Dissertationen/Habilitationen

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Impact of Anthropogenic and Natural Disturbances on Biodiversity Patterns of Macroinvertebrates at different Taxonomic Levels in African Freshwater Systems
(2025) Dusabe, Marie Claire
African freshwater ecosystems are subject to both natural and anthropogenic pressures that affect habitat quality, biodiversity, and ecosystem functioning. Macroinvertebrates have been used in routine bioassessments to detect disturbances for decades. However, it is unclear how accurately they reflect disturbances at different taxonomic levels. This thesis investigates the environmental impact of disturbances in selected East African freshwater ecosystems, and how macroinvertebrates respond to these changes at different temporal and spatial scales. The effects of dam construction and the effectiveness of family-level bioindication for detecting them were tested on the Ruzizi River. Multimetric indices (MMIs) were used in Lake Kivu to assess their ability to identify and distinguish between various environmental pressures. Mollusc community indices were used to assess long-term environmental changes in six Albertine volcanic lakes. Additionally, the freshwater snail Gabbiella was tested as a model taxon to reconstruct historical hydrological shifts and water level fluctuations across the African Great Lakes, major connected river systems, and the crater lakes of western Uganda based on phylogenetic and biogeographical analyses. Finally, an eDNA index was used at Lake Albert to test its applicability in biodiversity surveys and use in African freshwater biomonitoring systems. The results showed that on the Ruzizi River, family-level indi-cators did not adequately capture the impact of the dams, while on Lake Kivu multimetric indices more effectively distinguished between stressed and reference sites. Pollution patterns varied across the lake, with greater impacts in the northern basin than in the central and southern basins. Phylogenetic and biogeography indices proved useful in detecting historical disturbances. The diversification of Gabbiella mirrored earlier water-level changes, a trend also reported in other African molluscs and fish groups. A series of vicariance and dispersal events shaped the biogeographic history of Gabbiella humerosa, and allowed tracing historical drainage changes during the Pleistocene. However, eDNA analysis yielded limited records of macroinvertebrates, as plankton dominated because only surface water was sampled. The lack of a reference library makes it difficult to accurately assign eDNA sequences. Nevertheless, the results underscore the potential of using aquatic eDNA for taxonomy-free biomonitoring in tropical regions. The results of the historical molluscan biodiversity change in the six volcanic barrier lakes studied in this thesis show that new species have emerged and others have disappeared over time. Invasive taxa were common, with crayfish and non-native snails among those displacing native species. The biogeography of most Albertine volcanic barrier lakes exhibits a Nilotic affinity, except for invasive species and other taxa with wide distributions. The current findings provide a useful basis for conservation efforts and inform strategies to slow the ongoing loss of biodiversity.
Medic responses to water deficit alone or combined to salinity, evaluation of their yield and priming effects
(2025) Gharred, Jihed
This thesis investigates the responses of two forage species, M. ciliaris and M. polymorpha, to water deficit, both alone and in combination with salinity. Additionally, it explores strategies to enhance their productivity under these challenging conditions, focusing on approaches such as seed priming and the incorporation of biochar into the culture medium. In Medicago ciliaris, drought (36% water holding capacity) led to a significant reduction in plant growth and an increase in the root/shoot ratio. The growth response was accompanied by a decreased stomatal conductance and a reduction of the net CO2 assimilation rate and water use efficiency. The associated higher risk of ROS production was indicated by a high level of lipid peroxidation, high antioxidant activities, and high proline accumulation. Soil amendment with biochar (2%) enhanced the growth significantly and supported the photosynthetic apparatus of Medicago ciliaris species by boosting chlorophyll content and Anet both under well-watered and insufficiently watered plants and water use efficiency in case of water shortage. This increase in water use efficiency was correlated with the biochar-mediated decrease of the MDA and proline contents in the leaves, buffering the impact of drought on photosynthetic apparatus by increasing the activity of enzymatic antioxidants SOD, APX, GPOX, and GR and non-enzymatic antioxidants, such as AsA and DHAsA, giving the overall picture of a moderate stress response. These results confirmed the hypothesis that biochar application significantly reduces both the degree of stress and the negative impact of oxidative stress on Medicago ciliaris plants. These results implied that this species could be suitable as a cash pasture plant in the development of agriculture on dry wasteland in a future world of water shortages. This study aimed to evaluate the extent to which seed priming with ascorbic acid (0.2 mM) enhances the performance of M. polymorpha L. under osmotic stress induced by 50 mM NaCl (salinity) or 100 g/L PEG. Parameters related to growth and photosynthesis were assessed to understand the impact. Both NaCl-induced salinity and PEG-mediated osmotic stress significantly reduced plant biomass (-30% and -40%, respectively), leaf and ramification numbers, stem length, net CO₂ assimilation, and leaf water content. However, both treatments, particularly PEG, increased the root/shoot ratio and leaf proline content. Interestingly, seed priming with ascorbic acid alleviated these stress-induced effects, improving CO2/H2O gas-exchange and increasing plant biomass production. Water relations also improved, as indicated by reduced leaf osmotic potential, enhanced proline accumulation, and higher leaf water content. Additionally, ascorbic acid seed priming increased leaf carotenoid content by 65% and chlorophyll content by 45%, thereby enhancing photosynthetic activity. These improvements collectively contributed to better plant performance, particularly under salinity stress. Seed priming with ascorbic acid is an easy, cost-effective, and promising approach to mitigate the impact of osmotic stresses like drought and salinity, especially by improving plant water relations and photosynthetic efficiency. The effects of salinity, soil drying, and their interaction on the two forage species Medicago ciliaris and M. polymorpha were investigated. The results revealed that salinity and drought applied individually adversely affected growth, photosynthesis, and leaf water and potassium content in both species. However, the combined effects of both constraints were not significantly additive. Salinity affected the growth of both species to a similar extent. The major advantage of M. ciliaris under dry or saline conditions seems to be its higher water use efficiency and its corresponding positive impact on the ROS risk. Compared to M. polymorpha, M. ciliaris demonstrated superior biomass production under drought, salinity, and combined stresses, making it a strong candidate for forage production and soil rehabilitation in arid and semi-arid salinized regions.
