@phdthesis{FigueroaCampos2022,
  author    = {Figueroa Campos, Gustavo Adolfo},
  title     = {Wet-coffee processing production wastes},
  doi       = {10.25932/publishup-55882},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-558828},
  school      = {Universit{\"a}t Potsdam},
  pages     = {X, 159},
  year      = {2022},
  abstract  = {Countries processing raw coffee beans are burdened with low economical incomes to fight the serious environmental problems caused by the by-products and wastewater that is generated during the wet-coffee processing. The aim of this work was to develop alternative methods of improving the waste by-product quality and thus making the process economically more attractive with valorization options that can be brought to the coffee producers. The type of processing influences not only the constitution of green coffee but also of by-products and wastewater. Therefore, coffee bean samples as well as by-products and wastewater collected at different production steps of were analyzed. Results show that the composition of wastewater is dependent on how much and how often the wastewater is recycled in the processing. Considering the coffee beans, results indicate that the proteins might be affected during processing and a positive effect of the fermentation on the solubility and accessibility of proteins seems to be probable. The steps of coffee processing influence the different constituents of green coffee beans which, during roasting, give rise to aroma compounds and express the characteristics of roasted coffee beans. Knowing that this group of compounds is involved in the Maillard reaction during roasting, this possibility could be utilized for the coffee producers to improve the quality of green coffee beans and finally the coffee cup quality. The valorization of coffee wastes through modification to activated carbon has been considered as a low-cost option creating an adsorbent with prospective to compete with commercial carbons. Activation protocol using spent coffee and parchment was developed and prepared to assess their adsorption capacity for organic compounds. Spent coffee grounds and parchment proved to have similar adsorption efficiency to commercial activated carbon. The results of this study document a significant information originating from the processing of the de-pulped to green coffee beans. Furthermore, it showed that coffee parchment and spent coffee grounds can be valorized as low-cost option to produce activated carbons. Further work needs to be directed to the optimization of the activation methods to improve the quality of the materials produced and the viability of applying such experiments in-situ to bring the coffee producer further valorization opportunities with environmental perspectives. Coffee producers would profit in establishing appropriate simple technologies to improve green coffee quality, re-use coffee by-products, and wastewater valorization.},
  language  = {en}
}
@phdthesis{IgualGil2022,
  author    = {Igual Gil, Carla},
  title     = {Role of the GDF15-GFRAL pathway under skeletal muscle mitochondrial stress},
  doi       = {10.25932/publishup-55469},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-554693},
  school      = {Universit{\"a}t Potsdam},
  pages     = {IXIII, 73, XVII},
  year      = {2022},
  abstract  = {Growth differentiation factor 15 (GDF15) is a stress-induced cytokine secreted into the circulation by a number of tissues under different pathological conditions such as cardiovascular disease, cancer or mitochondrial dysfunction, among others. While GDF15 signaling through its recently identified hindbrain-specific receptor GDNF family receptor alpha-like (GFRAL) has been proposed to be involved in the metabolic stress response, its endocrine role under chronic stress conditions is still poorly understood. Mitochondrial dysfunction is characterized by the impairment of oxidative phosphorylation (OXPHOS), leading to inefficient functioning of mitochondria and consequently, to mitochondrial stress. Importantly, mitochondrial dysfunction is among the pathologies to most robustly induce GDF15 as a cytokine in the circulation. The overall aim of this thesis was to elucidate the role of the GDF15-GFRAL pathway under mitochondrial stress conditions. For this purpose, a mouse model of skeletal muscle-specific mitochondrial stress achieved by ectopic expression of uncoupling protein 1 (UCP1), the HSA-Ucp1-transgenic (TG) mouse, was employed. As a consequence of mitochondrial stress, TG mice display a metabolic remodeling consisting of a lean phenotype, an improved glucose metabolism, an increased metabolic flexibility and a metabolic activation of white adipose tissue. Making use of TG mice crossed with whole body Gdf15-knockout (GdKO) and Gfral-knockout (GfKO) mouse models, this thesis demonstrates that skeletal muscle mitochondrial stress induces the integrated stress response (ISR) and GDF15 in skeletal muscle, which is released into the circulation as a myokine (muscle-induced cytokine) in a circadian manner. Further, this work identifies GDF15-GFRAL signaling to be responsible for the systemic metabolic remodeling elicited by mitochondrial stress in TG mice. Moreover, this study reveals a daytime-restricted anorexia induced by the GDF15-GFRAL axis under muscle mitochondrial stress, which is, mechanistically, mediated through the induction of hypothalamic corticotropin releasing hormone (CRH). Finally, this work elucidates a so far unknown physiological outcome of the GDF15-GFRAL pathway: the induction of anxiety-like behavior. In conclusion, this study uncovers a muscle-brain crosstalk under skeletal muscle mitochondrial stress conditions through the induction of GDF15 as a myokine that signals through the hindbrain-specific GFRAL receptor to elicit a stress response leading to metabolic remodeling and modulation of ingestive- and anxiety-like behavior.},
  language  = {en}
}
@phdthesis{Herpich2021,
  author    = {Herpich, Catrin},
  title     = {Fibroblast growth factor 21 and its association with nutritional stimuli in older age},
  school      = {Universit{\"a}t Potsdam},
  pages     = {75},
  year      = {2021},
  abstract  = {Fibroblast growth differentiation factor 21 (FGF21) is known as a pivotal regulator of the glucose and lipid metabolism. As such, it is considered beneficial and has even been labelled a longevity hormone. Nevertheless, recent observational studies have shown that FGF21 is increased in higher age with possible negative effects such as loss of lean and bone mass as well as decreased survival. Hepatic FGF21 secretion can be induced by various nutritional stimuli such as starvation, high carbohydrate and fat intake as well as protein deficiency.. So far it is still unclear whether the FGF21 response to different macronutrients is altered in older age. An altered response would potentially contribute to explain the higher FGF21 concentrations found in older age. In this publication-based doctoral dissertation, a cross-sectional study as well as a dietary challenge were conducted to investigate the influence of nutrition on FGF21 concentrations and response in older age. In a cross-sectional study, FGF21 concentrations were assessed in older patients with and without cachexia anorexia syndrome anorexia syndrome compared to an older community-dwelling control group. Cachexia anorexia syndrome is a multifactorial syndrome frequently occurring in old age or in the context of an underlying disease. It is characterized by a severe involuntary weight loss, loss of appetite (anorexia) and reduced food intake, therefore representing a state of severe nutrient deficiency, in some aspects similar to starvation. The highest FGF21 concentrations were found in patients with cachexia anorexia syndrome. Moreover, FGF21 was positively correlated with weight loss and loss of appetite. In addition, cachexia anorexia syndrome itself was associated with FGF21 independent of sex, age and body mass index. As cachectic patients presumably exhibit protein malnutrition and FGF21 has been proposed a marker for protein insufficiency, the higher levels of FGF21 in patients with cachexia anorexia syndrome might be partly explained by insufficient protein intake. In order to investigate the acute response of FGF21 to different nutritional stimuli, a dietary challenge with a parallel group design was conducted. Here, healthy older (65-85 years) and younger (18-35 years) adults were randomized to one of four test meals: a dextrose drink, a high carbohydrate, high fat or high protein meal. Over the course of four hours, postprandial FGF21 concentrations (dynamics) were assessed and the FGF21 response (incremental area under the curve) to each test meal was examined.. In a sub-group of older and younger women, also the adiponectin response was investigated, as adiponectin is a known mediator of FGF21 effects on glucose and lipid metabolism. The dietary meal challenge revealed that dextrose and high carbohydrate intake result in higher FGF21 concentrations after four hours in older adults. This was partly explained by higher postprandial glucose concentrations in the old. For high fat ingestion no age differences were found. For the first time, acute FGF21 response to high protein intake was shown. Here, protein ingestion resulted in lower FGF21 concentrations in younger compared to older adults. Furthermore, sufficient protein intake, according to age-dependent recommendations, of the previous day, was associated with lower FGF21 concentrations in both age groups. The higher FGF21 response to dextrose ingestion resulted in a higher adiponectin response in older women, independent of fat mass, insulin resistance, triglyceride concentrations, inflammation and oxidative stress. Following the high fat meal, adiponectin concentrations declined in older women. Adiponectin response was not affected by meal composition in younger women. In summary, this thesis showed a positive association of FGF21 and cachexia anorexia syndrome with concomitant anorexia in older patients. Regarding the acute FGF21 response, a higher response following dextrose and carbohydrate ingestion was found in older compared with younger subjects. This might be attributed to a higher glucose response in older age. Furthermore, it was shown that the higher FGF21 response after dextrose ingestion possibly contributes to a higher adiponectin response in older women, independent of potential metabolic and inflammatory confounders. Acute protein ingestion resulted in a significant decrease in FGF21 concentrations. Moreover, protein intake of the previous day was inversely associated with fasting FGF21 concentrations. This might explain why FGF21 concentrations are higher in cachexia anorexia syndrome. These results therefore support the role of FGF21 as a sensor of protein restriction.},
  language  = {en}
}
@phdthesis{Grimmer2022,
  author    = {Grimmer, Benjamin},
  title     = {Pannexin 1},
  school      = {Universit{\"a}t Potsdam},
  pages     = {66, XXIX},
  year      = {2022},
  abstract  = {Hypoxic pulmonary vasoconstriction is an active alveolar hypoxia-caused physiological response redirecting pulmonary blood flow from poorly ventilated areas to better oxygenated lung regions in order to optimize oxygen supply. However, the signaling pathways underlying this pulmonary vascular response remain an area under investigation. In the present study I investigated the functional relevance of Pannexin 1 (Panx1)-mediated ATP release in hypoxic pulmonary vasoconstriction and chronic hypoxic pulmonary hypertension using murine isolated perfused lungs, chronic hypoxic mice, and pulmonary artery smooth muscle cell culture. In isolated mouse lungs, switch to hypoxic gas induced a marked increase in pulmonary artery pressure. Pharmacological inhibition of Panx1 using probenecid, Panx1 specific inhibitory peptide (10Panx1) or spironolactone as well as genetic deletion of Panx1 in smooth muscle cells diminished hypoxic pulmonary vasoconstriction in isolated perfused mouse lungs. Fura-2 imaging revealed a reduced Ca2+ response to hypoxia in pulmonary artery smooth muscle cells treated with spironolactone or 10Panx1. Although these findings suggested an important role of Panx1 in HPV, neither smooth muscle cell nor endothelial cell specific genetic deletion of Panx1 prevented the development of pulmonary hypertension in chronic hypoxic mice. Surprisingly, hypoxia did not induce ATP release and inhibition of purinergic receptors or ATP degradation by ATPase failed to decrease the pulmonary vasoconstriction response to hypoxia in isolated perfused mouse lungs. However, Panx1 antagonism as well as TRPV4 inhibition prevented the hypoxia-induced increase in intracellular Ca2+ concentration in pulmonary artery smooth muscle cells in an additive manner suggesting that Panx1 might modulate intracellular Ca2+ signaling independently of the ATP-P2-TRPV4 signaling axis. In line with this assumption, overexpression of Panx1 in HeLa cells increased intracellular Ca2+ concentrations in response to acute hypoxia. Conclusion: In this study I identifiy Panx1 as novel regulator of HPV.. Yet, the role of Panx1 was not attributable to the release of ATP and downstream P2 signaling pathways or activation of TRPV4 but rathter relates to a role of Panx1 as indirect or direct modulator of the Ca2+ response to hypoxia in PASMCs. Genetic deletion of Panx1 did not influence the development of chronic hypoxic pulmonary hypertension in mice.},
