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JLUpub ist das institutionelle Repositorium der Justus-Liebig-Universität.
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.
Neue Veröffentlichungen:
Effekt von BDNF auf die Angiogenese im humanen Kokultursystem aus Endothelzellen und osteoporotischen Osteoblasten
(2025) Holtkamp, Katharina Ines Carmen
Die Bildung und Stabilisierung von Blutgefäßen ist für die Frakturheilung von entscheidender Bedeutung. Im Herz konnte gezeigt werden, dass das Signalmolekül brain-derived neurotrophic factor (BDNF) die Angiogenese fördert. Vor diesem Hintergrund stellte sich die Frage, ob durch eine Applikation von BDNF die Bildung von Blutgefäßen stimuliert wird und ob die Osteoblasten osteoporotischer Spender hierbei regulierend wirken. Angelehnt an die gestellte Hypothese konnte kürzlich aufgezeigt werden, dass mesenchymale Stammzellen (MSC) und Osteoblasten bei Osteoporose phänotypische Veränderungen im Vergleich zu knochengesunden Zellen aufweisen. Zur Beantwortung der Frage wurden humane Osteoblasten und Endothelzellen im Kokultursystem untersucht. MSC wurden aus humaner Spongiosa isoliert, die bei der Endoprothetik als Restmaterial anfiel. Es wurden MSC von n = 5 knochengesunden und n = 5 osteoporotischen Spendern verwendet. Für das Kokultursystem wurden die MSC 10 Tage osteogen differenziert. Anschließend wurden immortalisierte humane dermale mikrovaskuläre Endothelzellen (HMEC), in einem Verhältnis von 1:4, sowie BDNF (20 ng/mL Medium) hinzugefügt. Nach 3 und 5 Tagen wurde der von-Willebrand-Faktor (vWF) im Zellkulturmedium mittels ELISA bestimmt. Die Zellen wurden ebenfalls nach 3 und 5 Tagen geerntet und zur Bestimmung der relativen alkalischen Phosphatase (ALP) Aktivität verwendet. Abschließend erfolgte eine statistische Analyse und graphische Darstellung. Die Konzentration des sezernierten vWF im Zellkulturmedium stieg von Tag 3 zu Tag 5 signifikant in Kokulturen mit humanen Osteoblasten von osteoporotischen Spendern nach Zugabe von BDNF an. In Kokulturen knochengesunder Osteoblasten konnte ein vergleichbarer Anstieg der vWF Konzentration auch ohne die zusätzliche Applikation von BDNF gemessen werden. Die Differenzierung und Aktivität der Osteoblasten wurde durch die relative Aktivität der ALP ermittelt. Es waren keine signifikanten Unterschiede in der ALP Aktivität in den Kokulturen knochengesunder und osteoporotische Osteoblasten, sowie nach Applikation von BDNF zu verzeichnen.
Die Ergebnisse zeigen, dass Osteoblasten osteoporotischer Spender nach Zugabe von BDNF keinen negativen Einfluss auf die Bildung des vWF und somit auf die Angiogenese ausüben. Diese stimulierende Wirkung von BDNF ist in Kokulturen knochengesunder Osteoblasten nicht notwendig. BDNF zeigte im Kokultursystem mit humanen Endothelzellen keinen Einfluss auf die ALP Aktivität, die als Zeichen für die Aktivität der Osteoblasten verwendet wurde. Zusammenfassend zeigte sich durch BDNF eine positive Beeinflussung der osteoporotischen Kokultur in Bezug auf die Angiogenese, womit ein zukünftiger Ansatz im Umgang mit Osteoporose aufgezeigt werden konnte.
Factor XII in community-acquired pneumonia - Sex specific differences and correlation between clinical parameters
(2025) Ehrlich, Kristin
Pneumonia accounts for one of the ten main causes of death worldwide with highest incident rates in small children and elderly people. Generally, men are more susceptible to an infection and show elevated rates of hospitalization.
The role of FXII as a coagulation factor has been highly questioned as people deficient in FXII do not show any kind of bleeding disorder and with the discovery of a TF- dependent coagulation pathway in vivo, FXII seemed to be dispensable for hemostasis. Therefore, current studies focus on alternative roles of FXII. A growing number of evidence supports the theory that FXII is directly and indirectly associated with inflammatory processes and thrombosis and thereby is playing an important role for innate host defense against infection. Multiple sources showed that FXII does not only lead to fibrin formation but also to production and release of proinflammatory cytokines and stimulation of neutrophils.
