@article{ChaykovskaHeunischvonEinemetal.2016,
  author    = {Chaykovska, Lyubov and Heunisch, Fabian and von Einem, Gina and Alter, Markus L. and Hocher, Carl-Friedrich and Tsuprykov, Oleg and Dschietzig, Thomas and Kretschmer, Axel and Hocher, Berthold},
  title     = {Urinary Vitamin D Binding Protein and KIM-1 Are Potent New Biomarkers of Major Adverse Renal Events in Patients Undergoing Coronary Angiography},
  series = {PLoS one},
  volume    = {11},
  journal   = {PLoS one},
  publisher = {PLoS},
  address   = {San Fransisco},
  issn      = {1932-6203},
  doi       = {10.1371/journal.pone.0145723},
  pages     = {11},
  year      = {2016},
  abstract  = {Background Vitamin-D-binding protein (VDBP) is a low molecular weight protein that is filtered through the glomerulus as a 25-(OH) vitamin D 3/VDBP complex. In the normal kidney VDBP is reabsorbed and catabolized by proximal tubule epithelial cells reducing the urinary excretion to trace amounts. Acute tubular injury is expected to result in urinary VDBP loss. The purpose of our study was to explore the potential role of urinary VDBP as a biomarker of an acute renal damage. Method We included 314 patients with diabetes mellitus or mild renal impairment undergoing coronary angiography and collected blood and urine before and 24 hours after the CM application. Patients were followed for 90 days for the composite endpoint major adverse renal events (MARE: need for dialysis, doubling of serum creatinine after 90 days, unplanned emergency rehospitalization or death). Results Increased urine VDBP concentration 24 hours after contrast media exposure was predictive for dialysis need (no dialysis: 113.06 +/- 299.61ng/ml, n = 303; need for dialysis: 613.07 +/- 700.45 ng/ml, n = 11, Mean +/- SD, p < 0.001), death (no death during follow-up: 121.41 +/- 324.45 ng/ml, n = 306; death during follow-up: 522.01 +/- 521.86 ng/ml, n = 8; Mean +/- SD, p < 0.003) and MARE (no MARE: 112.08 +/- 302.00ng/ml, n = 298; MARE: 506.16 +/- 624.61 ng/ml, n = 16, Mean +/- SD, p < 0.001) during the follow-up of 90 days after contrast media exposure. Correction of urine VDBP concentrations for creatinine excretion confirmed its predictive value and was consistent with increased levels of urinary Kidney Injury Molecule1 (KIM-1) and baseline plasma creatinine in patients with above mentioned complications. The impact of urinary VDBP and KIM-1 on MARE was independent of known CIN risk factors such as anemia, preexisting renal failure, preexisting heart failure, and diabetes. Conclusions Urinary VDBP is a promising novel biomarker of major contrast induced nephropathy-associated events 90 days after contrast media exposure.},
  language  = {en}
}
@article{NaglLouiRailaetal.2009,
  author    = {Nagl, Britta and Loui, Andrea and Raila, Jens and Felderhoff-Mueser, Ursula and Obladen, Michael and Schweigert, Florian J.},
  title     = {Urinary vitamin A excretion in very low birth weight infants},
  issn      = {0931-041X},
  doi       = {10.1007/s00467-008-0965-0},
  year      = {2009},
  abstract  = {Vitamin A (VA) deficiency in very low birth weight (VLBW) infants is associated with an increased risk for disorders related to kidney and lung maturation and function. VA losses through increased urinary retinol (ROH) excretion might contribute to this deficiency risk. The mechanism accounting for ROH loss in the urine has not yet been clarified. The aim of this study was to assess the excretion of ROH, retinol-binding protein 4 (RBP4) and transthyretin (TTR) in urine from VLBW infants in comparison with that in term infants in relation to kidney function. Urine specimens were collected from 15 VLBW infants (birth weight < 1,500 g) as well as from 20 term infants during the first 2 days after birth. ROH in urine was detectable in 14 of the 15 VLBW infants at a median concentration of 234 nmol/g creatinine. In the group of term infants, 17 of the 20 excreted ROH, but at an approximately five-times lower concentration (P<0.001). Excretion of RBP4 and TTR was also much higher in VLBW infants (both P<0.001). The urinary ROH excretion in VLBW infants may be related to the impaired tubular handling of its carrier proteins RBP4 and TTR. Thus, ROH excretion might contribute to an increased risk of VA deficiency, especially in VLBW infants.},
  language  = {en}
}
@article{HeunischvonEinemAlteretal.2014,
  author    = {Heunisch, Fabian and von Einem, Gina and Alter, Markus L. and Weist, Andreas and Dschietzig, Thomas and Kretschmer, Axel and Hocher, Berthold},
  title     = {Urinary ET-1 excretion after exposure to radio-contrast media in diabetic patients and patients with preexisting mild impaired renal function},
  series = {Life sciences : molecular, cellular and functional basis of therapy},
  volume    = {118},
  journal   = {Life sciences : molecular, cellular and functional basis of therapy},
  number    = {2},
  publisher = {Elsevier},
  address   = {Oxford},
  issn      = {0024-3205},
  doi       = {10.1016/j.lfs.2013.12.233},
  pages     = {440 -- 445},
  year      = {2014},
  abstract  = {Aims: Contrast media-induced nephropathy (CIN) is associated with increased morbidity and mortality. The renal endothelin system has been associated with disease progression of various acute and chronic renal diseases. However, robust data coming from adequately powered prospective clinical studies analyzing the short and long-term impacts of the renal ET system in patients with CIN are missing so far. We thus performed a prospective study addressing this topic. Main methods: We included 327 patients with diabetes or renal impairment undergoing coronary angiography. Blood and spot urine were collected before and 24 h after contrast media (CM) application. Patients were followed for 90 days for major clinical events like need for dialysis, unplanned rehospitalization or death. Key findings: The concentration of ET-1 and the urinary ET-1/creatinine ratio decreased in spot urine after CM application (ET-1 concentration: 0.91 +/- 1.23pg/ml versus 0.63 +/- 1.03pg/ml, p<0.001; ET-1/creatinine ratio: 0.14 +/- 0.23 versus 0.09 +/- 0.19, p<0.001). The urinary ET-1 concentrations in patients with CIN decreased significantly more than in patients without CIN (-0.26 +/- 1.42pg/ml vs. -0.79 +/- 1.69pg/ml, p=0.041), whereas the decrease of the urinary ET-1/creatinine ratio was not significantly different (non-CIN patients: -0.05 +/- 0.30; CIN patients: -0.11 +/- 0.21, p=0.223). Urinary ET-1 concentrations as well as the urinary ET-1/creatinine ratio were not associated with clinical events (need for dialysis, rehospitalization or death) during the 90day follow-up after contrast media exposure. However, the urinary ET-1 concentration and the urinary ET-1/creatinine ratio after CM application were higher in those patients who had a decrease of GFR of at least 25\% after 90days of follow-up. Significance: In general the ET-1 system in the kidney seems to be down-regulated after contrast media application in patients with moderate CIN risk. Major long-term complications of CIN (need for dialysis, rehospitalization or death) are not associated with the renal ET system. (C) 2014 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license.},
  language  = {en}
}
@article{ChaykovskaHeunischvonEinemetal.2018,
  author    = {Chaykovska, Lyubov and Heunisch, Fabian and von Einem, Gina and Hocher, Carl-Friedrich and Tsuprykov, Oleg and Pavkovic, Mira and Sandner, Peter and Kretschmer, Axel and Chu, Chang and Elitok, Saban and Stasch, Johannes-Peter and Hocher, Berthold},
  title     = {Urinary cGMP predicts major adverse renal events in patients with mild renal impairment and/or diabetes mellitus before exposure to contrast medium},
  series = {PLoS one},
  volume    = {13},
  journal   = {PLoS one},
  number    = {4},
  publisher = {PLoS},
  address   = {San Fransisco},
  issn      = {1932-6203},
  doi       = {10.1371/journal.pone.0195828},
  pages     = {13},
  year      = {2018},
  abstract  = {Background The use of iodine-based contrast agents entails the risk of contrast induced nephropathy (CIN). Radiocontrast agents elicit the third most common cause of nephropathy among hospitalized patients, accounting for 11-12\% of cases. CIN is connected with clinically significant consequences, including increased morbidity, prolonged hospitalization, increased risk of complications, potential need for dialysis, and increased mortality rate. The number of in hospital examinations using iodine-based contrast media has been significantly increasing over the last decade. In order to protect patients from possible complications of such examinations, new biomarkers are needed that are able to predict a risk of contrast-induced nephropathy. Urinary and plasma cyclic guanosine monophosphate (cGMP) concentrations are influenced by renal function. Urinary cGMP is primarily of renal cellular origin. Therefore, we assessed if urinary cGMP concentration may predict major adverse renal events (MARE) after contrast media exposure during coronary angiography. Methods Urine samples were prospectively collected from non-randomized consecutive patients with either diabetes or preexisting impaired kidney function receiving intra-arterial contrast medium (CM) for emergent or elective coronary angiography at the Charite Campus Mitte, University Hospital Berlin. Urinary cGMP concentration in spot urine was analyzed 24 hours after CM exposure. Patients were followed up over 90 days for occurrence of death, initiation of dialysis, doubling of plasma creatinine concentration or MARE. Results In total, 289 consecutive patients were included into the study. Urine cGMP/creatinine ratio 24 hours before CM exposure expressed as mean +/- SD was predictive for the need of dialysis (no dialysis: 89.77 +/- 92.85 mu M/mM, n = 277; need for dialysis: 140.3 +/- 82.90 mu M/mM, n = 12, p = 0.008), death (no death during follow-up: 90.60 +/- 92.50 mu M/mM, n = 280; death during follow-up: 169.88 +/- 81.52 mu M/mM, n = 9; p = 0.002), and the composite endpoint MARE (no MARE: 86.02 +/- 93.17 mu M/mM, n = 271; MARE: 146.64 +/- 74.68 mu M/mM, n = 18, p<0.001) during the follow-up of 90 days after contrast media application. cGMP/creatinine ratio stayed significantly increased at values exceeding 120 pM/mM in patients who developed MARE, required dialysis or died. Conclusions Urinary cGMP/creatinine ratio >= 120 mu M/mM before CM exposure is a promising biomarker for the need of dialysis and all-cause mortality 90 days after CM exposure in patients with preexisting renal impairment or diabetes.},
  language  = {en}
}
@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}
}
@article{RailaBuchholzSchweigert1997,
  author    = {Raila, Jens and Buchholz, Ingeborg and Schweigert, Florian J.},
  title     = {Untersuchungen zur Vitamin-A-Bindung im Harn von Hunden},
  year      = {1997},
  language  = {de}
}
@article{KertiBaumaneBuchholzetal.1997,
  author    = {Kerti, A. and Baumane, Anita and Buchholz, Ingeborg and Schweigert, Florian J.},
  title     = {Untersuchungen zur Verteilung von Vitamin A im Reproduktionstrakt der Wachtel, Coturnix coturnix japonica},
  year      = {1997},
  language  = {de}
}
@phdthesis{Herbst2012,
  author    = {Herbst, Uta},
  title     = {Untersuchungen zur In-vitro-Zelltransformation in Dickdarmepithelzellen des Menschen und D{\"u}nndarmephithelzellen der Ratte durch Benzo(c)phenanthren-3,4-dihydrodiol-1,2-epoxide},
  address   = {Potsdam},
  pages     = {105 S.},
  year      = {2012},
  language  = {de}
}
@misc{Mazurek2007,
  author    = {Mazurek, Nicole},
  title     = {Untersuchungen zur Genexpression und Differenzierung muriner embryonaler Stammzellen in vitro zur Pr{\"a}diktion eines embryotoxischen Potentials ausgew{\"a}hlter Chemikalien},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus-68912},
  year      = {2007},
  abstract  = {Der Embryonale Stammzelltest (EST) ist ein validierter In-vitro-Embryotoxizit{\"a}tstest, der zur Untersuchung embryotoxischer Wirkungen von Chemikalien eingesetzt werden kann. W{\"a}hrend des zehnt{\"a}gigen Differenzierungsassays differenzieren sich die pluripotenten murinen embryonalen Stammzellen (ES-Zellen) der Linie D3 in vitro in spontan kontrahierende Herzmuskelzellen. Dabei rekapitulieren sie Prozesse der fr{\"u}hen Embryogenese in vivo. Ein Zytotoxizit{\"a}tsassay mit D3-Zellen und ausdifferenzierten, adulten 3T3-Maus-Fibroblasten dient der Ermittlung allgemeiner zytotoxischer Effekte und unterschiedlicher Sensitivit{\"a}ten beider Zelllinien. Somit basiert der EST auf den beiden wichtigsten Mechanismen pr{\"a}nataler Toxizit{\"a}t, der St{\"o}rung der Differenzierung und der Zytotoxizit{\"a}t. Ziel dieser Arbeit war es, mit Hilfe des EST das embryotoxische Potential der vier Chemikalien Trichostatin A (TSA), Methylazoxymethanolacetat (MAMac), Natriumdodecylsulfat (SDS) und Benzoes{\"a}ure (BA) abzusch{\"a}tzen. Dazu wurde mikroskopisch ermittelt, bei welcher Testsubstanzkonzentration in 50 \% der w{\"a}hrend der In-vitro-Differenzierung gebildeten Embryonalk{\"o}rperchen die Kardiomyozytendifferenzierung inhibiert wird (ID50). Außerdem wurde die halbmaximale Hemmkonzentration des Zellwachstums auf die beiden Zelllinien bestimmt (IC50D3 bzw. IC503T3). Als Erweiterung dieses konventionellen EST wurden mittels quantitativer Real Time-PCR an den Tagen 5, 7 und 10 der Differenzierung zus{\"a}tzlich Genexpressionsanalysen etablierter herzmuskelspezifischer Markergene (Mesoderm Posterior 1, Tag 5; Myosin light chain 1, Tag 7 und 10) durchgef{\"u}hrt. Deren Expression korreliert in den ES-Zellen mit der embryonalen Herzdifferenzierung in vivo und kann zur Ermittlung der von der Pr{\"u}fsubstanz hervorgerufenen halbmaximalen Hemmung der Genexpression in den Kardiomyozyten (IC50 Exp) herangezogen werden. Um letztlich embryotoxische Effekte in vivo auf Grundlage der ermittelten In-vitro-Daten absch{\"a}tzen zu k{\"o}nnen, wurden die ermittelten Parameter mittels eines f{\"u}r den EST empirisch abgeleiteten mathematischen Pr{\"a}diktionsmodells (PM) zur Klassifizierung der Testsubstanzen als nicht, schwach oder stark embryotoxisch herangezogen. F{\"u}r jede der Substanzen waren die ermittelten Halbhemmkonzentrationen in den {\"u}berwiegenden F{\"a}llen vergleichbar und f{\"u}hrten unter Verwendung des PMs im konventionellen und im molekularen EST zu deren identischer Klassifizierung. TSA wurde als „stark embryotoxisch" klassifiziert und beeinflusste insbesondere das Differenzierungspotential der ES-Zellen. Das als „schwach embryotoxisch" klassifizierte SDS wirkte auf die D3-Zellen st{\"a}rker differenzierungsinhibierend als zytotoxisch, hemmte jedoch das Wachstum der 3T3-Zellen bereits in deutlich niedrigeren Konzentrationen. MAMac und BA wurden als „nicht embryotoxisch" klassifiziert. Bei ihnen stand die zytotoxische Wirkung deutlich im Vordergrund. Diese Pr{\"a}diktionen stimmten mit In-vivo-Befunden {\"u}berein, was von der Stabilit{\"a}t und der Brauchbarkeit der im konventionellen und molekularen EST ermittelten Parameter zeugte. Einzige Ausnahme war das als Entwicklungsneurotoxin in vivo bekannte MAMac. Da der EST auf mesodermaler Differenzierung basiert, k{\"o}nnen spezifische Effekte auf neuronale Entwicklungsprozesse offenbar nicht vollst{\"a}ndig erfasst werden. Substanzkonzentrationen, die sich als differenzierungsinhibierend auf die morphologische Kardiomyozytendifferenzierung erwiesen haben, f{\"u}hrten auch zu einer messbaren Repression der herzmuskelspezifischen Genexpression. Dabei erwies sich die IC50 Exp als ebenso sensitiv wie die konventionellen Parameter und als nutzbringende Erg{\"a}nzung zu diesen, da sie bereits nach 5 bzw. 7 Tagen der In-vitro-Differenzierung eine mit dem mikroskopischen Parameter {\"u}bereinstimmende Einsch{\"a}tzung des embryotoxischen Potentials der Chemikalien in vivo erm{\"o}glichte. Genexpressionsanalysen weiterer differenzierungsspezifischer Gene k{\"o}nnen zus{\"a}tzlich zur Aufkl{\"a}rung zu Grunde liegender Mechanismen der Embryotoxizit{\"a}t von Testsubstanzen dienen. Somit kann der EST durch die Vorteile der Stammzelltechnologie und der Genexpressionsanalyse als neues pr{\"a}diktives Screening-Instrument zur fr{\"u}hzeitigen Detektion embryotoxischer Substanzeffekte in der pharmazeutischen und chemischen Industrie genutzt werden.},
  language  = {de}
}
@phdthesis{Fuchs2006,
  author    = {Fuchs, Iris Judith},
  title     = {Untersuchungen zur chemischen Transformation von intestinalen Epithelzellen der Ratte und des Menschen durch 2-Hydroxyamino-1-methyl-6-phenylimidazo(4,5-b)pyridin},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus-11807},
  school      = {Universit{\"a}t Potsdam},
  year      = {2006},