  language  = {en}
}
@phdthesis{Engel2021,
  author    = {Engel, Anika},
  title     = {Endocrine effects of plasticizers and the development of a breast cell-based toxicity screening system},
  doi       = {10.25932/publishup-53117},
  school      = {Universit{\"a}t Potsdam},
  pages     = {VIII, 89},
  year      = {2021},
  abstract  = {Humans are frequently exposed to a variety of endocrine disrupting chemicals (EDCs), which can cause harmful effects, e.g. disturbance of growth, development and reproduction, and cancer (UBA, 2016). EDCs are often components of synthetically manufactured products. Materials made of plastics, building materials, electronic items, textiles or cosmetic products can be particularly contaminated (Ain et al., 2021). One group of EDCs that has gained increased interest in recent years is phthalates. They are used as plasticizers in plastic materials to which people are daily exposed to. Phthalate plasticizers exert their harmful effects among others via activation of the estrogen receptor α (ERα), the estrogen receptor β (ERβ) and via inhibition of the androgen receptor (AR). Some phthalates have already been classified by the EU as Cancerogenic-, Mutagenic-, Reprotoxic- (CMR) substances and their use in industry has been restricted. After oral ingestion, phthalates are metabolized and are finally excreted with the urine. Numerous toxicological studies exist on phthalates, but mainly with the parent substances, not with their primary and secondary metabolites. In the course of the restriction of phthalates by the EU, the phthalate-free plasticizer di-isononylcyclohexane-1,2-dicarboxylate (DINCH®), was introduced to the market. So far, almost no toxicologically relevant properties have been identified for DINCH®. However, the effects of DINCH® have only been studied in animal experiments and, as with phthalates, almost exclusively with the parent substance. However, toxic effects of a particular compound may be induced by its metabolites and not by the parent compound itself. Therefore, potential endocrine effects of 15 phthalates, 19 phthalate metabolites, DINCH®, and five of its metabolites were investigated using reporter gene assays on the ERα, ERβ, and the AR. In addition, studies of the influence of some selected plasticizers on peroxisome proliferator-activated receptor α (PPARα) and peroxisome proliferator-activated receptor γ (PPARγ) activity were performed. Furthermore, a H295R steroidogenesis assay was performed to determine the influence of DINCH® and its metabolites on estradiol or testosterone synthesis. Analysis of the experiments shows that the phthalates either stimulated or inhibited ERα and ERβ activity and inhibited AR activity, whereas the phthalate metabolites did not affect the activity of these human hormone receptors. In contrast, metabolites of di-(2-ethylhexyl) phthalate (DEHP) stimulated transactivation of the human PPARα and PPARγ in analogous reporter gene assays, although DEHP itself did not activate these nuclear receptors. Therefore, primary and secondary phthalate metabolites appear to exert different effects at the molecular level compared to the parent compounds. Similarly, the results showed that the phthalate-free plasticizer DINCH® itself did not affect the activity of ERα, ERβ, AR, PPARα and PPARγ, while the DINCH® metabolites were shown to activate all these receptors. In the case of AR, DINCH® metabolites mainly enhanced AR activity stimulated by dihydrotestosterone (DHT). In the H295R steroidogenesis assay, neither DINCH® nor any of its metabolites affected estradiol or testosterone synthesis. Primary and secondary metabolites of DINCH® thus exert different effects at the molecular level than DINCH® itself. However, all these in vitro effects of DINCH® metabolites were observed only at high concentrations, which were about three orders of magnitude higher than the reported DINCH® metabolite concentrations in human urine. Therefore, the in vitro data does not support the assumption that DINCH® or any of the metabolites studied could have significant endocrine effects in vivo at relevant exposure levels in humans. Following the demonstration of direct and indirect endocrine effects of the studied plasticizers, a new effect-based in vitro 3D screening tool for toxicity assays of non-genotoxic carcinogens was developed using estrogen receptor-negative (ER-) MCF10-A cells and estrogen receptor-positive (ER+) MCF-12A cells. This arose from the background that breast cancer is the most common cancer occurring in women and estrogenic substances, such as phthalates, can probably influence the disease. The human mammary epithelial cell lines MCF-10A and MCF-12A form well-differentiated acini-like structures when cultured in three-dimensional Matrigel culture for a period of 20 days. The model should make it possible to detect substance effects on cell differentiation and growth, on mammary cell acini, and to differentiate between estrogenic and non-estrogenic effects at the same time. In the present study, both cell lines were tested for their suitability as an effect-based in vitro assay system for non-genotoxic carcinogens. An Automated Acinus Detection And Morphological Evaluation (ADAME) software solution has been developed for automatic acquisition of acinus images and determination of morphological parameters such as acinus size, lumen size, and acinus roundness. Several test substances were tested for their ability to affect acinus formation and cellular differentiation. Human epithelial growth factor (EGF) stimulated acinus growth for both cell lines, while all trans retinoic acid (RA) inhibited acinar growth. The potent estrogen 17β-estradiol had no effect on acinus formation of MCF-10A cells but resulted in larger MCF-12A acini. Thus, the parallel use of both cell lines together with the developed high content screening and evaluation tool allows the rapid identification of the estrogenic and cancerogenic properties of a given test compound. The morphogenesis of the acini was only slightly affected by the test substances. On the one hand, this suggests a robust test system, on the other hand, it probably cannot detect low-potent estrogenic compounds such as phthalates or DINCH®. The advantage of the robustness of the system, however, may be that vast numbers of "positive" results with questionable biological relevance could be avoided, such as those observed in sensitive reporter gene assays.},
  language  = {en}
}
@phdthesis{Wandt2021,
  author    = {Wandt, Viktoria Klara Veronika},
  title     = {Trace elements, ageing, and sex},
  school      = {Universit{\"a}t Potsdam},
  pages     = {iii, 204},
  year      = {2021},
  language  = {en}
}
@phdthesis{Reichmann2021,
  author    = {Reichmann, Robin},
  title     = {Novel applications of machine learning techniques in epidemiology of age-related diseases},
  school      = {Universit{\"a}t Potsdam},
  pages     = {164, xlv},
  year      = {2021},
  language  = {en}
}
@phdthesis{Klauder2021,
  author    = {Klauder, Julia},
  title     = {Makrophagenaktivierung durch Hyperinsulin{\"a}mie als Ausl{\"o}ser eines Teufelkreises der Entz{\"u}ndung im Kontext des metabolischen Syndroms},
  doi       = {10.25932/publishup-52019},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-520199},
  school      = {Universit{\"a}t Potsdam},
  pages     = {IX, 227},
  year      = {2021},
  abstract  = {Insulinresistenz ist ein zentraler Bestandteil des metabolischen Syndroms und tr{\"a}gt maßgeblich zur Ausbildung eines Typ-2-Diabetes bei. Eine m{\"o}gliche Ursache f{\"u}r die Entstehung von Insulinresistenz ist eine chronische unterschwellige Entz{\"u}ndung, welche ihren Ursprung im Fettgewebe {\"u}bergewichtiger Personen hat. Eingewanderte Makrophagen produzieren vermehrt pro-inflammatorische Mediatoren, wie Zytokine und Prostaglandine, wodurch die Konzentrationen dieser Substanzen sowohl lokal als auch systemisch erh{\"o}ht sind. Dar{\"u}ber hinaus weisen {\"u}bergewichtige Personen einen gest{\"o}rten Fetts{\"a}uremetabolismus und eine erh{\"o}hte Darmpermeabilit{\"a}t auf. Ein gesteigerter Flux an freien Fetts{\"a}uren vom Fettgewebe in andere Organe f{\"u}hrt zu einer lokalen Konzentrationssteigerung in diesen Organen. Eine erh{\"o}hte Darmpermeabilit{\"a}t erleichtert das Eindringen von Pathogenen und anderer k{\"o}rperfremder Substanzen in den K{\"o}rper. Ziel dieser Arbeit war es, zu untersuchen, ob hohe Konzentrationen von Insulin, des bakteriellen Bestandteils Lipopolysaccharid (LPS) oder der freien Fetts{\"a}ure Palmitat eine Entz{\"u}ndungsreaktion in Makrophagen ausl{\"o}sen oder verst{\"a}rken k{\"o}nnen und ob diese Entz{\"u}ndungsantwort zur Ausbildung einer Insulinresistenz beitragen kann. Weiterhin sollte untersucht werden, ob Metabolite und Signalsubstanzen, deren Konzentrationen beim metabolischen Syndrom erh{\"o}ht sind, die Produktion des Prostaglandins (PG) E2 beg{\"u}nstigen k{\"o}nnen und ob dieses wiederum die Entz{\"u}ndungsreaktion und seine eigene Produktion in Makrophagen regulieren kann. Um den Einfluss dieser Faktoren auf die Produktion pro-inflammatorischer Mediatoren in Makrophagen zu untersuchen, wurden Monozyten-artigen Zelllinien und prim{\"a}re humane Monozyten, welche aus dem Blut gesunder Probanden isoliert wurden, in Makrophagen differenziert und mit Insulin, LPS, Palmitat und/ oder PGE2 inkubiert. {\"U}berdies wurden prim{\"a}re Hepatozyten der Ratte isoliert und mit {\"U}berst{\"a}nden Insulin-stimulierter Makrophagen inkubiert, um zu untersuchen, ob die Entz{\"u}ndungsanwort in Makrophagen an der Ausbildung einer Insulinresistenz in Hepatozyten beteiligt ist. Insulin induzierte die Expression pro-inflammatorischer Zytokine in Makrophagen-artigen Zelllinien wahrscheinlich vorrangig {\"u}ber den Phosphoinositid-3-Kinase (PI3K)-Akt-Signalweg mit anschließender Aktiverung des Transkriptionsfaktors NF-κB (nuclear factor 'kappa-light-chain-enhancer' of activated B-cells). Die dabei ausgesch{\"u}tteten Zytokine hemmten in prim{\"a}ren Hepatozyten der Ratte die Insulin-induzierte Expression der Glukokinase durch {\"U}berst{\"a}nde Insulin-stimulierter Makrophagen. Auch LPS oder Palmitat, deren lokale Konzentrationen im Zuge des metabolischen Syndroms erh{\"o}ht sind, waren in der Lage, die Expression pro-inflammatorischer Zytokine in Makrophagen-artigen Zelllinien zu stimulieren. W{\"a}hrend LPS seine Wirkung, laut Literatur, unbestritten {\"u}ber eine Aktivierung des Toll-{\"a}hnlichen Rezeptors (toll-like receptor; TLR) 4 vermittelt, scheint Palmitat jedoch weitestgehend TLR4-unabh{\"a}ngig wirken zu k{\"o}nnen. Vielmehr schien die de novo-Ceramidsynthese eine entscheidene Rolle zu spielen. Dar{\"u}ber hinaus verst{\"a}rkte Insulin sowohl die LPS- als auch die Palmitat-induzierte Ent-z{\"u}ndungsantwort in beiden Zelllinien. Die in Zelllinien gewonnenen Ergebnisse wurden gr{\"o}ßtenteils in prim{\"a}ren humanen Makrophagen best{\"a}tigt. Desweiteren induzierten sowohl Insulin als auch LPS oder Palmitat die Produktion von PGE2 in den untersuchten Makrophagen. Die Daten legen nahe, dass dies auf eine gesteigerte Expression PGE2-synthetisierender Enzyme zur{\"u}ckzuf{\"u}hren ist. PGE2 wiederum hemmte auf der einen Seite die Stimulus-abh{\"a}ngige Expression des pro-inflammatorischen Zytokins Tumornekrosefaktor (TNF) α in U937-Makrophagen. Auf der anderen Seite verst{\"a}rkte es jedoch die Expression der pro-inflammatorischen Zytokine Interleukin- (IL-) 1β und IL-8. Dar{\"u}ber hinaus verst{\"a}rkte es die Expression von IL-6-Typ-Zytokinen, welche sowohl pro- als auch anti-inflammatorisch wirken k{\"o}nnen. Außerdem vest{\"a}rkte PGE2 die Expression PGE2-synthetisierender Enzyme. Es scheint daher in der Lage zu sein, seine eigene Synthese zu verst{\"a}rken. Zusammenfassend kann die Freisetzung pro-inflammatorischer Mediatoren aus Makro-phagen im Zuge einer Hyperinsulin{\"a}mie die Entstehung einer Insulinresistenz beg{\"u}nstigen. Insulin ist daher in der Lage, einen Teufelskreis der immer st{\"a}rker werdenden Insulin-resistenz in Gang zu setzen. Auch Metabolite und Signalsubstanzen, deren Konzentrationen beim metabolischen Syndrom erh{\"o}ht sind (zum Beispiel LPS, freie Fetts{\"a}uren und PGE2), l{\"o}sten Entz{\"u}ndungsantworten in Makrophagen aus. Das wechselseitige Zusammenspiel von Insulin und diesen Metaboliten und Signalsubstanzen l{\"o}ste eine st{\"a}rkere Entz{\"u}ndungsantwort in Makrophagen aus als jeder der Einzelkomponenten. Die dadurch freigesetzten Zytokine k{\"o}nnten zur Manifestation einer Insulinresistenz und des metabolischen Syndroms beitragen.},
  language  = {de}
