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JLUpub bietet Mitgliedern und Angehörigen der Universität die Möglichkeit neben wissenschaftlichen Dokumenten auch Forschungsdaten elektronisch zu veröffentlichen und dauerhaft zugänglich zu machen. Alle Veröffentlichungen erhalten einen Digital Object Identifier (DOI) und werden über nationale und internationale Bibliothekskataloge sowie Suchmaschinen nachgewiesen und auffindbar.

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Molecular aspects of Besnoitia besnoiti-driven bovine neutrophil extracellular trap formation
(2026) Espinosa, Gabriel
Recent studies have collectively advanced our understanding of bovine neutrophil responses against tachyzoite stages of Besnoitia besnoiti, an apicomplexan parasite responsible for the re-emerging cattle disease bovine besnoitiosis. A central focus of the current work was to fill some gaps on the molecular mechanisms underlying the parasite-driven formation of neutrophil extracellular traps (NETs), a key innate effector mechanism. Therefore, in a first investigation, the role of neutrophil purinergic signalling was studied, revealing that B. besnoiti tachyzoites significantly induce NET formation without altering intracellular or extracellular ATP concentrations in bovine PMN. Despite this finding, extracellular supplementation with ATPγS, a non-hydrolyzable ATP analog, significantly enhanced NET release - specifically anchored NETs - whilst native ATP failed to do so. This response depended on the P2X1 purinergic receptor since treatments with the specific antagonist NF449 (IC50 = 1.27 μM) inhibited both NET formation and PMN clustering triggered by tachyzoite exposure. In contrast, pharmacological blockade of other purinergic receptors (P2Y2, P2Y6, P2X4, P2X7) did not affect NET formation, thereby highlighting a selective role for the P2X1 puringergic receptor in B. besnoiti tachyzoite-driven NET formation. Metabolic assays using Seahorse technology further revealed increased oxygen consumption rates (OCR) in tachyzoite-exposed PMN, while ATPγS treatment led to enhanced extracellular acidification rates (ECAR), suggesting mitochondrial involvement and metabolic adaptation during the early steps of the NETotic process. A second study complemented above-mentioned findings by focusing on the calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK)/AMPK signalling axis and its link to autophagy. B. besnoiti and Toxoplasma gondii tachyzoite exposure induced rapid phosphorylation of AMPK in bovine PMN within 30 minutes, a response mirrored by the AMPK activator AICAR. Referring to signalling pathways, AMPK phosphorylation correlated with an activation of the upstream regulator CAMKK in both B. besnoiti and T. gondii-exposed PMN and upregulation of the downstream autophagy-related protein ULK-1 (but not Beclin- 1) in the case of B. besnoiti-exposed PMN, indicating a selective autophagic signature. Notably, AICAR treatments alone led to enhanced NET formation without compromising PMN viability. However, in B. besnoiti tachyzoite-exposed PMN, AICAR co-treatments failed to affect oxidative response. Moreover, AICAR co-treatments induced additive effects on tachyzoite-induced NET formation. In the case of T. gondii, this NET formation response further depended on MAPK and store-operated calcium entry (SOCE) pathways, as shown by reduced DNA release upon MAPK- and SOCE inhibition. These findings suggest that autophagy and AMPK signaling signify parallel, ROS-independent pathways involved in the support of B. besnoiti-driven NET formation. A third line of investigation explored the role of extracellular vesicles (EVs) as potential modulators of B. besnoiti-driven bovine neutrophil responses. To obtain EVs from differential sources, EVs were isolated from B. besnoiti tachyzoites, infected and non-infected bovine umbilical vein endothelial cells (BUVEC), and tachyzoite-exposed PMN. Their identity was confirmed via nano-flow cytometry, by EV markers like CD9 and CD81, and morphologically by transmission electron microscopy. When bovine PMN were exposed to differential EVs, particularly those derived from tachyzoites and infected BUVECs induced a significant NET release. This was validated microscopically by the presence of extracellular DNA structures adorned with histones and neutrophil elastase - hallmarks of classical NETs. Interestingly, PMN-derived EVs failed to trigger NET formation. Moreover, none of the different EV types drove changes in the neutrophil metabolic profile (oxidative and glycolytic responses) or ROS production in exposed bovine neutrophils, as assessed by Seahorse analysis and chemiluminescence assays, respectively. These findings indicated a NADPH oxidase (NOX)- independent mechanism of EV-induced NET formation. Furthermore, cytokine analyses revealed that EVs from infected BUVECs selectively induced IL-1β and IL-6 secretion in PMN, without influencing CXCL8 production, thereby pointing towards a tailored inflammatory response modulated by EVs of distinct cellular origin.