  abstract  = {Die Zahl der Kolonkarzinome in den westlichen Industriel{\"a}ndern steigt in den letzten Jahren stetig an. Zu den Verbindungen, die mit der Zubereitung der Nahrung entstehen, mit ihr aufgenommen werden und die Kolonkanzerogenese m{\"o}glicherweise beg{\"u}nstigen, geh{\"o}rt das heterozyklische aromatische PhIP, das bei der Erhitzung proteinreicher Nahrungsmittel entsteht. Neben zahlreichen F{\"u}tterungsversuchen an Nagern existieren auch Zellkulturmodelle zur Untersuchung der molekularen Mechanismen der PhIP-induzierten Kolonkanzerogenese. Die chemische Transformation von Zellen sollte durch wiederholte Exposition gegen{\"u}ber dem hydroxylierten Metaboliten des Kanzerogens (N2-OH-PhIP) erzielt werden. Es wurden IEC-18-Zellen der Ratte und HCEC-Zellen des Menschen zur Untersuchung verwendet. Die Behandlung der IEC-18-Zellen f{\"u}hrt nach 25 Behandlungszyklen mit Konzentrationen von 5 bis 20 µM nicht zur Transformation der Zellen. Die Anwesenheit von N2-OH-PhIP f{\"u}hrt zu einer zehnfach erh{\"o}hten Induktion der GST-Aktivit{\"a}t, insbesondere der Untereinheiten GST-A1, -A3, -Pi und -T2, die f{\"u}r die effiziente Detoxifizierung des N-Acetoxy-Metaboliten vom N2-OH-PhIP verantwortlich sind. Bereits nach drei Behandlungen mit 1,5 µM N2-OH-PhIP konnte eine maligne Transformation der HCEC-Zellen erzielt werden. Die Zellen zeigten die charakteristischen Zeichen der Transformation: ver{\"a}nderte Wachstumseigenschaften wie klonales dreidimensionales Zellwachstum („pilling up"), Hemmung der Zell-Zell-Kontaktinhibierung, verk{\"u}rzte Populationsverdopplungszeiten und tumorigene und metastasierende Eigenschaften. Außerdem exprimierten die N2-OH-PhIP-exponierten humanen Kolonzellen mit steigender Anzahl der Behandlungen gr{\"o}ßere Mengen des trunkierten APC-Proteins. Die bekannten PhIP-spezifischen Mutationen im APC-Gen resultieren in der Expression eines trunkierten Proteinproduktes und werden als fr{\"u}he Ereignisse in der Kolonkanzerogenese betrachtet. Die zusammenfassende Betrachtung aller Ergebnisse zeigt, dass die IEC-18-Zelllinie zur chemischen Transformation durch N2-OH-PhIP ungeeignet ist. Dagegen wurde erstmalig eine vollst{\"a}ndige chemische Transformation von Humandickdarmepithelzellen in vitro durch Exposition der humanen Kolonepithelzelllinie HCEC gegen{\"u}ber dem Kolonkarzinogen N2-OH-PhIP erzielt.},
  subject      = {maligne Transformation},
  language  = {de}
}
@article{RailaBokBuchholzetal.1997,
  author    = {Raila, Jens and Bok, V. and Buchholz, Ingeborg and Schweigert, Florian J.},
  title     = {Untersuchungen zum Vitamin-A-Stoffwechsel der Niere des Hundes},
  year      = {1997},
  language  = {de}
}
@article{SteinhagenSiemannBuescheretal.2000,
  author    = {Steinhagen, Beate and Siemann, A. and B{\"u}scher, Ulrich and Dudenhausen, Joachim W. and Schweigert, Florian J.},
  title     = {Untersuchungen zum Transfer von Carotinoiden aus dem Plasma in die Follikelfl{\"u}ssigkeit der Frau},
  year      = {2000},
  language  = {de}
}
@phdthesis{Herles2003,
  author    = {Herles, Claudia},
  title     = {Untersuchungen zum enzymatischen Abbau ausgew{\"a}hlter Flavanoide durch Eubacterium ramulus},
  pages     = {109 S.},
  year      = {2003},
  language  = {de}
}
@article{BokSchweigert1997,
  author    = {Bok, V. and Schweigert, Florian J.},
  title     = {Untersuchungen zum Einfluß unterschiedlicher Vitamin A-Gehalte im Futter auf die Konzentration von Vitamin A im Plasma und die Ausscheidungen von Vitamin A {\"u}ber den Harn von Hunden},
  year      = {1997},
  language  = {de}
}
@phdthesis{Gehrke2002,
  author    = {Gehrke, Janin},
  title     = {Untersuchungen zu tanninbindenden Speichelproteinen des Rehs und anderer Wiederk{\"a}uer},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-0000444},
  school      = {Universit{\"a}t Potsdam},
  year      = {2002},
  abstract  = {Am Beispiel der Wiederk{\"a}uer wurde unter Zuhilfenahme von biochemischen und molekularbiologischen Methoden die Adaptation von Pflanzenfressern (Herbivoren) an pflanzliche Sekund{\"a}rmetabolite wie z.B. Tannine untersucht. Tannine k{\"o}nnen in nicht an ihren Verzehr adaptierten Spezies durch ihr Proteinbindungsverm{\"o}gen die Nahrungsverwertung und damit Wachstum und Gesundheit des Pflanzenfressers beeintr{\"a}chtigen (antinutritive Wirkung). Einige Wiederk{\"a}uerarten wie z.B. das Reh (Capreolus capreolus) haben in ihrem Nahrungsspektrum viele stark tanninhaltige Pflanzen, leiden aber nicht unter den erw{\"a}hnten postdigestiven Konsequenzen. Eine M{\"o}glichkeit, die antinutritive Wirkung von Tanninen zu neutralisieren, besteht in der Produktion tanninbindender Speichelproteine. Der Speichel verschiedener Wiederk{\"a}uerarten wurde auf das Vorhandensein tanninbindender Proteine untersucht. Diese Arten wurden so ausgew{\"a}hlt, dass alle drei Ern{\"a}hrungstypen (Konzentratselektierer, Intermedi{\"a}rtyp, Gras- und Rauhfutterfresser) in den Vergleich eingeschlossen werden konnten. Als Referenzspezies wurde der Konzentratselektierer Reh herangezogen. Die Speichelproteine des Rehs und die der Intermedi{\"a}rtypen (Rentier, Rangifer tarandus; Damhirsch, Cervus dama; Moschusochse, Ovibos moschatus) banden ungef{\"a}hr doppelt so effektiv an hydrolysierbare Tannine (Tannins{\"a}ure), wie die der untersuchten Gras- und Rauhfutterfresser (Rind, Bos taurus; und Mufflon, Ovis orientalis musimon). Diese Abstufung zeigte sich auch bei der Untersuchung der Bindung an kondensierte Tannine (Quebracho). Eine Ausnahme stellte Mufflonspeichel dar, dieser band ebenso gut an Quebracho wie die Speichelproteine der anderen Ern{\"a}hrungstypen. {\"U}ber eine Aminos{\"a}uretotalanalyse konnte festgestellt werden, dass der Speichel einiger untersuchter Wiederk{\"a}uerarten prolinreiche Proteine (PRPs) enthielt. Unter Ausnutzung ihrer Trichloressigs{\"a}ure (TCA)-L{\"o}slichkeit wurden diese angereichert und genauer untersucht. Die Analyse der TCA-l{\"o}slichen Speichelproteine der Konzentratselektierer (Reh, Elch) ergab einen relativen Prolingehalt von {\"u}ber 35 \%, w{\"a}hrend beim Moschusochsen noch 29 \% gemessen wurden. In Damhirsch- und Rinderspeichel wurden keine prolinreichen Proteine gefunden. F{\"u}r die TCA-l{\"o}slichen Speichelproteine des Rehs konnte eine hohe Tanninbindungskapazit{\"a}t nachgewiesen werden. Diese banden 24 - 30 x effektiver an Tannine als die TCA-l{\"o}slichen Speichelproteine des Rindes. Die Tanninbindungskapazit{\"a}ten der TCA-l{\"o}slichen Speichelproteine von Moschusochse und Damhirsch waren ebenfalls h{\"o}her als die des Rindes, aber niedriger als die des Rehs. Die Kohlenhydrat-Analyse der TCA-l{\"o}slichen Speichelproteine des Rehs erbrachte, dass es sich bei ihnen um Glykoproteine handelt. Mittels Gelfiltration und zweidimensionaler Polyacrylamidgelektrophorese konnten f{\"u}nf Proteingruppen mit Molekulargewichten zwischen 15 und 50 kd sowie isoelektrischen Punkten zwischen 4,0 und 8,2 detektiert werden. Von 15 dieser Proteine konnten die N-terminalen Aminos{\"a}uresequenzen ermittelt werden. Ausgehend von diesen Informationen wurden Reh-PRP spezifische mRNAs isoliert und partiell sequenziert. Die meisten dieser Fragmente hatten eine gemeinsame 18 Aminos{\"a}uren lange C-terminale Sequenz PPPEEQPEE/QSPDEE/DSPSE. Die Suche nach {\"U}bereinstimmungen der analysierten Sequenzen mit anderen S{\"a}ugetier-PRPs in der Genbank ergab keine sinnvollen {\"A}hnlichkeiten. Die Ergebnisse k{\"o}nnen zu Informationen {\"u}ber tanninbindende Proteine anderer Wiederk{\"a}uer f{\"u}hren. Die Sequenzinformationen stellen einen Ausgangspunkt bei der Analyse der evolutiven Zusammenh{\"a}nge der Cerviden dar.},
  language  = {de}
}
@phdthesis{Dokas2012,
  author    = {Dokas, Janine},
  title     = {Untersuchung zur Rolle von Tbc1d1 im Stoffwechsel anhand von Mausmodellen},
  address   = {Potsdam},
  pages     = {127 S.},
  year      = {2012},
  language  = {de}
}
@phdthesis{Bernhardt2008,
  author    = {Bernhardt, Ulrike},
  title     = {Untersuchung zur Rolle von Adapterprotein-Komplexen im Targeting der Glucosetransporter GLUT8 und GLUT4},
  pages     = {V, 117 Bl. : graph. Darst.},
  year      = {2008},
  language  = {de}
}
@phdthesis{Doecke2013,
  author    = {D{\"o}cke, Stephanie},
  title     = {Untersuchung von ausgew{\"a}hlten pathogenetischen Signalwegen der humanen nicht-alkoholischen Fettlebererkrankung},
  address   = {Potsdam},
  pages     = {113 S.},
  year      = {2013},
  language  = {de}
}
@phdthesis{Machowetz2006,
  author    = {Machowetz, Anja},
  title     = {Untersuchung kardioprotektiver Wirkungen des Oliven{\"o}les und seiner phenolischen Komponenten in einer Gruppe gesunder deutscher M{\"a}nner},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus-10432},
  school      = {Universit{\"a}t Potsdam},
  year      = {2006},
  abstract  = {"Untersuchung kardioprotektiver Wirkungen des Oliven{\"o}les und seiner phenolischen Komponenten in einer Gruppe gesunder deutscher M{\"a}nner" EINLEITUNG: Epidemiologische Daten belegen, dass die mediterrane Ern{\"a}hrung mit einer niedrigen Inzidenz an mit oxidativen Stress assoziierten kardiovaskul{\"a}ren Erkrankungen einhergeht. Dabei wird vor allem dem Oliven{\"o}l, als Hauptfettlieferant in der mediterranen Ern{\"a}hrung, eine kardioprotektive Wirkung zugesprochen. Oliven{\"o}l zeichnet sich neben dem hohen Gehalt an einfach unges{\"a}ttigten Fetts{\"a}uren (MUFA) durch ein reichhaltiges Spektrum an phenolischen Verbindungen aus, deren antioxidative Wirkung bereits zahlreichen in in vitro Studien beschrieben wurde. Demnach k{\"o}nnte der Verzehr von phenolreichem Oliven{\"o}l auch in vivo vor oxidativen Sch{\"a}digungen sch{\"u}tzen und somit das Risiko f{\"u}r kardiovaskul{\"a}re Erkrankungen senken. ZIELSTELLUNG: Untersuchung der kardioprotektiven Wirkung von Oliven{\"o}l und seiner phenolischen Komponenten in einer Gruppe gesunder deutscher M{\"a}nner. METHODE: Dazu wurde eine randomisierte cross-over doppelt-verblindete Interventionsstudie an 70 gesunden M{\"a}nnern zwischen 20 - 60 Jahren im Raum Berlin-Brandenburg durchgef{\"u}hrt. In jeweils drei dreiw{\"o}chigen Interventionsphasen konsumierten die Probanden t{\"a}glich 25 ml natives (phenolreich), gemischtes (mittlerer Phenolgehalt) und raffiniertes (ann{\"a}hernd phenolfrei) Oliven{\"o}l, was sich ausschließlich im Gehalt an phenolischen Verbindungen unterschied. Das Oliven{\"o}l sollte dabei die gew{\"o}hnlich verzehrten Fette ersetzen. Die Interventionsphasen waren durch zweiw{\"o}chige Wash out-Phasen unterbrochen. Die Erhebung der Blutlipide, Biomarker der Lipidperoxidation und endogene Antioxidantien erfolgte zu Studienbeginn sowie zu Beginn und Ende jeder Verzehrsperiode.ERGEBNISSE: Bei den Blutlipiden sowie den Biomarkern der Lipidperoxidation und den endogenen Antioxidantien konnte keine signifikante Ver{\"a}nderung in Abh{\"a}ngigkeit vom Phenolgehalt der applizierten Oliven{\"o}le nachgewiesen werden. Einzig die Glutathion-Reduktase-Aktivit{\"a}t stieg mit zunehmendem Gehalt an phenolischen Verbindungen (pTrend = 0,041). Unabh{\"a}ngig von der Konzentration der Phenole im Oliven{\"o}l wurde bei den Probanden durch den Oliven{\"o}lverzehr eine Senkung von Gesamtcholesterol (p = 0,007) und Triglyzeride (p = 0,013) im Serum erzielt. Diese Wirkung geht einher mit einem gestiegenen MUFA-Anteil in der Ern{\"a}hrung aufgrund des Oliven{\"o}lkonsums (p < 0,001). SCHLUSSFOLGERUNG: Die Hypothese, dass die Phenole im Oliven{\"o}l aufgrund ihrer in in vitro und Tierstudien beschriebenen antioxidativen Wirkung dem Oliven{\"o}l neben dem einzigartigen Fetts{\"a}ureprofil eine zus{\"a}tzliche kardioprotektive Wirkung bescheren, konnte in der vorliegenden Studie nicht gezeigt werden. Dennoch konnte durch den Oliven{\"o}lverzehr und der damit einhergehenden Erh{\"o}hung des MUFA-Anteils in der Ern{\"a}hrung eine vorteilhafte Beeinflussung der Blutlipide erzielt werden. Obgleich Oliven{\"o}l nicht das vorwiegend verzehrte Fett in Deutschland darstellt, zeigten die befragten Probanden eine hohe Akzeptanz. Folglich k{\"o}nnte die Integration von Oliven{\"o}l in die habituelle Ern{\"a}hrung einen Beitrag zur Senkung des kardiovaskul{\"a}ren Erkrankungsrisikos leisten.},
  subject      = {Oliven{\"o}l},
  language  = {de}
}
@phdthesis{Schmidt2009,
  author    = {Schmidt, Antje},
  title     = {Untersuchung des Recyclings Kaede-fusionierter Corticotropin-Releasing-Factor Rezeptoren Typ 1},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus-34902},
  school      = {Universit{\"a}t Potsdam},
  year      = {2009},
  abstract  = {Aktivierte G-Protein-gekoppelte Rezeptoren (GPCR) werden schnell desensitisiert, internalisiert und anschließend entweder lysosomal degradiert oder zur Plasmamembran (PM) recycelt. Zur Resensitisierung der Zellen tragen neben recycelten auch neusynthetisierte Rezeptoren bei. Die {\"U}berlagerung beider Prozesse erschwert die Untersuchung des Rezeptorrecyclings. In dieser Arbeit sollte mit Hilfe des photokonvertierbaren Fluoreszenzproteins Kaede eine Technik entwickelt werden, mit der es m{\"o}glich ist Recycling- von Neusyntheseprozessen zu trennen und das Recycling von GPCR mikroskopisch in Echtzeit zu beobachten. Als Modellproteine wurden der Vasopressin-1a-Rezeptor V1aR (recycelnder Rezeptor), der Vasopressin-2-Rezeptor V2R (degradierter Rezeptor) und der Corticotropin-Releasing Factor-Rezeptor Typ 1 (CRF1R) verwendet, wobei bei Letzterem untersucht werden sollte, ob er nach Stimulation zur PM zur{\"u}cktransportiert wird. Da Kaede als fluoreszierendes Protein mit den GPCR fusioniert wird, wurde zun{\"a}chst {\"u}berpr{\"u}ft, ob es die Eigenschaften der Rezeptoren ver{\"a}ndert und generell f{\"u}r Transportstudien geeignet ist. Eventuell k{\"o}nnte die bereits publizierte Tetramerisierung von Kaede seine Anwendung verhindern oder erschweren. Mittels Fluoreszenz-Korrelationsspektroskopie konnte gezeigt werden, dass Kaede nicht tetramerisiert, wenn es an ein Membranprotein fusioniert ist. Außerdem konnte in in vitro- und Zellkulturexperimenten belegt werden, dass die native und die photokonvertierte Form von Kaede gleichermaßen stabil sind. Dar{\"u}ber hinaus zeigten Kaede-fusionierte GPCR sowohl in Kolokalisationsstudien als auch in Agonistbindungs- und Rezeptoraktivierungsexperimenten die gleichen Eigenschaften wie CFP- bzw. die unfusionierte Rezeptoren. Lediglich die Expression der Kaede-fusionierten Rezeptoren war geringer. Parallel wurde anhand der bereits publizierten Kaede-Struktur versucht, die Tetramerisierung des Proteins durch den Austausch interagierender Aminos{\"a}uren zu unterbinden. Die eingef{\"u}hrten Mutationen bewirkten aber eine Fehlfaltung des Proteins und damit den Verlust der Fluoreszenz. Da zuvor gezeigt werden konnte, dass Kaede-fusionierte Membranproteine nicht tetramerisieren und nicht die Eigenschaften der fusionierten Proteine ver{\"a}ndern, war monomerisiertes Kaede zur Untersuchung des Rezeptorrecyclings nicht notwendig. Im zweiten Teil der Arbeit wurde mit Hilfe von Kaede-Fusionsproteinen und mikroskopischer Testsysteme das noch unbekannte Recyclingverhalten des CRF1R untersucht. Hierf{\"u}r wurden die Kaede-fusionierten Rezeptoren in eukaryotischen Zellen exprimiert und mit Agonisten internalisiert. Die internalisierten Rezeptoren wurden in Endosomen selektiv mit UV-Strahlung photokonvertiert. Anschließend wurde der Transport der photokonvertierten Form verfolgt. Sowohl beim CRF1R als auch beim V1aR wurden Signale in der PM detektiert, beim V2R hingegen nicht. Dies zeigt, dass es sich beim CRF1R um einen recycelnden Rezeptor handelt. Die als Kontrolle eingesetzten Rezeptoren verhielten sich in diesem Experiment wie erwartet: Der V1aR wurde zur PM zur{\"u}cktransportiert, der V2R nicht. Diese Ergebnisse konnten mit Hilfe biochemischer und durchflusscytometrischer Experimente best{\"a}tigt werden. Die Internalisierung des CRF1R verl{\"a}uft Clathrin-vermittelt in Anwesenheit von β-Arrestin. Je nach Stabilit{\"a}t der β Arrestin-Interaktion unterscheidet man zwei Klassen von Rezeptoren: Klasse A-Rezeptoren interagieren transient mit β Arrestin und k{\"o}nnen recyceln. Im Gegensatz dazu gehen Klasse B-Rezeptoren eine stabile Interaktion mit β Arrestin ein und werden nach Internalisierung degradiert. In mikroskopischen Untersuchungen konnte f{\"u}r die aktivierten CRF1R und V1aR eine Rekrutierung von β Arrestin zur PM und eine transiente Interaktion mit β Arrestin gezeigt werden (Klasse A-Rezeptoren). F{\"u}r den V2R wurde dagegen eine stabile Interaktion mit β Arrestin beobachtet (Klasse B-Rezeptor). Diese Daten st{\"u}tzen die Ergebnisse des Kaede-basierten Recyclingversuchs und zeigen, dass der CRF1R ein recycelnder Rezeptor ist. Ferner wurde untersucht, ob der CRF1R zu den schnell oder langsam recycelnden Rezeptoren z{\"a}hlt. Schnell recycelnde Rezeptoren werden direkt aus fr{\"u}hen Endosomen, langsam recycelnde hingegen {\"u}ber das Trans-Golgi-Netzwerk (TGN) bzw. {\"u}ber Recycling-Endosomen zur PM transportiert. Als Marker f{\"u}r das TGN oder die Recycling-Endosomen wurde Rab11 verwendet. In Kolokalisationsstudien konnte gezeigt werden, dass der CRF1R den langsam recycelnden Rezeptoren zugeordnet werden kann. Zusammenfassend konnte in dieser Arbeit belegt werden, dass Kaede als Fusionspartner f{\"u}r Membranproteine genutzt werden kann um deren Transport in Echtzeit zu studieren. Damit wurde erstmals eine mikroskopische Methode etabliert, die es erlaubt recycelnde von neusynthetisierten Rezeptoren zu unterscheiden. Mit Hilfe dieser Methode war es m{\"o}glich zu zeigen, dass der CRF1R ein recycelnder Rezeptor ist.},
  language  = {de}
}
@phdthesis{Engelke2000,
  author    = {Engelke, Christina},