}
@phdthesis{Saussenthaler2021,
  author    = {Saussenthaler, Sophie},
  title     = {The impact of DNA methylation on susceptibility to typ 2 diabetes in NZO mice},
  school      = {Universit{\"a}t Potsdam},
  pages     = {XIX, 150},
  year      = {2021},
  abstract  = {The development of type 2 diabetes (T2D) is driven by genetic as well as life style factors. However, even genetically identical female NZO mice on a high-fat diet show a broad variation in T2D onset. The main objective of this study was to elucidate and investigate early epigenetic determinants of type 2 diabetes. Prior to other experiments, early fat content of the liver (<55.2 HU) in combination with blood glucose concentrations (>8.8 mM) were evaluated as best predictors of diabetes in NZO females. Then, DNA methylome and transcriptome were profiled to identify molecular pathophysiological changes in the liver before diabetes onset. The major finding of this thesis is that alterations in the hepatic DNA methylome precede diabetes onset. Of particular interest were 702 differentially methylated regions (DMRs), of which 506 DMRs had genic localization. These inter-individual DMRs were enriched by fivefold in the KEGG pathway type 2 diabetes mellitus, independent of the level of gene expression, demonstrating an epigenetic predisposition toward diabetes. Interestingly, among the list of hepatic DMRs, eleven DMRs were associated with known imprinted genes in the mouse genome. Thereby, six DMRs (Nap1l5, Mest, Plagl1, Gnas, Grb10 and Slc38a4) localized to imprinting control regions, including five iDMRs that exhibited hypermethylation in livers of diabetes-prone mice. This suggests that gain of DNA methylation in multiple loci of the paternal alleles has unfavourable metabolic consequences for the offspring. Further, the comparative liver transcriptome analysis demonstrated differences in expression levels of 1492 genes related to metabolically relevant pathways, such as citrate cycle and fatty acid metabolism. The integration of hepatic transcriptome and DNA methylome indicated that 449 differentially expressed genes were potentially regulated by DNA methylation, including genes implicated in insulin signaling. In addition, liver transcriptomic profiling of diabetes-resistant and diabetes-prone mice revealed a potential transcriptional dysregulation of 17 hepatokines, in particular Hamp. The hepatic expression of Hamp was decreased by 52\% in diabetes-prone mice, on account of an increase in DNA methylation of promoter CpG-118. Hence, HAMP protein levels were lower in mice prone to develop diabetes, which correlated to higher liver triglyceride levels.. In sum, the identified DNA methylation changes appear to collectively favor the initiation and progression of diabetes in female NZO mice. In near future, epigenetic biomarkers are likely to contribute to improved diagnosis for T2D.},
  language  = {en}
}
@phdthesis{Schjeide2021,
  author    = {Schjeide, Brit-Maren},
  title     = {Development and characterization of the MoN-Light BoNT assay to determine the toxicity of botulinum neurotoxin in motor neurons differentiated from CRISPR-modified induced pluripotent stem cells},
  doi       = {10.25932/publishup-51627},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-516278},
  school      = {Universit{\"a}t Potsdam},
  pages     = {e, xviii, 265},
  year      = {2021},
  abstract  = {Botulinum neurotoxin (BoNT) is produced by the anaerobic bacterium Clostridium botulinum. It is one of the most potent toxins found in nature and can enter motor neurons (MN) to cleave proteins necessary for neurotransmission, resulting in flaccid paralysis. The toxin has applications in both traditional and esthetic medicine. Since BoNT activity varies between batches despite identical protein concentrations, the activity of each lot must be assessed. The gold standard method is the mouse lethality assay, in which mice are injected with a BoNT dilution series to determine the dose at which half of the animals suffer death from peripheral asphyxia. Ethical concerns surrounding the use of animals in toxicity testing necessitate the creation of alternative model systems to measure the potency of BoNT. Prerequisites of a successful model are that it is human specific; it monitors the complete toxic pathway of BoNT; and it is highly sensitive, at least in the range of the mouse lethality assay. One model system was developed by our group, in which human SIMA neuroblastoma cells were genetically modified to express a reporter protein (GLuc), which is packaged into neurosecretory vesicles, and which, upon cellular depolarization, can be released - or inhibited by BoNT - simultaneously with neurotransmitters. This assay has great potential, but includes the inherent disadvantages that the GLuc sequence was randomly inserted into the genome and the tumor cells only have limited sensitivity and specificity to BoNT. This project aims to improve these deficits, whereby induced pluripotent stem cells (iPSCs) were genetically modified by the CRISPR/Cas9 method to insert the GLuc sequence into the AAVS1 genomic safe harbor locus, precluding genetic disruption through non-specific integrations. Furthermore, GLuc was modified to associate with signal peptides that direct to the lumen of both large dense core vesicles (LDCV), which transport neuropeptides, and synaptic vesicles (SV), which package neurotransmitters. Finally, the modified iPSCs were differentiated into motor neurons (MNs), the true physiological target of BoNT, and hypothetically the most sensitive and specific cells available for the MoN-Light BoNT assay. iPSCs were transfected to incorporate one of three constructs to direct GLuc into LDCVs, one construct to direct GLuc into SVs, and one "no tag" GLuc control construct. The LDCV constructs fused GLuc with the signal peptides for proopiomelanocortin (hPOMC-GLuc), chromogranin-A (CgA-GLuc), and secretogranin II (SgII-GLuc), which are all proteins found in the LDCV lumen. The SV construct comprises a VAMP2-GLuc fusion sequence, exploiting the SV membrane-associated protein synaptobrevin (VAMP2). The no tag GLuc expresses GLuc non-specifically throughout the cell and was created to compare the localization of vesicle-directed GLuc. The clones were characterized to ensure that the GLuc sequence was only incorporated into the AAVS1 safe harbor locus and that the signal peptides directed GLuc to the correct vesicles. The accurate insertion of GLuc was confirmed by PCR with primers flanking the AAVS1 safe harbor locus, capable of simultaneously amplifying wildtype and modified alleles. The PCR amplicons, along with an insert-specific amplicon from candidate clones were Sanger sequenced to confirm the correct genomic region and sequence of the inserted DNA. Off-target integrations were analyzed with the newly developed dc-qcnPCR method, whereby the insert DNA was quantified by qPCR against autosomal and sex-chromosome encoded genes. While the majority of clones had off-target inserts, at least one on-target clone was identified for each construct. Finally, immunofluorescence was utilized to localize GLuc in the selected clones. In iPSCs, the vesicle-directed GLuc should travel through the Golgi apparatus along the neurosecretory pathway, while the no tag GLuc should not follow this pathway. Initial analyses excluded the CgA-GLuc and SgII-GLuc clones due to poor quality protein visualization. The colocalization of GLuc with the Golgi was analyzed by confocal microscopy and quantified. GLuc was strongly colocalized with the Golgi in the hPOMC-GLuc clone (r = 0.85±0.09), moderately in the VAMP2-GLuc clone (r = 0.65±0.01), and, as expected, only weakly in the no tag GLuc clone (r = 0.44±0.10). Confocal microscopy of differentiated MNs was used to analyze the colocalization of GLuc with proteins associated with LDCVs and SVs, SgII in the hPOMC-GLuc clone (r = 0.85±0.08) and synaptophysin in the VAMP2-GLuc clone (r = 0.65±0.07). GLuc was also expressed in the same cells as the MN-associated protein, Islet1. A significant portion of GLuc was found in the correct cell type and compartment. However, in the MoN-Light BoNT assay, the hPOMC-GLuc clone could not be provoked to reliably release GLuc upon cellular depolarization. The depolarization protocol for hPOMC-GLuc must be further optimized to produce reliable and specific release of GLuc upon exposure to a stimulus. On the other hand, the VAMP2-GLuc clone could be provoked to release GLuc upon exposure to the muscarinic and nicotinic agonist carbachol. Furthermore, upon simultaneous exposure to the calcium chelator EGTA, the carbachol-provoked release of GLuc could be significantly repressed, indicating the detection of GLuc was likely associated with vesicular fusion at the presynaptic terminal. The application of the VAMP2-GLuc clone in the MoN-Light BoNT assay must still be verified, but the results thus far indicate that this clone could be appropriate for the application of BoNT toxicity assessment.},
  language  = {en}
}
@phdthesis{Burkhardt2021,
  author    = {Burkhardt, Wiebke},
  title     = {Role of dietary sulfonates in the stimulation of gut bacteria promoting intestinal inflammation},
  doi       = {10.25932/publishup-51368},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-513685},
  school      = {Universit{\"a}t Potsdam},
  pages     = {XX, 79, XXXIX},
  year      = {2021},
  abstract  = {The interplay between intestinal microbiota and host has increasingly been recognized as a major factor impacting health. Studies indicate that diet is the most influential determinant affecting the gut microbiota. A diet rich in saturated fat was shown to stimulate the growth of the colitogenic bacterium Bilophila wadsworthia by enhancing the secretion of the bile acid taurocholate (TC). The sulfonated taurine moiety of TC is utilized as a substrate by B. wadsworthia. The resulting overgrowth of B. wadsworthia was accompanied by an increased incidence and severity of colitis in interleukin (IL)-10-deficient mice, which are genetically prone to develop inflammation. Based on these findings, the question arose whether the intake of dietary sulfonates also stimulates the growth of B. wadsworthia and thereby promotes intestinal inflammation in genetically susceptible mice. Dietary sources of sulfonates include green vegetables and cyanobacteria, which contain the sulfolipids sulfoquinovosyl diacylglycerols (SQDG) in considerable amounts. Based on literature reports, the gut commensal Escherichia coli is able to release sulfoquinovose (SQ) from SQDG and in further steps, convert SQ to 2,3-dihydroxypropane-1-sulfonate (DHPS) and dihydroxyacetone phosphate. DHPS may then be utilized as a growth substrate by B. wadsworthia, which results in the formation of sulfide. Both, sulfide formation and a high abundance of B. wadsworthia have been associated with intestinal inflammation. In the present study, conventional IL-10-deficient mice were fed either a diet supplemented with the SQDG-rich cyanobacterium Spirulina (20\%, SD) or a control diet. In addition SQ, TC, or water were orally applied to conventional or gnotobiotic IL-10-deficient mice. The gnotobiotic mice harbored a simplified human intestinal microbiota (SIHUMI) either with or without B. wadsworthia. During the intervention period, the body weight of the mice was monitored, the colon permeability was assessed and fecal samples were collected. After the three-week intervention, the animals were examined with regard to inflammatory parameters, microbiota composition and sulfonate concentrations in different intestinal sites. None of the mice treated with the above-mentioned sulfonates showed weight loss or intestinal inflammation. Solely mice fed SD or gavaged with TC displayed a slight immune response. These mice also displayed an altered microbiota composition, which was not observed in mice gavaged with SQ. The abundance of B. wadsworthia was strongly reduced in mice fed SD, while that of mice treated with SQ or TC was in part slightly increased. The intestinal SQ-concentration was elevated in mice orally treated with SD or SQ, whereas neither TC nor taurine concentrations were consistently elevated in mice gavaged with TC. Additional colonization of SIHUMI mice with B. wadsworthia resulted in a mild inflammatory response, but only in mice treated with TC. In general, TC-mediated effects on the immune system and abundance of B. wadsworthia were not as strong as described in the literature. In summary, neither the tested dietary sulfonates nor TC led to bacteria-induced intestinal inflammation in the IL-10-deficient mouse model, which was consistently observed in both conventional and gnotobiotic mice. For humans, this means that foods containing SQDG, such as spinach or Spirulina, do not increase the risk of intestinal inflammation.},
  language  = {en}
}
@phdthesis{Baeseler2021,
  author    = {Baeseler, Jessica},
  title     = {Trace element effects on longevity and neurodegeneration with focus on C. elegans},
  school      = {Universit{\"a}t Potsdam},
