@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{Wohlgemuth2010, author = {Wohlgemuth, Steffen}, title = {Microbial and host factors associated with chronic intestinal inflammation of the Interleukin-10 deficient mouse}, address = {Potsdam}, pages = {IX, 125 Bl. : Ill., graph. Darst.}, year = {2010}, language = {en} } @phdthesis{Winnig2006, author = {Winnig, Marcel}, title = {Struktur-Wirkungsbeziehungen der S{\"u}ßgeschmachsrezeptoren des Menschen und der Ratte}, address = {Potsdam}, pages = {VII, 121 Bl.}, year = {2006}, language = {de} } @phdthesis{Winkelbeiner2020, author = {Winkelbeiner, Nicola Lisa}, title = {Impact of element species on DNA repair processes}, pages = {XV, 182, iii}, year = {2020}, language = {en} } @phdthesis{Wiese2010, author = {Wiese, Stefanie}, title = {Biokinetik und biologische Aktivit{\"a}t von Flavan-3-olen}, pages = {IX, 190, XXI S. : graph. Darst.}, year = {2010}, language = {de} } @phdthesis{Wetzel2022, author = {Wetzel, Alexandra}, title = {Epigenetische Regulation des Epstein-Barr Virus-induzierten Gens 3 (EBI3) und dessen Bedeutung bei Colitis ulcerosa}, school = {Universit{\"a}t Potsdam}, pages = {164}, year = {2022}, abstract = {Epigenetische Mechanismen spielen eine entscheidende Rolle bei der Pathogenese von Colitis ulcerosa (CU). Ihr Einfluss auf das beobachtete Ungleichgewicht zwischen pro- und anti-inflammatorischen Cytokinen ist hingegen weitgehend unerforscht. Einige der wichtigsten immunmodulatorischen Cytokine sind die Mitglieder der heterodimeren Interleukin- (IL-) 12-Familie, die durch das Kombinieren einer der drei α-Ketten (IL-12p35, IL-27p28, IL-23p19) mit den ß-Untereinheiten IL-12p40 oder EBI3 (Epstein-Barr Virus-induziertes Gen 3) charakterisiert sind. IL-35 (IL-12p35/EBI3) spielt eine bedeutende anti-inflammatorische Rolle bei verschiedenen Erkrankungen, wohingegen seine Level bei chronischen Entz{\"u}ndungen erniedrigt sind. Eine m{\"o}gliche Ursache k{\"o}nnte eine transkriptionelle Stilllegung {\"u}ber epigenetische Modifikationen sein. Tats{\"a}chlich konnte durch die Stimulation mit dem DNA-Methyltransferase-Inhibitor (DNMTi) Decitabin (DAC; Dacogen®) eine Induktion von EBI3 in humanen Epithelzellen aus gesundem Colon (HCEC) erreicht werden, die als Modell f{\"u}r ein lokales Entz{\"u}ndungsgeschehen dienten. Diese Regulation {\"u}ber DNA-Methylierung konnte in weiteren humanen Zellen unterschiedlichen Ursprungs sowie durch Stimulation von HCEC-Zellen mit zwei weiteren DNMTi, dem Cytosin-Analogon Azacytidin (AZA; Vidaza®) und dem nat{\"u}rlich vorkommenden, epigenetisch wirksamen Polyphenol Epigallocatechingallat (EGCG), verifiziert werden. Die kombinierte Inkubation mit Tumor-Nekrose-Faktor α (TNFα) resultierte jeweils in einer {\"u}ber-additiven Induktion von EBI3. Weiterf{\"u}hrende Untersuchungen zeigten, dass TNFα trotz Beeinflussung der epigenetischen DNMT- und Ten-eleven Translocation- (TET-) Enzyme keinen Einfluss auf die globalen Methylierungs- oder Hydroxymethylierungslevel hatte, jedoch eine genspezifische DNA-Hypomethylierung im EBI3-Promotor induzierte. Durch Nutzung verschiedener Inhibitoren konnte dar{\"u}ber hinaus nachgewiesen werden, dass der beobachtete synergistische Effekt der gemeinsamen DAC und TNFα-Stimulation haupts{\"a}chlich {\"u}ber NFκB (Nuclear factor "kappa-light-chain-enhancer" of activated B-cells) vermittelt wird. Ein Teil verl{\"a}uft dabei {\"u}ber p38 MAPK (mitogen-activated protein kinases), w{\"a}hrend die JNK- (c-Jun N-terminale Kinasen-) und ERK- (extracellular-signal-regulated kinases) Signalwege keine Rolle spielen. In der vorliegenden Arbeit wurde zudem gezeigt, dass die DNA-Hypomethylierung w{\"a}hrend eines entz{\"u}ndlichen Zustandes auch in einer erh{\"o}hten EBI3-Proteinexpression resultiert. Die H{\"o}he der immunologisch detektierten Banden wies auf eine Dimerbildung sowohl im Zelllysat als auch im {\"U}berstand hin. Humane Colonepithelzellen sind demnach in der Lage, Cytokine zu bilden und zu sezernieren, was die Bedeutung von Nicht-Immunzellen bei der lokalen Immunantwort unterstreicht. Mittels Genexpressionsanalysen wurden IL-12p35 und IL-23p19 als m{\"o}gliche Bindungspartner identifiziert. Aufgrund kreuzreaktiver Antik{\"o}rper ist ein direkter Nachweis der EBI3-Dimere derzeit nicht m{\"o}glich. Die stattdessen genutzte Kombination verschiedener Methoden dient als geeigneter Ersatz f{\"u}r die problematischen Antik{\"o}rper-basierten Analysen wie Immunpr{\"a}zipitation oder ELISA. Durch molekularbiologische, immunologische und massenspektrometrische Methoden konnte IL-35 identifiziert werden, w{\"a}hrend IL-39 (IL-23p19/EBI3) nicht detektiert wurde. Dies ist in Einklang mit den Erkenntnissen mehrerer Forschungsgruppen, die eine Bildung des nativen humanen Dimers aus IL-23p19 und EBI3 bezweifeln. Des Weiteren wurde die biologische Aktivit{\"a}t des behandlungsinduzierten IL 35-Proteins durch einen Funktionsassay nachgewiesen. Neben einer DNMTi-bedingten transkriptionellen Aktivierung konnte eine Regulation von EBI3 {\"u}ber Histonacetylierungen gezeigt werden. Der EBI3-induzierende Effekt des Histondeacetylasen-Inhibitors (HDACi) Trichostatin A (TSA) wurde durch SAHA (suberoylanilide hydroxamic acid (Vorinostat; Zolinza®)) verifiziert. {\"A}hnlich