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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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Unraveling the role of heterotrophic feeding in coral tolerance to ocean warming and microplastic pollution
(2025) López Hernández, María Antonieta Panamá
Coral reefs harbor the highest biodiversity of all marine ecosystems and support the livelihoods of nearly 500 million people worldwide. Yet, they are increasingly threatened by global warming. Marine heatwaves disrupt the symbiosis between corals and Symbiodiniaceae algae, leading to coral bleaching. As these algae provide up to 90% of coral energy requirements, their loss results in energy deficits that compromise coral health, reducing growth and reproduction, increasing disease susceptibility, and often leading to mortality. Heterotrophic feeding, as a secondary pathway of energy acquisition in reef-building corals, can sustain up to 100% of their metabolic demands under stress, thereby enhancing survival and resilience to bleaching caused by ocean warming. Consequently, trophic plasticity, i.e., the ability to modulate trophic strategies in response to environmental change, has emerged as a key trait distinguishing potential “winners” under climate change. However, trophic plasticity varies among species and may be compromised by emerging stressors such as microplastic pollution, which can interfere with coral feeding. Despite the importance of heterotrophy in coral resilience, there are still knowledge gaps regarding the role of food type and food availability on coral physiology, and how these interact with pollutants such as microplastic, particularly in an ocean warming context. These uncertainties are further compounded by a lack of field-based data. This thesis addresses these knowledge gaps through two controlled laboratory experiments and the first in situ application of compound-specific isotope analysis of amino acids during a natural bleaching event. Five coral species (Galaxea fascicularis, Porites lobata, Stylophora pistillata, Ctenactis echinata, and Pocillopora verrucosa) were assessed for key physiological traits (photophysiology, growth, energy reserves, δ¹⁵N and δ¹3C), providing a comparative framework of heterotrophic strategies. Results indicated that complex diets enhanced the benefits of heterotrophy across coral species. Although these benefits varied among species when symbiotic, all bleached corals exhibited positive responses to more complex food sources. Physiological rates were consistently higher in symbiotic fragments compared to their bleached counterparts, with the magnitude of these differences increasing alongside the baseline productivity of the species, from G. fascicularis to P. lobata and S. pistillata. Food treatments did not affect respiration or photosynthetic rates, suggesting that growth gains were driven primarily by enhanced heterotrophic nutrient supply. In situ bleaching was associated with δ¹⁵N enrichment in the trophic amino acids alanine (ALA), glutamic acid (GLU), isoleucine (ISO), proline (PRO), and valine (VAL), suggesting alterations in nitrogen acquisition and processing under stress. The trophic position (TP) of the symbiotic host and symbionts of C. echinata was 1.3, consistent with a mixotrophic diet. In contrast, P. verrucosa exhibited TP values of 1.2 for the host and 1.0 for the symbionts, indicating a stronger reliance on autotrophy. Under bleaching, C. echinata maintained a TP of 1.4, reflecting a stable mixotrophic strategy, whereas P. verrucosa shifted to a TP of 1.5, suggesting an increased reliance I on heterotrophy. These findings suggest higher heterotrophic plasticity in P. verrucosa compared to C. echinata. Microplastics (MPs) exposure significantly decreased the energy reserves of P. verrucosa, although it increased photosynthesis and respiration. High food availability partially mitigated the loss of tissue energy content observed while maintaining photosynthesis and respiration rates comparable to control conditions. S. pistillata was not affected by MP exposure alone, but when combined with high feeding, photosynthesis decreased below that of the Control. When exposed to short-term heat stress, all corals bleached severely, however, both species bleached less in the MP treatment suggesting that MPs may also disrupt the relationship between energy balance and thermal resilience. Overall, this thesis provides evidence supporting the central role of heterotrophic feeding in modulating coral tolerance to the combined pressures of ocean warming and microplastic pollution, while emphasizing the need to integrate trophic plasticity and interspecific variability into future conservation and management strategies.