  pages     = {X,114,VIII},
  year      = {2021},
  abstract  = {The trace elements zinc and manganese are essential for human health, especially due to their enzymatic and protein stabilizing functions. If these elements are ingested in amounts exceeding the requirements, regulatory processes for maintaining their physiological concentrations (homeostasis) can be disturbed. Those homeostatic dysregulations can cause severe health effects including the emergence of neurodegenerative disorders such as Parkinson's disease (PD). The concentrations of essential trace elements also change during the aging process. However, the relations of cause and consequence between increased manganese and zinc uptake and its influence on the aging process and the emergence of the aging-associated PD are still rarely understood. This doctoral thesis therefore aimed to investigate the influence of a nutritive zinc and/or manganese oversupply on the metal homeostasis during the aging process. For that, the model organism Caenorhabditis elegans (C. elegans) was applied. This nematode suits well as an aging and PD model due to properties such as its short life cycle and its completely sequenced, genetically amenable genome. Different protocols for the propagation of zinc- and/or manganese-supplemented young, middle-aged and aged C. elegans were established. Therefore, wildtypes, as well as genetically modified worm strains modeling inheritable forms of parkinsonism were applied. To identify homeostatic and neurological alterations, the nematodes were investigated with different methods including the analysis of total metal contents via inductively-coupled plasma tandem mass spectrometry, a specific probe-based method for quantifying labile zinc, survival assays, gene expression analysis as well as fluorescence microscopy for the identification and quantification of dopaminergic neurodegeneration.. During aging, the levels of iron, as well as zinc and manganese increased.. Furthermore, the simultaneous oversupply with zinc and manganese increased the total zinc and manganese contents to a higher extend than the single metal supplementation. In this relation the C. elegans metallothionein 1 (MTL-1) was identified as an important regulator of metal homeostasis. The total zinc content and the concentration of labile zinc were age-dependently, but differently regulated. This elucidates the importance of distinguishing these parameters as two independent biomarkers for the zinc status. Not the metal oversupply, but aging increased the levels of dopaminergic neurodegeneration. Additionally, nearly all these results yielded differences in the aging-dependent regulation of trace element homeostasis between wildtypes and PD models. This confirms that an increased zinc and manganese intake can influence the aging process as well as parkinsonism by altering homeostasis although the underlying mechanisms need to be clarified in further studies.},
  language  = {en}
}
@phdthesis{Mancini2021,
  author    = {Mancini, Carola},
  title     = {Analysis of the effects of age-related changes of metabolic flux on brown adipocyte formation and function},
  doi       = {10.25932/publishup-51266},
  school      = {Universit{\"a}t Potsdam},
  pages     = {xvii, 134},
  year      = {2021},
  abstract  = {Brown adipose tissue (BAT) is responsible for non-shivering thermogenesis, thereby allowing mammals to maintain a constant body temperature in a cold environment. Thermogenic capacity of this tissue is due to a high mitochondrial density and expression of uncoupling protein 1 (UCP1), a unique brown adipocyte marker which dissipates the mitochondrial proton gradient to produce heat instead of ATP. BAT is actively involved in whole-body metabolic homeostasis and during aging there is a loss of classical brown adipose tissue with concomitantly reduced browning capacity of white adipose tissue. Therefore, an age-dependent decrease of BAT-related energy expenditure capacity may exacerbate the development of metabolic diseases, including obesity and type 2 diabetes mellitus. Given that direct effects of age-related changes of BAT-metabolic flux have yet to be unraveled, the aim of the current thesis is to investigate potential metabolic mechanisms involved in BAT-dysfunction during aging and to identify suitable metabolic candidates as functional biomarkers of BAT-aging. To this aim, integration of transcriptomic, metabolomic and proteomic data analyses of BAT from young and aged mice was performed, and a group of candidates with age-related changes was revealed. Metabolomic analysis showed age-dependent alterations of metabolic intermediates involved in energy, nucleotide and vitamin metabolism, with major alterations regarding the purine nucleotide pool. These data suggest a potential role of nucleotide intermediates in age-related BAT defects. In addition, the screening of transcriptomic and proteomic data sets from BAT of young and aged mice allowed identification of a 60-kDa lysophospholipase, also known as L-asparaginase (Aspg), whose expression declines during BAT-aging. Involvement of Aspg in brown adipocyte thermogenic function was subsequently analyzed at the molecular level using in vitro approaches and animal models. The findings revealed sensitivity of Aspg expression to β3-adrenergic activation via different metabolic cues, including cold exposure and treatment with β3-adrenergic agonist CL. To further examine ASPG function in BAT, an over-expression model of Aspg in a brown adipocyte cell line was established and showed that these cells were metabolically more active compared to controls, revealing increased expression of the main brown-adipocyte specific marker UCP1, as well as higher lipolysis rates. An in vitro loss-of-function model of Aspg was also functionally analyzed, revealing reduced brown adipogenic characteristics and an impaired lipolysis, thus confirming physiological relevance of Aspg in brown adipocyte function. Characterization of a transgenic mouse model with whole-body inactivation of the Aspg gene (Aspg-KO) allowed investigation of the role of ASPG under in vivo conditions, indicating a mild obesogenic phenotype, hypertrophic white adipocytes, impairment of the early thermogenic response upon cold-stimulation and dysfunctional insulin sensitivity. Taken together, these data show that ASPG may represent a new functional biomarker of BAT-aging that regulates thermogenesis and therefore a potential target for the treatment of age-related metabolic disease.},
  language  = {en}
}
@phdthesis{Rausch2021,
  author    = {Rausch, Ann-Kristin},
  title     = {Development of LC-MS/MS Multi-Methods for the Analysis of Contaminants and Residues},
  school      = {Universit{\"a}t Potsdam},
  pages     = {IX, 234, v},
  year      = {2021},
  abstract  = {Mycotoxins are secondary metabolites produced by several filamentous fungal species, thus occurring ubiquitously in the environment and food. While the heterogeneous group shows differences in their bioavailability and toxicity, the low-molecular-weight xenobiotics are capable of impacting human and animal health acutely and chronically. Therefore, maximum levels for the major mycotoxins in food and feed are regulated in the current European legislation. Besides free mycotoxins, naturally occurring modified mycotoxins are gaining more attention in recent years. Modified mycotoxins constitute toxins altered by plants, microorganisms, and living organisms in different metabolic pathways or food processing steps. The toxicological relevant compounds often co-occur with their free forms in infested food and feed. Thus, the toxins may contribute to the overall toxicity of mycotoxins, wherefore their presence and toxicity should be considered in risk assessment. Until now, however, there are no regulated limits for modified mycotoxins within the European Union. In this thesis, rapid, sensitive, and robust methods for the analysis of mycotoxins and their modified forms were developed and validated using state-of-the-art high performance liquid chromatography tandem mass spectrometry (LC-MS/MS) systems. Firstly, two analytical methods for determining 38 mycotoxins in cereals and 41 mycotoxins in beer were established since agricultural products count as the primary source of mycotoxin contamination. For the analysis of cereal samples, a QuEChERS- based extraction approach was pursued, while analytes from beer samples were extracted using an acetonitrile precipitation scheme. Validation in cereals, namely wheat, corn, rice, and barley, as well as in beer, demonstrated satisfactory results. To obtain information regarding the natural occurrence of mycotoxins in food products, the developed methods were applied to the analysis of several commercial samples partly produced worldwide. The Fusarium toxins deoxynivalenol and its conjugated metabolite deoxynivalenol-3-glucoside turned out to be the most abundant toxins. None of the other modified mycotoxins were quantified in the samples. However, one cereal sample showed traces of zearalenone- 14-sulfate below the limit of quantification. Moreover, pesticides, plant growth regulators, and tropane alkaloids were investigated in this thesis. Pesticides present biologically highly effective compounds applied in the environment to protect humans from the hazardous effects of pests. While plant growth regulators show similar functions, mainly improving agricultural production, tropane alkaloids are naturally occurring secondary metabolites mainly in the species of Solanaceae that may pose unintended poisoning of humans. The third part of the present thesis aimed to analyze cereal-relevant compounds simultaneously, wherefore a multi-method for the analysis of (modified) mycotoxins, pesticides, plant growth regulators, and tropane alkaloids was established. After processing the samples, this should be done in a single extraction step with subsequent one-time measurements. Various sample preparation procedures were compared, whereby an approach based on an acidified acetonitrile/water extraction, followed by an online clean-up, was finally chosen. The simultaneous determination of more than 350 analytes required an analytical tool that offered an increased resolving power, represented as an enhanced peak capacity, and the possibility of analyzing a broad polarity range. Thus, a two-dimensional LC-MS/MS system based on two different separation mechanisms that performed orthogonal to one another was used for the analysis. Validation of the developed method revealed good performance characteristics for most analytes, while subsequent application showed that 86\% of the samples were contaminated with at least one compound. In summary, this thesis provides novel insights into the analysis of food-relevant (modified) mycotoxins. Different sample preparation and LC-MS/MS approaches were introduced, resulting in the development of three new analytical methods. For the first time, such a high number of modified mycotoxins was included in multi-mycotoxin methods and a multi-method ranging both contaminants and residues. Although first steps towards the analysis of modified mycotoxins have been made, further research is needed to elucidate their (co-) occurrence and toxicological behavior in order to understand their relevance to human health in the future.},
  language  = {en}
}
@phdthesis{Hauffe2021,
  author    = {Hauffe, Robert},
  title     = {Investigating metabolic consequences of an HSP60 reduction during diet-induced obesity},
  doi       = {10.25932/publishup-50929},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-509294},
  school      = {Universit{\"a}t Potsdam},
  pages     = {xxi, 116},
  year      = {2021},