zu der Stimulation mit den hypomethylierenden Substanzen wurde ein synergistischer Effekt bei paralleler Inkubation mit TNFα beobachtet, der in einer gesteigerten Bildung des EBI3-Proteins resultierte. Um die Befunde in einem komplexeren in vivo-Modell zu untersuchen, wurde eine chronische Colitis in Ebi3-defizienten M{\"a}usen und dem dazugeh{\"o}rigen Wildtypstamm C57BL/6 durch zyklische Applikation von Natriumdextransulfat (Dextran sodium sulfate (DSS)) induziert. Der Vergleich klinischer Parameter wie Mortalit{\"a}tsrate und K{\"o}rper- sowie Milzgewicht wies bei Abwesenheit von Ebi3 signifikant st{\"a}rkere colitische Symptome auf. Dies best{\"a}tigte die zentrale Rolle von Ebi3 in der Colitisentwicklung und deutete auf eine bevorzugte Bildung des anti-inflammatorisch wirkenden IL-35 statt des pro-inflammatorischen IL-39 in den Wildtyptieren hin. Durch zus{\"a}tzliche therapeutische Behandlung der C57BL/6-M{\"a}use nach der DSS-Gabe konnte die in der Literatur beschriebene positive Wirkung von SAHA auf die Colitismanifestation best{\"a}tigt werden. Im Gegensatz dazu war der HDACi in den Ebi3-defizienten Tieren nicht in der Lage, die colitischen Parameter zu verbessern beziehungsweise verschlimmerte den Krankheitsph{\"a}notyp. Expressionsanalysen von Up- und Downstream-Target-Genen lieferten weitere Hinweise darauf, dass bei Anwesenheit von Ebi3 IL-35 statt IL-39 gebildet wird, was in Einklang mit den in vitro-Untersuchungen steht. Die vorliegende Arbeit konnte durch den Vergleich der C57BL/6-M{\"a}use mit den Ebi3-defizienten Tieren neue Erkenntnisse {\"u}ber die Wirkungsweise von SAHA erbringen. Histonacetylierende Bedingungen verbessern colitische Symptome {\"u}ber einen Mechanismus, der die epigenetische Induktion von Ebi3 mit nachfolgender IL-35-Bildung involviert. Durch Kooperation der epigenetischen Mechanismen Hypomethylierung und Histonacetylierung wurde der st{\"a}rkste Effekt auf die EBI3-Induktion bewirkt. Insgesamt konnte in der vorliegenden Arbeit durch in vitro- und in vivo-Analysen die epigenetische und NFκB-vermittelte Induktion von EBI3 {\"u}ber DNA-Demethylierung und Histonacetylierung mit nachfolgender IL-35-Bildung und -Sezernierung nachgewiesen werden. Da IL-35 in der Lage ist, colitische Symptome zu mildern, stellt die epigenetische Reaktivierbarkeit von EBI3 durch DNMTi und HDACi eine vielversprechende Alternative f{\"u}r die derzeit genutzten, oft nicht oder nur kurzfristig wirksamen Therapien bei der Behandlung einer CU dar. Einer {\"u}berm{\"a}ßigen Immunantwort w{\"a}hrend schubweiser entz{\"u}ndlicher Phasen k{\"o}nnte entgegengewirkt und Komplikationen wie die Bildung Colitis-assoziierter Karzinome verhindert werden.}, 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{Weitkunat2017, author = {Weitkunat, Karolin}, title = {Dietary fibers and short-chain fatty acids in the development of diet-induced obesity}, school = {Universit{\"a}t Potsdam}, pages = {121}, year = {2017}, language = {en} } @phdthesis{Weber2016, author = {Weber, Florian Till}, title = {In vitro Toxizit{\"a}t von Elektrolytl{\"o}sungen der Lithium-Ionen Batterie}, school = {Universit{\"a}t Potsdam}, pages = {119}, year = {2016}, language = {de} } @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{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{Voigt2007, author = {Voigt, Anja}, title = {Beziehung zwischen dem mitochondrialen Stoffwechsel und der Lebenserwartung in mammalen Knock-out-Modellen}, address = {Potsdam}, pages = {100 Bl. : graph. Darst.}, year = {2007}, language = {de} } @phdthesis{Vogel2009, author = {Vogel, Heike}, title = {Identifizierung, Charakterisierung und Eingrenzung eines Suszeptibilit{\"a}tslocus (Nob3) f{\"u}r Adipositas und Hyperglyk{\"a}mie im Mausgenom}, address = {Potsdam}, pages = {49 Bl., 104 S. : Ill., graph. Darst.}, year = {2009}, language = {de} } @phdthesis{Trenkmann2017, author = {Trenkmann, Tom}, title = {Bedeutung von Sphingosin-1-Phosphat in der Pathogenese des Morbus Crohn und Entwicklung und Charakterisierung eines murinen Colitis-Modells}, school = {Universit{\"a}t Potsdam}, pages = {165}, year = {2017}, language = {de} } @phdthesis{Stadion2017, author = {Stadion, Mandy}, title = {Validation and Characterization of lfi202b and Zfp69, two Novel Disease Genes in Obesity-Associated Insulin Resistance}, school = {Universit{\"a}t Potsdam}, pages = {158}, year = {2017}, language = {en} } @phdthesis{Spoelgen2003, author = {Spoelgen, Robert}, title = {Charakterisierung des Endozytose-Rezeptors Megalin in der Entwicklung des Vorderhirns und der Gonaden}, pages = {127 S.}, year = {2003}, language = {de} } @phdthesis{Sommer2006, author = {Sommer, Yasmin}, title = {5-(Hydroxymethyl)-2-furfural: Sulfokonjugation und ihre Bedeutung f{\"u}r die Genotoxizit{\"a}t}, pages = {108 Bl. : Ill., graph. Darst.}, year = {2006}, language = {de} } @phdthesis{Simmering1999, author = {Simmering, Rainer}, title = {Intestinale Metabolisierung sekund{\"a}rer Pflanzeninhaltstoffe : Vorkommen und Bedeutung von Lignan- und Flavonoidabbauenden Bakterien des humanen Intestinaltraktes}, address = {Potsdam}, pages = {VI, 135 S. : graph. Darst.