of two protagonists were rated as less natural than those anchored to the more prominent one. The findings suggest that autistic adults effectively use both nonverbal and verbal cues for perspective taking in these controlled tasks. Differences in cue preference may reflect alternative, possibly more systematic, strategies. While the tasks’ structured nature limits ecological validity, the results contribute to a more nuanced view of mentalizing in autism and call for future studies using more naturalistic designs

Kölner Zeitschrift für Wirtschaft und Pädagogik (Ausgabe 78: Menschenbilder)

Die 78. Ausgabe der Kölner Zeitschrift für Wirtschaft und Pädagogik widmet sich der Frage, was den Menschen ausmacht und wie dieses Verständnis Bildungs- und Beratungsprozesse prägt. Im Rahmen eines Seminars an der Universität zu Köln reflektierten Studierende ihr eigenes Menschenbild und stellten ihre Ergebnisse in vielfältigen Beiträgen vor. Die Ausgabe vereint theoretische, persönliche und künstlerische Zugänge: von der Auseinandersetzung mit individuellen und gesellschaftlichen Menschenbildern über humanistische und ganzheitliche Perspektiven bis hin zu bild- und liedtextgestützten Reflexionen. Deutlich wird, dass Vorstellungen vom Menschen dynamisch sind, professionelles Handeln beeinflussen und durch bewusste Reflexion weiterentwickelt werden können

Lobbyismus im politischen Wettbewerb

Lobbyismus ist ein fester Bestandteil politischer Entscheidungsprozesse und somit in jeder Demokratie verankert. Vor dem Hintergrund steigender Lobbyausgaben in Deutschland und den USA stellt sich die zentrale Frage: Bevorzugen Wählende unter Unsicherheit Kandidaten, deren Politik im Sinne der Lobby gestaltet ist? Zur Beantwortung dieser Frage dient der Fachaufsatz „Citizens or Lobbies: Who Controls Policy?“ (2019) von Paolo Roberti als theoretische Grundlage. Die Analyse zeigt, dass risikoaverse Wähler unter Unsicherheit nicht zwangsläufig den Kandidaten wählen, dessen Politik am stärksten ihren eigenen Interessen entspricht. Vielmehr eröffnet die Möglichkeit monetärer Transfers der Lobby einen Handlungsspielraum, die Politik zu ihrem Interesse zu beeinflussen

Transcriptional Regulation and Single Cell Damage Score in Podocytes

It is estimated that around 10% of the global population is affected by chronic kidney disease (CKD), placing a significant burden on healthcare systems worldwide (Francis et al. 2024). Among the causes of CKD, 90% are attributed to glomerular diseases, in which podocytes are damaged and lost (Wiggins 2007). Podocytes are terminally differentiated visceral epithelial cells, which play a crucial role in establishing the selective permeability in the glomerulus. Recent large-scale transcriptomic approaches in mice and humans have demonstrated that alterations in the glomerular transcriptional program are a pivotal feature of numerous diseases affecting podocytes. In this thesis, I investigate the transcriptional regulation of healthy and damaged podocytes through multiple approaches. First, I analyzed novel bulk RNA sequencing data from glomeruli to characterize transcriptional changes resulting from perturbation of the Wt1 transcription factor, a critical regulator of podocyte biology. I then leveraged novel ChIP-seq data to explore how podocyte damage rewires the transcriptional network, focusing on interactions regulated by Wt1 and co-regulated by Tead1. Second, using single-nucleus RNA sequencing (snRNA-seq), I distinguished podocyte-specific transcriptional changes from shifts in cellular composition induced by podocyte injury. Third, I developed a universal metric of podocyte health, termed the podocyte damage score (PDS), using transcriptomic data from published sources. Applying the PDS to single-cell RNA sequencing datasets from various podocyte damage models allowed us to identify both universal and model-specific features of the transcriptional response to injury. Additionally, by integrating these findings with a podocyte transcriptional regulatory network (TRN) constructed from podocyte-specific ATAC-seq data and transcription factor motifs, I characterized the transcriptional regulators involved in podocyte transcriptome rewiring under damage conditions. In conclusion, this research advances our understanding of gene regulation in healthy and damaged podocytes and establishes methodologies for studying cell-specific mechanisms of disease at the single-cell level. It is my hope that these findings will contribute to the development of new therapeutic strategies for CKD