  title     = {Untersuchung der Polymorphismen der humanen Sulfotransferasen 1A1 und 1A2 im Rahmen der "European Prospective Investigation into Cancer and Nutrition" in Potsdam},
  pages     = {86 S.},
  year      = {2000},
  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{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}
}
@article{KumarGoodwinUhouseetal.2015,
  author    = {Kumar, Kevin K. and Goodwin, Cody R. and Uhouse, Michael A. and Bornhorst, Julia and Schwerdtle, Tanja and Aschner, Michael A. and McLean, John A. and Bowman, Aaron B.},
  title     = {Untargeted metabolic profiling identifies interactions between Huntington's disease and neuronal manganese status},
  series = {Metallomics},
  volume    = {7},
  journal   = {Metallomics},
  publisher = {RSC Publ.},
  address   = {Cambridge},
  issn      = {1756-591X},
  doi       = {10.1039/C4MT00223G},
  pages     = {363 -- 370},
  year      = {2015},
  abstract  = {Manganese (Mn) is an essential micronutrient for development and function of the nervous system. Deficiencies in Mn transport have been implicated in the pathogenesis of Huntington's disease (HD), an autosomal dominant neurodegenerative disorder characterized by loss of medium spiny neurons of the striatum. Brain Mn levels are highest in striatum and other basal ganglia structures, the most sensitive brain regions to Mn neurotoxicity. Mouse models of HD exhibit decreased striatal Mn accumulation and HD striatal neuron models are resistant to Mn cytotoxicity. We hypothesized that the observed modulation of Mn cellular transport is associated with compensatory metabolic responses to HD pathology. Here we use an untargeted metabolomics approach by performing ultraperformance liquid chromatography-ion mobility-mass spectrometry (UPLC-IM-MS) on control and HD immortalized mouse striatal neurons to identify metabolic disruptions under three Mn exposure conditions, low (vehicle), moderate (non-cytotoxic) and high (cytotoxic). Our analysis revealed lower metabolite levels of pantothenic acid, and glutathione (GSH) in HD striatal cells relative to control cells. HD striatal cells also exhibited lower abundance and impaired induction of isobutyryl carnitine in response to increasing Mn exposure. In addition, we observed induction of metabolites in the pentose shunt pathway in HD striatal cells after high Mn exposure. These findings provide metabolic evidence of an interaction between the HD genotype and biologically relevant levels of Mn in a striatal cell model with known HD by Mn exposure interactions. The metabolic phenotypes detected support existing hypotheses that changes in energetic processes underlie the pathobiology of both HD and Mn neurotoxicity.},
  language  = {en}
}
@misc{KumarGoodwinUhouseetal.2015,
  author    = {Kumar, Kevin K. and Goodwin, Cody R. and Uhouse, Michael A. and Bornhorst, Julia and Schwerdtle, Tanja and Aschner, Michael A. and McLean, John A. and Bowman, Aaron B.},
  title     = {Untargeted metabolic profiling identifies interactions between Huntington's disease and neuronal manganese status},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-94314},
  pages     = {363 -- 370},
  year      = {2015},
  abstract  = {Manganese (Mn) is an essential micronutrient for development and function of the nervous system. Deficiencies in Mn transport have been implicated in the pathogenesis of Huntington's disease (HD), an autosomal dominant neurodegenerative disorder characterized by loss of medium spiny neurons of the striatum. Brain Mn levels are highest in striatum and other basal ganglia structures, the most sensitive brain regions to Mn neurotoxicity. Mouse models of HD exhibit decreased striatal Mn accumulation and HD striatal neuron models are resistant to Mn cytotoxicity. We hypothesized that the observed modulation of Mn cellular transport is associated with compensatory metabolic responses to HD pathology. Here we use an untargeted metabolomics approach by performing ultraperformance liquid chromatography-ion mobility-mass spectrometry (UPLC-IM-MS) on control and HD immortalized mouse striatal neurons to identify metabolic disruptions under three Mn exposure conditions, low (vehicle), moderate (non-cytotoxic) and high (cytotoxic). Our analysis revealed lower metabolite levels of pantothenic acid, and glutathione (GSH) in HD striatal cells relative to control cells. HD striatal cells also exhibited lower abundance and impaired induction of isobutyryl carnitine in response to increasing Mn exposure. In addition, we observed induction of metabolites in the pentose shunt pathway in HD striatal cells after high Mn exposure. These findings provide metabolic evidence of an interaction between the HD genotype and biologically relevant levels of Mn in a striatal cell model with known HD by Mn exposure interactions. The metabolic phenotypes detected support existing hypotheses that changes in energetic processes underlie the pathobiology of both HD and Mn neurotoxicity.},
  language  = {en}
}
@article{KumarGoodwinUhouseetal.2015,
  author    = {Kumar, Kevin K. and Goodwin, Cody R. and Uhouse, Michael A. and Bornhorst, Julia and Schwerdtle, Tanja and Aschner, Michael A. and McLean, John A. and Bowman, Aaron B.},
  title     = {Untargeted metabolic profiling identifies interactions between},
  series = {Metallomics : integrated biometal science},
  volume    = {7},
  journal   = {Metallomics : integrated biometal science},
  number    = {2},
  publisher = {Royal Society of Chemistry},
  address   = {Cambridge},
  issn      = {1756-5901},
  doi       = {10.1039/c4mt00223g},
  pages     = {363 -- 370},
  year      = {2015},
  language  = {en}
}
@article{SchellWardelmannKleinridders2021,
  author    = {Schell, Mareike and Wardelmann, Kristina and Kleinridders, Andre},
  title     = {Untangling the effect of insulin action on brain mitochondria and metabolism},
  series = {Journal of neuroendocrinology},
  volume    = {33},
  journal   = {Journal of neuroendocrinology},
  number    = {4},
  publisher = {Wiley},
  address   = {Hoboken},
  issn      = {0953-8194},
  doi       = {10.1111/jne.12932},
  pages     = {14},
  year      = {2021},
  abstract  = {The regulation of energy homeostasis is controlled by the brain and, besides requiring high amounts of energy, it relies on functional insulin/insulin-like growth factor (IGF)-1 signalling in the central nervous system. This energy is mainly provided by mitochondria in form of ATP. Thus, there is an intricate interplay between mitochondrial function and insulin/IGF-1 action to enable functional brain signalling and, accordingly, propagate a healthy metabolism. To adapt to different nutritional conditions, the brain is able to sense the current energy status via mitochondrial and insulin signalling-dependent pathways and exerts an appropriate metabolic response. However, regional, cell type and receptor-specific consequences of this interaction occur and are linked to diverse outcomes such as altered nutrient sensing, body weight regulation or even cognitive function. Impairments of this cross-talk can lead to obesity and glucose intolerance and are linked to neurodegenerative diseases, yet they also induce a self-sustainable, dysfunctional 'metabolic triangle' characterised by insulin resistance, mitochondrial dysfunction and inflammation in the brain. The identification of causal factors deteriorating insulin action, mitochondrial function and concomitantly a signature of metabolic stress in the brain is of utter importance to offer novel mechanistic insights into development of the continuously rising prevalence of non-communicable diseases such as type 2 diabetes and neurodegeneration. This review aims to determine the effect of insulin action on brain mitochondrial function and energy metabolism. It precisely outlines the interaction and differences between insulin action, insulin-like growth factor (IGF)-1 signalling and mitochondrial function; distinguishes between causality and association; and reveals its consequences for metabolism and cognition. We hypothesise that an improvement of at least one signalling pathway can overcome the vicious cycle of a self-perpetuating metabolic dysfunction in the brain present in metabolic and neurodegenerative diseases.},
  language  = {en}
}
@article{KnebelNeebZahnetal.2018,
  author    = {Knebel, Constanze and Neeb, Jannika and Zahn, Elisabeth and Schmidt, Flavia and Carazo, Alejandro and Holas, Ondej and Pavek, Petr and P{\"u}schel, Gerhard Paul and Zanger, Ulrich M. and S{\"u}ssmuth, Roderich and Lampen, Alfonso and Marx-Stoelting, Philip and Braeuning, Albert},
  title     = {Unexpected Effects of Propiconazole, Tebuconazole, and Their Mixture on the Receptors CAR and PXR in Human Liver Cells},
  series = {Toxicological sciences},
  volume    = {163},
  journal   = {Toxicological sciences},
  number    = {1},
  publisher = {Oxford Univ. Press},
  address   = {Oxford},
  issn      = {1096-6080},
  doi       = {10.1093/toxsci/kfy026},
  pages     = {170 -- 181},
  year      = {2018},
  abstract  = {Analyzing mixture toxicity requires an in-depth understanding of the mechanisms of action of its individual components. Substances with the same target organ, same toxic effect and same mode of action (MoA) are believed to cause additive effects, whereas substances with different MoAs are assumed to act independently. Here, we tested 2 triazole fungicides, propiconazole, and tebuconazole (Te), for individual and combined effects on liver toxicity-related endpoints. Both triazoles are proposed to belong to the same cumulative assessment group and are therefore thought to display similar and additive behavior. Our data show that Te is an antagonist of the constitutive androstane receptor (CAR) in rats and humans, while propiconazole is an agonist of this receptor. Both substances activate the pregnane X-receptor (PXR) and further induce mRNA expression of CYP3A4. CYP3A4 enzyme activity, however, is inhibited by propiconazole. For common targets of PXR and CAR, the activation of PXR by Te overrides CAR inhibition. In summary, propiconazole and Te affect different hepatotoxicity-relevant cellular targets and, depending on the individual endpoint analyzed, act via similar or dissimilar mechanisms. The use of molecular data based on research in human cell systems extends the picture to refine cumulative assessment group grouping and substantially contributes to the understanding of mixture effects of chemicals in biological systems.},
  language  = {en}
}
@phdthesis{Aleksandrova2020,
  author    = {Aleksandrova, Krasimira},
  title     = {Understanding the link between obesity and colorectal cancer},
  school      = {Universit{\"a}t Potsdam},
  year      = {2020},
  language  = {de}
}
@inproceedings{IntziegianniCasselMuelleretal.2012,
  author    = {Intziegianni, Konstantina and Cassel, Michael and M{\"u}ller, Steffen and Mayer, Frank},
  title     = {Ultrasound evaluation of the patellar tendon cross-sectional area and its relation to maximum force},
  series = {Medicine and science in sports and exercise : official journal of the American College of Sports Medicine},
  volume    = {44},
  booktitle = {Medicine and science in sports and exercise : official journal of the American College of Sports Medicine},
  publisher = {Lippincott Williams \& Wilkins},
  address   = {Philadelphia},
  issn      = {0195-9131},
  pages     = {714 -- 714},
  year      = {2012},
  language  = {en}
}
@article{GereckeMascherGottschalketal.2013,
  author    = {Gerecke, Christian and Mascher, Conny and Gottschalk, Uwe and Kleuser, Burkhard and Scholtka, Bettina},
  title     = {Ultrasensitive detection of unknown colon cancer-initiating mutations using the example of the adenomatous polyposis coli gene},
  series = {Cancer prevention research},
  volume    = {6},
  journal   = {Cancer prevention research},
  number    = {9},
  publisher = {American Association for Cancer Research},
  address   = {Philadelphia},
  issn      = {1940-6207},
  doi       = {10.1158/1940-6207.CAPR-13-0145},
  pages     = {898 -- 907},
  year      = {2013},
  abstract  = {Detection of cancer precursors contributes to cancer prevention, for example, in the case of colorectal cancer. To record more patients early, ultrasensitive methods are required for the purpose of noninvasive precursor detection in body fluids. Our aim was to develop a method for enrichment and detection of known as well as unknown driver mutations in the Adenomatous polyposis coli (APC) gene. By coupled wild-type blocking (WTB) PCR and high-resolution melting (HRM), referred to as WTB-HRM, a minimum detection limit of 0.01\% mutant in excess wild-type was achieved according to as little as 1 pg mutated DNA in the assay. The technique was applied to 80 tissue samples from patients with colorectal cancer (n = 17), adenomas (n = 50), serrated lesions (n = 8), and normal mucosa (n = 5). Any kind of known and unknown APC mutations (deletions, insertions, and base exchanges) being situated inside the mutation cluster region was distinguishable from wild-type DNA. Furthermore, by WTB-HRM, nearly twice as many carcinomas and 1.5 times more precursor lesions were identified to be mutated in APC, as compared with direct sequencing. By analyzing 31 associated stool DNA specimens all but one of the APC mutations could be recovered. Transferability of the WTB-HRM method to other genes was proven using the example of KRAS mutation analysis. In summary, WTB-HRM is a new approach for ultrasensitive detection of cancer-initiating mutations. In this sense, it appears especially applicable for noninvasive detection of colon cancer precursors in body fluids with excess wild-type DNA like stool. Cancer Prev Res; 6(9); 898-907. (C) 2013 AACR.},
  language  = {en}
}
@article{RoetzlerRomerBudzinskietal.2004,
  author    = {R{\"o}tzler, Jochen and Romer, R. L. and Budzinski, Hubertus and Oberh{\"a}nsli, Roland},
  title     = {Ultrahigh-temperature high-pressure granulites from Tirschheim, Saxon Granulite Massif, Germany : P-T-t path and geotectonic implications},
  issn      = {0935-1221},
  year      = {2004},
  abstract  = {The Saxon granulites, the type granulite locality, were deeply buried, extremely heated and then rapidly exhumed during the Variscan Orogeny; thus their evolution differs from many granulites elsewhere. The peak-metamorphic assemblages of layered felsic-mafic granulites from a 500 m deep borehole consist of garnet, kyanite, rutile, ternary feldspar and quartz in felsic granulite, and garnet, omphacite, titanite, ternary feldspar and quartz in mafic granulite. A minimum temperature of 1000-1020degreesC, calculated from reintegrated hypersolvus feldspar in felsic and mafic granulites, is consistent with the highest temperature estimates from garnet-clinopyroxene equilibria. Various equilibria in felsic and mafic granulites record a peak pressure of about 23 kbar. Diffusion zoning and local homogenisation of minerals reflect near-isothermal decompression that preceded cooling and partial hydration at medium- to low-pressure. U-Pb dating of titanite yields an age of peak metamorphism at 340.7+/-0.8 Ma (2sigma). However, chemical inheritance from precursor rutile and post-peak Pb loss are also evident, suggesting a protolith age of 499+/-2 Ma (2sigma) and partial resetting down to an age of 333+/-2 Ma (2sigma). Rb-Sr mica ages of 333.2+/-3.3 Ma (2sigma) are interpreted as dating cooling through about 620degreesC. Hence the Saxon granulites were exhumed to the upper crust during the short period of 6-11 Ma, which corresponds to average exhumation and cooling rates of 10 mm/year and 50degreesC/Ma, respectively. Such rapid exhumation is inconsistent with recent numerical models that assume foreland- directed transport of the Saxon granulites in the lower crust followed by extensional unroofing. Instead, high-pressure rocks of the Saxon Granulite Massif and the nearby Erzgebirge experienced a buoyant rise to the middle crust and subsequent juxtaposition with structurally higher units along a series of medium- to low-pressure detachment faults},
  language  = {en}
}
@article{HoieSjoholmGuldstrandetal.2006,
  author    = {Hoie, Lars H. and Sjoholm, Ake and Guldstrand, Marie and Zunft, Hans-Joachim Franz and Lueder, Wolfgang and Graubaum, Hans-Joachim and Gr{\"u}nwald, J{\"o}rg},
  title     = {Ultra heat treatment destroys cholesterol-lowering effect of soy protein},
  series = {International journal of food sciences and nutrition},
  volume    = {57},
  journal   = {International journal of food sciences and nutrition},
  publisher = {Taylor \& Francis},
  address   = {Abingdon},
  issn      = {0963-7486},
  doi       = {10.1080/09637480601009059},
  pages     = {512 -- 519},
  year      = {2006},