}, year = {1999}, language = {de} } @phdthesis{Sembries2001, author = {Sembries, Sabine}, title = {Freisetzung von Ballastoffen und planzlichen Phenolen aus Apfeltrester durch Einsatz cellulasehaltiger Enzympr{\"a}parate : Charakterisierung der gewonnenen Produkte}, pages = {133 S.}, year = {2001}, language = {de} } @phdthesis{Seltmann2013, author = {Seltmann, Anne-Cathrin}, title = {Nutrigenetik der metabolischen Adaptation an eine isokalorische Hochfettdi{\"a}t bei gesunden Zwillingen}, address = {Potsdam}, pages = {157 S.}, year = {2013}, language = {de} } @phdthesis{Schueler2011, author = {Sch{\"u}ler, Rita}, title = {Identifizierung und Charakterisierung neuer nat{\"u}rlicher Liganden des Peroxisomen-Proliferator aktivierten Rezeptors y (PPARy)}, address = {Potsdam}, pages = {165 S.}, year = {2011}, language = {de} } @phdthesis{Schaerfke2000, author = {Sch{\"a}rfke, Marco}, title = {Identifizierung von nutrivitiv-regulierten Transkriptionsfaktoren in HepG2-Zellen : Konstruktion einer 2-DE- Datenbank l{\"o}slicher Kernproteine}, pages = {195 S.}, year = {2000}, language = {de} } @phdthesis{Schwiertz2000, author = {Schwiertz, Andreas}, title = {Nachweis und Bedeutung ausgew{\"a}hlter Spezies der Gattung Eubacterium f{\"u}r den humanen Gastrointestinaltrakt}, pages = {123 S.}, year = {2000}, language = {de} } @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{Schulz2011, author = {Schulz, Nadja}, title = {Die Rolle der 3-L-Hydroxyacyl-Coenzym-A-Dehydrogenase in der Regulation des {\"o}rpergewichts, der Thermogenese sowie der Glucosehom{\"o}ostase}, address = {Potsdam}, pages = {92 S.}, year = {2011}, language = {de} } @phdthesis{Schroeder1999, author = {Schr{\"o}der, Insa Sigrid}, title = {Toxikologische Untersuchungen von Isothiocyanat-Proteinderivaten}, pages = {122 S.}, year = {1999}, language = {de} } @phdthesis{Schraplau2017, author = {Schraplau, Anne}, title = {Regulation der Expression von Xenobiotika-metabolisierenden Enzymen und Deiodasen durch die Xenobiotika-abh{\"a}ngige wechselseitige Induktion von Xenosensor-Transkriptionsfaktoren und Prostaglandin E2}, school = {Universit{\"a}t Potsdam}, pages = {x, 241}, year = {2017}, language = {de} } @phdthesis{Schoefer2002, author = {Schoefer, Lilian}, title = {Transformation of flavonoids by bacteria from the human intestinal tract}, pages = {65 S.}, year = {2002}, language = {en} } @phdthesis{Schneider2008, author = {Schneider, Mandy}, title = {Entwicklung eines Multitarget-DNA-Assays zur Detektion von Mutationen in pr{\"a}neoplastischen und neoplastischen L{\"a}sionen im humanen Kolon und Rektum}, address = {Potsdam}, pages = {147 S.}, year = {2008}, language = {de} } @phdthesis{Schneider1999, author = {Schneider, Heiko}, title = {Abbau von Flavonoiden durch Mikroorganismen des Gastrointestinaltrakts}, publisher = {Logos-Verl.}, address = {Berlin}, isbn = {3-89722-330-9}, pages = {VII, 172 S. : graph. Darst.}, year = {1999}, language = {de} } @phdthesis{Schmiedeberg2004, author = {Schmiedeberg, Kristin}, title = {Molekulare Klonierung, Charakterisierung und Struktur-Funktions-Beziehungen von olfaktorischen Rezeptoren f{\"u}r Schl{\"u}sselaromastoffe}, address = {Potsdam}, pages = {120 Bl. : graph. Darst.}, year = {2004}, language = {de} } @phdthesis{Schmiedchen2014, author = {Schmiedchen, Bettina}, title = {Vitamin D and its linkage between chronic kidney disease and cardiovascular integrity}, pages = {113}, year = {2014}, language = {en} } @phdthesis{Schmidt2007, author = {Schmidt, Stefan}, title = {Die Rolle von Glucosetransportern der GLUT-Familie f{\"u}r die Glucosehom{\"o}ostase und als Glucosesensor}, address = {Potsdam}, pages = {114 S. : Ill., graph. Darst.}, year = {2007}, language = {de} } @phdthesis{Schiess2015, author = {Schiess, Sonja}, title = {Effects of glucotropaeolin and its breakdown product benzyl isothiocyanate on metabolic, endocrine, and inflammatory parameters in humans}, school = {Universit{\"a}t Potsdam}, pages = {115}, year = {2015}, language = {en} } @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{Scherwinski2015, author = {Scherwinski, Ann-Christin}, title = {Die Phyllosph{\"a}re}, school = {Universit{\"a}t Potsdam}, pages = {83}, year = {2015}, language = {de} } @phdthesis{Scherneck2007, author = {Scherneck, Stephan}, title = {Identifizierung eines diabetogenen Allels im Suszeptibilit{\"a}tslocus Nidd/SJL der Maus}, address = {Potsdam}, pages = {85 Bl : Ill., graph. Darst.}, year = {2007}, language = {de} } @phdthesis{Schell2022, author = {Schell, Mareike}, title = {Investigating the effect of Lactobacillus rhamnosus GG on emotional behavior in diet-induced obese C57BL/6N mice}, school = {Universit{\"a}t Potsdam}, pages = {XVI, 117}, year = {2022}, abstract = {The prevalence of depression and anxiety is increased in obese patients compared to healthy humans, which is partially due to a shared pathogenesis, including insulin resistance and inflammation. These factors are also linked to intestinal dysbiosis. Additionally, the chronic consumption of diets rich in saturated fats results in body weight gain, hormonal resistances and unfavorable changes in the microbiome composition. The intake of Lactobacilli has already been shown to improve dysbiosis along with metabolism and mood. Yet, the beneficial role and the underlying mechanism of Lactobacillus rhamnosus