  abstract  = {The mitochondrial chaperone complex HSP60/HSP10 facilitates mitochondrial protein homeostasis by folding more than 300 mitochondrial matrix proteins. It has been shown previously that HSP60 is downregulated in brains of type 2 diabetic (T2D) mice and patients, causing mitochondrial dysfunction and insulin resistance. As HSP60 is also decreased in peripheral tissues in T2D animals, this thesis investigated the effect of overall reduced HSP60 in the development of obesity and associated co-morbidities. To this end, both female and male C57Bl/6N control (i.e. without further alterations in their genome, Ctrl) and heterozygous whole-body Hsp60 knock-out (Hsp60+/-) mice, which exhibit a 50 \% reduction of HSP60 in all tissues, were fed a normal chow diet (NCD) or a highfat diet (HFD, 60 \% calories from fat) for 16 weeks and were subjected to extensive metabolic phenotyping including indirect calorimetry, NMR spectroscopy, insulin, glucose and pyruvate tolerance tests, vena cava insulin injections, as well as histological and molecular analysis. Interestingly, NCD feeding did not result in any striking phenotype, only a mild increase in energy expenditure in Hsp60+/- mice. Exposing mice to a HFD however revealed an increased body weight due to higher muscle mass in female Hsp60+/- mice, with a simultaneous decrease in energy expenditure. Additionally, these mice displayed decreased fasting glycemia. Opposingly, male Hsp60+/- compared to control mice showed lower body weight gain due to decreased fat mass and an increased energy expenditure, strikingly independent of lean mass. Further, only male Hsp60+/- mice display improved HOMA-IR and Matsuda insulin sensitivity indices. Despite the opposite phenotype in regards to body weight development, Hsp60+/- mice of both sexes show a significantly higher cell number, as well as a reduction in adipocyte size in the subcutaneous and gonadal white adipose tissue (sc/gWAT). Curiously, this adipocyte hyperplasia - usually associated with positive aspects of WAT function - is disconnected from metabolic improvements, as the gWAT of male Hsp60+/- mice shows mitochondrial dysfunction, oxidative stress, and insulin resistance. Transcriptomic analysis of gWAT shows an up regulation of genes involved in macroautophagy. Confirmatory, expression of microtubuleassociated protein 1A/1B light chain 3B (LC3), as a protein marker of autophagy, and direct measurement of lysosomal activity is increased in the gWAT of male Hsp60+/- mice. In summary, this thesis revealed a novel gene-nutrient interaction. The reduction of the crucial chaperone HSP60 did not have large effects in mice fed a NCD, but impacted metabolism during DIO in a sex-specific manner, where, despite opposing body weight and body composition phenotypes, both female and male Hsp60+/- mice show signs of protection from high fat diet-induced systemic insulin resistance.},
  language  = {en}
}
@phdthesis{RodriguezSillke2021,
  author    = {Rodriguez-Sillke, Yasmina},
  title     = {Der Einfluss von Nahrungsmittelantigenen auf die mukosale sowie periphere Hom{\"o}ostase und Entz{\"u}ndung bei chronisch entz{\"u}ndlichen Darmerkrankungen},
  school      = {Universit{\"a}t Potsdam},
  pages     = {134},
  year      = {2021},
  language  = {de}
}
@phdthesis{Nieschalke2021,
  author    = {Nieschalke, Kai},
  title     = {Proteinaddukte und Urinmetaboliten des Nagetierkanzerogens Methyleugenol als Biomarker der Exposition},
  school      = {Universit{\"a}t Potsdam},
  pages     = {142, XLIV},
  year      = {2021},
  language  = {de}
}
@phdthesis{HaferkornStarke2021,
  author    = {Haferkorn-Starke, Robert Christian},
  title     = {Entwicklung eines Lebensmitteluntersuchungssystems f{\"u}r mikrobielle Erreger mit Hilfe molekularbiologischer Methoden},
  school      = {Universit{\"a}t Potsdam},
  pages     = {XVII, 239, vi},
  year      = {2021},
  language  = {de}
}
@phdthesis{LenihanGeels2020,
  author    = {Lenihan-Geels, Georgia Ngawai},
  title     = {The regulation of metabolic flexibility by p53 in skeletal muscle and brown adipose tissue},
  school      = {Universit{\"a}t Potsdam},
  year      = {2020},
  language  = {en}
}
@phdthesis{Alfine2021,
  author    = {Alfine, Eugenia},
  title     = {Investigation of Sirtuin 3 overexpression as a genetic model of fasting in hypothalamic neurons},
  school      = {Universit{\"a}t Potsdam},
  pages     = {134},
  year      = {2021},
  language  = {en}
}
@phdthesis{AgaBarfknecht2021,
  author    = {Aga-Barfknecht, Heja},
  title     = {Investigation of the phenotype and genetic variant(s) of the diabetes locus Nidd/DBA},
  school      = {Universit{\"a}t Potsdam},
  year      = {2021},
  abstract  = {Diabetes is a major public health problem with increasing global prevalence. Type 2 diabetes (T2D), which accounts for 90\% of all diagnosed cases, is a complex polygenic disease also modulated by epigenetics and lifestyle factors. For the identification of T2D-associated genes, linkage analyses combined with mouse breeding strategies and bioinformatic tools were useful in the past. In a previous study in which a backcross population of the lean and diabetes-prone dilute brown non-agouti (DBA) mouse and the obese and diabetes-susceptible New Zealand obese (NZO) mouse was characterized, a major diabetes quantitative trait locus (QTL) was identified on chromosome 4. The locus was designated non-insulin dependent diabetes from DBA (Nidd/DBA). The aim of this thesis was (i) to perform a detailed phenotypic characterization of the Nidd/DBA mice, (ii) to further narrow the critical region and (iii) to identify the responsible genetic variant(s) of the Nidd/DBA locus. The phenotypic characterization of recombinant congenic mice carrying a 13.6 Mbp Nidd/DBA fragment with 284 genes presented a gradually worsening metabolic phenotype. Nidd/DBA allele carriers exhibited severe hyperglycemia (~19.9 mM) and impaired glucose clearance at 12 weeks of age. Ex vivo perifusion experiments with islets of 13-week-old congenic mice revealed a tendency towards reduced insulin secretion in homozygous DBA mice. In addition, 16-week-old mice showed a severe loss of β-cells and reduced pancreatic insulin content. Pathway analysis of transcriptome data from islets of congenic mice pointed towards a downregulation of cell survival genes. Morphological analysis of pancreatic sections displayed a reduced number of bi-hormonal cells co-expressing glucagon and insulin in homozygous DBA mice, which could indicate a reduced plasticity of endocrine cells in response to hyperglycemic stress. Further generation and phenotyping of recombinant congenic mice enabled the isolation of a 3.3 Mbp fragment that was still able to induce hyperglycemia and contained 61 genes. Bioinformatic analyses including haplotype mapping, sequence and transcriptome analysis were integrated in order to further reduce the number of candidate genes and to identify the presumable causative gene variant. Four putative candidate genes (Ttc39a, Kti12, Osbpl9, Calr4) were defined, which were either differentially expressed or carried a sequence variant. In addition, in silico ChIP-Seq analyses of the 3.3 Mbp region indicated a high number of SNPs located in active regions of binding sites of β-cell transcription factors. This points towards potentially altered cis-regulatory elements that could be responsible for the phenotype conferred by the Nidd/DBA locus. In summary, the Nidd/DBA locus mediates impaired glucose homeostasis and reduced insulin secretion capacity which finally leads to β-cell death. The downregulation of cell survival genes and reduced plasticity of endocrine cells could further contribute to the β-cell loss. The critical region was narrowed down to a 3.3 Mbp fragment containing 61 genes, of which four might be involved in the development of the diabetogenic Nidd/DBA phenotype.},
  language  = {en}
}
@phdthesis{Martinez2020,
  author    = {Martinez, Maria Teresa Casta{\~n}o},
  title     = {Effects of Dietary Methionine and Protein Restriction on the Prevention and Treatment of Type 2 Diabetes},
  pages     = {100},
  year      = {2020},
  language  = {en}
}
@phdthesis{Winkelbeiner2020,
  author    = {Winkelbeiner, Nicola Lisa},
  title     = {Impact of element species on DNA repair processes},
  pages     = {XV, 182, iii},
  year      = {2020},
  language  = {en}
}
@phdthesis{Wolf2020,
  author    = {Wolf, Kristine},
  title     = {Produktentwicklung eines luteinhaltigen, kolloidalen Nahrungserg{\"a}nzungsmittels: physikochemische und ern{\"a}hrungsphysiologische Aspekte},
  doi       = {10.25932/publishup-48774},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-487743},
  school      = {Universit{\"a}t Potsdam},
  pages     = {xxi, 243},
  year      = {2020},
  abstract  = {Sekund{\"a}re Pflanzenstoffe und ihre gesundheitsf{\"o}rdernden Eigenschaften sind in den letzten zwei Jahrzehnten vielfach ern{\"a}hrungsphysiologisch untersucht und spezifische positive Effekte im humanen Organismus zum Teil sehr genau beschrieben worden. Zu den Carotinoiden z{\"a}hlend ist der sekund{\"a}re Pflanzenstoff Lutein insbesondere in der Pr{\"a}vention von ophthalmologischen Erkrankungen in den Mittelpunkt der Forschung ger{\"u}ckt. Das ausschließlich von Pflanzen und einigen Algen synthetisierte Xanthophyll wird {\"u}ber die pflanzliche Nahrung insbesondere gr{\"u}nes Blattgem{\"u}se in den humanen Organismus aufgenommen. Dort akkumuliert es bevorzugt im Makulapigment der Retina des menschlichen Auges und ist bedeutend im Prozess der Aufrechterhaltung der Funktionsf{\"a}higkeit der Photorezeptorzellen. Im Laufe des Alterns kann die Abnahme der Dichte des Makulapigments und der Abbau von Lutein beobachtet werden. Die dadurch eintretende Destabilisierung der Photorezeptorzellen im Zusammenhang mit einer ver{\"a}nderten Stoffwechsellage im alternden Organismus kann zur Auspr{\"a}gung der altersbedingten Makuladegeneration (AMD) f{\"u}hren. Die pathologische Symptomatik der Augenerkrankung reicht vom Verlust der Sehsch{\"a}rfe bis hin zum irreversiblen Erblinden. Da therapeutische Mittel ausschließlich ein Fortschreiten verhindern, bestehen hier Forschungsans{\"a}tze pr{\"a}ventive Maßnahmen zu finden. Die Supplementierung von luteinhaltigen Pr{\"a}paraten bietet dabei einen Ansatzpunkt. Auf dem Markt finden sich bereits Nahrungserg{\"a}nzungsmittel (NEM) mit Lutein in verschiedenen Applikationen. Limitierend ist dabei die Stabilit{\"a}t und Bioverf{\"u}gbarkeit von Lutein, welches teilweise kostenintensiv und mit unbekannter Reinheit zu erwerben ist. Aus diesem Grund w{\"a}re die Verwendung von Luteinestern als die pflanzliche Speicherform des Luteins im Rahmen eines NEMs vorteilhaft. Neben ihrer nat{\"u}rlichen, h{\"o}heren Stabilit{\"a}t sind Luteinester nachhaltig und kosteng{\"u}nstig einsetzbar. In dieser Arbeit wurden physikochemische und ern{\"a}hrungsphysiologisch relevante Aspekte in dem Produktentwicklungsprozess eines NEMs mit Luteinestern in einer kolloidalen Formulierung untersucht. Die bisher einzigartige Anwendung von Luteinestern in einem Mundspray sollte die Aufnahme des Wirkstoffes insbesondere f{\"u}r {\"a}ltere Menschen erleichtern und verbessern. Unter Beachtung der Ergebnisse und der ern{\"a}hrungsphysiologischen Bewertung sollten u.a. Empfehlungen f{\"u}r die Rezepturzusammensetzungen einer Miniemulsion (Emulsion mit Partikelgr{\"o}ßen <1,0 µm) gegeben werden. Eine Einsch{\"a}tzung der Bioverf{\"u}gbarkeit der Luteinester aus den entwickelten, kolloidalen Formulierungen konnte anhand von Studien zur Resorption- und Absorptionsverf{\"u}gbarkeit in vitro erm{\"o}glicht werden. In physikalischen Untersuchungen wurden zun{\"a}chst Basisbestandteile f{\"u}r die Formulierungen pr{\"a}zisiert. In ersten wirkstofffreien Musteremulsionen konnten ausgew{\"a}hlte {\"O}le als Tr{\"a}gerphase sowie Emulgatoren und L{\"o}slichkeitsvermittler (Peptisatoren) hinsichtlich ihrer Eignung zur Bereitstellung einer Miniemulsion physikalisch gepr{\"u}ft werden. Die beste Stabilit{\"a}t und optimale Eigenschaften einer Miniemulsion zeigten sich bei der Verwendung von MCT-{\"O}l (engl. medium chain triglyceride) bzw. Raps{\"o}l in der Tr{\"a}gerphase sowie des Emulgators Tween® 80 (Tween 80) allein oder in Kombination mit dem Molkenproteinhydrolysat Biozate® 1 (Biozate 1). Aus den physikalischen Untersuchungen der Musteremulsionen gingen die Pr{\"a}emulsionen als Prototypen hervor. Diese enthielten den Wirkstoff Lutein in verschiedenen Formen. So wurden Pr{\"a}emulsionen mit Lutein, mit Luteinestern sowie mit Lutein und Luteinestern konzipiert, welche den Emulgator Tween 80 oder die Kombination mit Biozate 1 enthielten. Bei der Herstellung der Pr{\"a}emulsionen f{\"u}hrte die Anwendung der Emulgiertechniken Ultraschall mit anschließender Hochdruckhomogenisation zu den gew{\"u}nschten Miniemulsionen. Beide eingesetzten Emulgatoren boten optimale Stabilisierungseffekte. Anschließend erfolgte die physikochemische Charakterisierung der Wirkstoffe. Insbesondere Luteinester aus Oleoresin erwiesen sich hier als stabil gegen{\"u}ber verschiedenen Lagerungsbedingungen. Ebenso konnte bei einer kurzzeitigen Behandlung der Wirkstoffe unter spezifischen mechanischen, thermischen, sauren und basischen Bedingungen eine Stabilit{\"a}t von Lutein und Luteinestern gezeigt werden. Die Zugabe von Biozate 1 bot dabei nur f{\"u}r Lutein einen zus{\"a}tzlichen Schutz. Bei l{\"a}ngerer physikochemischer Behandlung unterlagen die in den Miniemulsionen eingebrachten Wirkstoffe moderaten Abbauvorg{\"a}ngen. Markant war deren Sensitivit{\"a}t gegen{\"u}ber dem basischen Milieu. Im Rahmen der Rezepturentwicklung des NEMs war hier die Empfehlung, eine Miniemulsion mit einem leicht saurem pH-Milieu zum Schutz des Wirkstoffes durch kontrollierte Zugabe weiterer Inhaltstoffe zu gestalten. Im weiteren Entwicklungsprozess des NEMs wurden Fertigrezepturen mit dem Wirkstoff Luteinester aufgestellt. Die alleinige Anwendung des Emulgators Biozate 1 zeigte sich dabei als ungeeignet. Die weiterhin zur Verf{\"u}gung stehenden Fertigrezepturen enthielten in der {\"O}l-phase neben dem Wirkstoff das MCT-{\"O}L oder Raps{\"o}l sowie a-Tocopherol zur Stabilisierung. Die Wasserphase bestand aus dem Emulgator Tween 80 oder einer Kombination aus Tween 80 und Biozate 1. Zusatzstoffe waren zudem als mikrobiologischer Schutz Ascorbins{\"a}ure und Kaliumsorbat sowie f{\"u}r sensorische