  abstract  = {A randomized, placebo-controlled, double-blind clinical study was performed to investigate the dose-dependent response of serum cholesterol after consuming an ultra-heat-treated milk containing a soy protein preparation. Eighty hypercholesterolemic subjects were assigned to one of four study groups receiving 12.5 or 25 g soy protein (active treatment) or casein (placebo) daily over a period of 4 weeks. The trial substances were provided as ready-made, ultra-heated milk preparations. Before and after the treatment, serum concentrations of total, low-density lipoprotein, and high-density lipoprotein cholesterol were determined. Unexpectedly, at the end of the study, low-density lipoprotein cholesterol concentrations were significantly increased compared with baseline in all study groups. The magnitude of this increase (17 - 19\%) was similar in all active and placebo study groups. Soy protein supplements previously shown to be effective in reducing serum cholesterol had in this study no such lipid-lowering effect after ultra heat treatment.},
  language  = {en}
}
@article{WallmeyerDietertSochorovaetal.2017,
  author    = {Wallmeyer, Leonie and Dietert, Kristina and Sochorova, Michaela and Gruber, Achim D. and Kleuser, Burkhard and Vavrova, Katerina and Hedtrich, Sarah},
  title     = {TSLP is a direct trigger for T cell migration in filaggrin-deficient skin equivalents},
  series = {Scientific reports},
  volume    = {7},
  journal   = {Scientific reports},
  publisher = {Nature Publ. Group},
  address   = {London},
  issn      = {2045-2322},
  doi       = {10.1038/s41598-017-00670-2},
  pages     = {12},
  year      = {2017},
  abstract  = {Mutations in the gene encoding for filaggrin (FLG) are major predisposing factors for atopic dermatitis (AD). Besides genetic predisposition, immunological dysregulations considerably contribute to its pathophysiology. For example, thymic stromal lymphopoietin (TSLP) is highly expressed in lesional atopic skin and significantly contributes to the pathogenesis of AD by activating dendritic cells that then initiate downstream effects on, for example, T cells. However, little is known about the direct interplay between TSLP, filaggrin-deficient skin and other immune cells such as T lymphocytes. In the present study, FLG knockdown skin equivalents, characterised by intrinsically high TSLP levels, were exposed to activated CD4(+) T cells. T cell exposure resulted in an inflammatory phenotype of the skin equivalents. Furthermore, a distinct shift from a Th1/Th17 to a Th2/Th22 profile was observed following exposure of T cells to filaggrin-deficient skin equivalents. Interestingly, TSLP directly stimulated T cell migration exclusively in filaggrin-deficient skin equivalents even in the absence of dendritic cells, indicating a hitherto unknown role of TSLP in the pathogenesis of AD.},
  language  = {en}
}
@article{RohnRaschkeAschneretal.2019,
  author    = {Rohn, Isabelle and Raschke, Stefanie and Aschner, Michael and Tuck, Simon and Kuehnelt, Doris and Kipp, Anna Patricia and Schwerdtle, Tanja and Bornhorst, Julia},
  title     = {Treatment of caenorhabditis elegans with small selenium species enhances antioxidant defense systems},
  series = {Molecular nutrition \& food research : bioactivity, chemistry, immunology, microbiology, safety, technology},
  volume    = {63},
  journal   = {Molecular nutrition \& food research : bioactivity, chemistry, immunology, microbiology, safety, technology},
  number    = {9},
  publisher = {Wiley},
  address   = {Hoboken},
  issn      = {1613-4125},
  doi       = {10.1002/mnfr.201801304},
  pages     = {9},
  year      = {2019},
  abstract  = {ScopeSmall selenium (Se) species play a key role in Se metabolism and act as dietary sources of the essential trace element. However, they are redox-active and trigger pro- and antioxidant responses. As health outcomes are strongly species-dependent, species-specific characteristics of Se compounds are tested in vivo. Methods and resultsIn the model organism Caenorhabditis elegans (C. elegans), immediate and sustained effects of selenite, selenomethionine (SeMet), and Se-methylselenocysteine (MeSeCys) are studied regarding their bioavailability, incorporation into proteins, as well as modulation of the cellular redox status. While all tested Se compounds are bioavailable, only SeMet persistently accumulates and is non-specifically incorporated into proteins. However, the protection toward chemically-induced formation of reactive species is independent of the applied Se compound. Increased thioredoxin reductase (TXNRD) activity and changes in mRNA expression levels of antioxidant proteins indicate the activation of cellular defense mechanisms. However, in txnrd-1 deletion mutants, no protective effects of the Se species are observed anymore, which is also reflected by differential gene expression data. ConclusionSe species protect against chemically-induced reactive species formation. The identified immediate and sustained systemic effects of Se species give rise to speculations on possible benefits facing subsequent periods of inadequate Se intake.},
  language  = {en}
}
@article{SchweigertSehouli2005,
  author    = {Schweigert, Florian J. and Sehouli, Jalid},
  title     = {Transthyretin, a biomarker for nutritional status and ovarian cancer},
  issn      = {0008-5472},
  year      = {2005},
  language  = {en}
}
@article{HenzeEspeWanneretal.2012,
  author    = {Henze, Andrea and Espe, Katharina M. and Wanner, Christoph and Krane, Vera and Raila, Jens and Hocher, Berthold and Schweigert, Florian J. and Drechsler, Christiane},
  title     = {Transthyretin predicts cardiovascular outcome in hemodialysis patients with type 2 diabetes},
  series = {Diabetes care},
  volume    = {35},
  journal   = {Diabetes care},
  number    = {11},
  publisher = {American Diabetes Association},
  address   = {Alexandria},
  issn      = {0149-5992},
  doi       = {10.2337/dc12-0455},
  pages     = {2365 -- 2372},
  year      = {2012},
  abstract  = {OBJECTIVE-BMI and albumin are commonly accepted parameters to recognize wasting in dialysis patients and are powerful predictors of morbidity and mortality. However, both parameters reveal limitations and may not cover the entire range of patients with wasting. The visceral protein transthyretin (TTR) may be helpful in overcoming the diagnostic and prognostic gap. Therefore, the aim of this study was to assess the association of TTR with morbidity and mortality in hemodialysis patients. RESEARCH DESIGN AND METHODS-The TTR concentration was determined in plasma samples of 1,177 hemodialysis patients with type 2 diabetes. Cox regression analyses were used to determine hazard ratios (HRs) for the risk of cardiovascular end points (CVEs) and mortality according to quartiles of TTR concentration for the total study cohort and the subgroups BMI >= 23 kg/m(2), albumin concentration >= 3.8 g/dL, and a combination of both. RESULTS-A low TTR concentration was associated with an increased risk for CVE for the total study cohort (HR 1.65 [95\% CI 1.27-2.14]), patients with BMI >= 23 kg/m(2) (1.70 [1.22-2.37]), albumin >= 3.8 g/dL (1.68 [1.17-2.42]), and the combination of both (1.69 [1.13-2.53]). Additionally, a low TTR concentration predicted mortality for the total study cohort (1.79 [1.43-2.24]) and patients with BMI >= 23 kg/m(2) (1.46 [1.09-1.95]). CONCLUSIONS-The current study demonstrated that TTR is a useful predictor for cardiovascular outcome and mortality in diabetic hemodialysis patients. TTR was particularly useful in patients who were not identified to be at risk by BMI or albumin status.},
  language  = {en}
}
@article{XiongStibollerGlabonjatetal.2020,
  author    = {Xiong, Chan and Stiboller, Michael and Glabonjat, Ronald A. and Rieger, Jaqueline and Paton, Lhiam and Francesconi, Kevin A.},
  title     = {Transport of arsenolipids to the milk of a nursing mother after consuming salmon fish},
  series = {Journal of trace elements in medicine and biology},
  volume    = {61},
  journal   = {Journal of trace elements in medicine and biology},
  publisher = {Elsevier},
  address   = {M{\"u}nchen},
  issn      = {0946-672X},
  doi       = {10.1016/j.jtemb.2020.126502},
  pages     = {6},
  year      = {2020},
  abstract  = {Objective: We address two questions relevant to infants' exposure to potentially toxic arsenolipids, namely, are the arsenolipids naturally present in fish transported intact to a mother's milk, and what is the efficiency of this transport. Methods: We investigated the transport of arsenolipids and other arsenic species present in fish to mother's milk by analyzing the milk of a single nursing mother at 15 sampling times over a 3-day period after she had consumed a meal of salmon. Total arsenic values were obtained by elemental mass spectrometry, and arsenic species were measured by HPLC coupled to both elemental and molecular mass spectrometry. Results: Total arsenic increased from background levels (0.1 mu g As kg(-1)) to a peak value of 1.72 lig As kg(-1) eight hours after the fish meal. The pattern for arsenolipids was similar to that of total arsenic, increasing from undetectable background levels (< 0.01 mu g As kg(-1)) to a peak after eight hours of 0.45 mu g As kg(-1). Most of the remaining total arsenic in the milk was accounted for by arsenobetaine. The major arsenolipids in the salmon were arsenic hydrocarbons (AsHCs; 55 \% of total arsenolipids), and these compounds were also the dominant arsenolipids in the milk where they contributed over 90 \% of the total arsenolipids. Conclusions: Our study has shown that ca 2-3 \% of arsenic hydrocarbons, natural constituents of fish, can be directly transferred unchanged to the milk of a nursing mother. In view of the potential neurotoxicity of AsHCs, the effects of these compounds on the brain developmental stage of infants need to be investigated.},
  language  = {en}
}
@phdthesis{Vossenkuhl2015,
  author    = {Vossenkuhl, Birgit},
  title     = {Transmission of MRSA along the meat supply chain},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-85918},
  school      = {Universit{\"a}t Potsdam},
  pages     = {141},
  year      = {2015},
  abstract  = {Methicillin-resistente Staphylococcus aureus (MRSA) z{\"a}hlen zu den bedeutendsten antibiotikaresistenten Pathogenen, die vor allem in Krankenh{\"a}usern aber auch außerhalb von Einrichtungen des Gesundheitswesens weit verbreitet sind. Seit einigen Jahren ist eine neue Generation von MRSA auf dem Vormarsch, die vor allem Nutztierbest{\"a}nde als neue Nische besiedelt. Diese sogenannten Nutztier-assoziierten MRSA wurden wiederholt bei wirtschaftlich bedeutenden Nutztieren sowie daraus gewonnenem Fleisch nachgewiesen. Im Rahmen der vorliegenden Arbeit wurde ein methodischer Ansatz verfolgt, um die Hypothese einer m{\"o}glichen {\"U}bertragung von Nutztier-assoziierten MRSA entlang der Lebensmittelkette vom Tier auf dessen Fleisch zu best{\"a}tigen. Angepasst an die Unterschiede in den verf{\"u}gbaren Daten wurden daf{\"u}r zwei neue Konzepte erstellt. Zur Analyse der {\"U}bertragung von MRSA entlang der Schlachtkette wurde ein mathematisches Modell des Schweineschlachtprozesses entwickelt, welches dazu geeignet ist, den Verlauf der MRSA-Pr{\"a}valenz entlang der Schlachtkette zu quantifizieren sowie kritische Prozessschritte f{\"u}r eine MRSA-{\"U}bertragung zu identifizieren. Anhand von Pr{\"a}valenzdaten ist es dem Modell m{\"o}glich, die durchschnittlichen MRSA-Eliminations- und Kontaminationsraten jedes einzelnen Prozessschrittes zu sch{\"a}tzen, die anschließend in eine Monte-Carlo-Simulation einfließen. Im Ergebnis konnte gezeigt werden, dass es generell m{\"o}glich ist, die MRSA Pr{\"a}valenz im Laufe des Schlachtprozesses auf ein niedriges finales Niveau zwischen 0,15 bis 1,15\% zu reduzieren. Vor allem das Br{\"u}hen und Abfl{\"a}mmen der Schlachtk{\"o}rper wurden als kritische Prozesse im Hinblick auf eine MRSA-Dekontamination identifiziert. In Deutschland werden regelm{\"a}ßig MRSA-Pr{\"a}valenz und Typisierungsdaten auf allen Stufen der Lebensmittelkette verschiedener Nutztiere erfasst. Um die MRSA-Daten dieser Querschnittstudie hinsichtlich einer m{\"o}glichen {\"U}bertragung entlang der Kette zu analysieren, wurde ein neuer statistischer Ansatz entwickelt. Hierf{\"u}r wurde eine Chi-Quadrat-Statistik mit der Berechnung des Czekanowski-{\"A}hnlichkeitsindex kombiniert, um Unterschiede in der Verteilung stammspezifischer Eigenschaften zwischen MRSA aus dem Stall, von Karkassen nach der Schlachtung und aus Fleisch im Einzelhandel zu quantifizieren. Die Methode wurde am Beispiel der Putenfleischkette implementiert und zudem bei der Analyse der Kalbfleischkette angewendet. Die durchgehend hohen {\"A}hnlichkeitswerte zwischen den einzelnen Proben weisen auf eine m{\"o}gliche {\"U}bertragung von MRSA entlang der Lebensmittelkette hin. Die erarbeiteten Methoden sind nicht spezifisch bez{\"u}glich Prozessketten und Pathogenen. Sie bieten somit einen großen Anwendungsbereich und erweitern das Methodenspektrum zur Bewertung bakterieller {\"U}bertragungswege.},
  language  = {en}
}
@article{EckelLiKuxhausetal.2018,
  author    = {Eckel, Nathalie and Li, Yanping and Kuxhaus, Olga and Stefan, Norbert and Hu, Frank B. and Schulze, Matthias Bernd},
  title     = {Transition from metabolic healthy to unhealthy phenotypes and association with cardiovascular disease risk across BMI categories in 90 257 women (the Nurses' Health Study)},
  series = {The lancet diabetes \& endocrinology},
  volume    = {6},
  journal   = {The lancet diabetes \& endocrinology},
  number    = {9},
  publisher = {Elsevier},
  address   = {New York},
  issn      = {2213-8587},
  doi       = {10.1016/S2213-8587(18)30137-2},
  pages     = {714 -- 724},
  year      = {2018},
  abstract  = {Background Cardiovascular disease risk among individuals across different categories of BMI might depend on their metabolic health. It remains unclear to what extent metabolic health status changes over time and whether this affects cardiovascular disease risk. In this study, we aimed to examine the association between metabolic health and its change over time and cardiovascular disease risk across BMI categories. Findings During 2 127 391 person-years of follow-up with a median follow-up of 24 years, we documented 6306 cases of cardiovascular disease including 3304 myocardial infarction cases and 3080 strokes. Cardiovascular disease risk of women with metabolically healthy obesity was increased compared with women with metabolically healthy normal weight (HR 1.39, 95\% CI 1.15-1.68), but risk was considerably higher in women with metabolically unhealthy normal weight (2.43, 2.19-2.68), overweight (2.61, 2.36-2.89) and obesity (3.15, 2.83-3.50). The majority of metabolically healthy women converted to unhealthy phenotypes (2555 [84\%] of 3027 women with obesity, 22 215 [68\%] of 32 882 women with normal-weight after 20 years). Women who maintained metabolically healthy obesity during follow-up were still at a higher cardiovascular disease risk compared with women with stable healthy normal weight (HR 1.57, 1.03-2.38), yet this risk was lower than for initially metabolically healthy women who converted to an unhealthy phenotype (normal-weight 1.90, 1.66-2.17 vs obesity 2.74, 2.30-3.27). Particularly incident diabetes and hypertension increased the risk among women with initial metabolic health. Interpretation Even when metabolic health is maintained during long periods of time, obesity remains a risk factor for cardiovascular disease. However, risks are highest for metabolically unhealthy women across all BMI categories. A large proportion of metabolically healthy women converted to an unhealthy phenotype over time across all BMI categories, which is associated with an increased cardiovascular disease risk. Copyright (C) 2018 Elsevier Ltd. All rights reserved.},
  language  = {en}
}
@misc{PlankYeallandMicelietal.2019,
  author    = {Plank, Roswitha and Yealland, Guy and Miceli, Enrico and Cunha, Dulce Lima and Graff, Patrick and Thomforde, Sari and Gruber, Robert and Moosbrugger-Martinz, Verena and Eckl, Katja and Calderon, Marcelo and Hennies, Hans Christian and Hedtrich, Sarah},
  title     = {Transglutaminase 1 Replacement Therapy Successfully Mitigates the Autosomal Recessive Congenital Ichthyosis Phenotype in Full-Thickness Skin Disease Equivalents},
  series = {The journal of investigative dermatology},
  volume    = {139},
  journal   = {The journal of investigative dermatology},
  number    = {5},
  publisher = {Elsevier},
  address   = {New York},
  issn      = {0022-202X},
  doi       = {10.1016/j.jid.2018.11.002},
  pages     = {1191 -- 1195},
  year      = {2019},
  language  = {en}
}
@phdthesis{Schoefer2002,
  author    = {Schoefer, Lilian},
  title     = {Transformation of flavonoids by bacteria from the human intestinal tract},
  pages     = {65 S.},
  year      = {2002},
  language  = {en}
}
@article{SchweigertSteinhagenTruepschuchetal.2000,
  author    = {Schweigert, Florian J. and Steinhagen, Beate and Tr{\"u}pschuch, Annett and Siemann, A. and B{\"u}scher, Ulrich and Dudenhausen, Joachim W.},
  title     = {Transfer of carotenoids, alfa-tocopherol and retinol from plasma into follicular fluid in women},
  year      = {2000},
  language  = {en}
}
@article{SzantoBenkoSzatmarietal.2004,
  author    = {Szanto, Attila and Benko, Szilvia and Szatmari, Istv{\´a}n and Balint, Balint L. and Furtos, Ibolya and Ruehl, Ralph and Molnar, Sandor and Csiba, Laszlo and Garuti, Rita and Calandra, Sebastiano and Larsson, Hanna and Diczfalusy, Ulf and Nagy, Laszlo},