GG (LGG) to improve emotional behavior in established diet-induced obese conditions are, so far, unknown. To characterize the role of LGG in diet-induced obesity, female and male C57BL/6N mice were fed a semi-synthetic low-fat diet (LFD, 10 \% kcal from fat) or a conventional high-fat diet (HFD, 45 \% kcal from fat) for initial 6 weeks, which was followed by daily oral gavage of vehicle or 1x10^8 CFU of LGG until the end of the experiment. Mice were subjected to basic metabolic and extensive behavioral phenotyping, with a focus on emotional behavior. Moreover, composition of cecal gut microbiome, metabolomic profile in plasma and cerebrospinal fluid was investigated and followed by molecular analyses. Both HFD-feeding and LGG application resulted in sex-specific differences. While LGG prevented the increase of plasma insulin, adrenal gland weight and hyperactivity in diet-induced obese female mice, there was no regulation of anxiodepressive-like behavior. In contrast, metabolism of male mice did not benefit from LGG application, but strikingly, LGG decreased specifically depressive-like behavior in the Mousetail Suspension Test which was confirmed by the Splash Test characterizing motivation for 'self-care'. The microbiome analysis in male mice revealed that HFD-feeding, but not LGG application, altered cecal microbiome composition, indicating a direct effect of LGG on behavioral regulation. However, in female mice, both HFD-feeding and LGG application resulted in changes of microbiome composition, which presumably affected metabolism. Moreover, as diet-induced obese female mice unexpectedly did not exhibit anxiodepressive-like behavior, follow-up analyses were conducted in male mice. Here, HFD-feeding significantly altered abundance of plasma lipids whereas LGG decreased branched chain amino acids which associated with improved emotional behavior. In nucleus accumbens (NAcc) and VTA/SN, which belong to the dopaminergic system, LGG restored HFD-induced decrease of tyrosine hydroxylase, the rate-limiting enzyme in dopamine synthesis, on gene expression level. Lastly, transcriptome analysis in the NAcc identified gene expression of cholecystokinin as a potential mediator of the effect of LGG on HFD-induced emotional alterations. In summary, this thesis revealed the beneficial effects of LGG application on emotional alterations in established diet-induced obesity. Furthermore, both HFD-feeding and LGG treatment exhibited sex-specific effects, resulting in metabolic improvements in female mice while LGG application mitigated depressive-like behavior in obese male mice along with a molecular signature of restored dopamine synthesis and neuropeptide signaling.}, language = {en} } @phdthesis{Scheepers2003, author = {Scheepers, Andrea}, title = {Charakterisierung der genomischen Organisation, Expression und Funktion der Glucosetransporter GLUT8 und GLUT11}, pages = {111 S.}, year = {2003}, 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{Sachse2015, author = {Sachse, Benjamin Christian Daniel}, title = {Metabolische Aktivierung und Inaktivierung der genotoxischen Nahrungsmittelinhaltsstoffe 5-Hydroxymethylfurfural und Furfurylalkohol in Mensch, Maus und Ratte}, pages = {I-IV, 172, i-v}, year = {2015}, language = {de} } @phdthesis{Roediger2017, author = {R{\"o}diger, Maria}, title = {The Impact of the ARFRP1 Action at the Golgi Apparatus on Adipocyte Function}, school = {Universit{\"a}t Potsdam}, pages = {116}, year = {2017}, language = {en} } @phdthesis{Rohn2002, author = {Rohn, Sascha}, title = {Reaktionen von phenolischen Verbindungen als Inhaltsstoffe pflanzlicher Lebensmittel mit ausgew{\"a}hlten Enzymen : Einfluss auf physikochemische Proteineigenschaften und Enzymaktivit{\"a}t}, publisher = {Logos}, address = {Berlin}, isbn = {3-8325-0079-0}, pages = {152 S.}, year = {2002}, language = {de} } @phdthesis{Rohn, author = {Rohn, Isabelle}, title = {Food-relevant selenium species}, school = {Universit{\"a}t Potsdam}, pages = {132,VIII}, 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{Rinne2024, author = {Rinne, Theresa Charlotte}, title = {The effects of nutrients on bone stem cell function and regeneration}, school = {Universit{\"a}t Potsdam}, pages = {V, 134}, year = {2024}, abstract = {Aging is associated with bone loss, which can lead to osteoporosis and high fracture risk. This coincides with the enhanced formation of bone marrow adipose tissue (BMAT), suggesting a negative effect of bone marrow adipocytes on skeletal health. Increased BMAT formation is also observed in pathologies such as obesity, type 2 diabetes and osteoporosis. However, a subset of bone marrow adipocytes forming the constitutive BMAT (cBMAT), arise early in life in the distal skeleton, contain high levels of unsaturated fatty acids and are thought to provide a physiological function. Regulated BMAT (rBMAT) forms during aging and obesity in proximal regions of the bone and contain a large proportion of saturated fatty acids. Paradoxically, BMAT accumulation is also enhanced during caloric restriction (CR), a life-span extending dietary intervention. This indicates, that different types of BMAT can form in response to opposing nutritional stimuli with potentially different