Evidence for Training-Induced Changes in miRNA Levels in the Skeletal Muscle of Patients With Type 2 Diabetes Mellitus

Durch körperliche Aktivität kann bei PatientInnen mit Diabetes mellitus Typ II (DM Typ II) die glykämische Kontrolle positiv beeinflusst werden. Die dieser Verbesserung zugrunde liegenden molekularen Mechanismen sind jedoch noch nicht vollständig erforscht. MicroRNAs (miRNAs), bekannt als wichtige Regulatoren der Proteinexpression, könnten hier einen neuen Ansatzpunkt darstellen. Einige miRNAs wurden bereits sowohl mit einer reduzierten glykämischen Kontrolle (nachgewiesen bei in vivo und/ oder in vitro Studien) als auch mit einer veränderten Regulation in der Skelettmuskulatur bei DM Typ II PatientInnen in Zusammenhang gebracht. In der nachfolgenden Pilotstudie wurde untersucht, ob durch körperliche Aktivität (dreimonatiges Ausdauertraining, drei Mal pro Woche bei einer Herzfrequenz von 70-80% der maximalen Herzfrequenz) bei männlichen DM Typ II Patienten (n=7) diese muskulären miRNAs eine Veränderung in ihrer Menge erfahren. Den Patienten wurde eine Muskelbiopsie aus dem Musculus vastus lateralis zu drei verschiedenen Zeitpunkten entnommen (T1= sechs Wochen vor Trainingsbeginn; T2= eine Woche vor Trainingsbeginn, T3= drei bis vier Tage nach der Trainingsphase). Mittels Echtzeit-PCR wurden die Level von miRNA-27a-3p, -29a-3p, -29b-3p, -29c-3p, -106b-5p, -135a-5p, -143-3p, -144-3p, -194-5p und -206 analysiert. Nach statistischer Analyse durch Friedman Test mit Post-hoc-Tests zeigten die Ergebnisse, dass die Level von miRNA-29b-3p, -29c-3p und -135a-5p nach dem Training signifikant reduziert waren (T3 gegenüber T2 und/ oder T1). Beim glykierten Hämoglobin (HbA1c) sowie dem HOMA Index kam es zu keinen signifikanten Veränderungen, jedoch zeigte sich nach dem Training eine Reduktion des HbA1c Wertes bei sechs von sieben Patienten. Der Rangkorrelationskoeffizient nach Spearman zeigte signifikante negative Korrelationen zwischen den Leveln von miRNA-29c-3p, -106b-5p, -144-3p und -194-5p und der kardiorespiratorischen Fitness (VO2peak). Die Ergebnisse implizieren, dass körperliche Aktivität einen Effekt auf die Regulation der miRNAs im Skelettmuskel bei DM Typ II Patienten haben kann. Inwiefern hierdurch auch eine tatsächliche Veränderung der klinischen Situation bei DM Typ II Patienten erzielt werden kann, erfordert weitere Forschung