Although previous studies highlighted the role of FXII and its downstream products during ARDS, a common complication of pulmonary infection, corresponding data for FXII in the context of pneumonia is missing. The present study investigated levels of FXII, FXIIa and HK in plasma of 140 CAP patients and 60 sex- and age-matched healthy donors by performing analysis of data collected via western blot and ELISA. The results were further analyzed to determine sex-specific differences and correlations with CRP levels, CRB-65-score and mortality. Additionally, FXII levels in BALF of 20 CAP patients and 10 donors was measured by western blot and ELISA. Finally, immunohistochemical stainings for FXII and pro-SP-C, CD-68 and vWF in human lung tissue of 3 CAP patients were performed.
Previous studies showed that levels of FXII and its inhibitor decline simultaneously during infection, hypothesizing a progressive consumption of both. In contrast to that I found elevated levels of FXIIa-C1INH-complexes in plasma of CAP patients, while no parallel decrease of FXII levels was observed. That could be a sign of either inhibited degradation of FXII or stimulation of production and secretion of FXII. Multiple studies suggest neutrophils as a source of FXII and show a proinflammatory influence of estrogen on neutrophil function.
In line with these findings the present work shows sex specific differences with regard to FXII and HK levels in CAP patients. Female CAP patients showed higher amounts of FXII than sex-matched donors, while HK levels in women suffering from CAP were decreased in comparison to sex-matched donors. As estradiol is known to stimulate FXII production and studies have shown an association between estradiol levels and FXII levels in plasma, these observations let me speculate that changes of FXII plasma levels may be influenced by alterations of estradiol levels in the healthy elderly population as well as in the context of pulmonary infection. Epidemiological data show that male individuals are more prone to infectious diseases than female individuals. These sex- specific differences in the susceptibility to but also the outcome of pulmonary infection are hypothesized to originate from sex-hormone-dependent but also sex-hormone- independent variations of innate and adaptive immune responses. The results presented add further evidence to sex specific differences in the context of pulmonary infection and emphasize the need to support further research on that matter.
Moreover, the sex-specific differences in FXII and HK levels let me speculate about the role of FXII and its downstream products with regard to immunothrombosis as women are more prone to thrombosis and elevated levels of estrogens are related to an increased risk of thromboembolic events. Currently contradictory results have been published, leaving the question of a rather protective or a harmful role of FXII and its downstream products in the context of inflammation and related coagulopathy unanswered. That is why further studies regarding this question need to be performed. Although I would have expected more correlations of FXII and its downstream products with clinical parameters, only a negative correlation of CRP levels and FXII levels in women with CAP, as well as a corresponding positive correlation with CRP levels and FXIIa-C1INH complexes in female CAP patients was detected. Furthermore, a negative correlation of HK levels and the CRB-65 score in female CAP patients was found. The weak correlations to CRP and CRB-65 score imply a supplementary, rather than a substitutive role of FXII, FXIIa and HK in the prediction of disease outcome of CAP. Finally, elevated levels of FXII in BALF of CAP patients were shown, indicating local production or accumulation of plasma-derived FXII in CAP lungs.
Via immunolocalization of FXII to endothelial cells a binding of FXII to endothelial cells has been proposed in this study. While FXII-uPAR-associated signalling seems to have a rather protective role in the context of inflammation the consequent activation of the KKS by FXIIa can result in extensive vascular inflammation.
Immunolocalization of FXII to the surface of macrophages implies a binding of FXII to macrophages with a probable consequent activation of FXII into FXIIa leading to a secretion of pro-inflammatory cytokines and fatal disease outcome.
Moreover, FXII was immunolocalized to ATII cells which, together with endothelial cells, play an important role in maintaining a functioning capillary-alveolar barrier, which is essential for host defense. In this study a possible association of FXII and the regulation of ATII cell function is proposed.
All in all, the work presented shows altered levels of FXII, FXIIa and HK during CAP with sex-specific differences, indicating that FXII plays an important role in the context of pulmonary inflammation and associated coagulopathy. Not only the role of FXII as an effector of host defense but especially sex-specific effects of FXII should be investigated further in the future. Only then we will be able to draw conclusions on individual disease outcome and can develop personalized therapeutic strategies.