N-Glycanase-1-Mangel – Charakterisierung von Genvarianten
(2025) Orczyk, Ralph Rene
N-Glycanase-1-Mangel ist eine kongenitale Störung der Deglykosylierung. Die Krankheit ist durch fünf Kernsymptome geprägt: globale Entwicklungsverzögerung, Choreoathetose, Erhöhung von Leberwerten in Blutuntersuchungen, Hypo-/Alakrimie und eine progressive, sensomotorische Neuropathie. Der Erkrankung liegen Mutationen im Enzym N-Glycanase-1 (NGLY1) zu Grunde. Die N-Glycanase-1 ist vor allem an der ER-assoziierten Degradation von Proteinen beteiligt. Dabei werden N-Glykane vor der proteasomalen Degradation entfernt. Daneben interagiert es unter anderem mit NRF1/NFE2L1 und hat einen Einfluss auf unterschiedliche Signalwege. Bisher sind etwa 56 Mutationen bekannt, die zu der Erkrankung führen. Die Konsequenz jener Mutationen ist ein verminderter Spiegel von N-Glycanase-1 und somit eine verminderte Enzymaktivität. Der genaue Pathomechanismus ist jedoch Gegenstand aktueller Forschung und noch nicht abschließend geklärt. Mögliche Ansätze beziehen sich unter anderem auf eine Verminderung des oben genannten NRF1/NFE2L1 als Transkriptionsfaktor für proteasomale Gene. Diese Arbeit hatte das Ziel, die zwei NGLY1-Varianten, R390Q und R401*, des N-Glycanase-1-Mangels zu charakterisieren. Dafür wurde zunächst eine NGLY1-KO-Zelllinie generiert. Mit dieser wurde dann das Expressionsverhalten der Genvarianten nach transienter Transfektion untersucht. Die Expression von R390Q konnte mit den verwendeten NGLY1-Antikörpern nachgewiesen werden, während dieser Nachweis bei R401* ausblieb. Im Weiteren sollte ein Aktivitätsassay zur Bestimmung der Enzymaktivität von NGLY1 bzw. dessen Genvarianten etabliert werden. Hierzu wurde ein Venuskonstrukt, genannt ddVenus, verwendet, das erst nach Deglykosylierung durch NGLY1 fluoresziert. Damit konnte ein Rückschluss aus der Fluoreszenz auf die NGLY1-Enzymaktivität gezogen werden. Die Ergebnisse zeigten, dass die Enzymaktivität bei beiden Genvarianten hoch signifikant vermindert war. In weiteren Versuchen konnte die Aktivität von R390Q mit Betain nicht gesteigert werden, während bei R401* und der Verwendung von 50 μM Amlexanox mit einer Inkubationszeit von 48 Stunden eine Aktivitätssteigerung festgestellt werden konnte, die jedoch nicht signifikant war. Darüber hinaus wurde aufgezeigt, dass NRF1/NFE2L1 in den KO-Zellen in prozessierter Form akkumuliert. Eine Kompensation durch transiente Transfektion von NGLY1 oder der Genvarianten R390Q oder R401* konnte nicht erreicht werden.
Media Frames of Climate Justice in China
(2025) Cheng, Yan
This study examines how Chinese newspapers frame climate justice. It asks what media frames appear, how media outlets differ, and what social and political implications emerge. Using a multidisciplinary framework and critical discourse analysis, the study finds that Chinese media mainly reflect elite discourses, stressing climate diplomacy, distributive justice, historical responsibility, per capita emissions, and the right to development. China insists on these principles while cooperating internationally, especially on technology transfer and carbon intensity reductions. Energy security is central to its position, shaped by cultural and historical factors. China’s global identity remains ambiguous, shifting between developing nation and responsible major power. While frames are similar, market-oriented media take more bottom-up views. The study calls for a cosmopolitan approach, highlighting individual agency and the media’s potential to advance climate justice discourse.
Genetically-encoded fluorescent ATP sensors for mode of action analyses of antiparasitic compounds in Plasmodium falciparum
(2025) Springer, Eric
This dissertation is based on publications that have established the usage of novel methods for adenosine triphosphate (ATP) and pH determinations in Plasmodium falciparum (P. falciparum). Based on these and complementary methods, mode of action (MoA) analyses of established drugs and novel antiparasitic compounds were conducted to support drug development. The deadliest form of malaria, malaria tropica, caused by the intracellular parasite P. falciparum, claims more than half a million casualties annually. With resistances against each established antimalarial drug class against P. falciparum found in the field, the development of novel and improved antiparasitic compounds poses a matter of highest concern for global health. To this end, understanding of the underlying mechanisms is crucial. Therefore, within the scope of this work, genetically-encoded fluorescence-based ATP and pH sensors were stably integrated into the genome of P. falciparum. Within the adult blood stages of the parasite, this allowed an analysis of its energy metabolism, which is central for parasite survival. Based on this system, MoA analyses of a panel of antiparasitic compounds were carried out. In the case of a promising drug candidate, these were complemented with additional methods for elucidation of its mechanism. Thereby, two different variants of ATP sensors, ATeam1.03nD/nA and ATeam1.03YEMK, as well as an improved pH sensor, sfpHluorin, were established and characterized via plate reader spectrofluorometry and epifluorescence microscopy, for the first time in P. falciparum. In vitro and in cellulo characterization of the sensors demonstrated their proof of principle and unveiled advantages of the ATeam1.03YEMK sensor cell line in respect to fluorescence intensity and pH stability. Based on that, the effects of a selection of antiparasitic compounds on the sensor readouts were determined. This revealed characteristic response patterns caused by 4-aminoquinolines, arylamino alcohols, redox cyclers, as well as dihydroartemisinin, doxycycline, atovaquone, and cycloheximide. In a next step, the effects of the drug candidate arylmethylamino steroid compound 1o (1o) on the sensor readouts were determined. The investigation uncovered parallels to arylamino alcohols such as mefloquine. Based on these parallels, subsequent analyses via transmission electron microscopy (TEM), the parasitederived heme species distribution, as well as light microscopic morphology of stage-specific 1o incubations suggest that the parasite-killing activity could be based on interference with the parasite’s hemoglobin uptake. The results of this work benefit the understanding of P. falciparum’s parasite biology and the MoA of antiparasitic compounds to support drug development. Furthermore, the established system is now available for the malaria community to address a broad range of research questions.