functions. To this end, two types of nutritional interventions, CR and high fat diet (HFD), that are both described to induce BMAT accumulation were carried out. CR markedly increased BMAT formation in the proximal tibia and led to a higher proportion of unsaturated fatty acids, making it similar to the physiological cBMAT. Additionally, proximal and diaphyseal tibia regions displayed higher adiponectin expression. In aged mice, CR was associated with an improved trabecular bone structure. Taken together, these findings demonstrate, that the type of BMAT that forms during CR might provide beneficial effects for local bone stem/progenitor cells and metabolic health. The HFD intervention performed in this thesis showed no effect on BMAT accumulation and bone microstructure. RNA Seq analysis revealed alterations in the composition of the collagen-containing extracellular matrix (ECM). In order to investigate the effects of glucose homeostasis on osteogenesis, differentiation capacity of immortalized multipotent mesenchymal stromal cells (MSCs) and osteochondrogenic progenitor cells (OPCs) was analyzed. Insulin improved differentiation in both cell types, however, combination of with a high glucose concentration led to an impaired mineralization of the ECM. In the MSCs, this was accompanied by the formation of adipocytes, indicating negative effects of the adipocytes formed during hyperglycemic conditions on mineralization processes. However, the altered mineralization pattern and structure of the ECM was also observed in OPCs, which did not form any adipocytes, suggesting further negative effects of a hyperglycemic environment on osteogenic differentiation. In summary, the work provided in this thesis demonstrated that differentiation commitment of bone-resident stem cells can be altered through nutrient availability, specifically glucose. Surprisingly, both high nutrient supply, e.g. the hyperglycemic cell culture conditions, and low nutrient supply, e.g. CR, can induce adipogenic differentiation. However, while CR-induced adipocyte formation was associated with improved trabecular bone structure, adipocyte formation in a hyperglycemic cell-culture environment hampered mineralization. This thesis provides further evidence for the existence of different types of BMAT with specific functions.}, 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{Reinke2016, author = {Reinke, Julia}, title = {The Role of Kallistatin in Energy Metabolism and Glucose Homeostasis in Mice}, school = {Universit{\"a}t Potsdam}, pages = {77}, year = {2016}, 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{Reichardt2008, author = {Reichardt, Nicole}, title = {Die Abbaubarkeit hochmolekularer Inhaltsstoffe des Kaffeegetr{\"a}nks durch die humane Darmmikrobiota}, address = {Potsdam}, pages = {107 Bl. : Ill., graph. Darst.}, year = {2008}, language = {de} } @phdthesis{Reeg2016, author = {Reeg, Sandra}, title = {Degradation of oxidized proteins by the proteasome - Involvement of chaperones and the ubiquitin-system}, school = {Universit{\"a}t Potsdam}, pages = {117}, year = {2016}, language = {en} } @phdthesis{Rawel2002, author = {Rawel, Harshadrai Manilal}, title = {Reactions of selected secondary plant metabolites (glucosinolates and phenols) with food proteins and enzymes- influence on physico-chemical protein properties, enzyme activity and proteolytic degradation}, pages = {51 S. ; Anhang}, year = {2002}, 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{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{RadeKukic2009, author = {Rade-Kukic, Koraljka}, title = {Interactionof ß-lactoglobulin with sinigin and allyl-isothiocyanate - effect on protein's physico- chemical and functional properties}, address = {Potsdam}, pages = {123, VIII S.}, year = {2009}, language = {en} } @phdthesis{Prandi2015, author = {Prandi, Simone}, title = {Characterization of the expression and function of bitter taste receptor genes in gastrointestinal tissues}, school = {Universit{\"a}t Potsdam}, pages = {165}, year = {2015}, language = {en} } @phdthesis{Ott2013, author = {Ott, Ina Mirijam}, title = {Alternative Therapieans{\"a}tze im murinen Modell der diabetischen Nephropathie : Stimulation der l{\"o}slichen Guanylatzyklase und Inhabition der Dipeptidylpeptidase-4}, address = {Potsdam}, pages = {116 S.}, year = {2013}, language = {de} } @phdthesis{Ott2016, author = {Ott, Christiane}, title = {Untersuchung der intrazellul{\"a}ren Proteolyse w{\"a}hrend der Zellalterung}, school = {Universit{\"a}t Potsdam}, pages = {100}, year = {2016}, language = {de} } @phdthesis{Nowotny2016, author = {Nowotny, Kerstin}, title = {The impact of collagen modifications by methylglyoxal on fibroblast function and the role in aging}, school = {Universit{\"a}t Potsdam}, pages = {107}, year = {2016}, 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{NeuschaeferRube2003, author = {Neusch{\"a}fer-Rube, Frank}, title = {Struktur-Funktionsbeziehungen von Postaglandinrezeptoren sowie transkriptionelle und posttranslationale Regulation ihrer Aktivit{\"a}t}, pages = {Getr. Z{\"a}hlung}, year = {2003}, language = {de} } @phdthesis{Neumann2014, author = {Neumann, Franziska}, title = {In vitro-Charakterisierung von TBC1D1 und funktionelle Untersuchung an murinen Inselzellen des Pankreas}, pages = {167}, year = {2014}, language = {de} } @phdthesis{Neuber2017, author = {Neuber, Corinna}, title = {Analytik zur Biotransformation des Sphingosin 1-phosphat-abbauproduktes (2E)-Hexadecenal}, school = {Universit{\"a}t Potsdam}, pages = {161}, year = {2017}, language = {de} } @phdthesis{Mueller2006, author = {M{\"u}ller, Susanne}, title = {Einfluss von Alter und Ern{\"a}hrung auf die Zusammensetzung der intestinalen Mikrobiota und auf ausgew{\"a}hlte Parameter der Darmfunktion bei vier europ{\"a}ischen Studiengruppen (Querschnittstudie)}, address = {Potsdam}, pages = {IX, 113 Bl. : graph. Darst.