Functional characterization of the membrane-depolarizing toxin TisB in Escherichia coli
(2025-01) Leinberger, Florian Hartmut
Bacteria are frequently exposed to environmental stressors that threaten their survival. This leads to the activation of stress response systems that adjust gene expression to maintain cellular in- tegrity. However, if these systems are inadequate, bacteria can form persister cells. These are a dormant subpopulation with reduced metabolic activity and increased antibiotic tolerance. Unlike other forms of bacterial dormancy, such as endospores, persister cells are morphologically similar to active cells but are in a transient state of reduced activity. This survival strategy allows bacteria to withstand adverse conditions that can lead to relapse of infection and the spread of antibiotic resistance.
This work examines the functionality of TisB, a toxin of the type I toxin-antitoxin system tisB/istR-1 in Escherichia coli (E. coli), and its role in maintaining dormancy through specific physiological mechanisms. The research suggests that insertion of TisB into the inner membrane leads to membrane depolarization and ATP depletion, which can be considered as key triggers for the dormant state associated with antibiotic tolerance. The results presented illustrate the influence of TisB on persister cell physiology and its role in bacterial survival under antibiotic stress. An important aspect of this work is the use of a moderate expression system for TisB, which allows a controlled investigation of its effects without causing excessive toxicity. This allows for an exam- ination of the relationship between TisB-induced dormancy and protein aggregation. The results show that TisB-dependent protein aggregation influences the duration of dormancy during antibi- otic exposure. In addition, amino acids critical for TisB functionality were identified. This provided insight into the structural elements that are essential for its activity. These findings contribute to a deeper understanding of TisB and highlight the importance of specific amino acids in maintaining its functionality within the membrane.
In summary, the results presented here deepen our understanding of the tisB/istR-1 system and its role in bacterial persistence. By elucidating the mechanisms by which TisB influences persistence, protein aggregation and energy content, this study provides a foundation of knowledge that can serve as a starting point for developing strategies to curb bacterial persistence and improve the efficacy of antibiotics.
Intergroup Relationships, Discrimination, and Prejudice in Germany and Europe
(2024) Huth-Stöckle, Nora
This dissertation investigates perceived group threats and their role in intergroup relations between native majorities and immigrant minorities in Germany and Europe. The first study investigates how economic downturns and perceptions thereof affect the perception of immigrants as a threat to the national economy. The second study examines whether pandemic-related challenges and concerns are associated with group-level threat perceptions and anti-immigrant prejudice. The third study investigates the relationship between empathy and prejudice towards refugees. This study further examines whether group threats moderate the relationship between empathy and prejudice. The fourth study investigates the impact of German natives’ social distance towards immigrant groups on these groups’ social distance toward Germans, and to what extent perceived discrimination mediates this association.
Examining the role of genetic variability for drought stress responses in wheat (Triticum aestivum L.) and sorghum (Sorghum bicolor L. Moench.) and its implications for water and nitrogen use efficiency
(2024) Vukasovic, Stjepan
In the present dissertation, an investigation of the physiological characteristics of traits related to drought stress resistance and a detailed analysis of the morphological and physiological responses to drought stress in wheat and sorghum were carried out. In addition, this dissertation provides an validation of the root growth-associated haplotypeblocks Hap-5B-RDMa and Hap-5B-RDMb in relation to nitrogen uptake, nitrogen remobilization and water use.
In sorghum, the use of a modern gravimetric phenotyping platform showed the impact of early vegetative drought stress on morphological and physiological responses, such as plant development, biomass and flowering time.
In wheat, a cost-effective phenotyping method was evaluated both in the field and under controlled conditions. Normalized difference vegetation index (NDVI) in the field as well as digital image analysis (PLA) under controlled conditions showed a significant (p < 0.05) influence of the second leaf on early plant development (early vigour). In addition, genome-wide association studies were performed to identify the genomic determination for Early Vigour, identifying 42 markers associated with NDVI and two markers associated with PLA.
Furthermore, the gravimetric measurement in combination with the 15N tracer-based analysis showed significant (p < 0.05) effects for carriers of Hap-5B-RDMa and Hap-5B-RDMb on nitrogen uptake in the root. In addition, significantly (p < 0.1) lower transpiration rates were found for certain genotype-haplotypeblock interactions.
In view of the changing climatic growing conditions and the goal of achieving more climate-neutral production systems, the development of new varieties is essential. These lines have to be more resilient to abiotic stress factors such as drought stress and must be able to meet food demand under lower input factors. This dissertation provides a significant contribution in understanding early vegetative drought stress on morphological and physiological growth parameters in sorghum. In addition, this work presents a cost-effective method for phenotyping early vigor and novel insights into the genetic influence of root-associated haplotypeblocks on nitrogen uptake in wheat. The findings presented here can be used as potential targets in pre-breeding to develop more efficient varieties.