Charakterisierung der zellulären Stressantwort in embryonalen im Vergleich zu adulten Kardiomyozyten bei mitochondrialer Dysfunktion
(2025) Schraps, Nina
Mitochondrien als zelluläre Energielieferanten sind wesentlich an der Pathogenese verschiedener kardiovaskulärer Erkrankungen beteiligt. Mit seinem hohen Energiebedarf ist das Herz auf eine regelrechte Funktion der Zellorganelle angewiesen. Doch insbesondere mit zunehmendem Alter kommt es zu mitochondrialen Funktionseinschränkungen. Mitochondriale Dysfunktionen äußern sich unter anderem in einer erhöhten Konzentration von ROS und einer verminderten Bildung von ATP. Mit kardiovaskulären Erkrankungen als eine der Haupttodesursachen weltweit, können die Erkenntnisse über das zelluläre Überleben im Hinblick auf eine Schädigung der Mitochondrien wichtige therapeutisch und präventive Optionen bieten. Durch ihre Beteiligung an der Pathogenese kardialer Erkrankungen rücken Mitochondrien daher immer wieder in den Fokus der sogenannten Kardioprotektion. Die Ergebnisse unserer Arbeit bestätigen die Unterschiede embryonaler und adulter Kardiomyozyten bei einer mitochondrialen Dysfunktion. Embryonale Kardiomyozyten zeigen eine hohe Resistenz gegenüber einer Komplex-III-Inhibition. Die Phasenkontrastmikroskopie zeigt einen konfluenten und synchron schlagenden Zellverbund ohne den Nachweis eines signifikanten Zellverlustes in der Zellzählung, trotz einer nachweislich vermehrten Bildung reaktiver Sauerstoffe. Dabei aktivieren die embryonalen Kardiomyozyten verschiedene molekulare Schutzmechanismen, darunter die Integrated-Stress-Response, die Heat-Shock-Response, antioxidative Proteine und Enzyme oder auch die ER-Stress-Achse. Dabei handelt es sich um Signalwege zur Aufrechterhaltung der zellulären Integrität und der Proteinhomöostase. Im Gegensatz dazu kommt es bei adulten Kardiomyozyten bereits bei deutlich geringeren Konzentrationen des verwendeten Inhibitors schnell zu einem Zellverlust. Auch im Hinblick auf die Aktivierung der verschiedenen Signalwege zeigen sie deutliche Unterschiede zu den embryonalen Kardiomyozyten, sodass sich daraus mögliche Erklärungen der verminderten Toleranz adulter Kardiomyozyten ergeben. Sowohl für die pränatale Entwicklung des Herzens, als auch für das Verständnis und den Umgang mit kardiovaskulären Erkrankungen im Alter, kann eine genauere Differenzierung der molekularen Hintergründe und der zellulären Veränderungen bei mitochondrialen Funktionseinschränkungen wesentliche Möglichkeiten bieten.
Geoheritage perspectives through creation of Geoparks in Kazakhstan - A case study
(2025) Valentin, Maral
This research project examines the possibilities for creating Geoparks in Kazakhstan. In recent years, not only the rich cultural history but also the geological heritage of the country between the Altai Mountains and the Caspian Sea has attracted the interest of international researchers. The sheer number of geologically significant sites makes selecting an area for a Geopark a challenging undertaking. This makes it all the more important to conduct thorough research in advance of creating Geoparks in Kazakhstan in order to identify the best possible location. Another important aspect is the fact that, in a corner of the world that has always been fraught with tension, the Geopark movement could prove to be a useful tool for cross-border cooperation. This work attempts to link the many aspects together and present a potential overall picture of the future of Geoparks in Kazakhstan. The basic research carried out in the course of this work provides useful input for further Geopark research in Kazakhstan.
Solving the Gender Equation? Measuring and Refuting Teachers' Math-Gender Misconceptions
(2025) Dersch, Anna-Sophia
This cumulative dissertation contains three publications/manuscripts, researching (1) teachers' math-gender misconceptions (specific, plausible-sounding yet scientifically unsupported knowledge conceptions that contradict empiric evidence and/or established theoretical frameworks, e.g., "Girls think more empathically than boys, but lack systematic thinking abilities and are hence not as good in mathematics."), their relation to their explicit math-gender stereotype (the mere connotation of mathematics as male), (2) their relation to teachers' awareness of math-gender stereotype-reinforcing behaviors in the classroom (e.g., stereotypical task selection, hampering female learners' self-efficacy), and (3) the effectiveness of personalized refutation texts in reducing teachers' math-gender misconceptions (in comparison to non-personalized refutation text, common expository text and personalized expository text). Study 1 introduces and validates the Math-Gender Misconception Questionnaire (MGMQ), with three distinct but related misconceptions (Empathizing-Systemizing, Girls' Compensation and Girls' Non-Compensability). Nearly half of the 303 researched pre-service teachers endorsed at least one misconception. These misconceptions were correlated with the explicit math-gender stereotype, suggesting that math-gender misconceptions and the math-gender stereotype are two related but distinct constructs and that math-gender misconceptions contribute to the manifestation of the math-gender stereotype. Study 2 examines 278 (student and in-service) teachers’ awareness of stereotype-reinforcing teaching behaviors in the classroom using video vignettes depicting a male vs. female model teacher. Teachers reliably detected explicit but rarely implicit biased behaviors. Teachers were more aware of a male vs. female model teacher's math-gender stereotype-reinforcing behaviors. Furthermore, model-observer-gender-similarity improved awareness. Awareness correlated negatively with misconception endorsement, suggesting that misconceptions may influence teachers’ interpretation of, and potentially their engagement in, classroom behavior. Study 3 tests the effectiveness of personalized refutation texts (vs. standard refutation text, personalized expository text and standard expository text) in promoting conceptual change among 336 student teachers and in-service teachers. Personalized refutation fostered the strongest misconception reduction among teachers who initially held math-gender misconceptions, but also elicted backfire effects—ironic misconception reinforcement—in participants without prior misconceptions. Effects on broader attitudes (e.g., math-gender stereotypes) were limited, though reduced misconceptions were associated with more gender-equitable views, suggesting that future interventions should not only be personalized but tailored to teachers' prior knowledge. Methodologically, the dissertation contributes two validated tools—the Math-Gender Misconception Questionnaire and a video-based awareness measure—that enable precise assessment of misconceptions and teachers’ sensitivity to stereotype-reinforcing behaviors, and that can also be meaningfully applied in teacher training. Theoretically, the findings clarify how misconceptions are embedded within broader stereotype systems and identify conditions under which personalized refutation texts promote or hinder conceptual change. Practically, the results underscore the importance of explicitly addressing math-gender misconceptions in teacher education and show that well-aligned, personalized interventions can effectively reduce misconceptions, whereas misaligned feedback may trigger defensive reactions.