  title     = {Transcriptional regulation of human CYP27 integrates retinoid, peroxisome proliferator-activated receptor, and liver X receptor signaling in macrophages},
  issn      = {0270-7306},
  year      = {2004},
  abstract  = {Cholesterol uptake and efflux are key metabolic processes associated with macrophage physiology and atherosclerosis. Peroxisome proliferator-activated receptor gamma (PPARgamma) and liver X receptor alpha (LXRalpha) have been linked to the regulation of these processes. It remains to be identified how activation of these receptors is connected and regulated by endogenous lipid molecules. We identified CYP27, a p450 enzyme, as a link between retinoid, PPARgamma, and LXR signaling. We show that the human CYP27 gene is under coupled regulation by retinoids and ligands of PPARs via a PPAR-retinoic acid receptor response element in its promoter. Induction of the enzyme's expression results in an increased level of 27-hydroxycholesterol and upregulation of LXR-mediated processes. Upregulated CYP27 activity also leads to LXR-independent elimination of CYP27 metabolites as an alternative means of cholesterol efflux. Moreover, human macrophage-rich atherosclerotic lesions have an increased level of retinoid-, PPARgamma-, and LXR- regulated gene expression and also enhanced CYP27 levels. Our findings suggest that nuclear receptor-regulated CYP27 expression is likely to be a key integrator of retinoic acid receptor-PPARgamma-LXR signaling, relying on natural ligands and contributing to lipid metabolism in macrophages},
  language  = {en}
}
@article{MarschallKroepflJensenetal.2017,
  author    = {Marschall, Talke Anu and Kroepfl, Nina and Jensen, Kenneth Bendix and Bornhorst, Julia and Meermann, B. and K{\"u}hnelt, Doris and Schwerdtle, Tanja},
  title     = {Tracing cytotoxic effects of small organic Se species in human liver cells back to total cellular Se and Se metabolites},
  series = {Metallomics},
  volume    = {9},
  journal   = {Metallomics},
  publisher = {Royal Society of Chemistry},
  address   = {Cambridge},
  issn      = {1756-5901},
  doi       = {10.1039/c6mt00300a},
  pages     = {268 -- 277},
  year      = {2017},
  abstract  = {Small selenium (Se) species play a major role in the metabolism, excretion and dietary supply of the essential trace element selenium. Human cells provide a valuable tool for investigating currently unresolved issues on the cellular mechanisms of Se toxicity and metabolism. In this study, we developed two isotope dilution inductively coupled plasma tandem-mass spectrometry based methods and applied them to human hepatoma cells (HepG2) in order to quantitatively elucidate total cellular Se concentrations and cellular Se species transformations in relation to the cytotoxic effects of four small organic Se species. Species-and incubation time-dependent results were obtained: the two major urinary excretion metabolites trimethylselenonium (TMSe) and methyl-2-acetamido-2-deoxy-1-seleno-beta- D-galactopyranoside (SeSugar 1) were taken up by the HepG2 cells in an unmodified manner and did not considerably contribute to the Se pool. In contrast, Se-methylselenocysteine (MeSeCys) and selenomethionine (SeMet) were taken up in higher amounts, they were largely incorporated by the cells (most likely into proteins) and metabolized to other small Se species. Two new metabolites of MeSeCys, namely gamma-glutamyl-Se-methylselenocysteine and Se-methylselenoglutathione, were identified by means of HPLC-electrospray-ionization-Orbitrap-MS. They are certainly involved in the (de-) toxification modes of Se metabolism and require further investigation.},
  language  = {en}
}
@inproceedings{WandtWinkelbeinerLossowetal.2021,
  author    = {Wandt, Viktoria Klara Veronika and Winkelbeiner, Nicola and Loßow, Kristina and Kopp, Johannes and Simon, Luise and Ebert, Franziska and Kipp, Anna Patricia and Schwerdtle, Tanja},
  title     = {Trace elements, ageing, and sex. Impact on genome stability},
  series = {Naunyn-Schmiedeberg's archives of pharmacology},
  volume    = {394},
  booktitle = {Naunyn-Schmiedeberg's archives of pharmacology},
  number    = {Suppl. 1},
  publisher = {Springer},
  address   = {Berlin ; Heidelberg},
  issn      = {0028-1298},
  doi       = {10.1007/s00210-021-02066-6},
  pages     = {S13 -- S13},
  year      = {2021},
  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{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{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{Schroeder1999,
  author    = {Schr{\"o}der, Insa Sigrid},
  title     = {Toxikologische Untersuchungen von Isothiocyanat-Proteinderivaten},
  pages     = {122 S.},
  year      = {1999},
  language  = {de}
}
@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}
}
@article{EbertMeyerLeffersetal.2016,
  author    = {Ebert, Franziska and Meyer, S{\"o}ren and Leffers, Larissa and Raber, Georg and Francesconi, Kevin A. and Schwerdtle, Tanja},
  title     = {Toxicological characterisation of a thio-arsenosugar-glycerol in human cells},
  series = {Journal of trace elements in medicine and biology},
  volume    = {38},
  journal   = {Journal of trace elements in medicine and biology},
  publisher = {Springer Publishing Company},
  address   = {Jena},
  issn      = {0946-672X},
  doi       = {10.1016/j.jtemb.2016.04.013},
  pages     = {150 -- 156},
  year      = {2016},
  abstract  = {Arsenosugars are water-soluble arsenic species predominant in marine algae and other seafood including mussels and oysters. They typically occur at levels ranging from 2 to 50 mg arsenic/kg dry weight. Most of the arsenosugars contain arsenic as a dimethylarsinoyl group (Me2As(O)-), commonly referred to as the oxo forms, but thio analogues have also been identified in marine organisms and as metabolic products of oxo-arsenosugars. So far, no data regarding toxicity and toxicokinetics of thio-arsenosugars are available. This in vitro-based study indicates that thio-dimethylarsenosugar-glycerol exerts neither pronounced cytotoxicity nor genotoxicity even though this arsenical was bioavailable to human hepatic (HepG2) and urothelial (UROtsa) cells. Experiments with the Caco-2 intestinal barrier model mimicking human absorption indicate for the thio-arsenosugar-glycerol higher intestinal bioavailability as compared to the oxo-arsenosugars. Nevertheless, absorption estimates were much lower in comparison to other arsenicals including arsenite and arsenic-containing hydrocarbons. Arsenic speciation in cell lysates revealed that HepG2 cells are able to metabolise the thio-arsenosugar-glycerol to some extent to dimethylarsinic acid (DMA). These first in vitro data cannot fully exclude risks to human health related to the presence of thio-arsenosugars in food. (C) 2016 Elsevier GmbH. All rights reserved.},
  language  = {en}
}
@article{WittMeyerEbertetal.2017,
  author    = {Witt, Barbara and Meyer, S{\"o}ren and Ebert, Franziska and Francesconi, Kevin A. and Schwerdtle, Tanja},
  title     = {Toxicity of two classes of arsenolipids and their water-soluble metabolites in human differentiated neurons},
  series = {Archives of toxicology : official journal of EUROTOX},
  volume    = {91},
  journal   = {Archives of toxicology : official journal of EUROTOX},
  publisher = {Springer},
  address   = {Heidelberg},
  issn      = {0340-5761},
  doi       = {10.1007/s00204-017-1933-x},
  pages     = {3121 -- 3134},
  year      = {2017},
  abstract  = {Arsenolipids are lipid-soluble organoarsenic compounds, mainly occurring in marine organisms, with arsenic-containing hydrocarbons (AsHCs) and arsenic-containing fatty acids (AsFAs) representing two major subgroups. Recently, toxicity studies of several arsenolipids showed a high cytotoxic potential of those arsenolipids in human liver and bladder cells. Furthermore, feeding studies with Drosophila melanogaster indicated an accumulation of arsenolipids in the fruit fly's brain. In this study, the neurotoxic potential of three AsHCs, two AsFAs and three metabolites (dimethylarsinic acid, thio/oxo-dimethylarsenopropanoic acid) was investigated in comparison to the toxic reference arsenite (iAsIII) in fully differentiated human brain cells (LUHMES cells). Thereby, in the case of AsHCs both the cell number and cell viability were reduced in a low micromolar concentration range comparable to iAsIII, while AsFAs and the applied metabolites were less toxic. Mechanistic studies revealed that AsHCs reduced the mitochondrial membrane potential, whereas neither iAsIII nor AsFAs had an impact. Furthermore, neurotoxic mechanisms were investigated by examining the neuronal network. Here, AsHCs massively disturbed the neuronal network and induced apoptotic effects, while iAsIII and AsFAs showed comparatively lesser effects. Taking into account the substantial in vitro neurotoxic potential of the AsHCs and the fact that they could transfer across the physiological barriers of the brain, a neurotoxic potential in vivo for the AsHCs cannot be excluded and needs to be urgently characterized.},
  language  = {en}
}
@article{BornhorstEbertMeyeretal.2020,
  author    = {Bornhorst, Julia and Ebert, Franziska and Meyer, S{\"o}ren and Ziemann, Vanessa and Xiong, Chan and Guttenberger, Nikolaus and Raab, Andrea and Baesler, Jessica and Aschner, Michael and Feldmann, J{\"o}rg and Francesconi, Kevin and Raber, Georg and Schwerdtle, Tanja},
  title     = {Toxicity of three types of arsenolipids},
  series = {Metallomics},
  volume    = {12},
  journal   = {Metallomics},
  number    = {5},
  publisher = {Oxford University Press},
  address   = {Cambridge},
  issn      = {1756-591X},
  doi       = {https://doi.org/10.1039/d0mt00039f},
  pages     = {794 -- 798},
  year      = {2020},
  abstract  = {Although fish and seafood are well known for their nutritional benefits, they contain contaminants that might affect human health. Organic lipid-soluble arsenic species, so called arsenolipids, belong to the emerging contaminants in these food items; their toxicity has yet to be systematically studied. Here, we apply the in vivo model Caenorhabditis elegans to assess the effects of two arsenic-containing hydrocarbons (AsHC), a saturated arsenic-containing fatty acid (AsFA), and an arsenic-containing triacylglyceride (AsTAG) in a whole organism. Although all arsenolipids were highly bioavailable in Caenorhabditis elegans, only the AsHCs were substantially metabolized to thioxylated or shortened metabolic products and induced significant toxicity, affecting both survival and development. Furthermore, the AsHCs were several fold more potent as compared to the toxic reference arsenite. This study clearly indicates the need for a full hazard identification of subclasses of arsenolipids to assess whether they pose a risk to human health.},
  language  = {en}
}
@article{LohrenBlagojevicFitkauetal.2015,
  author    = {Lohren, Hanna and Blagojevic, Lara and Fitkau, Romy and Ebert, Franziska and Schildknecht, Stefan and Leist, Marcel and Schwerdtle, Tanja},
  title     = {Toxicity of organic and inorganic mercury species in human neurons and human astrocytes},
  series = {Journal of trace elements in medicine and biology},
  volume    = {32},
  journal   = {Journal of trace elements in medicine and biology},
  publisher = {Elsevier},
  address   = {Jena},
  issn      = {0946-672X},
  doi       = {10.1016/j.jtemb.2015.06.008},
  pages     = {200 -- 208},
  year      = {2015},
  abstract  = {Organic mercury (Hg) species exert their toxicity primarily in the central nervous system. The food relevant Hg species methylmercury (MeHg) has been frequently studied regarding its neurotoxic effects in vitro and in vivo. Neurotoxicity of thiomersal, which is used as a preservative in medical preparations, is to date less characterised. Due to dealkylation of organic Hg or oxidation of elemental Hg, inorganic Hg is present in the brain albeit these species are not able to readily cross the blood brain barrier. This study compared for the first time toxic effects of organic MeHg chloride (MeHgCl) and thiomersal as well as inorganic mercury chloride (HgCl2) in differentiated human neurons (LUHMES) and human astrocytes (CCF-STTG1). The three Hg species differ in their degree and mechanism of toxicity in those two types of brain cells. Generally, neurons are more susceptible to Hg species induced cytotoxicity as compared to astrocytes. This might be due to the massive cellular mercury uptake in the differentiated neurons. The organic compounds exerted stronger cytotoxic effects as compared to inorganic HgCl2. In contrast to HgCl2 exposure, organic Hg compounds seem to induce the apoptotic cascade in neurons following low-level exposure. No indicators for apoptosis were identified for both inorganic and organic mercury species in astrocytes. Our studies clearly demonstrate species-specific toxic mechanisms. A mixed exposure towards all Hg species in the brain can be assumed. Thus, prospectively coexposure studies as well as cocultures of neurons and astrocytes could provide additional information in the investigation of Hg induced neurotoxicity.},
  language  = {en}
}
@article{UnterbergLeffersHuebneretal.2014,
  author    = {Unterberg, Marlies and Leffers, Larissa and Huebner, Florian and Humpf, Hans-Ulrich and Lepikhov, Konstantin and Walter, Joern and Ebert, Franziska and Schwerdtle, Tanja},
  title     = {Toxicity of arsenite and thio-DMA(V) after long-term (21 days) incubation of human urothelial cells: cytotoxicity, genotoxicity and epigenetics},
  series = {Toxicology research},
  volume    = {3},
  journal   = {Toxicology research},
  number    = {6},
  publisher = {Royal Society of Chemistry},
  address   = {Cambridge},
  issn      = {2045-452X},
  doi       = {10.1039/c4tx00036f},
  pages     = {456 -- 464},
  year      = {2014},
  abstract  = {This study aims to further mechanistically understand toxic modes of action after chronic inorganic arsenic exposure. Therefore long-term incubation studies in cultured cells were carried out, to display chronically attained changes, which cannot be observed in the generally applied in vitro short-term incubation studies. Particularly, the cytotoxic, genotoxic and epigenetic effects of an up to 21 days incubation of human urothelial (UROtsa) cells with pico- to nanomolar concentrations of iAs(III) and its metabolite thio-DMA(V) were compared. After 21 days of incubation, cytotoxic effects were strongly enhanced in the case of iAs(III) and might partly be due to glutathione depletion and genotoxic effects on the chromosomal level. These results are in strong contrast to cells exposed to thio-DMA(V). Thus, cells seemed to be able to adapt to this arsenical, as indicated among others by an increase in the cellular glutathione level. Most interestingly, picomolar concentrations of both iAs(III) and thio-DMA(V) caused global DNA hypomethylation in UROtsa cells, which was quantified in parallel by 5-medC immunostaining and a newly established, reliable, high resolution mass spectrometry (HRMS)-based test system. This is the first time that epigenetic effects are reported for thio-DMA(V); iAs(III) induced epigenetic effects occur in at least 8000 fold lower concentrations as reported in vitro before. The fact that both arsenicals cause DNA hypomethylation at really low, exposure-relevant concentrations in human urothelial cells suggests that this epigenetic effect might contribute to inorganic arsenic induced carcinogenicity, which for sure has to be further investigated in future studies.},
  language  = {en}
}
@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{Drobyshev2023,
  author    = {Drobyshev, Evgenii},
  title     = {Toxic or beneficial? What is the role of food-relevant selenium species selenoneine?},
  doi       = {10.25932/publishup-57379},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-573794},
  school      = {Universit{\"a}t Potsdam},
  pages     = {xiv, 100},
  year      = {2023},