Predictive Modelling with Machine Learning in Plant Breeding
(2025) Heilmann, Philipp Georg
Genomic prediction, originally proposed as a solution to the limitations of marker-assisted selection for complex traits, has become the standard for estimating breeding values in both inbred and hybrid crops. While linear models such as GBLUP and RR-BLUP remain effective in many cases, especially when assuming an additive genetic architecture, recent years have seen a growing interest in applying machine learning (ML) methods to overcome some of their constraints, including their limited capacity to model non-additive effects and nonlinear interactions. This thesis explored the influence of three key aspects on the success of genomic prediction: The choice of input features, the statistical model used, and the target trait or crop.
In terms of input features, marker data was compared to minimalist parentage-based models, haplotype blocks, and features generated using autoencoders. It was shown that even simple ML models using parentage-based information can rival marker-based GBLUP under certain conditions, which holds potential for small breeding programs with large amounts of historical, but ungenotyped, records. At the same time, dimensionality reduction techniques, especially a novel haplotype-based autoencoder that was developed during this thesis, were introduced to compress genomic data while preserving prediction accuracy and successfully accelerated model training.
Concerning the model aspect, a variety of ML algorithms were benchmarked using different approaches for hyperparameter tuning. Although no single model outperformed others across all traits and crops, ensemble approaches typically performed better than the individual models they were based on. Support vector machines seemed to be relatively unstable when compared to other ML based algorithms, such as tree-based models.
Finally, results showed that the accuracy of the genomic predictions was strongly dependent on differences between traits, crops with different breeding schemes, and different populations. For hybrids, ML performed well when SCA was more important for determining the hybrid yield than GCA. Large differences were observed for different fungal diseases in wheat, while differences among methods for the same disease were relatively similar.
While ML has not yet provided a significant improvement over traditional methods in many scenarios, its flexibility and potential for multi-modal data integration remain promising. The development of plant breeding-specific model architectures, such as haplotype-based autoencoders, may represent a more promising path than the general application of standard ML models.
Impact of compressive force on macrophages and cementoblasts and the possible interrelation with orthodontically induced inflammatory root resorption
(2025) Wang, Yao
This study analyzes the impacts of orthodontic compressive force on both innate immune responses and cementum homeostasis (Figure 22). In macrophages, compressive force induces chromatin rearrangement, nuclear shrinkage, and polarization. Two distinct mechanotransduction pathways were identified: 1. Histone H3 hyperacetylation: This mediates M2 polarization during the late stage of the immune response. 2. Lamin A/C downregulation: Orthodontic compressive force transiently reduces lamin A/C levels, compromising the nuclear envelope and increasing nuclear permeability to YAP1. This facilitates enhanced force-induced cytokine expression and proliferative inhibition. Concurrently, it reduces force-induced IRF4 expression, DNA damage, and phagocytosis enhancement, likely due to LINC complex disruption. These opposing effects of lamin A/C deficiency jointly regulate cellular behavior under compressive force. Furthermore, cementoblasts respond directly to compressive force but do not respond to macrophage-conditioned medium, suggesting that excessive orthodontic force, rather than macrophage activation, is the primary driver of OIIRR. Mechanistically, Piezo1 activation under force mediates enhanced hypoxia and suppressed mineralization in a Ca2+-independent manner. Lastly, LMCD1 and POSTN were identified as downstream mediators of Piezo1, representing potential therapeutic targets for OIIRR.