Epithelial Factors Affecting Smooth Muscle Contraction of the Mouse Epididymis
(2025) Haas, Dirk Stefan
Urinary tract infections (UTIs) are some of the most common human bacterial infections, ascending up to the kidneys in severe cases. The epididymis, beyond its known functions in sperm maturation, storage, and transport, may also act through its epithelium as a sensory organ capable of detecting pathogens and initiating defensive response, i.e. contraction of its smooth muscles. This study investigates the role of epithelial taste receptor signaling, particularly the Trpm5 ion channel, in mediating smooth muscle contraction in the mouse epididymis. Using immunohistochemistry, a subpopulation of keratin5-positive basal cells with slender processes extending into the lumen was identified. Co-expression with GNAT3, representing the gustatory signaling cascade, and Dclk1, a marker for tuft cells, indicates the presence of the gustatory signaling cascade and the chemosensory nature of these cells, suggesting these cells may detect luminal stimuli, often linked to danger or infection. Time-lapse imaging experiments revealed that application of the bitter compound denatonium benzoate induced a statistically significant increase in contraction frequency in wild type mice, but not in Trpm5 knockout (KO) mice. These findings confirm the involvement of Trpm5-mediated signaling in the contractile response and suggest that epithelial chemosensory cells play a critical role in the defense mechanism of the epididymis. This mechanism may represent a key evolutionary adaptation for protecting ascending UTI.
The role of small open reading frames in Shewanella oneidensis phage λSo in host takeover and phage proliferation
(2025-08) Thöneböhn, Svenja Wiebke
Bacteriophages are the most abundant biological entities on Earth. They wield an immense influence on microbial ecosystems in almost all habitats by regulating bacterial population dynamics. Most phages follow one of two well-characterised strategies for host exploitation: the lytic or the lysogenic cycle. In both pathways, host cell lysis represents the terminal event and is therefore central to phage fitness. The temperate phage λSo is one of four known prophages in the genome of Shewanella oneidensis MR-1 and has a genome size of about 51 kbp. During lysogeny, λSo remains integrated into the host chromosome, replicating in concert with the host cell. In this study, the lysis system of λSo was characterised as a pinholin-SAR endolysin-two-component spanin pathway. The λSo holin protein, SSo, contains two transmembrane do-mains and also produces an antagonistic isoform through an alternative translation start, named antiholin. This regulatory mechanism enables precise temporal control over the in-itiation of host lysis. In addition to the pinholin and the SAR endolysin, the lysis system requires a two-component spanin complex, made up of an inner membrane protein (i-Spanin, RzSo) and an outer membrane protein (o-Spanin, Rz1So). The corresponding genes are present in an overlapping reading frame structure, and the encoded proteins likely form a functional dimer of two dimers. This putative dimer enables the fusion of the inner and outer membrane. In addition, this work has shown that further, previously uncharacterised gene products are involved in cell lysis. Like many phages, λSo harbours genes encoding small proteins of unknown function. A gene cluster, so called cluster C, was identified, whose deletion significantly reduced the number of plaque-forming units. Cluster C consists of six genes (lcc1 - lcc6) encoding proteins between 41 and 137 amino acids in length that have no obvious homologies to known protein domains. Bioinformatic analysis suggests that Lcc4 and Lcc6 contain putative transmembrane domains. Functional characterisation revealed that Lcc6 plays a critical role in phage-induced host cell lysis. In lcc6 deletion strains, induction of the lytic cycle of λSo using mitomycin C resulted in the formation of phage particles, which, however, failed to lyse the host cells and are therefore not released. These findings suggest that Lcc6 participates in an early phase of the lysis cascade, likely acting in concert with pinholin-mediated membrane disruption. The ectopic expression of the Lcc4 protein on the other hand resulted in a pronounced elongation of the host cells and delocalisation of the FtsZ rings - a phenotype that is compatible with a disruption of cell division. The modelling of plausible protein interactions confirmed that this phenotype results from a direct interaction of Lcc4 with key components of the bacterial divisome, particularly FtsZ and ZipA. Site-directed mutagenesis identified isoleucine residues at positions 16 and 19 as essential for the interaction with FtsZ, and tryptophan 80 and arginine 84 as critical for binding to ZipA. Taken together, these results suggest that Lcc4 specifically inhibits bacterial cytokinesis following prophage induction in order to maximise the availability of the metabolic resources of the host cell during phage replication. The Lcc proteins, encoded by genes of the cluster C, thus represents a previously undescribed phage-host effector system with profound influence on cellular organisation and the course of lysis.