Disordered System Approaches to the Yang-Mills Vacuum

Two novel dual descriptions of d = 4 U(Nc) Yang-Mills theory (YM) are constructed and studied in this dissertation. We consider a network theory inspired by Budczies-Zirnbauer model (BZ), which will be abbreviated as BZN, and a continuum field theory, Dirac-Yang- Mills model (DYM). In either BZN or DYM, the dual theory is obtained by integrating out the original gluon degrees of freedom, which leads to a strongly-disordered system of some auxiliary matter fields. We examine the possibilities of applying a modern method, superbosonization (SuB) formula for disordered systems, in the investigation of the dual theories. In the first project, we reformulate BZN using Gaussian integral representation, and derive a master action for gluons and auxiliary matter fields, both of which live on the links of a lattice. The dual description, dual-BZN, is derived using Cayley parametrisation and a gauge-averaging trick, and the resulting dual action is a large−Nc series of color-neutral composite operators. However, using SuB for a direct replacement of these operators by some supermatrix-valued fields is not possible due to the rank-deficiency in the boson-boson sector of the supermatrix. The rank-deficiency is a result of the universality condition Nf ≥ Nc, which is necessary for BZN to flow to YM in its continuum-limit. In the second project, we study both sides of DYM: the induced Yang-Mills (IYM) and its dual (dual-IYM). The theory of dual-IYM describes a system of massive Dirac bosons and Dirac fermions constrained by a zero-current condition (ZC). A beautiful connection between gluon condensates in IYM and matter condensates in dual-IYM inspires a low-energy effective theory (dual-EFT). We discover the relevant dual symmetry groups and assemble a Lagrangian for dual-EFT in analogy with the chiral perturbation theory. Furthermore, we explore the ZC solution space and find out dual-IYM contains all Lorentz-types components, which suggests an energy- hierarchy scheme where dual-EFT is included as the low-energy sector of dual-IYM. Dual-IYM is color gauge-invariant. However, Witten’s bosonization method leads to a divergent effective action for the external field, and hence it is difficult to derive an action for some color-neutral dual-field. An attempt to directly transform the composite super-meson to the dual-field by SuB also fails because of rank-deficiency. In the absence of successful color-neutralisation, we proceed to explore some physical aspects of dual-BZN and dual-IYM. For dual-BZN, the masses and interaction strength of the composite operators are identified. We briefly examine the dual symmetry group and the saddle-point solutions, and point out a challenge to a semi-classical approximation due to the universality condition. For dual-IYM, we present two possible applications for YM mass gap and quark confinement. Furthermore, we explain a possibility of a large−Nc analysis, which might lead to a description of dual-IYM as a gravitational theory and/or a nonlinear sigma model

Quantification of microbial fitness: costs of protein overexpression and phage infection

Fitness is the most fundamental variable in quantitative biology. It is used to understand and predict evolutionary dynamics, analyze the effects of gene expression, and evaluate how organisms interact with each other and their environment. Scalable, quantitative fitness measurements are therefore essential tools for microbial systems biology. The absence of practical, standardized methods for such measurements hampers progress and results in less comparable data across studies. In this work, we developed and applied two high-throughput techniques to address these challenges—one for bacterial fitness and the other for phage fitness. These methods significantly improve accessibility to fitness measurements and enabled us to tackle questions that were previously beyond scope due to infeasible experimental demands. Protein overexpression is linked to many diseases and plays a central role in antibiotic resistance, particularly through drug targets or resistance genes like membrane-localized efflux pumps. Using a high-throughput colony-imaging technique, we performed a genome-wide analysis of overexpression fitness costs in Escherichia coli at finely resolved expression levels. Our analysis revealed that most membrane proteins impose steep fitness costs, with bacterial growth collapsing abruptly once a critical expression threshold is exceeded. The prevailing hypothesis for the high fitness costs of membrane proteins is the supposed saturation of the Sec translocon, the cornerstone of the primary membrane translocation pathway. Through the use of synthetic membrane proteins targeting different translocation pathways, we excluded Sec translocon saturation as the origin of the fitness costs. We used single-cell time-lapse imaging with fluorescently tagged membrane proteins to observe competition between membrane proteins during overexpression. These experiments showed that the overexpression costs stem from the displacement of endogenous membrane proteins. This displacement of the endogenous membrane proteome can abruptly diminish growth during membrane protein overexpression. Displacing 10% of the endogenous membrane proteins traps bacteria in a non-functional membrane proteome state. Compared to bacterial fitness measurements, techniques for quantifying phage fitness remain significantly underdeveloped and often rely on century-old methods like the plaque assay. This severely limits throughput in phage fitness measurements and therefore systematic comparisons of phage phenotypes, such as their amplification rates in bacterial populations and their bactericidal effects under varying environmental conditions, are rare. To address this gap, we developed a novel high-throughput approach termed PHORCE (Phage-Host Observation for Rate Estimation from Collapse Events). PHORCE uses a minimal mathematical model to analyze bacterial population growth and collapse dynamics under phage predation, enabling accurate quantification of lytic phage amplification rates. Our findings demonstrate that the amplification rate quantified through PHORCE reliably captures the bactericidal effect of phages, independent of the initial bacterial and phage population sizes and for different growth conditions. Using this approach, we observed amplification rate differences of more than three orders of magnitude across E. coli phages. Moreover, PHORCE revealed that phage-antibiotic interactions are primarily influenced by the antibiotic rather than the phage. For instance, the ribosome-inhibiting antibiotic doxycycline exhibited antagonistic interactions with phage amplification, whereas the DNA-damaging antibiotic nitrofurantoin showed synergistic effects. By enabling quantitative, high-throughput characterization of phage phenotypes, PHORCE provides a robust framework for systematic phage studies and facilitates screens to identify phage candidates for antibacterial therapeutics. The results of this thesis highlight the importance of developing high-throughput methods and show that their application leads to a comprehensive knowledge gain and can have an impact on various areas of microbiology, biomedicine and biotechnology