}, year = {2006}, language = {de} } @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{Mueller1999, author = {M{\"u}ller, Cordula}, title = {Die gastrointestinale Glutathionperoxidase : eine intestinale Barriere gegen die Resorption von Lipidhydroperoxiden?}, address = {Potsdam}, pages = {X, 117 S. : graph. Darst.}, year = {1999}, language = {de} } @phdthesis{Mueller2009, author = {M{\"u}ller, Carsten}, title = {Nachweis antioxidativer und chemopr{\"a}ventiver Eigenschaften von Naturstoffen zur Verwendung als potenzielle Nahrungserg{\"a}nzungsmittel}, address = {Potsdam}, pages = {139 Bl. : graph. Darst.}, year = {2009}, language = {de} } @phdthesis{Muehlenbruch2013, author = {M{\"u}hlenbruch, Kristin}, title = {Updating the german diabetes risk score - model extensions, validation and reclassification}, address = {Potsdam}, pages = {131 S.}, year = {2013}, language = {en} } @phdthesis{Monien2012, author = {Monien, Bernhard}, title = {LC-MS/MS-Methoden zur Untersuchung von Bildung, Transport und Gentoxizit{\"a}t reaktiver Sulfatester einiger Lebensmittelkanzerogene}, address = {Potsdam}, pages = {119 S.}, year = {2012}, language = {de} } @phdthesis{Mohan2006, author = {Mohan, Ruchika}, title = {Microbial colonization of the gastrointestinal tract of preterm infants: Microbial diversity and new ways of prevention of infections}, address = {Potsdam}, pages = {VII, 102 Bl. : graph. Darst.}, year = {2006}, language = {en} } @phdthesis{Mirhashemi2011, author = {Mirhashemi, Farshad}, title = {Einfluss von Fetten und Kohlenhydraten auf die Entwicklung der Insulinresistenz und des Typ-2-Diabetes in verschiedenen Mausmodellen}, address = {Potsdam}, pages = {122 S.}, year = {2011}, language = {de} } @phdthesis{Meyer2015, author = {Meyer, S{\"o}ren}, title = {Toxicity and toxicokinetics of arsenolipids and their metabolites}, school = {Universit{\"a}t Potsdam}, pages = {152, VIII}, year = {2015}, language = {en} } @phdthesis{Metges2000, author = {Metges, Cornelia C.}, title = {Investigations on kinetics and dietary requirements of amino acids in healthy adults using stable isotope tracer techniques}, pages = {128 S.}, year = {2000}, language = {en} } @phdthesis{Matzke2014, author = {Matzke, Daniela}, title = {Einfluss des Adipositas-QTL Nob3 auf die Entstehung von Typ-2-Diabetes in schlanken und adip{\"o}sen Mausmodellen}, pages = {119}, year = {2014}, language = {de} } @phdthesis{Matthies2012, author = {Matthies, Anastasia}, title = {Die Rolle der Darmbakterien bei der Bioaktivierung von Isoflavonen}, address = {Potsdam}, pages = {121 S.}, year = {2012}, language = {de} } @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{Marschall2017, author = {Marschall, Talke Anu}, title = {Zytotoxizit{\"a}t, Bioverf{\"u}gbarkeit und Metabolismus kleiner Selenspezies in humanen Zellen und Entwicklung von ICP-QQQ-MS-basierten Methoden f{\"u}r deren Nachweis}, school = {Universit{\"a}t Potsdam}, pages = {115, VI}, year = {2017}, language = {de} } @phdthesis{Marinovic2003, author = {Marinovic, Morana}, title = {Ver{\"a}nderungen der PKC-Isoenzym-, der NF-KB- und der ß-Catenin-Muster bei der kolorektalen Karzinogenese und chronisch-entz{\"u}ndlichen Darmerkrankungen; effekt der resistenten St{\"a}rketyp III am TNBS und DMH-Modell}, pages = {157 S.}, year = {2003}, language = {de} } @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{Luckert2016, author = {Luckert, Claudia}, title = {Molekulare Mechanismen von hepatotoxischen Pyrrolizidinalkaloiden}, school = {Universit{\"a}t Potsdam}, pages = {127, LXXVII}, year = {2016}, language = {de} } @phdthesis{LopesFernando2023, author = {Lopes Fernando, Raquel Sofia}, title = {The impact of aging on proteolytic systems, transcriptome and metabolome of slow and fast muscle fiber types}, doi = {10.25932/publishup-60579}, school = {Universit{\"a}t Potsdam}, pages = {XI, 125}, year = {2023}, abstract = {Aging is a complex process characterized by several factors, including loss of genetic and epigenetic information, accumulation of chronic oxidative stress, protein damage and aggregates and it is becoming an emergent drug target. Therefore, it is the utmost importance to study aging and agerelated diseases, to provide treatments to develop a healthy aging process. Skeletal muscle is one of the earliest tissues affected by age-related changes with progressive loss of muscle mass and function from 30 years old, effect known as sarcopenia. Several studies have shown the accumulation of protein aggregates in different animal models, as well as in humans, suggesting impaired proteostasis, a