Cholinerge Regulation der ATP-vermittelten Freisetzung des pro-inflammatorischen Zytokins Interleukin-1β
(2024-10-31) Richter, Katrin
Trotz intensiver Forschung führen Polytraumata und schwere Operationen auch heute noch zu lebensbedrohlichen systemischen Entzündungen, Sepsis und Multiorganversagen, mit einer nicht akzeptablen hohen Gesamtletalität (Westphal und Kampmeier 2015). Eine bedeutende Rolle in der Pathogenese dieser traumainduzierten Immundysfunktion spielt das hochpotente pro-inflammatorische Zytokin IL-1β, welches von Monozyten, Makrophagen sowie von Epithelzellen synthetisiert wird und unerlässlich für die Immunabwehr gegen Infektionen ist. Die Synthese und Freisetzung von IL-1β muss strikt reguliert werden (Dinarello 2018). Nach Verletzungen wird die Reifung und Ausschüttung von IL-1β durch extrazelluläres ATP, das aus dem Zytoplasma geschädigter Zellen stammt, stimuliert und aktives IL-1β sezerniert. Unter normalen Bedingungen bleiben diese pro-inflammatorischen Reaktionen lokal begrenzt. Bei schweren Traumata und großen chirurgischen Eingriffen kommt es hingegen durch massive Gewebeschädigung zu einer überschießenden Zytokin-Ausschüttung und folglich zur traumainduzierten Immundysfunktion. Bis heute gibt es neben entzündungshemmenden Therapien, welche die Infektanfälligkeit aber maßgeblich erhöhen können, keine geeigneten Behandlungen für die traumainduzierte Immundysfunktion. In dieser kumulativen Habilitationsschrift wurden verschiedene Forschungsprojekte zusammengefasst, die einen neuen anti-inflammatorischen cholinergen Kontrollmechanismus der ATP-vermittelten Freisetzung von IL-1β aus mononukleären Phagozyten identifizieren und charakterisieren (Hecker et al. 2015; Zakrzewicz & Richter et al. 2017; Richter et al. 2016; Backhaus et al. 2017 Richter et al. 2018a). Diese cholinerge Regulation beruht auf der Aktivierung von unkonventionellen nAChRs mit den evolutionär hoch konservierten Untereinheiten α7, α9 und/oder α10 durch klassische Agonisten wie ACh, Cholin und Nikotin. Es konnten aber auch mehrere bisher unbekannte, endogene nAChR-Agonisten identifiziert werden: Phosphatidylcholine sowie deren Metabolite wie PC und PC-haltige Moleküle. Gleichzeitig konnte eine vollkommen neue biologische Funktion des Akute-Phase-Proteins CRP, ein sensitiver Entzündungsmarker und Standardparameter in der klinischen Blutanalyse, aufgeklärt werden: In seiner endogenen, PC-bindenden, pentameren Form inhibiert CRP effizient und über nAChR-vermittelt die monozytäre ATP-induzierte Freisetzung von IL-1β (Richter et al. 2018b). Interessanterweise hängt dieser inhibitorische Effekt nicht nur von dem CRP-gebundenen Liganden ab, vielmehr noch potenziert CRP die cholinerge Wirkung von freiem PC um ein Vielfaches (Richter et al. 2018b). Eine prospektive klinische Studie legt zudem nahe, dass erhöhte CRP-Konzentrationen vor einer traumainduzierten Immundysfunktion schützen (Richter et al. 2018b). Demnach scheint CRP Teil einer negativen Rückkopplungsschleife zu sein, welche die IL-1β-Freisetzung bei systemischer Entzündung limitiert. Als einen potenziellen Gegenspieler des cholinergen Regulationsmechanismus, konnte das Aβ1-42-Peptid identifiziert werden (Richter et al. 2020), welches bisher hauptsächlich im Zusammenhang mit der Alzheimer-Krankheit untersucht wurde. An unkonventionellen, monozytären nAChRs wirkt Aβ1-42 in vitro antagonistisch und ermöglicht so die ATP-induzierte IL-1β-Freisetzung in Anwesenheit von nAChR-Agonisten. Da wir zudem Hinweise erbringen konnten, dass das Aβ1-42-Peptid auch in vivo wirkt (Richter et al. 2020), könnte das Aβ1-42-Peptid somit als endogener, pro-inflammatorischer Regulator präventiv gegen Infektionen und Sepsis sein. Die hier zusammengefassten Arbeiten haben zudem wesentlich zu einem Paradigmenwechsel im wissenschaftlichen Blick auf die nAChRs beigetragen. Während nAChRs kanonisch als ionotrope Rezeptoren eine unerlässliche Rolle für die Reizweiterleitung im neuronalen System spielen, sind es metabotrope Funktionen der unkonventionellen nAChRs in mononukleären Phagozyten, die zur Inhibition des ATP-sensitiven P2X7 Rezeptors führen und somit die IL-1β-Freisetzung inhibieren (Hecker et al. 2015; Zakrzewicz & Richter et al. 2017; Richter et al. 2016; Richter et al. 2023a). Diese Erkenntnisse sind von großer Bedeutung für die Rezeptorforschung und gehen weit über die cholinerge Kontrolle der IL-1β-Freisetzung hinaus. Durch unsere Erkenntnisse rückte auch die α9-nAChR-Untereinheit immer mehr in den Fokus. In weiteren Arbeiten konnten neben synthetischen nAChR-silent agonists auch spezifische α9-Agonisten charakterisiert werden (Richter et al. 2022; Richter et al. 2023b). Dabei zeigten sich neben der anti-inflammatorischen Wirkung auch eine potente analgetischen Wirkung von α9-nAChR-Liganden, die somit eine vielversprechende therapeutische Option zur Behandlung von inflammatorischen Erkrankungen und Schmerz sein könnten. Ein großer Vorteil des hier identifizierten cholinergen Kontrollmechanismus ist, dass gezielt die traumainduzierte (ATP-abhängige) Freisetzung von IL-1β inhibiert, gleichzeitig die IL-1β-abhängige Pathogenabwehr jedoch nicht völlig unterbunden wird. Zudem erwarten wir von den endogenen nAChR-Agonisten wie Phosphatidylcholine und seine Metabolie, sowie von den synthetischen silent agonists, dass sie nicht mit den kanonischen nAChR-Funktionen im Nervensystem interferieren. Somit ist dieser Mechanismus ein vielversprechender Ansatzpunkt für die dringend benötigten präventiven Therapien einer traumainduzierten Immundysfunktion.
Feasibility Studies towards Accessing Generalised Distribution Amplitudes in Exclusive γ-Meson and γγ Production with PANDA at FAIR
(2025) Khalid, Faiza
Understanding the fundamental properties and interactions of the proton remains a central focus in contemporary hadron physics. Its internal structure and the dynamics of hadronic interactions can be explored through exclusive reactions involving antiproton–proton annihilation. This work presents a study of three exclusive channels: $\bar{p}$p → π⁰γ, $\bar{p}$p → π⁰π⁰, and $\bar{p}$p → γγ, with a focus on their potential to probe nucleon structure and reaction dynamics. The studies are performed at four discrete beam momenta of 2.5, 5, 10, and 15 GeV/c. These investigations are carried out in the framework of the PANDA experiment at the upcoming FAIR facility in Darmstadt, which will utilize a high-intensity antiproton beam in the momentum range of 1.5–15 GeV/c. Data samples for both the signal and all relevant background channels were generated and simulated using the PANDARoot framework. This study includes the optimization of the signal-to-background ratio, estimation of count rates, and determination of expected cross sections along with their statistical uncertainties. The results demonstrate that all relevant background channels can be sufficiently suppressed, confirming the feasibility of measuring these reactions at PANDA with sufficient accuracy to significantly advance the understanding of hadron structure in the time-like regime.
