The Faculty of Mathematics and Natural Sciences: Search
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Climate field reconstructions from pollen and macrofossil syntheses using Bayesian hierarchical models
Studying past climate states is important to understand climate changes and climate variability on centennial to orbital timescales, to analyze the reaction of the Earth system to large-scale changes in external forcings, ...
Verbesserung der Befundinterpretation bei forensisch-toxikologischen Fragestellungen am Beispiel von Prothipendyl, Cannabinoiden und neuen psychoaktiven Substanzen: Bedeutung von Metaboliten und Referenzdaten
Für eine umfassende forensisch-toxikologische Interpretation von Substanznachweisen in biologischen Matrizes bedarf es einer fundierten Datenlage. Neben pharmakologischen bzw. toxikologischen Eigenschaften der Substanzen ...
Spaceborne SAR Remote Sensing for Monitoring of Vegetation Dynamics in Arid and Semi-arid Environment
Drylands are under constant threat from multiple stresses and challenges, which occur as a result of a complex interaction of natural processes, and human-induced processes caused by unsustainable land use practices, leading ...
Evaluating onco-geriatric scores and medication risks to improve cancer care for older patients
The cancer therapy of older patients is challenging, being more complex than the therapy of younger patients. Older cancer patients show a higher toxicity risk during therapy and drug-related problems are common. In order ...
Mining and small-scale farming in the Andes: Socio-environmental roots of land-use conflict
The Peruvian Andes are one of the most important water sources for the country. Therefore, their exploitation might pose critical threats for local farming activities, national economy, and water quantity and quality. At ...
Design, Entwicklung und Herstellung modifizierter gastroretentiver schwimmender Systeme auf Basis von schmelzextrudierten hohlen Zylindermatrices
Die Entwicklung gastroretentiver Arzneiformen ist komplex, da neben der kontrollierten Freisetzung des Wirkstoffs zusätzlich die Verlängerung der Verweilzeit im Magen gewährleistet werden muss. Hierfür werden meist hydrophile ...
Geriatrische Medikationsanalyse für Pflegeheimbewohner durch öffentliche Apotheken
Pflegeheimbewohner sind häufig von Polymedikation und damit einhergehenden arzneimittelbezogenen Problemen (ABP) betroffen. Medikationsanalysen können die Angemessenheit der Medikation bei Älteren verbessern. Mit der ...
The enzyme HPGD is critical for regulatory T cell function in adipose tissue
Regulatory T cells (T<sub>reg</sub> cells) are essential for maintaining immune homeostasis. However, how T<sub>reg</sub> cells exert their function in tissue specific environments is often unknown. We have found hydroxyprostaglandin dehydrogenase (Hpgd), the major Prostaglandin E<sub>2</sub> (PGE<sub>2</sub>) metabolizing enzyme, to be significantly upregulated in T<sub>reg</sub> cells compared to conventional T cells (T<sub>conv</sub>). In the murine system, this upregulation is especially pronounced in the visceral adipose tissue (VAT), a prostaglandin-rich environment.<br /> Furthermore, we could show that through the metabolism of PGE<sub>2</sub> into 15-keto-PGE<sub>2</sub> Hpgd enhances the suppressive capabilities of T<sub>reg</sub> cells in an, at least partially, Pparγ-dependent manner. In vivo, we found that Hpgd-deficient T<sub>reg</sub> cells were less efficient in preventing the onset of both DSS-induced and adoptive transfer colitis, further indicating that Hpgd plays a role in the suppressive capacity of T<sub>reg</sub> cells. However, analysis of the transcriptome of these Hpgd-deficient T<sub>reg</sub> cells did not differ significantly from Hpgd-competent T<sub>reg</sub> cells, indicating that the observed changes are due to the extrinsic effect caused by the loss of the enzymatic function of Hpgd.<br /> When analyzing the VAT of aged animals with Hpgd-deficient T<sub>reg</sub> cells, we could detect an influx of non-functional T<sub>reg</sub> cells as well as an accumulation of pro-inflammatory macrophages and an increase in adipocyte size. Furthermore, while we could neither detect a change in body or organ weight of these animals, nor a change in motility, food and water intake, or respiration, we could observe impaired metabolic signaling. Aged animals with Hpgd-deficient T<sub>reg</sub> cells respond less to insulin and glucose challenge and show a reduction in insulin signaling.<br /> When subjecting animals with Hpgd-deficient T<sub>reg</sub> cells to a high fat diet (HFD), we could not detect a difference in weight gain when compared to wildtype littermate control animals. Even though we could detect a slight decrease in insulin responsiveness in animals on a HFD with Hpgd-deficient T<sub>reg</sub> cells, no difference in the VAT-resident immune cell population or in any other metabolic parameters could be observed.<br /> Additionally, in peripheral blood from human type II diabetes (T2D) patients we observed a dysregulation of the T<sub>reg</sub> cell population as well as a decrease in HPGD expression in these cells compared to healthy, age-matched controls. Taken together, these data indicate<br /> that both in humans and in the murine system, HPGD expression in T<sub>reg</sub> cells might be involved in metabolic regulation.<br /> Finally, we analyzed the role of the T<sub>reg</sub> cell specific transcription factor mesenchyme homeobox 1 (MEOX1) for HPGD expression. We found that MEOX1 is highly upregulated in human T<sub>reg</sub> cells, especially after stimulation with interleukin (IL) 2. Furthermore, we could show that while MEOX1 expression, like HPGD, is regulated by FOXP3, a loss of MEOX1 does not affect HPGD expression, thus disproving our hypothesis that HPGD may be regulated by the transcription factor MEOX1.<br /> Taken together, we could describe that HPGD is an important mediator of T<sub>reg</sub> cell suppression, independently of MEOX1. We found that a T<sub>reg</sub> cell specific deletion of Hpgd in the mouse leads to a dysregulation of the metabolism, and that HPGD levels are significantly decreased in T<sub>reg</sub> cells isolated from the peripheral blood of T2D patients compared to T<sub>reg</sub> cells isolated from healthy subjects....
Petrological analyses and Lu-Hf geochronology of subducted continental and oceanic crust from different locations in the upper and lower plate of the Caledonian Orogen
In this thesis I conducted Lu-Hf analyses on samples from locations all over the Caledonian Orogen. I combined these ages with petrological analyses in order to help to unravel some of the open questions concerning the ...
Impact of UGT1A polymorphisms on inflammation and fibrogenesis in a humanized transgenic mouse model
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