Effekte Xylitol und Orangenaroma. Die Anordnung der Basisrezeptur und das angewendete Emulgierverfahren lieferten stabile Miniemulsionen. Weiterhin zeigten langfristige Lagerungsversuche mit den Fertigrezepturen bei 4°C, dass eine Aufrechterhaltung der geforderten Luteinestermenge im Produkt gew{\"a}hrleistet war. Analoge Untersuchungen an einem luteinhaltigen, marktg{\"a}ngigen Pr{\"a}parat best{\"a}tigten dagegen eine bereits bei kurzfristiger Lagerung auftretende Instabilit{\"a}t von Lutein. Abschließend wurde durch Resorptions- und Absorptionsstudien in vitro mit den Pr{\"a}emulsionen und Fertigrezepturen die Bioverf{\"u}gbarkeit von Luteinestern gepr{\"u}ft. Nach Behandlung in einem etablierten in vitro Verdaumodell konnte eine geringf{\"u}gige Resorptionsverf{\"u}gbarkeit der Luteinester definiert werden. Limitiert war eine Micellarisierung des Wirkstoffes aus den konzipierten Formulierungen zu beobachten. Eine enzymatische Spaltung der Luteinester zu freiem Lutein wurde nur begrenzt festgestellt. Spezifit{\"a}t und Aktivit{\"a}t von entsprechenden hydrolytischen Lipasen sind als {\"a}ußerst gering gegen{\"u}ber Luteinestern zu bewerten. In sich anschließenden Zellkulturversuchen mit der Zelllinie Caco-2 wurden keine zytotoxischen Effekte durch die relevanten Inhaltsstoffe in den Pr{\"a}emulsionen gezeigt. Dagegen konnten eine Sensibilit{\"a}t gegen{\"u}ber den Fertigrezepturen beobachtet werden. Diese sollte im Zusammenhang mit Irritationen der Schleimh{\"a}ute des Magen-Darm-Traktes bedacht werden. Eine weniger komplexe Rezeptur k{\"o}nnte die beobachteten Einschr{\"a}nkungen m{\"o}glicherweise minimieren. Abschließende Absorptionsstudien zeigten, dass grunds{\"a}tzlich eine geringf{\"u}gige Aufnahme von vorrangig Lutein, aber auch Luteinmonoestern in den Enterocyten aus Miniemulsionen erfolgen kann. Dabei hatte weder Tween 80 noch Biozate 1 einen f{\"o}rderlichen Einfluss auf die Absorptionsrate von Lutein oder Luteinestern. Die Metabolisierung der Wirkstoffe durch vorherigen in vitro-Verdau steigerte die zellul{\"a}re Aufnahme von Wirkstoffen aus Formulierungen mit Lutein und Luteinestern gleichermaßen. Die beobachtete Aufnahme von Lutein und Luteinmonoestern in den Enterocyten scheint {\"u}ber passive Diffusion zu erfolgen, wobei auch der aktive Transport nicht ausgeschlossen werden kann. Dagegen k{\"o}nnen Luteindiester aufgrund ihrer Molek{\"u}lgr{\"o}ße nicht {\"u}ber den Weg der Micellarisierung und einfachen Diffusion in die Enterocyten gelangen. Ihre Aufnahme in die D{\"u}nndarmepithelzellen bedarf einer vorherigen hydrolytischen Spaltung durch spezifische Lipasen. Dieser Schritt limitiert wiederum die effektive Aufnahme der Luteinester in die Zellen bzw. stellt eine Einschr{\"a}nkung in ihrer Bioverf{\"u}gbarkeit im Vergleich zu freiem Lutein dar. Zusammenfassend konnte f{\"u}r die physikochemisch stabilen Luteinester eine geringe Bioverf{\"u}gbarkeit aus kolloidalen Formulierungen gezeigt werden. Dennoch ist die Verwendung als Wirkstoffquelle f{\"u}r den sekund{\"a}ren Pflanzenstoff Lutein in einem NEM zu empfehlen. Im Zusammenhang mit der Aufnahme von luteinreichen, pflanzlichen Lebensmitteln kann trotz der zu erwartenden geringen Bioverf{\"u}gbarkeit der Luteinester aus dem NEM ein Beitrag zur Verbesserung des Luteinstatus erreicht werden. Entsprechende Publikationen zeigten eindeutige Korrelationen zwischen der Aufnahme von luteinesterhaltigen Pr{\"a}paraten und einem Anstieg der Luteinkonzentration im Serum bzw. der Makulapigmentdichte in vivo. Die geringf{\"u}gig bessere Bioverf{\"u}gbarkeit von freiem Lutein steht im kritischen Zusammenhang mit seiner Instabilit{\"a}t und Kostenintensit{\"a}t. Bilanzierend wurde im Rahmen dieser Arbeit das marktg{\"a}ngige Produkt Vita Culus® konzipiert. Im Ausblick sollten humane Interventionsstudien mit dem NEM die abschließende Bewertung der Bioverf{\"u}gbarkeit von Luteinestern aus dem Pr{\"a}parat m{\"o}glich machen.},
  language  = {de}
}
@phdthesis{Schiborn2020,
  author    = {Schiborn, Catarina},
  title     = {Extension of the German Diabetes Risk Score with regard to risk communication and cardiovascular outcomes},
  school      = {Universit{\"a}t Potsdam},
  pages     = {218},
  year      = {2020},
  language  = {en}
}
@phdthesis{Finke2020,
  author    = {Finke, Hannah},
  title     = {Toxicological Characterization of Arsenolipids in vitro and Analysis of Global DNA (Hydroxy)methylation in the Context of Aging, Trace Element Status, and Genomic Stability},
  school      = {Universit{\"a}t Potsdam},
  pages     = {t, 222, XXVII},
  year      = {2020},
  language  = {de}
}
@phdthesis{Seebeck2020,
  author    = {Seebeck, Nicole},
  title     = {Regulation of the organokines FGF21 and chemerin by diet},
  doi       = {10.25932/publishup-47114},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-471140},
  school      = {Universit{\"a}t Potsdam},
  pages     = {i, 132},
  year      = {2020},
  abstract  = {The hepatokine FGF21 and the adipokine chemerin have been implicated as metabolic regulators and mediators of inter-tissue crosstalk. While FGF21 is associated with beneficial metabolic effects and is currently being tested as an emerging therapeutic for obesity and diabetes, chemerin is linked to inflammation-mediated insulin resistance. However, dietary regulation of both organokines and their role in tissue interaction needs further investigation. The LEMBAS nutritional intervention study investigated the effects of two diets differing in their protein content in obese human subjects with non-alcoholic fatty liver disease (NAFLD). The study participants consumed hypocaloric diets containing either low (LP: 10 EN\%, n = 10) or high (HP: 30 EN\%, n = 9) dietary protein 3 weeks prior to bariatric surgery. Before and after the intervention the participants were anthropometrically assessed, blood samples were drawn, and hepatic fat content was determined by MRS. During bariatric surgery, paired subcutaneous and visceral adipose tissue biopsies as well as liver biopsies were collected. The aim of this thesis was to investigate circulating levels and tissue-specific regulation of (1) FGF21 and (2) chemerin in the LEMBAS cohort. The results were compared to data obtained in 92 metabolically healthy subjects with normal glucose tolerance and normal liver fat content. (1) Serum FGF21 concentrations were elevated in the obese subjects, and strongly associated with intrahepatic lipids (IHL). In accordance, FGF21 serum concentrations increased with severity of NAFLD as determined histologically in the liver biopsies. Though both diets were successful in reducing IHL, the effect was more pronounced in the HP group. FGF21 serum concentrations and mRNA expression were bi-directionally regulated by dietary protein, independent from metabolic improvements. In accordance, in the healthy study subjects, serum FGF21 concentrations dropped by more than 60\% in response to the HP diet. A short-term HP intervention confirmed the acute downregulation of FGF21 within 24 hours. Lastly, experiments in HepG2 cell cultures and primary murine hepatocytes identified nitrogen metabolites (NH4Cl and glutamine) to dose-dependently suppress FGF21 expression. (2) Circulating chemerin concentrations were considerably elevated in the obese versus lean study participants and differently associated with markers of obesity and NAFLD in the two cohorts. The adipokine decreased in response to the hypocaloric interventions while an unhealthy high-fat diet induced a rise in chemerin serum levels. In the lean subjects, mRNA expression of RARRES2, encoding chemerin, was strongly and positively correlated with expression of several cytokines, including MCP1, TNFα, and IL6, as well as markers of macrophage infiltration in the subcutaneous fat depot. However, RARRES2 was not associated with any cytokine assessed in the obese subjects and the data indicated an involvement of chemerin not only in the onset but also resolution of inflammation. Analyses of the tissue biopsies and experiments in human primary adipocytes point towards a role of chemerin in adipogenesis while discrepancies between the in vivo and in vitro data were detected. Taken together, the results of this thesis demonstrate that circulating FGF21 and chemerin levels are considerably elevated in obesity and responsive to dietary interventions. FGF21 was acutely and bi-directionally regulated by dietary protein in a hepatocyte-autonomous manner. Given that both, a lack in essential amino acids and excessive nitrogen intake, exert metabolic stress, FGF21 may serve as an endocrine signal for dietary protein balance. Lastly, the data revealed that chemerin is derailed in obesity and associated with obesity-related inflammation. However, future studies on chemerin should consider functional and regulatory differences between secreted and tissue-specific isoforms.},
  language  = {en}
}
@phdthesis{ColemanMacGregorofInneregny,
  author    = {Coleman Mac Gregor of Inneregny, Charles Dominic},
  title     = {Rolle von mPGES1-abh{\"a}ngig gebildetem Prostaglandin E2 bei der Ausbildung von Insulinresistenz und nicht-alkoholischer Fettlebererkrankung durch die Modulation der Funktion von Lebermakrophagen},
  school      = {Universit{\"a}t Potsdam},
  pages     = {183},
  abstract  = {Eine St{\"o}rung des Leberstoffwechsels durch die Ausbildung einer Insulinresistenz kann zu Folgeerkrankungen wie der nicht alkoholischen Fettlebererkrankung (NAFLD) bis hin zur Steatohepatitis (NASH) und zur Entwicklung eines Diabetes Typ II f{\"u}hren. Am Krankheitsverlauf sind residente (Kupfferzellen) sowie infiltrierende Makrophagen beteiligt, die durch inflammatorische Stimuli aktiviert werden und zur Progression von Lebererkrankungen f{\"u}hren k{\"o}nnen. Im Rahmen dieser Arbeit wurde die Rolle von mPGES1-abh{\"a}ngig gebildetem Prostaglandin E2 (PGE2) an der Modulation von aktivierten Lebermakrophagen untersucht. Dazu wurden Kupfferzellen und Peritonealmakrophagen (als Modell f{\"u}r infiltrierende Makrophagen) aus Wildtyp und mPGES1-defizienten M{\"a}usen isoliert. Beide Makrophagen­populationen wurden in Zellkulturversuchen mit Lipopolysacchariden (LPS) aktiviert und auf ihre PGE2-Synthese, Genexpression und Sekretion von verschiedenen Cytokinen hin untersucht. Die beiden Makrophagenpopulationen unterschieden sich hinsichtlich der PGE2-Synthese bei mPGSE1-Defizienz. W{\"a}hrend bei Peritonealmakrophagen die LPS-abh{\"a}ngige PGE2-Synthese bei Abwesenheit der mPGES1 fast vollst{\"a}ndig reprimiert war, war bei Kupfferzellen nur eine 25\%ige Abnahme zu verzeichnen. Die postulierte selbstverst{\"a}rkende R{\"u}ckkopplungsschleife von PGE2 im Hinblick auf seine eigene Synthese konnte in isolierten Peritonealmakrophagen, nicht jedoch in Kupfferzellen, best{\"a}tigt werden. In Kupfferzellen f{\"u}hrte exogenes PGE2 ferner zu einer Repression von den pro-inflammatorischen Cytokinen TNFα und IL-1β und f{\"u}r endogenes PGE2 konnte in diesem Zelltyp kein Effekt festgestellt werden. In Peritonealmakrophagen konnte hingegen auch f{\"u}r endogenes PGE2 eine reprimierende Wirkung auf die Expression von TNFα beobachtet werden. Das ist eventuell auf eine h{\"o}here Sensitivit{\"a}t gegen{\"u}ber PGE2 von Peritonealmakrophagen im Vergleich zu Kupfferzellen zur{\"u}ckzuf{\"u}hren. PGE2 wirkte unter den gew{\"a}hlten Versuchsbedingungen in vitro somit eher anti-inflammatorisch. Cholesterolkristalle induzierten in Kupfferzellen die Expression der PGE2-synthetisierenden Enzyme und verschiedener pro-inflammatorische Cytokine. Sie k{\"o}nnten somit zu einer Progression von NAFL zu NASH beitragen. Die Daten aus dieser Arbeit deuten darauf hin, dass PGE2 im Rahmen von entz{\"u}ndlichen Leberver{\"a}nderungen eine eher protektive Wirkung im Hinblick auf die Progression von NAFLD und Insulinresistenz haben k{\"o}nnte.},
  language  = {de}
}
@phdthesis{Ziemann2020,
  author    = {Ziemann, Vanessa},
  title     = {Toxische Effekte von Arsenolipiden in humanen Kulturzellen und Caenorhabditis elegans},
  school      = {Universit{\"a}t Potsdam},
  pages     = {112},
  year      = {2020},
  language  = {de}
}
@phdthesis{Kochlik2019,
  author    = {Kochlik, Bastian Max},
  title     = {Relevance of biomarkers for the diagnosis of the frailty syndrome},
  doi       = {10.25932/publishup-44118},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-441186},
  school      = {Universit{\"a}t Potsdam},
  pages     = {IV, 99},
  year      = {2019},
