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Item type: Item , Genetically-encoded fluorescent ATP sensors for mode of action analyses of antiparasitic compounds in Plasmodium falciparum(2025) Springer, EricThis 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.Item type: Item , Data for "Between Order and Confusion: Clearing Up Structural Misconceptions in Carbon Materials Nomenclature"(2025-11-28) Glatthaar, ChantalThis data presents the raw data that was additionally collected for the publication "Between Order and Confusion: Clearing Up Structural Misconceptions in Carbon Materials Nomenclature". It consists of Raman spectroscopy and X-Ray scattering data of Graphite and Kraft-Lignin samples. Further information about the purpose of the data collection, details about the materials and data acquisition, as well as structure and re-usage of provided data can be found in the Readme.pdf file.Item type: Item , Equine adipose-derived stem cells modulate in vitro neutrophil extracellular trap release by polymorphonuclear neutrophils(2025) Salinas-Varas, Constanza; Espinosa, Gabriel; Muñoz-Caro, Tamara; Conejeros, Iván; Gärtner, Ulrich; Fey, Kerstin; Arnhold, Stefan; Taubert, Anja; Hermosilla, CarlosNeutrophil extracellular trap (NET) are thin and long web-like structures composed of DNA and antimicrobial proteins released by activated polymorphonuclear neutrophils (PMN) as part of the innate immune response. Adipose-derived stem cells (ADSCs) represent an accessible, abundant and minimal invasive source of mesenchymal stem cells (MSCs), with high regenerative potential, immunomodulatory and antiinflammatory properties. Although recognized immunomodulatory properties of ADSCs, their interaction with PMN and their role on NET formation remains poorly characterized. The present study aimed to evaluate the in vitro effects of equine ADSCs on NET formation by equine PMN. Equine ADSCs were isolated from two different sources of adipose tissue, subcutaneous and retroperitoneal adipose stores. Equine PMN were isolated from peripheral blood with a discontinuous density gradient and stimulated with phorbol 12-myristate 13-acetate (PMA) to induce NET release as positive control. Scanning electron microscopy (SEM) and immunofluorescence microscopy (IFM) analyses were performed to assess NET release by equine PMN co-cultured with ADSCs. In vitro IFM-NET quantification revealed a significant NET decrease for PMN co-cultured with ADSCs and PMA. Furthermore, extracellular DNA quantification showed that inhibition of equine NET is dependent on the ADSCs to PMN ratio, for PMA and ionomycin stimulated PMN. Moreover, our findings unveil no modulation of reactive oxygen species (ROS) production by equine PMN when co-cultured with ADSCs. In summary, our results provide evidence of ADSCs on equine PMN, particularly in their capacity to attenuate NET formation and release. These results support the potential role of ADSCs on host innate immune response and thereby maintaining immune homeostasis. Further investigation is needed to better understand the specific molecular pathways involved in NETosis via ADSCs.Item type: Item , Labor turnover in Ethiopia's textile industry: a hotspot of social transformation(2025) Fink, MichaelaThe Ethiopian textile industry is particularly affected by high labor turnover. In a compelling social study, Michaela Fink investigates the causes of this issue, focusing primarily on the voices of the (female) workforce. She illustrates the tension between rural, community-based orientations of women workers and the industrial working environment in which they find themselves. For the women, it is often a balancing act between the rural world they come from and the urban consumerist world they live and work in. They are attracted to modern values of career, consumption and urbanity. At the same time, it is hardly possible for them to achieve modest prosperity.Item type: Item , Charakterisierung der zellulären Stressantwort in embryonalen im Vergleich zu adulten Kardiomyozyten bei mitochondrialer Dysfunktion(2025) Schraps, NinaMitochondrien 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.