hallmark of aging, especially regarding degradation systems. Thus, different publications have explored the role of the main proteolytic systems in skeletal muscle from rodents and humans, like ubiquitin proteasomal system (UPS) and autophagy lysosomal system (ALS), however with contradictory results. Yet, most of the published studies are performed in muscles that comprise more than one fiber type, that means, muscles composed by slow and fast fibers. These fiber types, exhibit different metabolism and contraction speed; the slow fibers or type I display an oxidative metabolism, while fast fibers function towards a glycolytic metabolism ranging from fast oxidative to fast glycolytic fibers. To this extent, the aim of this thesis sought to understand on how aging impacts both fiber types not only regarding proteostasis but also at a metabolome and transcriptome network levels. Therefore, the first part of this thesis, presents the differences between slow oxidative (from Soleus muscle) and fast glycolytic fibers (Extensor digitorum longus, EDL) in terms of degradation systems and how they cope with oxidative stress during aging, while the second part explores the differences between young and old EDL muscle transcriptome and metabolome, unraveling molecular features. More specifically, the results from the present work show that slow oxidative muscle performs better at maintaining the function of UPS and ALS during aging than EDL muscle, which is clearly affected, accounting for the decline in the catalytic activity rates and accumulation of autophagy-related proteins. Strinkingly, transcriptome and metabolome analyses reveal that fast glycolytic muscle evidences significant downregulation of mitochondrial related processes and damaged mitochondria morphology during aging, despite of having a lower oxidative metabolism compared to oxidative fibers. Moreover, predictive analyses reveal a negative association between aged EDL gene signature and lifespan extending interventions such as caloric restriction (CR). Although, CR intervention does not alter the levels of mitochondrial markers in aged EDL muscle, it can reverse the higher mRNA levels of muscle damage markers. Together, the results from this thesis give new insights about how different metabolic muscle fibers cope with age-related changes and why fast glycolytic fibers are more susceptible to aging than slow oxidative fibers.}, language = {en} } @phdthesis{Lohren2015, author = {Lohren, Hanna}, title = {Mechanisms of mercury species-mediated neurotoxicity}, school = {Universit{\"a}t Potsdam}, pages = {141, viii}, year = {2015}, language = {en} } @phdthesis{Lippmann2013, author = {Lippmann, Doris}, title = {Der Einfluss glucosinolatreicher Brassica Gem{\"u}se auf das endogene Schutzsystem und die entz{\"u}ndungsassoziierte Colonkanzerogenese in der Maus}, address = {Potsdam}, pages = {105 S.}, year = {2013}, 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{Leicht2008, author = {Leicht, Katja}, title = {Positionelle Klonierung von Tbc1d1 als Kandidatengen f{\"u}r Adipositas}, address = {Potsdam}, pages = {[10], 106, [32] Bl. : graph. Darst.}, year = {2008}, language = {de} } @phdthesis{LehnerWieternik2005, author = {Lehner-Wieternik, Angelika}, title = {Die Bedeutung des Instruktionsdesigns f{\"u}r die Entwicklung und Gestaltung computerbasierter Lehr- und Lernsysteme}, pages = {240 S. : Ill., graph. Darst.}, year = {2005}, language = {de} } @phdthesis{Lehmann2013, author = {Lehmann, Carsten}, title = {Glucosinolate in der entz{\"u}ndungsgetriebenen Kolonkanzerogenese - Induktion von Phase I und Phase II Enzymen sowie der Einfluss der intestinalen Mikrobiota}, address = {Potsdam}, pages = {117 S.}, year = {2013}, language = {de} } @phdthesis{Lang2014, author = {Lang, Iris Scarlett}, title = {Fetal programming of growth and metabolism by maternal dietary composition}, pages = {99}, year = {2014}, language = {en} } @phdthesis{Koenig2017, author = {K{\"o}nig, Jeannette}, title = {Lipofuscin - Entstehung und Rolle in der Zellalterung}, school = {Universit{\"a}t Potsdam}, pages = {115}, year = {2017}, language = {de} } @phdthesis{Kutschera2010, author = {Kutschera, Maren}, title = {Interaktionen von Flavanolen mit der humanen intestinalen Mikrobiota}, address = {Potsdam}, pages = {X, 113 S.}, year = {2010}, language = {de} } @phdthesis{Kuhlow2007, author = {Kuhlow, Doreen}, title = {Mitochondriale Dysfunktion aufgrund Frataxinmangels induziert ern{\"a}hrungsabh{\"a}ngig Symptome des Metabolischen Syndroms in der Maus}, address = {Potsdam}, pages = {131 Bl. : graph. Darst.}, year = {2007}, language = {de} } @phdthesis{Kuhlow2001, author = {Kuhlow, Andreas}, title = {Bildung, Verteilung und DNA-Bindung des reaktiven Sulfatesters 1-Sulfooxymethylpyren in der Ratte}, pages = {98 S.}, year = {2001}, language = {de} } @phdthesis{Kucia2009, author = {Kucia, Marzena}, title = {Impact of a high protein diet on maternal health status, milk composition and rearing success during pregnancy and lactation of two mouse genotypes}, address = {Potsdam}, pages = {X, 109 Bl. : graph. Darst.