Longitudinale Analyse der Knochengesundheit bei Kindern mit Zerebralparese (CP)

Die Zerebralparese (CP) ist die häufigste Ursache für motorische Behinderungen im Kindesalter und entsteht durch eine Schädigung des sich entwickelnden Gehirns, meist während der Schwangerschaft oder um den Geburtszeitpunkt herum. Diese neurologische Störung führt zu Problemen bei der Muskelkontrolle und -koordination. Zusätzlich zu den motorischen Einschränkungen leiden Kinder mit CP häufig unter weiteren gesundheitlichen Komplikationen, einschließlich einer deutlich reduzierten Knochendichte. Dies kann zu einem erhöhten Risiko für Knochenbrüche und Osteoporose im späteren Leben führen. Die eingeschränkte Mobilität und der reduzierte mechanische Reiz auf das Skelettsystem tragen erheblich zu dieser verminderten Knochenentwicklung bei. Darüber hinaus ist die Ernährung bei diesen Kindern oft beeinträchtigt, was ebenfalls die Knochenstärke negativ beeinflussen kann. Die Dissertation untersucht die Entwicklung der Knochenmasse und -dichte bei Kindern mit CP über einen längeren Zeitraum. Die Studie basiert auf longitudinalen DXA-Messungen (Dual-Energy X-ray Absorptiometry), bei denen die gesamte Knochendichte ohne Kopf (TBLH-BMC und TBLH-BMD) erfasst wurde, und sie bietet neue Erkenntnisse über das Knochenwachstum bei Kindern mit CP im Vergleich zu gesunden Kindern. Die meisten bisherigen Studien in diesem Bereich basieren auf Querschnittsdaten. In der Studie wurden 109 Kinder mit CP einbezogen, die zwischen 2006 und 2018 an einem intensiven Rehabilitationsprogramm („Auf die Beine“) teilnahmen. Die Ergebnisse zeigen, dass die Knochenwachstumstrajektorien von Kindern mit CP weitgehend dem dritten Perzentil gesunder Kinder entsprechen. Dabei wiesen Kinder mit schwerer motorischer Einschränkung (GMFCS III-V) tendenziell geringere Werte für die Knochengröße und ein langsameres Knochenwachstum auf als Kinder mit leichterer motorischer Einschränkung (GMFCS I-II). Es zeigte sich jedoch, dass der jährliche Zuwachs der Knochendichte in beiden Gruppen insgesamt ähnlich war, wobei die Gruppe GMFCS I-II eine durchschnittliche Zunahme von 5,12 % und GMFCS III-V eine Zunahme von 5,79 % zeigte. Dies könnte ein Hinweis darauf sein, dass die intensive Rehabilitation möglicherweise zu einer stärkeren Zunahme der Knochendichte bei Kindern mit schwerer CP beigetragen hat, da diese Kinder 8 weniger mobil sind und durch das Training größere Fortschritte erzielen konnten. Frühzeitige Interventionen, wie sie in der Studie durchgeführt wurden, könnten demnach entscheidend sein, um die Knochenentwicklung zu fördern und das Risiko für Osteoporose und Frakturen zu verringern. Zu den Stärken der Studie gehört, dass Kinder mit CP aller Schweregrade gemäß der GMFCS-Klassifikation vertreten sind, sowie die longitudinale Datenerhebung, die es ermöglicht, Veränderungen der Knochendichte über die Zeit zu analysieren. Die Anwendung fortschrittlicher statistischer Modelle wie SITAR und GAMLSS bietet detaillierte Einblicke in das Knochenwachstum. Die Limitationen der Studie umfassen das Fehlen einer Kontrollgruppe sowie die Variabilität der Nachbeobachtungsdauer, was die Vergleichbarkeit der Ergebnisse einschränkt. Zudem kann die Teilnahme aller Kinder an einem intensiven Rehabilitationsprogramm die Verallgemeinerbarkeit der Ergebnisse auf die gesamte CP-Population beeinflussen. Zusammenfassend bietet die Studie wertvolle Einblicke in die Knochenentwicklung bei Kindern mit CP und unterstreicht die Bedeutung frühzeitiger und gezielter Interventionen, um die langfristige Knochengesundheit dieser Patientengruppe zu fördern