  abstract  = {Selenium (Se) is an essential trace element that is ubiquitously present in the environment in small concentrations. Essential functions of Se in the human body are manifested through the wide range of proteins, containing selenocysteine as their active center. Such proteins are called selenoproteins which are found in multiple physiological processes like antioxidative defense and the regulation of thyroid hormone functions. Therefore, Se deficiency is known to cause a broad spectrum of physiological impairments, especially in endemic regions with low Se content. Nevertheless, being an essential trace element, Se could exhibit toxic effects, if its intake exceeds tolerable levels. Accordingly, this range between deficiency and overexposure represents optimal Se supply. However, this range was found to be narrower than for any other essential trace element. Together with significantly varying Se concentrations in soil and the presence of specific bioaccumulation factors, this represents a noticeable difficulty in the assessment of Se epidemiological status. While Se is acting in the body through multiple selenoproteins, its intake occurs mainly in form of small organic or inorganic molecular mass species. Thus, Se exposure not only depends on daily intake but also on the respective chemical form, in which it is present. The essential functions of selenium have been known for a long time and its primary forms in different food sources have been described. Nevertheless, analytical capabilities for a comprehensive investigation of Se species and their derivatives have been introduced only in the last decades. A new Se compound was identified in 2010 in the blood and tissues of bluefin tuna. It was called selenoneine (SeN) since it is an isologue of naturally occurring antioxidant ergothioneine (ET), where Se replaces sulfur. In the following years, SeN was identified in a number of edible fish species and attracted attention as a new dietary Se source and potentially strong antioxidant. Studies in populations whose diet largely relies on fish revealed that SeN represents the main non-protein bound Se pool in their blood. First studies, conducted with enriched fish extracts, already demonstrated the high antioxidative potential of SeN and its possible function in the detoxification of methylmercury in fish. Cell culture studies demonstrated, that SeN can utilize the same transporter as ergothioneine, and SeN metabolite was found in human urine. Until recently, studies on SeN properties were severely limited due to the lack of ways to obtain the pure compound. As a predisposition to this work was firstly a successful approach to SeN synthesis in the University of Graz, utilizing genetically modified yeasts. In the current study, by use of HepG2 liver carcinoma cells, it was demonstrated, that SeN does not cause toxic effectsup to 100 μM concentration in hepatocytes. Uptake experiments showed that SeN is not bioavailable to the used liver cells. In the next part a blood-brain barrier (BBB) model, based on capillary endothelial cells from the porcine brain, was used to describe the possible transfer of SeN into the central nervous system (CNS). The assessment of toxicity markers in these endothelial cells and monitoring of barrier conditions during transfer experiments demonstrated the absence of toxic effects from SeN on the BBB endothelium up to 100 μM concentration. Transfer data for SeN showed slow but substantial transfer. A statistically significant increase was observed after 48 hours following SeN incubation from the blood-facing side of the barrier. However, an increase in Se content was clearly visible already after 6 hours of incubation with 1 μM of SeN. While the transfer rate of SeN after application of 0.1 μM dose was very close to that for 1 μM, incubation with 10 μM of SeN resulted in a significantly decreased transfer rate. Double-sided application of SeN caused no side-specific transfer of SeN, thus suggesting a passive diffusion mechanism of SeN across the BBB. This data is in accordance with animal studies, where ET accumulation was observed in the rat brain, even though rat BBB does not have the primary ET transporter - OCTN1. Investigation of capillary endothelial cell monolayers after incubation with SeN and reference selenium compounds showed no significant increase of intracellular selenium concentration. Speciesspecific Se measurements in medium samples from apical and basolateral compartments, as good as in cell lysates, showed no SeN metabolization. Therefore, it can be concluded that SeN may reach the brain without significant transformation. As the third part of this work, the assessment of SeN antioxidant properties was performed in Caco-2 human colorectal adenocarcinoma cells. Previous studies demonstrated that the intestinal epithelium is able to actively transport SeN from the intestinal lumen to the blood side and accumulate SeN. Further investigation within current work showed a much higher antioxidant potential of SeN compared to ET. The radical scavenging activity after incubation with SeN was close to the one observed for selenite and selenomethionine. However, the SeN effect on the viability of intestinal cells under oxidative conditions was close to the one caused by ET. To answer the question if SeN is able to be used as a dietary Se source and induce the activity of selenoproteins, the activity of glutathione peroxidase (GPx) and the secretion of selenoprotein P (SelenoP) were measured in Caco-2 cells, additionally. As expected, reference selenium compounds selenite and selenomethionine caused efficient induction of GPx activity. In contrast to those SeN had no effect on GPx activity. To examine the possibility of SeN being embedded into the selenoproteome, SelenoP was measured in a culture medium. Even though Caco-2 cells effectively take up SeN in quantities much higher than selenite or selenomethionine, no secretion of SelenoP was observed after SeN incubation. Summarizing, we can conclude that SeN can hardly serve as a Se source for selenoprotein synthesis. However, SeN exhibit strong antioxidative properties, which appear when sulfur in ET is exchanged by Se. Therefore, SeN is of particular interest for research not as part of Se metabolism, but important endemic dietary antioxidant.},
  language  = {en}
}
@article{StrehlauWeberLuerenbaumetal.2017,
  author    = {Strehlau, Jenny and Weber, Till and Luerenbaum, Constantin and Bornhorst, Julia and Galla, Hans-Joachim and Schwerdtle, Tanja and Winter, Martin and Nowak, Sascha},
  title     = {Towards quantification of toxicity of lithium ion battery electrolytes - development and validation of a liquid-liquid extraction GC-MS method for the determination of organic carbonates in cell culture materials},
  series = {Analytical and bioanalytical chemistry : a merger of Fresenius' journal of analytical chemistry, Analusis and Quimica analitica},
  volume    = {409},
  journal   = {Analytical and bioanalytical chemistry : a merger of Fresenius' journal of analytical chemistry, Analusis and Quimica analitica},
  publisher = {Springer},
  address   = {Heidelberg},
  issn      = {1618-2642},
  doi       = {10.1007/s00216-017-0549-6},
  pages     = {6123 -- 6131},
  year      = {2017},
  abstract  = {A novel method based on liquid-liquid extraction with subsequent gas chromatography separation and mass spectrometric detection (GC-MS) for the quantification of organic carbonates in cell culture materials is presented. Method parameters including the choice of extraction solvent, of extraction method and of extraction time were optimised and the method was validated. The setup allowed for determination within a linear range of more than two orders of magnitude. The limits of detection (LODs) were between 0.0002 and 0.002 mmol/L and the repeatability precisions were in the range of 1.5-12.9\%. It could be shown that no matrix effects were present and recovery rates between 98 and 104\% were achieved. The methodology was applied to cell culture models incubated with commercial lithium ion battery (LIB) electrolytes to gain more insight into the potential toxic effects of these compounds. The stability of the organic carbonates in cell culture medium after incubation was studied. In a porcine model of the blood-cerebrospinal fluid (CSF) barrier, it could be shown that a transfer of organic carbonates into the brain facing compartment took place.},
  language  = {en}
}
@article{HackethalKoppSarvanetal.2021,
  author    = {Hackethal, Christin and Kopp, Johannes Florian and Sarvan, Irmela and Schwerdtle, Tanja and Lindtner, Oliver},
  title     = {Total arsenic and water-soluble arsenic species in foods of the first German total diet study (BfR MEAL Study)},
  series = {Food chemistry},
  volume    = {346},
  journal   = {Food chemistry},
  publisher = {Elsevier},
  address   = {Amsterdam [u.a.]},
  issn      = {0308-8146},
  doi       = {10.1016/j.foodchem.2020.128913},
  pages     = {10},
  year      = {2021},
  abstract  = {Arsenic can occur in foods as inorganic and organic forms. Inorganic arsenic is more toxic than most watersoluble organic arsenic compounds such as arsenobetaine, which is presumed to be harmless for humans. Within the first German total diet study, total arsenic, inorganic arsenic, arsenobetaine, dimethylarsinic acid and monomethylarsonic acid were analyzed in various foods. Highest levels of total arsenic were found in fish, fish products and seafood (mean: 1.43 mg kg(-1); n = 39; min-max: 0.01-6.15 mg kg(-1)), with arsenobetaine confirmed as the predominant arsenic species (1.233 mg kg 1; n = 39; min-max: 0.01-6.23 mg kg (1)). In contrast, inorganic arsenic was determined as prevalent arsenic species in terrestrial foods (0.02 mg kg (1); n = 38; min-max: 0-0.11 mg kg (1)). However, the toxicity of arsenic species varies and measurements are necessary to gain information about the composition and changes of arsenic species in foods due to household processing of foods.},
  language  = {en}
}
@article{DraudePelsterKoersgenetal.2014,
  author    = {Draude, F. and Pelster, A. and Koersgen, M. and Kassenboehmer, R. and Schwerdtle, Tanja and Muething, J. and Arlinghaus, H. F.},
  title     = {ToF-SIMS imaging of plasma membrane lipids with sub-micrometer resolution},
  series = {Surface and interface analysis : an international journal devoted to the development and application of techniques for the analysis surfaces, interfaces and thin films},
  volume    = {46},
  journal   = {Surface and interface analysis : an international journal devoted to the development and application of techniques for the analysis surfaces, interfaces and thin films},
  publisher = {Wiley-Blackwell},
  address   = {Hoboken},
  issn      = {0142-2421},
  doi       = {10.1002/sia.5576},
  pages     = {127 -- 130},
  year      = {2014},
  abstract  = {Time-of-flight secondary ion mass spectrometry (ToF-SIMS) was used for label-free analyses of the molecular lateral distribution of two different epithelial cell membranes (PANC-1 and UROtsa). The goal of the research was to enhance the ion yield of specific membrane molecules for improving the membrane imaging capability of ToF-SIMS on the nanoscale lateral dimension. For this task, a special silicon wafer sandwich preparation technique was optimized using different wafer materials, spacers, and washing procedures. Under optimized preparation conditions, the yield could be significantly enhanced, allowing imaging of the inhomogeneous distribution of phosphocholine (common head group for phosphatidylcholine and sphingomyelin) of a PANC-1 cell membrane's outer lipid layer with a lateral resolution of less than 200nm. Copyright (c) 2014 John Wiley \& Sons, Ltd.},
  language  = {en}
}
@article{DoellDjalaliFarahaniKofoetZrenneretal.2021,
  author    = {D{\"o}ll, Stefanie and Djalali Farahani-Kofoet, Roxana and Zrenner, Rita and Henze, Andrea and Witzel, Katja},
  title     = {Tissue-specific signatures of metabolites and proteins in asparagus roots and exudates},
  series = {Horticulture research},
  volume    = {8},
  journal   = {Horticulture research},
  number    = {1},
  publisher = {Nanjing Agricultural Univ.},
  address   = {Nanjing},
  issn      = {2052-7276},
  doi       = {10.1038/s41438-021-00510-5},
  pages     = {14},
  year      = {2021},
  abstract  = {Comprehensive untargeted and targeted analysis of root exudate composition has advanced our understanding of rhizosphere processes. However, little is known about exudate spatial distribution and regulation. We studied the specific metabolite signatures of asparagus root exudates, root outer (epidermis and exodermis), and root inner tissues (cortex and vasculature). The greatest differences were found between exudates and root tissues. In total, 263 non-redundant metabolites were identified as significantly differentially abundant between the three root fractions, with the majority being enriched in the root exudate and/or outer tissue and annotated as 'lipids and lipid-like molecules' or 'phenylpropanoids and polyketides'. Spatial distribution was verified for three selected compounds using MALDI-TOF mass spectrometry imaging. Tissue-specific proteome analysis related root tissue-specific metabolite distributions and rhizodeposition with underlying biosynthetic pathways and transport mechanisms. The proteomes of root outer and inner tissues were spatially very distinct, in agreement with the fundamental differences between their functions and structures. According to KEGG pathway analysis, the outer tissue proteome was characterized by a high abundance of proteins related to 'lipid metabolism', 'biosynthesis of other secondary metabolites' and 'transport and catabolism', reflecting its main functions of providing a hydrophobic barrier, secreting secondary metabolites, and mediating water and nutrient uptake. Proteins more abundant in the inner tissue related to 'transcription', 'translation' and 'folding, sorting and degradation', in accord with the high activity of cortical and vasculature cell layers in growth- and development-related processes. In summary, asparagus root fractions accumulate specific metabolites. This expands our knowledge of tissue-specific plant cell function.},
  language  = {en}
}
@phdthesis{Trendelenburg2017,
  author    = {Trendelenburg, Val{\´e}rie},
  title     = {Therapie der Erdnussallergie durch orale Immuntherapie},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-403557},
  school      = {Universit{\"a}t Potsdam},
  pages     = {XIV, 198},
  year      = {2017},
  abstract  = {Einleitung: Die Erdnussallergie z{\"a}hlt zu den h{\"a}ufigsten Nahrungsmittelallergien im Kindesalter. Bereits kleine Mengen Erdnuss (EN) k{\"o}nnen zu schweren allergischen Reaktionen f{\"u}hren. EN ist der h{\"a}ufigste Ausl{\"o}ser einer lebensbedrohlichen Anaphylaxie bei Kindern und Jugendlichen. Im Gegensatz zu anderen fr{\"u}hkindlichen Nahrungsmittelallergien entwickeln Patienten mit einer EN-Allergie nur selten eine nat{\"u}rliche Toleranz. Seit mehreren Jahren wird daher an kausalen Therapiem{\"o}glichkeiten f{\"u}r EN-Allergiker, insbesondere an der oralen Immuntherapie (OIT), geforscht. Erste kleinere Studien zur OIT bei EN-Allergie zeigten erfolgsversprechende Ergebnisse. Im Rahmen einer randomisierten, doppelblind, Placebo-kontrollierten Studie mit gr{\"o}ßerer Fallzahl werden in der vorliegenden Arbeit die klinische Wirksamkeit und Sicherheit dieser Therapieoption bei Kindern mit EN-Allergie genauer evaluiert. Des Weiteren werden immunologische Ver{\"a}nderungen sowie die Lebensqualit{\"a}t und Therapiebelastung unter OIT untersucht. Methoden: Kinder zwischen 3-18 Jahren mit einer IgE-vermittelten EN-Allergie wurden in die Studie eingeschlossen. Vor Beginn der OIT wurde eine orale Provokation mit EN durchgef{\"u}hrt. Die Patienten wurden 1:1 randomisiert und entsprechend der Verum- oder Placebogruppe zugeordnet. Begonnen wurde mit 2-120 mg EN bzw. Placebo pro Tag, abh{\"a}ngig von der Reaktionsdosis bei der oralen Provokation. Zun{\"a}chst wurde die t{\"a}gliche OIT-Dosis alle zwei Wochen {\"u}ber etwa 14 Monate langsam bis zu einer Erhaltungsdosis von mindestens 500 mg EN (= 125 mg EN-Protein, ~ 1 kleine EN) bzw. Placebo gesteigert. Die maximal erreichte Dosis wurde dann {\"u}ber zwei Monate t{\"a}glich zu Hause verabreicht. Im Anschluss erfolgte erneut eine orale Provokation mit EN. Der prim{\"a}re Endpunkt der Studie war die Anzahl an Patienten der Verum- und Placebogruppe, die unter oraler Provokation nach OIT ≥1200 mg EN vertrugen (=„partielle Desensibilisierung"). Sowohl vor als auch nach OIT wurde ein Hautpricktest mit EN durchgef{\"u}hrt und EN-spezifisches IgE und IgG4 im Serum bestimmt. Außerdem wurden die Basophilenaktivierung sowie die Aussch{\"u}ttung von T-Zell-spezifischen Zytokinen nach Stimulation mit EN in vitro gemessen. Anhand von Frageb{\"o}gen wurde die Lebensqualit{\"a}t vor und nach OIT sowie die Therapiebelastung w{\"a}hrend OIT erfasst. Ergebnisse: 62 Patienten wurden in die Studie eingeschlossen und randomisiert. Nach etwa 16 Monaten unter OIT zeigten 74,2\% (23/31) der Patienten der Verumgruppe und nur 16,1\% (5/31) der Placebogruppe eine „partielle Desensibilisierung" gegen{\"u}ber EN (p<0,001). Im Median vertrugen Patienten der Verumgruppe 4000 mg EN (~8 kleine EN) unter der Provokation nach OIT wohingegen Patienten der Placebogruppe nur 80 mg EN (~1/6 kleine EN) vertrugen (p<0,001). Fast die H{\"a}lfte der Patienten der Verumgruppe (41,9\%) tolerierten die H{\"o}chstdosis von 18 g EN unter Provokation („komplette Desensibilisierung"). Es zeigte sich ein vergleichbares Sicherheitsprofil unter Verum- und Placebo-OIT in Bezug auf objektive Nebenwirkungen. Unter Verum-OIT kam es jedoch signifikant h{\"a}ufiger zu subjektiven Nebenwirkungen wie oralem Juckreiz oder Bauchschmerzen im Vergleich zu Placebo (3,7\% der Verum-OIT-Gaben vs. 0,5\% der Placebo-OIT-Gaben, p<0,001). Drei Kinder der Verumgruppe (9,7\%) und sieben Kinder der Placebogruppe (22,6\%) beendeten die Studie vorzeitig, je zwei Patienten beider Gruppen aufgrund von Nebenwirkungen. Im Gegensatz zu Placebo, zeigten sich unter Verum-OIT signifikante immunologische Ver{\"a}nderungen. So kam es zu einer Abnahme des EN-spezifischen Quaddeldurchmessers im Hautpricktest, einem Anstieg der EN-spezifischen IgG4-Werte im Serum sowie zu einer verminderten EN-spezifischen Zytokinsekretion, insbesondere der Th2-spezifischen Zytokine IL-4 und IL-5. Hinsichtlich der EN-spezifischen IgE-Werte sowie der EN-spezifischen Basophilenaktivierung zeigten sich hingegen keine Ver{\"a}nderungen unter OIT. Die Lebensqualit{\"a}t von Kindern der Verumgruppe war nach OIT signifikant verbessert, jedoch nicht bei Kindern der Placebogruppe. W{\"a}hrend der OIT wurde die Therapie von fast allen Kindern (82\%) und M{\"u}ttern (82\%) als positiv bewertet (= niedrige Therapiebelastung). Diskussion: Die EN-OIT f{\"u}hrte bei einem Großteil der EN-allergischen Kinder zu einer Desensibilisierung und einer deutlich erh{\"o}hten Reaktionsschwelle auf EN. Somit sind die Kinder im Alltag vor akzidentellen Reaktionen auf EN gesch{\"u}tzt, was die Lebensqualit{\"a}t der Kinder deutlich verbessert. Unter den kontrollierten Studienbedingungen zeigte sich ein akzeptables Sicherheitsprofil, mit vorrangig milder Symptomatik. Die klinische Desensibilisierung ging mit Ver{\"a}nderungen auf immunologischer Ebene einher. Langzeitstudien zur EN-OIT m{\"u}ssen jedoch abgewartet werden, um die klinische und immunologische Wirksamkeit hinsichtlich einer m{\"o}glichen langfristigen oralen Toleranzinduktion sowie die Sicherheit unter langfristiger OIT zu untersuchen, bevor das Therapiekonzept in die Praxis {\"u}bertragen werden kann.},