Einfluss inflammatorischer Stimuli auf das kardiomyozytäre Differenzierungspotential mesenchymaler Stammzellen
(2024) Hellwig, Yuliya
The results of this project show that an inflammatory environment impairs the cardiac differentiation of stem cells. The meta-analyses show that stem cell therapies significantly reduce mortality and improve LVEF moderately, but significantly. However, the effect that was hoped for, namely the regeneration of infarcted tissue, does not materialize. The results of this study show that the inflammatory environment prevailing after a heart attack has a negative effect on the cardiac differentiation of stem cells. Modulation of the inflammatory niche could improve the cardiac differentiation rate of stem cells and thus achieve regeneration of the damaged myocardium. Further studies could focus on identifying factors that interfere with cardiac differentiation more precisely. Another starting point for research could be the modulation of inflammation, which would lead to better differentiation of the injected stem cells.
Interphase Growth Kinetics and the Partial Electronic Conductivity of Constituents in Sulfide Solid-State Batteries
(2025-06) Alt, Christoph Daniel
Large-scale electrification of transportation and advancements in energy storage are key to achieving net-zero emissions. Solid-state batteries present a promising energy storage solution, expected to enable the use of high-capacity electrode materials such as lithium metal and lithium alloys, while also improving safety. However, effectively integrating high-capacity electrode materials remains a key challenge in unlocking the potential of solid-state batteries. The high reactivity of lithium metal poses both safety and operational challenges, leading to dendrite formation and loss of active redox species (i.e., long-term capacity fading). Since most inorganic solid electrolytes undergo reduction upon contact with alkali metal, the corresponding interphase formation and the resulting long-term increase in cell resistance are often underestimated. However, interphase kinetics and the consequent impact on cell performance strongly depend on the composition and properties of the reaction products. Revealing the interphase composition, growth kinetics, and the influence and role of its individual constitu-ents is crucial for developing protective strategies and enhancing material compatibility. Within this doctoral thesis, the intrinsic transport properties and growth kinetics of the interphase and its constituents for lithiated Li6PS5Cl are investigated, emphasizing their impact on long-term cell operation. Following the quantification of the interphase's partial conductivities through bulk-material synthesis, which revealed a significant resistance contribution over the battery's lifespan, conventional physiochemical concepts were revisited. The Wagner diffusion model, predicting diffusion-controlled interphase growth based on experimental data, was analyzed for solid|solid interfaces alongside the Hebb-Wagner method for accurately quantifying low electronic conductivities in lithium-ion conductors. The former addressed the influence of different interface morphologies on evaluating interphase rate constants by impedance measurements, while the latter revealed the partial electronic conductivity of lithium halides (i.e., LiCl, LiBr, and LiI) present in various interphases. Alloy electrodes, owing to their higher electrode potentials relative to lithium metal, are expected to cause reduced degradation of sulfide solid electrolytes. In this context, In/(InLi)x electrodes – prominent for exhibiting a stable potential of 0.62 V vs. Li+/Li – were first investigated to assess how preparation influences electrode microstructure and performance. Controlling microstructure is critical to avoid current constriction and ensure consistent operation. Studies on thin indium films deposited on current collectors offered insights into interphase growth kinetics at alloying interlayers – an essential challenge for reservoir-free cells – and highlighted the gradual degradation of Li6PS5Cl at the electrode potential of In/(InLi)x. Overall, this doctoral thesis advances the fundamental understanding of intrinsic degradation processes at the electrode|electrolyte interface. In particular, this work provides a new perspective on how multiphase interphases form and evolve over time, depending on their partial ionic and electronic transport properties. It delivers essential insights on previously inaccessible kinetic parameters that now enable more accurate computational simulations, improve the prediction by analytical models, and guide the rational design of more stable materials and interfaces to minimize capacity losses in (reservoir-free) solid-state batteries.
Essays on Climate Change, Migration and Labor Mobility
(2025) Braun, Marius
This dissertation consists of five papers that explore different themes from the fields of environmental and migration economics. The first two papers are concerned with the impacts of climate change and natural disasters on international as well as regional migration patterns. The following two articles investigate the distributional and regional effects of CO2 pricing in Germany. The final paper analyzes differences in labor mobility across immigrant generations in the context of the European Debt Crisis.
Visualization of parasite–host interactions using atmospheric-pressure MALDI mass spectrometry imaging
(2025) Wiedemann, Katja Rebecca
Endoparasites completely rely on the host organism to survive, once they entered their host. Though, hosts do not capitulate but try to protect themselves against potential damage induced by the parasite. Taking these two effects together, leads to measurable changes in the composition and lateral distribution of metabolites in host tissue (upon infection). In order to find novel drug targets, further knowledge on such changes is crucial. Using mass spectrometry imaging to investigate host-parasite interactions in vivo in an untargeted fashion whilst maintaining the lateral information of metabolites is a powerful approach. Therefore, two distinct models were studied: Schistosoma-mansoni-egg-containing liver samples of hamsters infected with the blood flukes, and bovine skin tissue, showing cysts formed by the apicomplexan parasite Besnoitia besnoiti.
For both parasite-host systems, characteristic infection markers were found with significant changes in signal intensities.
Additionally, by benefiting from the fact that lateral information is kept during mass spectrometry imaging analysis, the lateral distribution of infection markers was revealed. For some of them, co-localized biological structures were observed in optical images of the analyzed tissues.
During schistosomiasis, Schistosoma mansoni eggs are deposited in the hamster liver, leading to granuloma formation around the eggs. The high lateral resolution of the AP-SMALDI5 AF ion source enabled the unambiguous visualization of both, eggs (100 µm to 200 µm in diameter) and local abundance changes of lipids in granulomatous tissue compared to healthy hepatic tissue. Guided by results obtained with liquid chromatography-tandem mass spectrometry, we observed a substructure in formed granulomas by applying mass spectrometry imaging. For example, ether-phosphatidyl-ethanolamines were mainly found in the outer part of the granulomas. In total, 372 substances were found to be significantly changed due to infection.
In the skin of Besnoitia besnoiti-infected cattle, MS images showed both, enrichment and depletion of several lipid species inside parasite-formed cysts. Due to the high lateral resolution at 2 µm pixel size, some of them were even found to be characteristic for the thin cyst walls. Applying multiple MSI methodologies, cysts were further characterized by on-tissue tandem mass spectrometry as well as 3-dimensional imaging. Overall, 552 ions were found to be altered due to infection.
Overall, gained insights into parasite-host interactions can now be used as starting points for further metabolism studies and also serve as potential drug targets.