Optimizing Magnetotelluric Studies for Geothermal Exploration in Western Saudi Arabia: A Comprehensive Study of 3D Forward and Inverse Modeling Approaches

With its ambitious vision of 2030, Saudi Arabia has recognized the need to reduce its dependence on fossil-based energy and has taken concrete steps to diversify its energy sources. Among the priorities is the development of renewable energy, including geothermal resources. This thesis focuses on the application of Electromagnetic (EM) methods, specifically Magnetotellurics (MT) and Transient Electromagnetics (TEM), for the exploration of geothermal resources in the Al-Lith’s area, western Saudi Arabia, one of the most promising sites for geothermal development in Saudi Arabia. To comprehensively investigate and explore the prospect of geothermal resources in the area, broadband MT data covering a period range of 0.001–512 seconds were acquired at 50 locations, along with 13 TEM soundings. The phase tensor and its skew calculations revealed a complex subsurface conductivity structure, characterized by predominantly 1D/2D geoelectric behavior for short periods (< 2 sec) and a more complex 3D structure for longer periods. Prior to the inversion of the MT data, 3D MT synthetic modeling and inversion studies were carried out to assess the detectability of geothermal anomalies, optimize survey parameters, and evaluate the sensitivity of various parameter inputs applied in the 3D inversion. In order to ensure the robustness of the inversion results, extensive 3D MT inversion tests were performed. The resistivity model derived from TEM data was incorporated to optimize the 3D MT inversion. The final 3D resistivity model, with an RMS of 1.96, provides a high-resolution image of the geothermal system, delineating the heat source, convection pattern, and groundwater system. The geothermal reservoir is represented by deep elongated conductive bodies (< 20 Ωm) extending from 2.5 to over 8 km in depth. The individual protrusions above the reservoir indicate the pathways for geothermal fluids, forming convection cells from the reservoir to the surface or near the surface, potentially leading to an active geothermal surface manifestation (hot spring). The outcome of this study serves as the key input to understanding the complexity and characterization of the geothermal system of the Al-Lith region, confirming its potential for geothermal exploration and development efforts in Saudi Arabia

The protist microbiota of maize and their functional roles for the self-organization of the rhizosphere bacterial microbiome

Plants interact closely with their belowground environment. The rhizosphere is a dynamic habitat where biotic and abiotic factors, along with the plant itself, shape the microbial community. This study, conducted within the DFG Priority Program “Rhizosphere Spatiotemporal Organisation” (SPP 2089), aimed to investigate the spatiotemporal organization of microbial communities in the rhizosphere of Zea mays (maize), with a particular focus on the role of protists as bacterial predators. Using high-throughput amplicon sequencing, we analyzed microbial compositions and co-occurrence patterns along the root axis. Microbial community structures varied markedly between developmental zones, with stochastic processes dominating in young root regions and deterministic processes, such as selective protistan predation, prevailing in more mature zones. Targeted manipulations revealed that the root cap significantly influences microbial assembly. Network and plant gene expression analyses indicated active, plant-mediated modulation of microbial communities. Additionally, we showed that both the composition and concentration of root exudates substantially impact microbial metabolism. Experiments with varying soil textures highlighted the strong influence of abiotic factors on root development and microbial community structure. A protist diversity experiment demonstrated that increasing protist diversity altered bacterial community composition and enhanced bacterial diversity, although this did not improve plant nitrogen uptake. Overall, our findings underscore the role of protists as active regulators within microbial networks and contribute to a deeper understanding of self-organizing processes in the rhizosphere