  language  = {de}
}
@article{StoofAngerKruse1994,
  author    = {Stoof, Gisela and Anger, Horst and Kruse, Hans-Peter},
  title     = {The yield of resistant starch after hydrothermal treatment},
  year      = {1994},
  language  = {en}
}
@inproceedings{HenkelCamargoSchanzeetal.2014,
  author    = {Henkel, Janine and Camargo, Rodolfo Gonzalez and Schanze, Nancy and P{\"u}schel, Gerhard Paul},
  title     = {The vicious circle of prostaglandin- and cytokine-dependent hepatic insulin resistance: a key role of prostaglandin E2},
  series = {Diabetologia : journal of the European Association for the Study of Diabetes (EASD)},
  volume    = {57},
  booktitle = {Diabetologia : journal of the European Association for the Study of Diabetes (EASD)},
  publisher = {Springer},
  address   = {New York},
  issn      = {0012-186X},
  pages     = {S241 -- S242},
  year      = {2014},
  language  = {en}
}
@misc{CastroGruneSpeckmann2017,
  author    = {Castro, Jos{\´e} Pedro and Grune, Tilman and Speckmann, Bodo},
  title     = {The two faces of reactive oxygen species (ROS) in adipocyte function and dysfunction},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-398039},
  pages     = {16},
  year      = {2017},
  abstract  = {White adipose tissue (WAT) is actively involved in the regulation of whole-body energy homeostasis via storage/release of lipids and adipokine secretion. Current research links WAT dysfunction to the development of metabolic syndrome (MetS) and type 2 diabetes (T2D). The expansion of WAT during oversupply of nutrients prevents ectopic fat accumulation and requires proper preadipocyte-to-adipocyte differentiation. An assumed link between excess levels of reactive oxygen species (ROS), WAT dysfunction and T2D has been discussed controversially. While oxidative stress conditions have conclusively been detected in WAT of T2D patients and related animal models, clinical trials with antioxidants failed to prevent T2D or to improve glucose homeostasis. Furthermore, animal studies yielded inconsistent results regarding the role of oxidative stress in the development of diabetes. Here, we discuss the contribution of ROS to the (patho)physiology of adipocyte function and differentiation, with particular emphasis on sources and nutritional modulators of adipocyte ROS and their functions in signaling mechanisms controlling adipogenesis and functions of mature fat cells. We propose a concept of ROS balance that is required for normal functioning of WAT. We explain how both excessive and diminished levels of ROS, e.g. resulting from over supplementation with antioxidants, contribute to WAT dysfunction and subsequently insulin resistance.},
  language  = {en}
}
@misc{CastroGruneSpeckmann2016,
  author    = {Castro, Jos{\´e} Pedro and Grune, Tilman and Speckmann, Bodo},
  title     = {The two faces of reactive oxygen species (ROS) in adipocyte function and dysfunction},
  series = {Biological chemistry},
  volume    = {397},
  journal   = {Biological chemistry},
  publisher = {De Gruyter},
  address   = {Berlin},
  issn      = {1431-6730},
  doi       = {10.1515/hsz-2015-0305},
  pages     = {709 -- 724},
  year      = {2016},
  abstract  = {White adipose tissue (WAT) is actively involved in the regulation of whole-body energy homeostasis via storage/ release of lipids and adipokine secretion. Current research links WAT dysfunction to the development of metabolic syndrome (MetS) and type 2 diabetes (T2D). The expansion of WAT during oversupply of nutrients prevents ectopic fat accumulation and requires proper preadipocyte-to-adipocyte differentiation. An assumed link between excess levels of reactive oxygen species (ROS), WAT dysfunction and T2D has been discussed controversially. While oxidative stress conditions have conclusively been detected in WAT of T2D patients and related animal models, clinical trials with antioxidants failed to prevent T2D or to improve glucose homeostasis. Furthermore, animal studies yielded inconsistent results regarding the role of oxidative stress in the development of diabetes. Here, we discuss the contribution of ROS to the (patho) physiology of adipocyte function and differentiation, with particular emphasis on sources and nutritional modulators of adipocyte ROS and their functions in signaling mechanisms controlling adipogenesis and functions of mature fat cells. We propose a concept of ROS balance that is required for normal functioning of WAT. We explain how both excessive and diminished levels of ROS, e. g. resulting from over supplementation with antioxidants, contribute to WAT dysfunction and subsequently insulin resistance.},
  language  = {en}
}
@article{ZhouZengFuetal.2016,
  author    = {Zhou, Ying and Zeng, Lanting and Fu, Xiumin and Mei, Xin and Cheng, Sihua and Liao, Yinyin and Deng, Rufang and Xu, Xinlan and Jiang, Yueming and Duan, Xuewu and Baldermann, Susanne and Yang, Ziyin},
  title     = {The sphingolipid biosynthetic enzyme Sphingolipid delta8 desaturase is important for chilling resistance of tomato},
  series = {Scientific reports},
  volume    = {6},
  journal   = {Scientific reports},
  publisher = {Nature Publ. Group},
  address   = {London},
  issn      = {2045-2322},
  doi       = {10.1038/srep38742},
  pages     = {10},
  year      = {2016},
  abstract  = {The physiological functions of sphingolipids in animals have been intensively studied, while less attention has been paid to their roles in plants. Here, we reveal the involvement of sphingolipid delta8 desaturase (SlSLD) in the chilling resistance of tomato (Solanum lycopersicum cv. Micro-Tom). We used the virus-induced gene silencing (VIGS) approach to knock-down SlSLD expression in tomato leaves, and then evaluated chilling resistance. Changes in leaf cell structure under a chilling treatment were observed by transmission electron microscopy. In control plants, SlSLD was highly expressed in the fruit and leaves in response to a chilling treatment. The degree of chilling damage was greater in SlSLD-silenced plants than in control plants, indicating that SlSLD knock-down significantly reduced the chilling resistance of tomato. Compared with control plants, SlSLD-silenced plants showed higher relative electrolytic leakage and malondialdehyde content, and lower superoxide dismutase and peroxidase activities after a chilling treatment. Chilling severely damaged the chloroplasts in SlSLD-silenced plants, resulting in the disruption of chloroplast membranes, swelling of thylakoids, and reduced granal stacking. Together, these results show that SlSLD is crucial for chilling resistance in tomato.},
  language  = {en}
}
@article{SchlegerHeckSteinberg2000,
  author    = {Schleger, C. and Heck, R. and Steinberg, Pablo},
  title     = {The role of wild-type and mutated N-ras in the malignant transformation of liver cells},
  year      = {2000},
  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{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}
}
@misc{PrueferKleuservanderGiet2015,
  author    = {Pr{\"u}fer, Nicole and Kleuser, Burkhard and van der Giet, Markus},
  title     = {The role of serum amyloid A and sphingosine-1-phosphate on high-density lipoprotein functionality},
  series = {Biological chemistry},
  volume    = {396},
  journal   = {Biological chemistry},
  number    = {6-7},
  publisher = {De Gruyter},
  address   = {Berlin},
  issn      = {1431-6730},
  doi       = {10.1515/hsz-2014-0192},
  pages     = {573 -- 583},
  year      = {2015},
  abstract  = {The high-density lipoprotein (HDL) is one of the most important endogenous cardiovascular protective markers. HDL is an attractive target in the search for new pharmaceutical therapies and in the prevention of cardiovascular events. Some of HDL's anti-atherogenic properties are related to the signaling molecule sphingosine-1-phosphate (S1P), which plays an important role in vascular homeostasis. However, for different patient populations it seems more complicated. Significant changes in HDL's protective potency are reduced under pathologic conditions and HDL might even serve as a proatherogenic particle. Under uremic conditions especially there is a change in the compounds associated with HDL. S1P is reduced and acute phase proteins such as serum amyloid A (SAA) are found to be elevated in HDL. The conversion of HDL in inflammation changes the functional properties of HDL. High amounts of SAA are associated with the occurrence of cardiovascular diseases such as atherosclerosis. SAA has potent pro-atherogenic properties, which may have impact on HDL's biological functions, including cholesterol efflux capacity, antioxidative and anti-inflammatory activities. This review focuses on two molecules that affect the functionality of HDL. The balance between functional and dysfunctional HDL is disturbed after the loss of the protective sphingolipid molecule S1P and the accumulation of the acute-phase protein SAA. This review also summarizes the biological activities of lipid-free and lipid-bound SAA and its impact on HDL function.},
  language  = {en}
}
@article{KhozroughiJanderSchirrmannetal.2017,
  author    = {Khozroughi, Amin Ghadiri and Jander, Elisabeth and Schirrmann, Michael and Rawel, Harshadrai Manilal and Kroh, Lothar W. and Schlueter, Oliver},
  title     = {The role of myoglobin degradation in the formation of zinc protoporphyrin IX in the longissimus lumborum of pork},
  series = {LWT - food science and technology : an official journal of the Swiss Society of Food Science and Technology (SGLWT/SOSSTA) and the International Union of Food Science and Technology (IUFoST)},
  volume    = {85},
  journal   = {LWT - food science and technology : an official journal of the Swiss Society of Food Science and Technology (SGLWT/SOSSTA) and the International Union of Food Science and Technology (IUFoST)},
  publisher = {Elsevier},
  address   = {Amsterdam},
  issn      = {0023-6438},
  doi       = {10.1016/j.lwt.2017.06.047},
  pages     = {22 -- 27},
  year      = {2017},
  abstract  = {Investigations on the post mortal formation of fluorescent zinc protoporphyrin (ZnPP) IX in pork meat are currently in focus of meat science research. The role of myoglobin degradation in this context appears to be one of the most diversely discussed issues. To address this question meat-extracts of longissimus lumborum (LL) muscle (0.8 mg/mL) were incubated at 30 degrees C for up to 72 h and investigated by HPSEC-UV-fluorescence, SDS-PAGE and MALDI-TOF-MS. Between 0 and 72 h of incubation the fluorescence intensity (lambda(ex)./(em). = 420/590 nm) of the meat-extracts rose significantly (p < 0.001) from 10.9 +/- 0.8 to 34.8 +/- 0.3 (rel. units) while the staining intensity of the SDS-PAGE of myoglobin non-significantly (p > 0.4) changed from 6.2 +/- 0.5 x 105 to 5.0 +/- 0.3 x 105 (rel. units). The results indicate that ZnPP is formed by a Fe(II)-Zn(II)-substitution in myoglobin heme where an accompanying myoglobin degradation is not necessarily obligatory. (C) 2017 Elsevier Ltd. All rights reserved.},
  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}
}
@article{StarkPoratVolohonskyetal.2003,
  author    = {Stark, Avishay abraham and Porat, Noga and Volohonsky, Gloria and Konlosh, A. and Bluvshtein, Evgenia and Tubi, C. and Steinberg, Pablo},
  title     = {The role of gamma-glutamyl transpeptidase in the biosynthesis of glutathione},
  year      = {2003},
  language  = {en}
}
@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{Ambrosi2016,
  author    = {Ambrosi, Thomas H.},
  title     = {The Role of Bone-residing Adipocyte Progenitors in Age-related Stem Cell Dysfunction and Regenerative Processes},
  school      = {Universit{\"a}t Potsdam},
  pages     = {132},
  year      = {2016},
  language  = {en}
}
@article{FuchsTeubnerSteinberg2004,
  author    = {Fuchs, J. and Teubner, Wera and Steinberg, Pablo},
  title     = {The resistance of intestinal epithelial cells towards the transforming activity of 2-hydroxyamino-1-methyl-6- phenylimidazo[4,5-B]pyridine is accompanied by glutathione S-transferase induction},
  issn      = {0028-1298},
  year      = {2004},
  language  = {en}
}
@article{JannaschNickelSchulze2021,
  author    = {Jannasch, Franziska and Nickel, Daniela and Schulze, Matthias Bernd},
  title     = {The reliability and relative validity of predefined dietary patterns were higher than that of exploratory dietary patterns in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam population},
  series = {British journal of nutrition : BJN : an international journal of nutritional science / published on behalf of The Nutrition Society},
  volume    = {125},
  journal   = {British journal of nutrition : BJN : an international journal of nutritional science / published on behalf of The Nutrition Society},
  number    = {11},
  publisher = {Cambridge University Press},
  address   = {Cambridge},
  issn      = {1475-2662},
  doi       = {10.1017/S0007114520003517},
  pages     = {1270 -- 1280},
  year      = {2021},
  abstract  = {The aim of this study was to assess the ability of the FFQ to describe reliable and valid dietary pattern (DP) scores. In a total of 134 participants of the European Prospective Investigation into Cancer and Nutrition-Potsdam study aged 35-67 years, the FFQ was applied twice (baseline and after 1 year) to assess its reliability. Between November 1995 and March 1997, twelve 24-h dietary recalls (24HDR) as reference instrument were applied to assess the validity of the FFQ. Exploratory DP were derived by principal component analyses. Investigated predefined DP were the Alternative Healthy Eating Index (AHEI) and two Mediterranean diet indices. From dietary data of each FFQ, two exploratory DP were retained, but differed in highly loading food groups, resulting in moderate correlations (r 0 center dot 45-0 center dot 58). The predefined indices showed higher correlations between the FFQ (r(AHEI) 0 center dot 62, r(Mediterranean Diet Pyramid Index (MedPyr)) 0 center dot 62 and r(traditional Mediterranean Diet Score (tMDS)) 0 center dot 51). From 24HDR dietary data, one exploratory DP retained differed in composition to the first FFQ-based DP, but showed similarities to the second DP, reflected by a good correlation (r 0 center dot 70). The predefined DP correlated moderately (r 0 center dot 40-0 center dot 60). To conclude, long-term analyses on exploratory DP should be interpreted with caution, due to only moderate reliability. The validity differed extensively for the two exploratory DP. The investigated predefined DP showed a better reliability and a moderate validity, comparable to other studies. Within the two Mediterranean diet indices, the MedPyr performed better than the tMDs in this middle-aged, semi-urban German study population.},
  language  = {en}
}
@inproceedings{BoehmPolzinLuethetal.2012,
  author    = {Boehm, Andreas and Polzin, A. and Lueth, Anja and Kleuser, Burkhard and Rassaf, T. and Kelm, M. and Kroemer, H. K. and Schroer, K. and Rauch, B. H.},
  title     = {The release of sphingosine-1-phosphate from human platelets during acute coronary syndrome is attenuated by aspirin},
  series = {NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY},
  volume    = {385},
  booktitle = {NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY},
  publisher = {Springer},
  address   = {New York},
  issn      = {0028-1298},
  pages     = {12 -- 12},
  year      = {2012},
  language  = {en}
}
@misc{SchmiedchenLongardtBuehreretal.2017,
  author    = {Schmiedchen, Bettina and Longardt, Ann Carolin and B{\"u}hrer, Christoph and Raila, Jens and Loui, Andrea and Schweigert, Florian J.},