Dynamic critical behavior of hot and dense QCD matter from the real-time functional renormalization group
(2025) Roth, Johannes
In this work, we study dynamic critical behavior of hot and dense QCD matter near second-order phase transitions. We consider the chiral phase transition for two flavors of massless quarks, as well as the conjectured critical point at physical quark masses and finite baryon chemical potential. These are plausibly in the same dynamic universality classes as a four-component Heisenberg antiferromagnet and the liquid-gas critical point of a pure fluid, respectively, whose critical dynamics are described by Models G and H in the Halperin-Hohenberg classification.
Our central tool in this work is a real-time generalization of the functional renormalization group (FRG) based on the Schwinger-Keldysh contour. Starting with Model G, we develop a novel formulation of the real-time FRG which preserves all relevant symmetries of dynamical systems with reversible mode couplings. We show that associated Ward identities imply exact statements about the FRG flow, including the non-renormalization of the mode-coupling constant, and the independence of the static free energy on the dynamics. We show that the formalism reproduces the non-trivial value z=d/2 for the dynamic critical exponent in d spatial dimensions, and we compute a novel scaling function which describes the universal temperature and momentum dependence of the iso-vector and iso-axial-vector charge diffusion coefficient in the chiral limit.
As a next step, we adapt this novel FRG technique to Model H. We derive analytical expressions for dynamic critical exponents that describe the universal power-law divergence of the heat conductivity and the shear viscosity near the QCD critical point. As a central result, we find that the critical exponent of the shear viscosity as a function of d exhibits a maximum in the range 2 < d < 4 and approaches zero for d=2 spatial dimensions. We verify the robustness of this result by considering improved truncations of the static free energy. In parallel, we emphasize the structural similarities and differences with Model G by comparing the fixed-point structures of both models and discuss the presence/absence of weak and strong dynamic scaling relations.
While the leading universal scaling behavior can be described by Models G and H, non-universal corrections require a real-time description of the microscopic dynamics. In this regard, we consider a real-time formulation of the quark-meson model as a particular low-energy effective theory for QCD. As a first application, we study the influence of bosonic dissipation on the phase diagram and the excitation spectrum. We find that dissipation has a non-vanishing but quantitatively small effect on equilibrium observables. The influence on the excitation spectrum, on the other hand, can be drastic, as (over-)damping potentially turns weakly-damped quasiparticles into purely relaxational excitations.
Insect mediated bioconversion in the circular bioeconomy: evaluation of quality, safety and environmental impact
(2024) Rossi, Giacomo
Industrially farmed insects are receiving increasing attention within the modern bioeconomy. Due to a diverse range of microorganisms living in their gut, insects are able to grow on biological waste and by-products, recover nutrients and produce new high-quality materials to be exploited within the agriculture, food, feed, medical and industrial sectors. Their high adaptability to different conditions, along with their limited production of greenhouse gasses, low use of resources, high feed conversion and valuable nutritional profile, has also suggested them as potential food and feed sources for the future. However, despite such interesting properties, legislative limitations, often led by fragmented and contradictory knowledge or lack of data, appear to be a serious limitation for their affirmation in the circular bioeconomy. This thesis focuses on the evaluation of quality, safety and environmental impact of edible insects produced by applying circular economy concepts. Chapter 1 defines the overall background knowledge motivating the performed experiments. It offers an overview of the research gaps that form the basis for the experimental work and describes the overall structure of the thesis. A general introduction covering several aspects concerning the use of insects in the circular bioeconomy, with a specific focus on insects as waste management tool and as future food and feed is summarised in Chapter 2. Chapter 3 represents the core of the thesis. Six experiments, carried out with the aim of answering the research questions defined in Chapter 1 and addressing the identified research gaps are presented and discussed. Specifically, section 3.1 focuses on the development of a new, non-destructive optical system for the rapid monitoring of quality changes of edible insect products. Fluorescence spectra of dry insect powders, produced by milling insects of five different species belonging to the Orthoptera order, were recorded. The 3D data were organised into an Excitation Emission Matrix (EEM) and analysed through machine learning tools. Five independent fluorescence peaks, each resulting from a different class of chemical compounds, were identified. The obtained results were therefore further applied to detect the oxidation status of insect paste subjected to high hydrostatic pressure (HHP) processing (section 3.2). Two experiments were conducted by applying HHP to insect paste at 600 MPa for 5 min. In the first experiment (experiment 2.1), three modified atmosphere packaging (MAP) and normal air packaging were applied after HHP treatment and microbial load as well as lipid and protein oxidation status were monitored during 28 days of refrigerated storage. Results suggested that the combination of HHP with oxygen-free MAP allowed shelf-life extension up to 10 days when refrigeration was applied. However, HHP treatment was found to be responsible for oxidation initialisation. Therefore, the second experiment (experiment 2.2) aimed to validate such observation and test whether addition of commercial antioxidant mixtures before applying HHP could delay the oxidation process. Results showed that although antioxidants exhibited their activity differently during the storage (with the synthetic antioxidant being more active in the initial stage of the storage while the natural antioxidant being more active in a later stage), HHP alone was not responsible for any significant oxidation. Considering the most interesting aspect of edible insects regarding waste conversion, section 3.3 investigates the possibility of using black soldier fly larvae (BSFL) as a tool for managing waste from aquaculture production (ASW). Two experiments, the first using fresh (daily-collected) ASW and the second applying anaerobically digested (bulk-accumulated) ASW, were therefore carried out. The first experiment (experiment 3.1) demonstrated that BSFL can conveniently convert ASW; however, the high water content of the initial material required the inclusion of other ingredients in the diet. Mixtures consisting of 75% ASW and 25% of chicken feed were found to be optimal for supporting larval growth and waste conversion. However, the amount of nutrients assimilated by the larvae was extremely low, indicating a significant loss of nutrients. High nutrients retention and consequently a low environmental impact was observed in substrate 100ASW, which was characterised by low dry matter content, resulting in feed limitation for the BSFL. These results were further confirmed in the second experiment (experiment 3.2), which showed that conditions leading to high larval growth performances were negatively correlated with the reduction of environmental impact. Furthermore, experiment 3.2 also displayed low growth ability of BSFL on bulk accumulated ASW, indicating that fresh ASW should be preferred for insect-mediated aquaculture waste conversion processes. However, although these two experiments showed low nutrient retention by BSFL reared under optimal conditions, the actual amounts of nutrients lost by the larvae in form of gas were not quantified. Therefore, in order to accurately quantify the gas emissions from edible insects during the rearing process, a new open dynamic gas emission chamber was designed and validated for monitoring the greenhouse gas (GHG) emissions from edible insects on a small scale (section 3.4). Validation experiment was carried out by rearing BSFL on moistened chicken feed. Obtained results showed that BSFL produced neither CH4 nor N2O, while CO2 production strictly depended on insect growth and metabolic activity. Accordingly, CO2 emission curves closely resembled the larval growth curves, indicating that an accurate estimation of GHG emission from insects should consider the overall life cycle of the insect, from eggs to harvesting stage, including the neonate stage. Based on the obtained results, an overall conclusion highlighting the main findings and addressing the research questions defined at the beginning of the thesis is presented in the final chapter (Chapter 4). Relevance of the overall thesis within the circular bioeconomy framework and the future steps needed to promote a full transition to the circular bioeconomy, are also illustrated in this chapter.