  abstract  = {Frailty and sarcopenia share some underlying characteristics like loss of muscle mass, low muscle strength, and low physical performance. Imaging parameters and functional examinations mainly assess frailty and sarcopenia criteria; however, these measures can have limitations in clinical settings. Therefore, finding suitable biomarkers that reflect a catabolic muscle state e.g. an elevated muscle protein turnover as suggested in frailty, are becoming more relevant concerning frailty diagnosis and risk assessment. 3-Methylhistidine (3-MH) and its ratios 3-MH-to-creatinine (3-MH/Crea) and 3 MH-to-estimated glomerular filtration rate (3-MH/eGFR) are under discussion as possible biomarkers for muscle protein turnover and might support the diagnosis of frailty. However, there is some skepticism about the reliability of 3-MH measures since confounders such as meat and fish intake might influence 3-MH plasma concentrations. Therefore, the influence of dietary habits and an intervention with white meat on plasma 3-MH was determined in young and healthy individuals. In another study, the cross-sectional associations of plasma 3-MH, 3-MH/Crea and 3-MH/eGFR with the frailty status (robust, pre-frail and frail) were investigated. Oxidative stress (OS) is a possible contributor to frailty development, and high OS levels as well as low micronutrient levels are associated with the frailty syndrome. However, data on simultaneous measures of OS biomarkers together with micronutrients are lacking in studies including frail, pre-frail and robust individuals. Therefore, cross-sectional associations of protein carbonyls (PrCarb), 3-nitrotyrosine (3-NT) and several micronutrients with the frailty status were determined. A validated UPLC-MS/MS (ultra-performance liquid chromatography tandem mass spectrometry) method for the simultaneous quantification of 3-MH and 1-MH (1 methylhistidine, as marker for meat and fish consumption) was presented and used for further analyses. Omnivores showed higher plasma 3-MH and 1-MH concentrations than vegetarians and a white meat intervention resulted in an increase in plasma 3-MH, 3 MH/Crea, 1-MH and 1-MH/Crea in omnivores. Elevated 3-MH and 3-MH/Crea levels declined significantly within 24 hours after this white meat intervention. Thus, 3-MH and 3-MH/Crea might be used as biomarker for muscle protein turnover when subjects did not consume meat 24 hours prior to blood samplings. Plasma 3-MH, 3-MH/Crea and 3-MH/eGFR were higher in frail individuals than in robust individuals. Additionally, these biomarkers were positively associated with frailty in linear regression models, and higher odds to be frail were found for every increase in 3 MH and 3-MH/eGFR quintile in multivariable logistic regression models adjusted for several confounders. This was the first study using 3-MH/eGFR and it is concluded that plasma 3-MH, 3-MH/Crea and 3-MH/eGFR might be used to identify frail individuals or individuals at higher risk to be frail, and that there might be threshold concentrations or ratios to support these diagnoses. Higher vitamin D3, lutein/zeaxanthin, γ-tocopherol, α-carotene, β-carotene, lycopene and β-cryptoxanthin concentrations and additionally lower PrCarb concentrations were found in robust compared to frail individuals in multivariate linear models. Frail subjects had higher odds to be in the lowest than in the highest tertile for vitamin D3 α-tocopherol, α-carotene, β-carotene, lycopene, lutein/zeaxanthin, and β cryptoxanthin, and had higher odds to be in the highest than in the lowest tertile for PrCarb than robust individuals in multivariate logistic regression models. Thus, a low micronutrient together with a high PrCarb status is associated with pre-frailty and frailty.},
  language  = {en}
}
@phdthesis{Kehm2019,
  author    = {Kehm, Richard},
  title     = {The impact of metabolic stress and aging on functionality and integrity of pancreatic islets and beta-cells},
  doi       = {10.25932/publishup-44109},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-441099},
  school      = {Universit{\"a}t Potsdam},
  pages     = {VI, 138},
  year      = {2019},
  abstract  = {The increasing age of worldwide population is a major contributor for the rising prevalence of major pathologies and disease, such as type 2 diabetes, mediated by massive insulin resistance and a decline in functional beta-cell mass, highly associated with an elevated incidence of obesity. Thus, the impact of aging under physiological conditions and in combination with diet-induced metabolic stress on characteristics of pancreatic islets and beta-cells, with the focus on functionality and structural integrity, were investigated in the present dissertation. Primarily induced by malnutrition due to chronic and excess intake of high caloric diets, containing large amounts of carbohydrates and fats, obesity followed by systemic inflammation and peripheral insulin resistance occurs over time, initiating metabolic stress conditions. Elevated insulin demands initiate an adaptive response by beta-cell mass expansion due to increased proliferation, but prolonged stress conditions drive beta-cell failure and loss. Aging has been also shown to affect beta-cell functionality and morphology, in particular by proliferative limitations. However, most studies in rodents were performed under beta-cell challenging conditions, such as high-fat diet interventions. Thus, in the first part of the thesis (publication I), a characterization of age-related alterations on pancreatic islets and beta-cells was performed by using plasma samples and pancreatic tissue sections of standard diet-fed C57BL/6J wild-type mice in several age groups (2.5, 5, 10, 15 and 21 months). Aging was accompanied by decreased but sustained islet proliferative potential as well as an induction of cellular senescence. This was associated with a progressive islet expansion to maintain normoglycemia throughout lifespan. Moreover, beta-cell function and mass were not impaired although the formation and accumulation of AGEs occurred, located predominantly in the islet vasculature, accompanied by an induction of oxidative and nitrosative (redox) stress. The nutritional behavior throughout human lifespan; however, is not restricted to a balanced diet. This emphasizes the significance to investigate malnutrition by the intake of high-energy diets, inducing metabolic stress conditions that synergistically with aging might amplify the detrimental effects on endocrine pancreas. Using diabetes-prone NZO mice aged 7 weeks, fed a dietary regimen of carbohydrate restriction for different periods (young mice - 11 weeks, middle-aged mice - 32 weeks) followed by a carbohydrate intervention for 3 weeks, offered the opportunity to distinguish the effects of diet-induced metabolic stress in different ages on the functionality and integrity of pancreatic islets and their beta-cells (publication II, manuscript). Interestingly, while young NZO mice exhibited massive hyperglycemia in response to diet-induced metabolic stress accompanied by beta-cell dysfunction and apoptosis, middle-aged animals revealed only moderate hyperglycemia by the maintenance of functional beta-cells. The loss of functional beta-cell mass in islets of young mice was associated with reduced expression of PDX1 transcription factor, increased endocrine AGE formation and related redox stress as well as TXNIP-dependent induction of the mitochondrial death pathway. Although the amounts of secreted insulin and the proliferative potential were comparable in both age groups, islets of middle-aged mice exhibited sustained PDX1 expression, almost regular insulin secretory function, increased capacity for cell cycle progression as well as maintained redox potential. The results of the present thesis indicate a loss of functional beta-cell mass in young diabetes-prone NZO mice, occurring by redox imbalance and induction of apoptotic signaling pathways. In contrast, aging under physiological conditions in C57BL/6J mice and in combination with diet-induced metabolic stress in NZO mice does not appear to have adverse effects on the functionality and structural integrity of pancreatic islets and beta-cells, associated with adaptive responses on changing metabolic demands. However, considering the detrimental effects of aging, it has to be assumed that the compensatory potential of mice might be exhausted at a later point of time, finally leading to a loss of functional beta-cell mass and the onset and progression of type 2 diabetes. The polygenic, diabetes-prone NZO mouse is a suitable model for the investigation of human obesity-associated type 2 diabetes. However, mice at advanced age attenuated the diabetic phenotype or do not respond to the dietary stimuli. This might be explained by the middle age of mice, corresponding to the human age of about 38-40 years, in which the compensatory mechanisms of pancreatic islets and beta cells towards metabolic stress conditions are presumably more active.},
  language  = {en}
}
@phdthesis{Schwerbel2019,
  author    = {Schwerbel, Kristin},
  title     = {Der Einfluss zweier immun-assoziierter GTPasen auf die Entstehung einer Hepatosteatose},
  school      = {Universit{\"a}t Potsdam},
  pages     = {133},
  year      = {2019},
  language  = {de}
}
@phdthesis{Gaballa2019,
  author    = {Gaballa, Mohamed Mahmoud Salem Ahmed},
  title     = {New pharmacological approaches targeting vascular calcification in chronic kidney disease},
  address   = {Potsdam},
  school      = {Universit{\"a}t Potsdam},
  pages     = {X, 110},
  year      = {2019},
  language  = {en}
}
@phdthesis{Eichelmann2019,
  author    = {Eichelmann, Fabian},
  title     = {Novel adipokines as inflammatory biomarkers of chronic disease risk},
  school      = {Universit{\"a}t Potsdam},
  pages     = {133},
  year      = {2019},
  language  = {en}
}
@phdthesis{Gottmann2019,
  author    = {Gottmann, Pascal},
  title     = {In silico Analyse zur Kl{\"a}rung der Beteiligung von micro-RNAs, die in QTL lokalisiert sind, an den metabolischen Erkrankungen Adipositas und Typ-2-Diabetes mit Hilfe von Mausmodellen},
  school      = {Universit{\"a}t Potsdam},
  pages     = {XIII, 106},
  year      = {2019},
  language  = {de}
}
@phdthesis{Rohn,
  author    = {Rohn, Isabelle},
  title     = {Food-relevant selenium species},
  school      = {Universit{\"a}t Potsdam},
  pages     = {132,VIII},
  language  = {en}
}
@phdthesis{Bertz2018,
  author    = {Bertz, Martin},
  title     = {Funktion von Selenoproteinen  w{\"a}hrend der kolorektalen Karzinogenese},
  doi       = {10.25932/publishup-42780},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-427808},
  school      = {Universit{\"a}t Potsdam},
  pages     = {VII, 109},
  year      = {2018},
  abstract  = {Kolorektalkrebs (CRC) ist die dritth{\"a}ufigste Tumorerkrankung weltweit. Neben dem Alter spielt auch die Ern{\"a}hrung eine wichtige Rolle bei der Entstehung der Krankheit. Eine vermutlich krebspr{\"a}ventive Wirkung wird dabei dem Spurenelement Selen zugeschrieben, das fast ausschließlich {\"u}ber Lebensmittel aufgenommen wird. So h{\"a}ngt beispielsweise ein niedriger Selenstatus mit dem Risiko, im Laufe des Lebens an CRC zu erkranken, zusammen. Seine Funktionen vermittelt Selen dabei {\"u}berwiegend durch Selenoproteine, in denen es in Form von Selenocystein eingebaut wird. Zu den bisher am besten untersuchten Selenoproteinen mit m{\"o}glicher Funktion w{\"a}hrend CRC z{\"a}hlen die Glutathionperoxidasen (GPXen). Die Mitglieder dieser Familie tragen aufgrund ihrer Hydroperoxid-reduzierenden Eigenschaften entscheidend zum Schutz der Zellen vor oxidativem Stress bei. Dies kann je nach Art und Stadium des Tumors entweder krebshemmend oder -f{\"o}rdernd wirken, da auch transformierte Zellen von dieser Schutzfunktion profitieren. In dieser Arbeit wurde die GPX2 in HT29-Darmkrebszellen mithilfe stabil-transfizierter shRNA herunterreguliert, um die Funktion des Enzyms vor allem in Hinblick auf regulierte Signalwege zu untersuchen. Ein Knockdowns (KD) der strukturell {\"a}hnlichen GPX1 kam ebenfalls zum Einsatz, um gezielt Isoform-spezifische Funktionen unterscheiden zu k{\"o}nnen. Anhand eines PCR-Arrays wurden Signalwege identifiziert, die auf einen Einfluss der beiden Proteine im Zellwachstum hindeuteten. Anschließende Untersuchungen ließen auf einen verminderten Differenzierungsstatus in den GPX1- und GPX2-KDs aufgrund einer geringeren Aktivit{\"a}t der Alkalischen Phosphatase schließen. Zudem war die Zellviabilit{\"a}t im Neutralrot-Assay (NRU) bei Fehlen der GPX1 bzw. GPX2 im Vergleich zur Kontrolle reduziert. Die Ergebnisse des PCR-Arrays, und speziell f{\"u}r die GPX2 fr{\"u}here Untersuchungen der Arbeitsgruppe, wiesen weiterhin auf eine Rolle der beiden Proteine in der entz{\"u}ndungsgetriebenen Karzinogenese hin. Daher wurden auch m{\"o}gliche Interaktionen mit dem NFκB-Signalweg analysiert. Eine Stimulation der Zellen mit dem proinflammatorischen Zytokin IL1β ging mit einer verst{\"a}rkten Aktivierung der MAP-Kinasen ERK1/2 in den Zellen mit GPX1- bzw. GPX2-KD einher. Die gleichzeitige Behandlung mit dem Antioxidans NAC f{\"u}hrte nicht zur R{\"u}cknahme der Effekte in den KDs, sodass m{\"o}glicherweise nicht nur die antioxidativen Eigenschaften der Enzyme bei der Interaktion mit diesen Signalwegsproteinen relevant sind. Weiterhin wurden Analysen zum Substratspektrum der GPX2 in HCT116-Zellen mit einer {\"U}berexpression des Proteins durchgef{\"u}hrt. Dabei zeigte sich mittels NRU-Assay und DNA-Laddering, dass die GPX2 besonders vor den proapoptotischen Effekten einer Behandlung mit den Lipidhydroperoxiden HPODE und HPETE sch{\"u}tzt. Im Gegensatz zur GPX2 l{\"a}sst sich Selenoprotein H (SELENOH) st{\"a}rker durch die aliment{\"a}re Selenzufuhr beeinflussen. Einer m{\"o}glichen Nutzung als Biomarker oder gar als Ansatzpunkt bei der Pr{\"a}vention bzw. Behandlung von CRC steht allerdings unvollst{\"a}ndiges Wissen {\"u}ber die Funktion des Proteins gegen{\"u}ber. Zur genaueren Charakterisierung von SELENOH wurden daher stabil-transfizierte KD-Klone in HT29- und Caco2-Zellen hergestellt und zun{\"a}chst auf ihre Tumorigenit{\"a}t untersucht. Zellen mit SELENOH-KD bildeten mehr und gr{\"o}ßere Kolonien im Soft Agar und zeigten ein erh{\"o}htes Proliferations- und Migrationspotenzial im Vergleich zur Kontrolle. Ein Xenograft in Nacktm{\"a}usen resultierte zudem in einer st{\"a}rkeren Tumorbildung nach Injektion von KD-Zellen. Untersuchungen zur Beteiligung von SELENOH an der Zellzyklusregulation deuten auf eine hemmende Rolle des Proteins in der G1/S-Phase hin. Die weiterhin beobachtete Hochregulation von SELENOH in humanen Adenokarzinomen und pr{\"a}kanzer{\"o}sem Mausgewebe l{\"a}sst sich m{\"o}glicherweise mit der postulierten Schutzfunktion vor oxidativen Zell- und DNA-Sch{\"a}den erkl{\"a}ren. In gesunden Darmepithelzellen war das Protein vorrangig am Kryptengrund lokalisiert, was zu einer potenziellen Rolle w{\"a}hrend der gastrointestinalen Differenzierung passt.},