Speckle Tracking zur Detektion von Liquorzirkulationsstörungen: Deformationsanalyse des dritten Hirnventrikels anhand transkranieller Ultraschallvideos
(2025) Radder, Markus
Einleitung: Die intrakranielle Dynamik beschreibt das komplexe Zusammenspiel aus pulsatilen Blut-, Liquor- und Hirnparenchymbewegungen, die den Gesetzmäßigkeiten der Monroe-Kellie-Doktrin unterliegen. Liquorzirkulationsstörungen wie der nicht-kommunizierende Hydrozephalus gehen mit einem erhöhten intrakraniellen Druck (ICP) einher, dessen Überwachung bislang nur mittels invasiver Methoden möglich ist. Ausgehend von der Annahme, dass pulsatile Bewegungen der Wandstrukturen des dritten Ventrikels biomechanisch eng mit der intrakraniellen (Liquor-)Dynamik und somit auch mit dem ICP gekoppelt sind, wurde in dieser Arbeit untersucht, ob die ultraschallbasierte Methode des Speckle Trackings zur Gewebsdeformationsanalyse als nicht-invasives Verfahren geeignet ist, Veränderungen in der intrakraniellen (Liquor-)Dynamik nachzuweisen, die zukünftig Rückschlüsse auf den ICP ermöglichen könnten. Material und Methoden: Bei allen Studienteilnehmern wurden transkranielle Ultraschallvideos aufgenommen und anschließend die relative Deformation des dritten Ventrikels mithilfe einer Speckle-Tracking-Software analysiert. Die Studie erfolgte in zwei Phasen: In Phase 1 wurde ein Normalkollektiv aus 25 gesunden Probanden untersucht und die physiologische relative Deformation des dritten Ventrikels quantifiziert. Aus 9 Messpositionen im dritten Ventrikel wurde eine optimale Messposition für die Methode ermittelt. In Phase 2 wurde ein Kollektiv aus sechs Patienten mit nicht-kommunizierendem Hydrozephalus prä- und postoperativ untersucht und deren (pathologisch) veränderte relative Deformation des dritten Ventrikels aufgezeigt. Ergebnisse: Die optimale Messposition für eine zuverlässige Analyse konnte mithilfe eines Mixed-Effects-Modells identifiziert werden. Die Speckle-Tracking-Analyse zeigte Unterschiede in den Deformationsmustern zwischen gesunden Probanden und Patienten mit Hydrozephalus. Bei einigen Hydrozephalus-Patienten waren postoperative Veränderungen der Deformationsmuster erkennbar, die sich teilweise dem physiologischen Zustand annäherten. Diskussion: Die ermittelten Deformationsmuster lassen sich in die Erkenntnisse anderer Arbeitsgruppen zur intrakraniellen Dynamik einordnen. Der Vergleich zwischen Normal- und Patientenkollektiv zeigt, dass Speckle Tracking pathologische Veränderungen in den Pulsationsmustern des dritten Ventrikels erkennen kann. Dies unterstreicht das Potenzial dieser Methode als nicht-invasives Verfahren zur Erkennung und Überwachung von Liquorzirkulationsstörungen im klinischen Alltag. In Zukunft könnten hieraus Rückschlüsse auf den ICP gezogen werden. Weitere Studien sind erforderlich, um die klinische Anwendbarkeit und den diagnostischen Nutzen des Speckle Trackings des dritten Ventrikels umfassend zu bestätigen.