Analyse der Wirkung von microRNAs auf die Monozyten-Makrophagen Differenzierung am Beispiel von THP-1 Zellen
(2025) Aslantas, Özden
Die Erforschung von microRNAs verspricht in Zukunft bahnbrechende Ergebnisse in der Diagnose und Therapie von Erkrankungen zu liefern. Sie beteiligen sich auch an der Entstehung der Atherosklerose, welche den Grundpfeiler für kardiovaskuläre Erkrankungen bildet. Ein wesentlicher Schritt bei der Entstehung der Atherosklerose ist die Differenzierung von Monozyten zu Makrophagen. Die hier vorgelegte Studie untersucht die Expression ausgewählter microRNAs während der Monozyten- Makrophagen-Differenzierung. Die Untersuchung erfolgte an THP-1 Zellen, einer monozytären Zelllinie. Unter Stimulation der Zellen mit Phorbol-12-myristat-13-acetat (5ng /ml PMA) differenzierten diese zu Makrophagen, was schon mikroskopisch an einem veränderten Phänotyp mit Pseudopodien und polymorpher Erscheinungsform zu erkennen war. Auch die CD14- mRNA Expression, als Marker für die Makrophagendifferenzierung, zeigte eine signifikante Erhöhung nach 72-stündiger PMA-Stimulation. Unter dieser PMA- Stimulation wurden Expressionen verschiedener microRNAs analysiert. let-7f und miR- 92a wurden unter PMA-Gabe runterreguliert. Eine Hochregulation erfuhren miR-1, miR- 22 und miR-143. Die Expression von miR-21, miR-99a und miR-223 blieb unverändert. Die unter PMA-Gabe runterregulierten microRNAs, let-7f und miR-92a, zeigten nach Transfektion mit ihren jeweiligen AgomiRen einen Anstieg der Expression in den behandelten Zellen. AgomiR-let-7f steigerte die CD14-mRNA Expression, wohingegen der Einsatz von AgomiR-92a dazu führte, dass die CD14-mRNA Expression unter PMA reduziert wurde. Unter den AntagomiRen bewirkte lediglich AntagomiR-1 eine signifikante Erniedrigung der miR-1 Expression unter PMA. Unter diesen Bedingungen stieg die CD14-mRNA Expression. Die Makrophagendifferenzierung ist demnach bei niedriger miR-1 Expression verstärkt. Schlussfolgernd kann man sagen, dass von den untersuchten microRNAs let-7f, miR-92a und miR-1 die Differenzierung von Monozyten zu Makrophagen unter PMA-Gabe beeinflussen. Verhindert man den Abfall von miR-92a, so wird die CD14-mRNA Expression und somit die Makrophagendifferenzierung reduziert. Dagegen bewirkt eine Reduktion von let-7f oder miR-1 eine erhöhte CD14-mRNA Expression, was auf eine verstärkte Differenzierung zu Makrophagen hinweist. Somit könnte eine Modulation der miR-1, miR-92a oder let-7f Expression therapeutisch genutzt werden, um atherosklerotische Vorgänge zu reduzieren.
Structural development and functional reconstitution in the olfactory system of the clawed frog Xenopus laevis
(2025) Kahl, Melina
The transition of tetrapods to terrestrial habitats is concomitant with the adaptation of the olfactory system (OS) to the environment. This is reflected at the anatomical and functional levels with the formation of different subsystems, including cell subpopulations that exhibit distinct protein expression at the molecular level. The expression patterns of specific proteins vary between different species, although the olfactory systems show general anatomical similarities. For instance, in fish the calcium-binding protein S100Z is expressed in different cell types in their olfactory epithelium, while in mammals it is associated with cells within the vomeronasal organ (VNO). In the course of my thesis, I analyzed the expression pattern of S100Z in the OS of the anuran Xenopus laevis. Using immunohistochemistry in whole mount and slice preparations I identified a subgroup of S100Z expressing olfactory receptor neurons (ORNs) in the larval main OS and in the middle cavity of adult Xenopus laevis. In larval animals, these ORNs showed a lateral distribution bias in the olfactory epithelium and exclusively projected into the intermediate and lateral glomerular cluster. In conclusion, S100Z expression in the OS of Xenopus laevis is exclusively associated with the main OS and not with the VNO. Maintaining regenerative capacity is essential for the OS because of its exposed position to toxic substances or physical trauma. This capacity is attributed to the presence of two main cell types. Firstly, the basal cells of the olfactory epithelium, which are neuronal stem cells and support constant renewal by developing new supporting cells and ORNs. Secondly, the olfactory ensheathing cells (OECs), which enwrap the axons of ORNs until they project into the olfactory bulb (OB) in the forebrain. To date, the existence and role of OECs in the OS of Xenopus laevis have not been investigated in detail. I found vimentin expressing OECs enwrapping ORN axon bundles from the epithelium until the OB in larval Xenopus using immunohistochemistry. The presence of fibroblasts and macrophages in the olfactory nerve (ON) was determined through the utilization of immunohistochemistry and transgenic Xenopus lines. Unilateral ON transection induced a temporary transient and dynamic phosphorylation of the ribosomal protein S6 in these non-neuronal cells. In summary, I identified various cell types within the ON which protein expression is influenced by ON injury. The exact function of phosphorylated ribosomal protein S6 in the OS of Xenopus is still unknown.

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