The role of remote sensing and geospatial modelling in mapping ecosystem condition und functioning
(2024) Große-Stoltenberg, André
The main scope of this habilitation thesis is to present a broad range of approaches on how remote sensing and geospatial modelling can be applied to map condition and degradation of different types of ecosystems. Data from both active and passive remote sensing instruments acquired by aircraft and satellite platforms at single dates or in multitemporal mode were used in the presented studies. Main drivers of ecosystem degradation such as Land Use/Land Cover changes, climate change and invasive alien species are addressed, and different types of ecosystems such as urban areas, temperate forests, Central European agricultural landscapes, tropical high-mountain grassland and dryland rangelands are examined. Beyond technical remote sensing aspects, the studies give insights on the importance of spatial modeling approaches in ecological applications, e.g. to account for the spatial heterogeneity of ecosystem properties. However, the increasing availability of remote sensing data poses both new opportunities and challenges in ecological or ecosystem studies, which are addressed in the conceptual and review paper of this thesis, e.g., dealing with large data volumes during processing and analysis. Future progress can be expected in fast evolving fields such as the use of drones, sensor-networks and crowd-sourced data together with interpretable artificial intelligence to study ecosystems. Further, very high resolution multispectral, thermal and radar satellite data is becoming more and more available, adding to the already filled toolbox from a data point of view. Nevertheless, a profound understanding of the ecological processes or mechanisms to be studied remains a fundamental requirement, as technological progress does not per se imply progress in using sensor-based approaches to study ecological phenomena. The increasing amount of studies and initiatives joining knowledge from different disciplines demonstrate that if we succeed in integrating expertise from different backgrounds, then we can create an innovative atmosphere that can lead to progress in using novel technologies to tackle urgent challenges regarding the degradation of our ecosystems.
Unveiling Hematopoietic Stem Cell Dynamics: Identification and Isolation of Hematopoietic Stem Cells at Single-Cell Level
(2025-06) Schmachtel, Tessa
The human bone marrow constitutes the principal site of hematopoiesis, sustaining the continuous generation of platelets, erythrocytes and immune cells through the activity of hematopoietic stem and progenitor cells (HSPCs) residing within specialized microenvironmental niches. Within this compartment, a rare subset of hematopoietic stem cells (HSCs) maintains lifelong hematopoiesis by precisely regulating the balance between self-renewal and differentiation, predominantly persisting in a quiescent state under homeostatic conditions but capable of rapid activation in response to acute physiological stressors such as infection or hemorrhage. The equilibrium between steady-state and emergency hematopoiesis is fundamental to hematopoietic homeostasis; however, chronic inflammation and aging can disrupt this balance, leading to impaired blood cell production and increased risk of developing hematologic malignancies. Although substantial progress has been made in the characterization and prospective isolation of distinct human HSPC subsets using surface marker-based strategies, current strategies often yield in heterogeneous populations and several differentiation models have been proposed. To address this challenge and map differentiation trajectories, the presented research employed a single cell Transcriptomic/AbSeq approach, simultaneously quantifying the expression of 596 genes at mRNA level and 46 surface markers, on over 62,000 FACS-enriched HSPCs from 15 healthy donors across different age groups. Comprehensive computational analysis revealed four main lineage pathways, supporting a stepwise model of differentiation with an early branching point for megakaryocyte-erythroid progenitors. Notably, HSPCs from older donors exhibited a higher proportion of undifferentiated cells and diminished differentiation across all lineages. A key finding of this study is the identification of Programmed death ligand 2 (PD-L2/CD273) as a surface marker highly expressed on the most primitive HSPCs. CD273/PD-L2-positive HSPCs, isolated from mobilized PB samples, demonstrated a distinct molecular signature characterized by the enrichment of stemness genes such as Thy1, DLK1 and MPL, as well as delayed entry into the cell cycle, reduced mitochondrial activity and delayed in