Retrospektive Analyse des GC-MS Harnsteroidmetaboloms bei Säuglingen und Kleinkindern mit 21-Hydroxylase-Mangel
(2024) Friedrich, Clemens
Hintergrund: Das Adrenogenitale Syndrom, ausgelöst durch eine Mutation im CYP21A2-Gen, ist eine gravierende Erkrankung. Insbesondere wenige Wochen nach Geburt sind potenziell lebensgefährliche Verläufe mit schweren Elektrolytentgleisungen bis hin zum Schock möglich. Auch die schwerwiegenden Auswirkungen der Erkrankung, gerade bei ausbleibender bzw. insuffizienter Therapie, verdeutlichen die Gefahren dieser Erkrankung. Die adäquate Therapie mittels Fludrocortison und Hydrocortison ist aufgrund des schmalen Grades zwischen Unter- und Überbehandlung, gerade bei sehr jungen Patienten, schwierig. Zusätzlich ist der Therapieerfolg bei aktuell fehlenden verlässlichen Monitoring-Parametern zum großen Teil vom Behandler abhängig. Die Intention dieser Arbeit bestand darin, das Patientenkollektiv anhand einer retrospektiven Metabotypisierung in einzelne Behandlungsgruppen einzuteilen, das Wachstum und das Harnsteroidmetabolom zu analysieren und mittels konkreter Biomarker das Therapiemonitoring im Sinne einer möglichst individualisierten Therapie zu verbessern. Methoden: Die Studie nutzte, bei hoher Spezifität und Nicht-Selektivität, das Verfahren der GC-MS zur Analyse der Harnsteroidprofile in Kombination mit einer Clusteranalyse zur Metabotypisierung derer. Ergebnisse: Anhand der in der Arbeit ausgewerteten Daten konnte einerseits gezeigt werden, dass die Patienten mit einem Jahr über ein vermindertes Wachstum verfügten und somit in den ersten Lebensmonaten überbehandelt waren. Mit Hilfe der in dieser Studie durchgeführten Clusteranalyse war es außerdem möglich, die Probanden in drei verschiedene Cluster, für unter-, über- und adäquat behandelte Patienten, einzuteilen. Es stellten sich die 11-oxygenierten Androgene, allen voran 11β-Hydroxyandrosteron, als die dominierenden Androgene bei Patienten im Alter von 0 bis 4 Jahren mit AGS heraus. Es zeigte sich, dass 11β-Hydroxyandrosteron und 11-Ketopregnanetriol die wichtigsten Differenzierungsmerkmale zwischen den Clustern bildeten und daher perspektivisch als Biomarker zum Therapiemonitoring genutzt werden könnten. Schlussfolgerung: Die mittels Metabotypisierung erfolgte Einteilung in unter-, über- und adäquat behandelte Patienten ermöglicht eine differenzierte Therapiekontrolle und ein individualisiertes diagnostisches und therapeutisches Vorgehen. Es bedarf jetzt weiterer Forschung, um auf Grundlage dessen noch spezifischere Handlungsanweisungen für die klinische Praxis zu schaffen und das Therapie-Outcome von Patienten mit AGS zu verbessern.
Background: Congenital adrenal hyperplasia (CAH), due to a mutation in the CYP21A2 gene, is a serious disease. Especially in the first few weeks after birth, potentially life-threatening courses with severe electrolyte imbalances and even shock are possible. The serious consequences of the disease, particularly in the absence of or insufficient therapy, illustrate its dangers. Adequate therapy with fludrocortisone and hydrocortisone is challenging, especially in very young patients, due to the fine balance between under-treatment and over-treatment. Additionally, in the absence of reliable monitoring parameters, the success of therapy currently relies very much on the practitioner's expertise. The aim of this study was to divide the group of patients into individual treatment groups through retrospective metabotyping, to analyze growth and the urinary steroid metabolome, and to improve therapy monitoring by identifying concrete biomarkers to enable the most individualized therapy possible. Methods: The study utilized the method of GC-MS, known for its high specificity and non-selectivity, to analyze the urinary steroid profiles. This was combined with cluster analysis to metabotype the profiles. Results: Based on the data analysed in the paper, it was shown that, on the one hand, the patients had reduced growth at one year of age and were also over-treated in the first months of life. On the other hand, the 11-oxygenated androgens, foremost 11β-hydroxyandrosterone, turned out to be the dominant androgens in patients aged 0 to 4 years with AGS. With the help of the GC-MS-based cluster analysis performed in this study, it was possible to divide the subjects into three different clusters, for under-, over-and adequately treated patients. It was shown that 11β-hydroxyandrosterone and 11-ketopregnanetriol were the most important differentiating features between the clusters and could therefore be used in the future as biomarkers for therapy monitoring. Conclusion: The classification into under-, over-, and adequately treated patients by means of metabotyping enables differentiated therapy monitoring and an individualised diagnostic as well as therapeutic approach. Further research is now needed to create even more specific guidelines for clinical practice and to improve the therapy outcome of patients with AGS.