  language  = {de}
}
@phdthesis{ColemanMacGregorofInneregny,
  author    = {Coleman Mac Gregor of Inneregny, Verena},
  title     = {Cell-autonomous and cell-non-autonomous adaptation to skeletal muscle mitochondrial stress},
  school      = {Universit{\"a}t Potsdam},
  pages     = {86},
  language  = {en}
}
@phdthesis{Ring2018,
  author    = {Ring, Christiane},
  title     = {The role of the commensal gut bacterium Akkermansia muciniphila in acute and chronic intestinal inflammation},
  year      = {2018},
  abstract  = {Microbiota analyses of patients suffering from various diseases suggest a beneficial role of Akkermansia muciniphila in the maintenance of health, whereas several studies in animal models of intestinal inflammation report that this organism may aggravate inflammation. Therefore, it is important to clarify under which circumstances A. muciniphila exerts negative effects in the intestine of its host. The previously reported observation that A. muciniphila aggravates acute intestinal inflammation in the Salmonella enterica serovar Typhimurium infection mouse model colonized with a simplified human intestinal microbiota was investigated in this study. To unravel the underlying mechanism that led to the observed phenomenon, the time course of events following the infection was analyzed. In mice colonized with a simplified human intestinal microbiota, Salmonella infection induced clear signs of intestinal inflammation three days post infection. The inflammatory response was similar in mice colonized with A. muciniphila before Salmonella infection. These observations were independent of the time when colonization with the simplified human intestinal microbiota occurred, right after birth or only after weaning, and contradict the previous report. To find out whether A. muciniphila influences the development of chronic intestinal inflammation in a genetically predisposed host, mono-associated interleukin-10-deficient (Il10-/-) mice, Il10-/- mice dual-associated with A. muciniphila and colitogenic Escherichia coli NC101, as well as Il10-/- mice associated with A. muciniphila and a simplified human intestinal microbiota were compared to the respective mice without A. muciniphila. The data clearly show that in these gnotobiotic Il10-/- mice, A. muciniphila neither induces intestinal inflammation itself nor modulates it after induction by a colitogenic bacterium or by a simplified human intestinal microbiota. The experiments lead to the conclusion that the promotion of intestinal inflammation is not an intrinsic feature of this bacterium. The results of this study encourage the proposed use of A. muciniphila for the prevention or treatment of metabolic disorders.},
  language  = {en}
}
@phdthesis{Radloff2018,
  author    = {Radloff, Katrin},
  title     = {The role of the fatty acid profile and its modulation by cytokines in the systemic inflammation in cancer cachexia},
  school      = {Universit{\"a}t Potsdam},
  pages     = {156},
  year      = {2018},
  abstract  = {Systemic inflammation is a hallmark of cancer cachexia. Among tumor-host interactions, the white adipose tissue (WAT) is an important contributor to inflammation as it suffers morphological reorganization and lipolysis, releasing free fatty acids (FA), bioactive lipid mediators (LM) and pro-inflammatory cytokines, which accentuate the activation of pro-inflammatory signaling pathways and the recruitment of immune cells to the tissue. This project aimed to investigate which inflammatory factors are involved in the local adipose tissue inflammation and what is the influence of such factors upon enzymes involved in FA or LM metabolism in healthy individuals (Control), weight stable gastro-intestinal cancer patients (WSC) and cachectic cancer patients (CC). The results demonstrated that the inflammatory signature of systemic inflammation is different from local adipose tissue inflammation. The systemic inflammation of the cachectic cancer patients was characterized by higher levels of circulating saturated fatty acids (SFA), tumor-necrosis-factor-α (TNF-α), interleukins IL-6, IL-8 and CRP while levels of polyunsaturated fatty acids (PUFAs), especially n3-PUFAs, were lower in CC than in the other groups. In vitro and in adipose tissue explants, pro-inflammatory cytokines and SFAs were shown to increase the chemokines IL-8 and CXCL10 that were found to be augmented in adipose tissue inflammation in CC which was more profound in the visceral adipose tissue (VAT) than in subcutaneous adipose tissue (SAT). Systemic inflammation was negatively associated with the expression of PUFA synthesizing enzymes, though gene and protein expression did hardly differ between groups. The effects of inflammatory factors on enzymes in the whole tissue could have been masked by differentiated modulation of the diverse cell types in the same tissue. In vitro experiments showed that the expression of FA-modifying enzymes such as desaturases and elongases in adipocytes and macrophages was regulated into opposing directions by TNF-α, IL-6, LPS or palmitate. The higher plasma concentration of the pro-resolving LM resolvin D1 in CC cannot compensate the overall inflammatory status and the results indicate that inflammatory cytokines interfere with synthesis pathways of pro-resolving LM. In summary, the data revealed a complex inter-tissue and inter-cellular crosstalk mediated by pro-inflammatory cytokines and lipid compounds enhancing inflammation in cancer cachexia by feed-forward mechanisms.},
  language  = {en}
}
@phdthesis{Dambeck2018,
  author    = {Dambeck, Ulrike},
  title     = {Kohlenhydratarme, n-6-reiche Di{\"a}t versus fettarme Di{\"a}t},
  school      = {Universit{\"a}t Potsdam},
  pages     = {187},
  year      = {2018},
  language  = {de}
}
@phdthesis{Hasan2018,
  author    = {Hasan, Ahmed Abdallah Abdalrahman Mohamed},
  title     = {GLP-1 receptor-independent mechanisms of DPP-4 inhibition on renal disease progression},
  school      = {Universit{\"a}t Potsdam},
  pages     = {113},
  year      = {2018},
  language  = {en}
}
@phdthesis{Kammel2018,
  author    = {Kammel, Anne},
  title     = {Identifizierung fr{\"u}her epigenetischer Ver{\"a}nderungen, die zur Ausbildung einer Fettleber beitragen},
  school      = {Universit{\"a}t Potsdam},
  pages     = {130},
  year      = {2018},
  language  = {de}
}
@phdthesis{Waizenegger2018,
  author    = {Waizenegger, Julia},
  title     = {Untersuchung der molekularen Toxizit{\"a}t von Pyrrolizidinalkaloiden in der humanen Hepatomzelllinie HepaRG},
  school      = {Universit{\"a}t Potsdam},
  pages     = {129, XLI},
  year      = {2018},
  language  = {de}
}
@phdthesis{Eckel2017,
  author    = {Eckel, Nathalie},
  title     = {Metabolically healthy obesity and metabolically unhealthy normal weight - identification and associated risks},
  school      = {Universit{\"a}t Potsdam},
  pages     = {177},
  year      = {2017},
  language  = {en}
}
@phdthesis{Leupelt2017,
  author    = {Leupelt, Anke Verena},
  title     = {Hormonelle K{\"o}rpergewichtsregulation nach Gewichtsreduktion im Rahmen der multimodalen randomisierten Interventionsstudie MAINTAIN},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-413181},
  school      = {Universit{\"a}t Potsdam},
  pages     = {XIII, 104},
  year      = {2017},
  abstract  = {Adipositas wird mit einer Vielzahl schwerwiegender Folgeerkrankungen in Verbindung gebracht. Eine Gewichtsreduktion f{\"u}hrt zu einer Verbesserung der metabolischen Folgen der Adipositas. Es ist bekannt, dass die Mehrzahl der adip{\"o}sen Personen in den Monaten nach der Gewichtsreduktion einen Großteil des abgenommenen Gewichts wieder zunimmt. Nichtsdestotrotz existiert eine hohe Variabilit{\"a}t hinsichtlich des Langzeiterfolges einer Gewichtsreduktion. Der erfolgreiche Erhalt des reduzierten K{\"o}rpergewichts einiger Personen f{\"u}hrt zu der Frage nach den Faktoren, die einen Gewichtserhalt beeinflussen, mit dem Ziel einen Ansatzpunkt f{\"u}r m{\"o}gliche Therapiestrategien zu identifizieren. In der vorliegenden Arbeit wurde im Rahmen einer kontrollierten, randomisierten Studie mit 143 {\"u}bergewichtigen Probanden untersucht, ob nach einer dreimonatigen Gewichtsreduktion eine zw{\"o}lfmonatige gewichtsstabilisierende Lebensstilintervention einen Einfluss auf die Ver{\"a}nderungen der neuroendokrinen Regelkreisl{\"a}ufe und damit auf den langfristigen Gewichtserhalt {\"u}ber einen Zeitraum von achtzehn Monaten hat. Hierbei wurde im Vergleich der beiden Behandlungsgruppen prim{\"a}r festgestellt, dass die multimodale Lebensstilintervention zu einer Gewichtstabilisierung {\"u}ber die Dauer dieser zw{\"o}lfmonatigen Behandlungsphase f{\"u}hrte. In der Kontrollgruppe kam es zu einer moderaten Gewichtszunahme . Dadurch war nach Beendigung der Interventionsphase der BMI der Teilnehmer in der Kontrollgruppe h{\"o}her als der in der Interventionsgruppe (34,1±6,0 kg*m-2 vs. 32,4±5,7 kg*m-2; p<0,01). W{\"a}hrend der Nachbeobachtungszeit war die Interventionsgruppe durch eine signifikant st{\"a}rkere Gewichtswiederzunahme im Vergleich zur Kontrollgruppe gekennzeichnet, so dass der BMI zwischen beiden Behandlungsgruppen bereits sechs Monate nach der Intervention keinen Unterschied mehr aufwies. Bez{\"u}glich der hormonellen Ver{\"a}nderung durch die Gewichtsreduktion wurde, wie erwartet, eine Auslenkung des endokrinen Systems beobachtet. Jedoch konnte kein Unterschied der untersuchten Hormone im Vergleich der beiden Behandlungsgruppen ausfindig gemacht werden. Im Verlauf der Gewichtsabnahme und der anschließenden Studienphasen zeigten sich tendenziell drei verschiedene Verlaufsmuster in den hormonellen Ver{\"a}nderungen. Nach einer zus{\"a}tzlichen Adjustierung auf den jeweiligen BMI des Untersuchungszeitpunktes konnte f{\"u}r die TSH-Spiegel (p<0,05), die Schilddr{\"u}senhormone (p<0,001) und f{\"u}r die IGF 1-Spiegel (p<0,001) eine {\"u}ber die Studienzeit anhaltende Ver{\"a}nderung festgestellt werden. Abschließend wurde behandlungsgruppenunabh{\"a}ngig untersucht, ob die Hormonspiegel nach Gewichtsreduktion oder ob die relative hormonelle Ver{\"a}nderung w{\"a}hrend der Gewichtsreduktion pr{\"a}diktiv f{\"u}r den Erfolg der Gewichterhaltungsphase ist. Hier fand sich f{\"u}r die Mehrzahl der hormonellen Parameter kein Effekt auf die Langzeitentwicklung der Gewichtszunahme. Jedoch konnte gezeigt werden, dass eine geringere Abnahme der 24h Urin-Metanephrin-Ausscheidung w{\"a}hrend der Gewichtsabnahmephase mit einem besseren Erfolg bez{\"u}glich des Gewichtserhalts {\"u}ber die achtzehnmonatige Studienzeit assoziiert war (standardisiertes Beta= -0,365; r2=0,133 p<0,01). Die anderen hormonellen Achsen zeigten keinen nachweislichen Effekt.},
  language  = {de}
}
@phdthesis{Edlich2018,
  author    = {Edlich, Alexander},
  title     = {Interaktionen zwischen Nanotransportern und antigenpr{\"a}sentierenden Zellen der Haut},
  school      = {Universit{\"a}t Potsdam},
  pages     = {181},
  year      = {2018},
  language  = {de}
}
@phdthesis{Weiss2018,
  author    = {Weiß, Stefanie},
  title     = {Contribution of bacterially synthesized folate vitamers to folate status and impact on crohn's Disease},
  school      = {Universit{\"a}t Potsdam},
  pages     = {148},
  year      = {2018},
  language  = {en}
}
@phdthesis{Mueller2018,
  author    = {M{\"u}ller, Sandra Marie},
  title     = {Food-relevant arsenic species},
  school      = {Universit{\"a}t Potsdam},
  pages     = {163, Viii},
  year      = {2018},
  language  = {en}
}
@phdthesis{Jank2017,
  author    = {Jank, Anne-Marie},
  title     = {Effects of senescence on microenvironment-progenitor cell interaction},
  school      = {Universit{\"a}t Potsdam},
  pages     = {156},
  year      = {2017},
  language  = {en}
}