vitro differentiation indicating a deeper quiescent state. Functional assays, including in vitro colony forming assays and in vivo xenograft experiments, confirmed that CD273/PD-L2high HSPCs possess the capacity for multi-lineage reconstitution. Beyond their stem cell properties, CD273/PD-L2-expressing HSPCs exhibited notable immunomodulatory functions. In allogeneic lymphocyte reaction assays, these cells suppressed CD8+ T-cell proliferation and activation. Blocking PD-L2 promoted the secretion of pro-inflammatory cytokines (IFN-γ, TNF-α, IL-6), showed a reduced abundance of regulatory T-cells and a shift toward myeloid lineage bias in HSPCs, implying an increased inflammatory response reaction. These findings highlight a dual role for PD-L2: First as a marker of more quiescent, primitive HSPCs and second as a mediator of immune regulation within the hematopoietic compartment. In summary, this integrated study provides valuable insights into the organization of human hematopoiesis and the identification of PD-L2/CD273 as a defining marker of a particularly quiescent, immunomodulatory HSPC subset. These discoveries may have important implications for stem cell transplantation and the treatment of blood malignancies, as understanding and manipulating these pathways may improve therapeutic outcomes and help maintaining healthy hematopoiesis throughout life.
Data Driven Perspectives on Societal Issues: Addressing Challenges in the Digital Age
(2025) Drolsbach, Chiara Patricia
This dissertation examines three interconnected societal challenges emerging from digital transformation and globalization: the spread of misinformation on social media, the regulation of digital platforms, and the effectiveness of economic policy responses to global crises. Using large-scale behavioral datasets combined with robust empirical methods including econometric identification strategies, natural language processing, and computational techniques, the research provides evidence-based insights into contemporary societal issues. The first part analyzes misinformation dynamics, focusing extensively on Community Notes, X's crowdsourced fact-checking initiative. The study of 15,000+ annotated posts reveals that misleading posts receive 35.85% fewer retweets than accurate posts. Further analysis shows that misinformation perceived as believable receives 217.09% more retweets, while posts perceived as harmful receive 41.32% fewer retweets, suggesting that easily believable yet non-harmful misinformation spreads most effectively. A survey of 1,800+ participants demonstrates that community-based fact-checking is perceived as significantly more trustworthy than simple misinformation flags across the political spectrum, with explanatory context—rather than source—driving this trust boost. An analysis of 91,452 flagged posts reveals that AI-generated misinformation differs systematically from human-generated content: it originates from more influential accounts, is more visually engaging and positively toned, and significantly outperforms non-AI content in virality despite being rated as slightly less harmful or believable. The second part addresses digital platform regulation by analyzing 156+ million moderation decisions submitted to the EU's Digital Services Act Transparency Database. The findings reveal significant variation in moderation volumes across platforms, with TikTok accounting for 64% of submissions despite having fewer EU users than competitors. Notably, 60.67% of moderation decisions were fully automated, though automation levels varied substantially by platform, with TikTok relying primarily on automation while X and YouTube relied on manual review. These inconsistent practices suggest varied interpretations of regulatory obligations and raise concerns about enforcement consistency. The third part evaluates economic policy effectiveness by examining temporary fuel tax reductions implemented in France, Germany, and Italy in 2022 using a staggered Difference-in-Differences design. The analysis finds very high pass-through rates, indicating that tax cuts were effectively transmitted to consumers, with gasoline showing higher pass-through than diesel. However, the study cautions that such tax cuts, while effective short-term measures, raise concerns about distributional equity and long-term climate goals. By integrating computational techniques with econometric rigor and grounding analysis in real-world behavioral data, this dissertation demonstrates how Big Data can illuminate contemporary societal risks and evaluate policy interventions, providing insights for policymakers, platform designers, and researchers addressing the interconnected challenges of digital transformation and global crises.