}, year = {2009}, language = {en} } @phdthesis{Kohl2008, author = {Kohl, Angela}, title = {Einfluss zweier unl{\"o}slicher Ballaststoffe auf ausgesuchte Parameter des Metabolischen Syndroms bei {\"u}bergewichtigen/adip{\"o}sen gesunden Erwachsenen}, address = {Potsdam}, pages = {113 S.}, year = {2008}, language = {de} } @phdthesis{Koelman2023, author = {Koelman, Liselot A.}, title = {The role of diet in immune health and ageing}, school = {Universit{\"a}t Potsdam}, year = {2023}, language = {en} } @phdthesis{Knoche2022, author = {Knoche, Lisa}, title = {Untersuchung von Transformationsprodukten ausgew{\"a}hlter Tierarzneimittel generiert durch Elektrochemie, Mikrosomal Assay, Hydrolyse und Photolyse}, pages = {163, III}, year = {2022}, abstract = {The knowledge of transformation pathways and transformation products of veterinary drugs is important for health, food and environmental matters. Residues, consisting of original veterinary drug and transformation products, are found in food products of animal origin as well as the environment (e.g., soil or surface water). Several transformation processes can alter the original veterinary drug, ranging from biotransformation in living organism to environmental degradation processes like photolysis, hydrolysis, or microbial processes. In this thesis, four veterinary drugs were investigated, three ionophore antibiotics Monensin, Salinomycin and Lasalocid and the macrocyclic lactone Moxidectin. Ionophore antibiotics are mainly used to cure and prevent coccidiosis in poultry especially prophylactic in broiler farming. Moxidectin is an antiparasitic drug that is used for the treatment of internal and external parasites in food-producing and companion animals. The main objective of this work is to employ different laboratory approaches to generate and identify transformation products. The identification was conducted using high-resolution mass spectrometry (HRMS). A major focus was placed on the application of electrochemistry for simulation of transformation processes. The electrochemical reactor - equipped with a three-electrode flow-through cell - enabled the oxidation or reduction by applying a potential. The transformation products derived were analyzed by online coupling of the electrochemical reactor and a HRMS and offline by liquid chromatography (LC) combined with HRMS. The main modification reaction of the identified transformation products differed for each investigated veterinary drug. Monensin showed decarboxylation and demethylation as the main modification reactions, for Salinomycin mostly decarbonylation occurred and for Lasalocid methylation was prevalent. For Moxidectin, I observed an oxidation (hydroxylation) reaction and adduct formation with solvent. In general, for Salinomycin and Lasalocid, more transient transformation products (online measurement) than stable transformation products (offline measurements) were detected. By contrast, the number of transformation products using online and offline measurements were identical for Monensin and Moxidectin. As a complementary approach, metabolism tests with rat or human liver microsomes were conducted for the ionophore antibiotics. Monensin was investigated by using rat liver microsomes and the transformation products identified were based on decarboxylation and demethylation. Salinomycin and Lasalocid were converted by human and rat liver microsomes. For both substances, more transformation products were found by using human liver microsomes. The transformation products of the rat liver microsome conversion were redundant, and the transformation products were also found at the human liver microsome assay. Oxidation (hydroxylation) was found to be the main modification reaction for both. In addition, a frequent ion exchange between sodium and potassium was identified. The final two experiments were performed for one substance each, whereby the hydrolysis of Monensin and the photolysis of Moxidectin was investigated. The transformation products of the pH-dependent hydrolysis were based on ring-opening and dehydration. Moxidectin formed several transformation products by irradiation with UV-C light and the main modification reactions were isomeric changes, (de-)hydration and changes of the methoxime moiety. In summary, transformation products of the four investigated veterinary drugs were generated by the different laboratory approaches. Most of the transformation products were identified for the first time. The resulting findings provide an improved understanding of clarifying the transformation behavior.}, language = {en} } @phdthesis{Khalil2013, author = {Khalil, Mahmoud Abd Elhamid}, title = {Improvement of stability and bioavailability of lutein and lutein ester in emulsion-based delivery systems}, address = {Potsdam}, pages = {145 S.}, year = {2013}, language = {en} } @phdthesis{Keipert2011, author = {Keipert, Susanne}, title = {The effects of mitochondrial uncoupling in skeletal muscle on lifespan, substrate and energy metabolism in mice}, address = {Potsdam}, pages = {75 S.}, year = {2011}, 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{Kamitz2016, author = {Kamitz, Anne}, title = {Identification and positional cloning of Ltg/NZO; a novel susceptibility locus associated with fatty liver disease}, school = {Universit{\"a}t Potsdam}, pages = {102}, year = {2016}, language = {en} }