Mesoporöse Materialien für elektrochemische Anwendungen: Porendesign und Konnektivität
(2025) Wagner, Lysander Quentin
Geordnet mesoporöse Materialien werden aufgrund ihrer hohen Oberfläche in zahlreichen Anwendungsgebieten, beispielsweise in der Katalyse, in Membranen, oder in Batterien, als Modellmaterialien untersucht. Vor allem in der sauren Wasserelektrolyse zur Herstellung des sogenannten grünen Wasserstoffs erscheint ein mesoporöser Elektrokatalysator vielver-sprechend, um das kritische Iridium auf der Anodenseite möglichst effizient zu nutzen. Allerdings ist unklar, welche Porenstruktur (Porengröße und Wanddicke) eine maximale Stabilität und Aktivität in der Katalyse liefert. Die systematische Beantwortung dieser Frage erfordert maßgeschneiderte Modellmaterialien, weshalb sich diese Arbeit der Etablierung einer Bibliothek solcher mesoporösen Materialien mit variabler Porenstruktur widmet. In Publikation 1 wurde dafür zunächst eine einfache Synthese eines Block-Copolymers aus Polyethylenoxid (PEO) und Polyhexylacrylat (PHA) vorgestellt, mit dem mesoporöse Metalloxide mit großen Mesoporen (etwa 40 nm) hergestellt werden können. Da solch große Poren aufgrund des Kompromisses zwischen einer noch hohen Oberfläche und der Vermeidung von Diffusionslimitierungen aussichtsreich erscheinen, aber mit gängigen Methoden wie Physisorption nicht trivial untersucht werden können, wurde eine Routine entwickelt, wie solche Strukturen zuverlässig charakterisiert werden können. Mit dieser Methodik wurde in Publikation 2 eine Vielzahl an PEO-b-PHA-Proben hergestellt und als Templat untersucht und so abgeleitet, wie die Porengröße, Wanddicke und Porenkonnektivität in Silika über die Polymermenge und die PHA-Blocklänge eingestellt werden kann. In Publikation 3 konnte gezeigt werden, dass das Porensystem im Silika nach Soft Templating mit PEO-b-PHA analog zu dem in mesoporösem Kohlenstoff aufgebaut ist, sodass die Gültigkeit der zuvor erwähnten Leitfäden zum Porendesign auch für das elektrochemisch relevante Material Kohlenstoff zu erwarten ist. In Publikation 4 wurden mesoporöse Kohlenstofffilme hergestellt und hinsichtlich ihrer Eignung in der Elektrokatalyse untersucht. Die beobachtete hohe elektrische Leitfähigkeit, elektrochemische Stabilität und variable Zugänglichkeit des Porensystems bestätigen, dass die mesoporösen Dünnfilme ein vielversprechendes Modellsystem für elektrochemische Studien darstellen, beispielsweise als Trägermaterial für die Elektrokatalyse. Die hier gewonnenen Erkenntnisse bilden die Grundlage für eine Vielzahl systematischer Studien zur Korrelation makroskopischer Eigenschaften mit der Porenstruktur mesoporöser Materialien, zum Beispiel wie die Morphologie von mesoporösem Iridiumoxid mit dessen Aktivität und Stabilität in der sauren Wasserelektrolyse zusammenhängt.