  title     = {The Relative Dose Response Test Based on Retinol-Binding Protein 4 Is Not Suitable to Assess Vitamin A Status in Very Low Birth Weight Infants},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-399853},
  pages     = {6},
  year      = {2017},
  abstract  = {Background: The relative dose response (RDR) test, which quantifies the increase in serum retinol after vitamin A administration, is a qualitative measure of liver vitamin A stores. Particularly in preterm infants, the feasibility of the RDR test involving blood is critically dependent on small sample volumes. Objectives: This study aimed to assess whether the RDR calculated with retinol-binding protein 4 (RBP4) might be a substitute for the classical retinol-based RDR test for assessing vitamin A status in very preterm infants. Methods: This study included preterm infants with a birth weight below 1,500 g (n = 63, median birth weight 985 g, median gestational age 27.4 weeks) who were treated with 5,000 IU retinyl palmitate intramuscularly 3 times a week for 4 weeks. On day 3 (first vitamin A injection) and day 28 of life (last vitamin A injection), the RDR was calculated and compared using serum retinol and RBP4 concentrations. Results: The concentrations of retinol (p < 0.001) and RBP4 (p < 0.01) increased significantly from day 3 to day 28. On day 3, the median (IQR) retinol-RDR was 27\% (8.4-42.5) and the median RBP4-RDR was 8.4\% (-3.4 to 27.9), compared to 7.5\% (-10.6 to 20.8) and -0.61\% (-19.7 to 15.3) on day 28. The results for retinol-RDR and RBP4-RDR revealed no significant correlation. The agreement between retinol-RDR and RBP4-RDR was poor (day 3: Cohen's κ = 0.12; day 28: Cohen's κ = 0.18). Conclusion: The RDR test based on circulating RBP4 is unlikely to reflect the hepatic vitamin A status in preterm infants.},
  language  = {en}
}
@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}
}
@article{BrauneMaulSchebbetal.2010,
  author    = {Braune, Annett and Maul, Ronald and Schebb, Nils Helge and Kulling, Sabine E. and Blaut, Michael},
  title     = {The red clover isoflavone irilone is largely resistant to degradation by the human gut microbiota},
  issn      = {1613-4125},
  doi       = {10.1002/mnfr.200900233},
  year      = {2010},
  abstract  = {Intestinal bacteria may influence bioavailability and physiological activity of dietary isoflavones. We therefore investigated the ability of human intestinal microbiota to convert irilone and genistein in vitro. In contrast to genistein, irilone was largely resistant to transformation by fecal slurries of ten human subjects. The fecal microbiota converted genistein to dihydrogenistein, 6'-hydroxy-O-desmethylangolensin, and 2-(4-hydroxyphenyl)- propionic acid. However, considerable interindividual differences in the rate of genistein degradation and the pattern of metabolites formed from genistein were observed. Only one metabolite, namely dihydroirilone, was formed from irilone in minor amounts. In further experiments, Eubacterium ramulus, a prevalent flavonoid-degrading species of the human gut, was tested for transformation of irilone. In contrast to genistein, irilone was not converted by E. ramulus. Irilone only differs from genistein by a methylenedioxy group attached to the A-ring of the isoflavone skeleton. This substitution obviously restricts the degradability of irilone by human intestinal bacteria.},
  language  = {en}
}
@article{SteinbergZschalerThometal.2001,
  author    = {Steinberg, Pablo and Zschaler, Ingrid and Thom, Elke and Kuna, Manuela and W{\"u}st, G{\"u}nter and Sch{\"a}fer-Schwebel, Angelika and M{\"u}ller, Rolf and Kramer, Peter-J{\"u}rgen and Weiße, G{\"u}nter},
  title     = {The polycyclic musk 7-acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydronaphthaline lacks liver tumor initiating and promoting activity in rats exposed to human-relevant doses},
  issn      = {0340-5761},
  doi       = {10.1007/s002040100274},
  year      = {2001},
  language  = {en}
}
@article{BergerBaldermannRuppel2017,
  author    = {Berger, Beatrice and Baldermann, Susanne and Ruppel, Silke},
  title     = {The plant growth-promoting bacterium Kosakonia radicincitans improves fruit yield and quality of Solanum lycopersicum},
  series = {Journal of the Science of Food and Agriculture},
  volume    = {97},
  journal   = {Journal of the Science of Food and Agriculture},
  publisher = {Wiley},
  address   = {Hoboken},
  issn      = {0022-5142},
  doi       = {10.1002/jsfa.8357},
  pages     = {4865 -- 4871},
  year      = {2017},
  abstract  = {BACKGROUNDProduction and the quality of tomato fruits have a strong economic relevance. Microorganisms such as the plant growth-promoting bacterium (PGPB) Kosakonia radicincitans (DSM 16656) have been demonstrated to improve shoot and root growth of young tomato plants, but data on yield increase and fruit quality by K. radicincitans are lacking. RESULTSThis study investigated how K. radicincitans affects tomato fruits. After inoculation of tomato seeds with K. radicincitans or a sodium chloride buffer control solution, stalk length, first flowering and the amount of ripened fruits produced by inoculated and non-inoculated plants were monitored over a period of 21 weeks. Inoculation of tomato seeds with K. radicincitans accelerated flowering and ripening of tomato fruits. Sugars, acidity, amino acids, volatile organic compounds and carotenoids in the fruits were also analyzed. CONCLUSIONIt was found that the PGPBK. radicincitans affected the amino acid, sugar and volatile composition of ripened fruits, contributing to a more pleasant-tasting fruit without forfeiting selected quality indicators. (c) 2017 Society of Chemical Industry},
  language  = {en}
}
@article{SchwingshacklRuzanskaAntonetal.2018,
  author    = {Schwingshackl, Lukas and Ruzanska, Ulrike Alexandra and Anton, Verena and Wallroth, Raphael and Ohla, Kathrin and Knueppel, Sven and Schulze, Matthias Bernd and Pischon, Tobias and Deutschbein, Johannes and Schenk, Liane and Warschburger, Petra and Harttig, Ulrich and Boeing, Heiner and Bergmann, Manuela M.},
  title     = {The NutriAct Family Study: a web-based prospective study on the epidemiological, psychological and sociological basis of food choice},
  series = {BMC public health},
  volume    = {18},
  journal   = {BMC public health},
  publisher = {BMC},
  address   = {London},
  issn      = {1471-2458},
  doi       = {10.1186/s12889-018-5814-x},
  pages     = {12},
  year      = {2018},
  abstract  = {Background: Most studies on food choice have been focussing on the individual level but familial aspects may also play an important role. This paper reports of a novel study that will focus on the familial aspects of the formation of food choice among men and women aged 50-70 years by recruiting spouses and siblings (NutriAct Family Study; NFS). Discussion: Until August 4th 2017, 4783 EPIC-Participants were contacted by mail of which 446 persons recruited 2 to 5 family members (including themselves) resulting in 1032 participants, of whom 82\% had started answering or already completed the questionnaires. Of the 4337 remaining EPIC-participants who had been contacted, 1040 (24\%) did not respond at all, and 3297 (76\%) responded but declined, in 51\% of the cases because of the request to recruit at least 2 family members in the respective age range. The developed recruitment procedures and web-based methods of data collection are capable to generate the required study population including the data on individual and inter-personal determinants which will be linkable to food choice. The information on familial links among the study participants will show the role of familial traits in midlife for the adoption of food choices supporting healthy aging.},
  language  = {en}
}
@article{HocherSharkovskaMarketal.2013,
  author    = {Hocher, Berthold and Sharkovska, Yuliya and Mark, Michael and Klein, Thomas and Pfab, Thiemo},
  title     = {The novel DPP-4 inhibitors linagliptin and BI 14361 reduce infarct size after myocardial ischemia/reperfusion in rats},
  series = {International journal of cardiology},
  volume    = {167},
  journal   = {International journal of cardiology},
  number    = {1},
  publisher = {Elsevier},
  address   = {Clare},
  issn      = {0167-5273},
  doi       = {10.1016/j.ijcard.2011.12.007},
  pages     = {87 -- 93},
  year      = {2013},
  abstract  = {Background: Dipeptidylpeptidase-4 inhibition is reported to have beneficial effects on myocardial ischemia. Mechanisms might include a reduced degradation of stromal cell-derived factor-1 alpha with subsequent increased recruitment of circulating stem cells and/or incretin receptor-dependent pathways. This study evaluated the novel xanthine-based dipeptidylpeptidase-4 inhibitors linagliptin (BI 1356) and BI 14361 in cardiac ischemia. Methods: Male Wistar rats were pretreated with linagliptin or BI 14361 and subjected to ligation of the left anterior descending coronary artery for 30 min. Results: Dipeptidylpeptidase-4 inhibition significantly reduced the infarct size after 7 days (-27.7\%, p<0.05) and 8 weeks (-18.0\%, p<0.05). There was a significantly improved maximum rate of left ventricular pressure decline (dP/dt min) in linagliptin-treated animals 8 weeks after ischemia/reperfusion. Apart from that, treatment did not improve cardiac function as determined by echocardiography and cardiac catheterization. Immunohistological staining revealed an increased number of cells positive for stromal cell-derived factor-1 alpha, CXCR-4 and CD34 within and around the infarcted area of BI 14361-treated animals. Conclusions: Linagliptin and BI 14361 are able to reduce infarct size after myocardial ischemia. The immunohistological findings support the hypothesis that dipeptidylpeptidase-4 inhibition via reduced cleavage of stromal cell-derived factor-1 alpha might lead to an enhanced recruitment of CXCR-4+ circulating progenitor cells.},
  language  = {en}
}
@article{ReegJungCastroetal.2016,
  author    = {Reeg, Sandra and Jung, Tobias and Castro, Jos{\´e} Pedro and Davies, Kelvin J. A. and Henze, Andrea and Grune, Tilman},
  title     = {The molecular chaperone Hsp70 promotes the proteolytic removal of oxidatively damaged proteins by the proteasome},
  series = {Free radical biology and medicine : the official journal of the Oxygen Society, a constituent member of the International Society for Free Radical Research},
  volume    = {99},
  journal   = {Free radical biology and medicine : the official journal of the Oxygen Society, a constituent member of the International Society for Free Radical Research},
  publisher = {Elsevier},
  address   = {New York},
  issn      = {0891-5849},
  doi       = {10.1016/j.freeradbiomed.2016.08.002},
  pages     = {153 -- 166},
  year      = {2016},
  abstract  = {One hallmark of aging is the accumulation of protein aggregates, promoted by the unfolding of oxidized proteins. Unraveling the mechanism by which oxidized proteins are degraded may provide a basis to delay the early onset of features, such as protein aggregate formation, that contribute to the aging phenotype. In order to prevent aggregation of oxidized proteins, cells recur to the 20S proteasome, an efficient turnover proteolysis complex. It has previously been shown that upon oxidative stress the 26S proteasome, another form, dissociates into the 20S form. A critical player implicated in its dissociation is the Heat Shock Protein 70 (Hsp70), which promotes an increase in free 20S proteasome and, therefore, an increased capability to degrade oxidized proteins. The aim of this study was to test whether or not Hsp70 is involved in cooperating with the 20S proteasome for a selective degradation of oxidatively damaged proteins. Our results demonstrate that Hsp70 expression is induced in HT22 cells as a result of mild oxidative stress conditions. Furthermore, Hsp70 prevents the accumulation of oxidized proteins and directly promotes their degradation by the 20S proteasome. In contrast the expression of the Heat shock cognate protein 70 (Hsc70) was not changed in recovery after oxidative stress and Hsc70 has no influence on the removal of oxidatively damaged proteins. We were able to demonstrate in HT22 cells, in brain homogenates from 129/SV mice and in vitro, that there is an increased interaction of Hsp70 with oxidized proteins, but also with the 20S proteasome, indicating a role of Hsp70 in mediating the interaction of oxidized proteins with the 20S proteasome. Thus, our data clearly implicate an involvement of Hsp70 oxidatively damaged protein degradation by the 20S proteasome. c) 2016 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).},
  language  = {en}
}
@article{HechtFreisevonWebskyetal.2016,
  author    = {Hecht, Eva and Freise, Christian and von Websky, Karoline and Nasser, Hamoud and Kretzschmar, Nadja and Stawowy, Philipp and Hocher, Berthold and Querfeld, Uwe},
  title     = {The matrix metalloproteinases 2 and 9 initiate uraemic vascular calcifications},
  series = {Nephrology, dialysis, transplantation},
  volume    = {31},
  journal   = {Nephrology, dialysis, transplantation},
  publisher = {Oxford Univ. Press},
  address   = {Oxford},
  issn      = {0931-0509},
  doi       = {10.1093/ndt/gfv321},
  pages     = {789 -- 797},
  year      = {2016},
  abstract  = {The matrix metalloproteinases (MMP) MMP-2 and MMP-9 are physiological regulators of vascular remodelling. Their dysregulation could contribute to vascular calcification. We examined the role of the MMP-2 and MMP-9 in uraemic vascular calcification in vivo and in vitro. The impact of pharmacological MMP inhibition on the development of media calcifications was explored in an aggressive animal model of uraemic calcification. In addition, the selective effects of addition and inhibition, respectively, of MMP-2 and MMP-9 on calcium-/phosphate-induced calcifications were studied in a murine cell line of vascular smooth muscle cells (VSMCs). High-dose calcitriol treatment of uraemic rats given a high phosphate diet induced massive calcifications, apoptosis and increased gene expressions of MMP-2, MMP-9 and of osteogenic transcription factors and proteins in aortic VSMC. The MMP inhibitor doxycycline prevented the VSMC transdifferentiation to osteoblastic cells, suppressed transcription of mediators of matrix remodelling and almost completely blocked aortic calcifications while further increasing apoptosis. Similarly, specific inhibitors of either MMP-2 or -9, or of both gelatinases (Ro28-2653) and a selective knockdown of MMP-2/-9 mRNA expression blocked calcification of murine VSMC induced by calcification medium (CM). In contrast to MMP inhibition, recombinant MMP-2 or MMP-9 enhanced CM-induced calcifications and the secretion of gelatinases. These data indicate that both gelatinases provide essential signals for phenotypic VSMC conversion, matrix remodelling and the initiation of vascular calcification. Their inhibition seems a promising strategy in the prevention of vascular calcifications.},
  language  = {en}
}
@article{NeuschaeferRubeLieskeKunaetal.2014,
  author    = {Neuschaefer-Rube, Frank and Lieske, Stefanie and Kuna, Manuela and Henkel, Janin and Perry, Rachel J. and Erion, Derek M. and Pesta, Dominik and Willmes, Diana M. and Brachs, Sebastian and von Loeffelholz, Christian and Tolkachov, Alexander and Schupp, Michael and Pathe-Neuschaefer-Rube, Andrea and Pfeiffer, Andreas F. H. and Shulman, Gerald I. and P{\"u}schel, Gerhard Paul and Birkenfeld, Andreas L.},
  title     = {The mammalian INDY homolog is induced by CREB in a rat model of type 2 diabetes},
  series = {Diabetes : a journal of the American Diabetes Association},
  volume    = {63},
  journal   = {Diabetes : a journal of the American Diabetes Association},
  number    = {3},
  publisher = {American Diabetes Association},
  address   = {Alexandria},
  issn      = {0012-1797},
  pages     = {1048 -- 1057},
  year      = {2014},
  language  = {en}
}
@misc{WotingBlaut2016,
  author    = {Woting, Anni and Blaut, Michael},
  title     = {The intestinal microbiota in metabolic disease},
  series = {Nutrients},
  journal   = {Nutrients},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-407687},
  pages     = {19},
  year      = {2016},
  abstract  = {Gut bacteria exert beneficial and harmful effects in metabolic diseases as deduced from the comparison of germfree and conventional mice and from fecal transplantation studies. Compositional microbial changes in diseased subjects have been linked to adiposity, type 2 diabetes and dyslipidemia. Promotion of an increased expression of intestinal nutrient transporters or a modified lipid and bile acid metabolism by the intestinal microbiota could result in an increased nutrient absorption by the host. The degradation of dietary fiber and the subsequent fermentation of monosaccharides to short-chain fatty acids (SCFA) is one of the most controversially discussed mechanisms of how gut bacteria impact host physiology. Fibers reduce the energy density of the diet, and the resulting SCFA promote intestinal gluconeogenesis, incretin formation and subsequently satiety. However, SCFA also deliver energy to the host and support liponeogenesis. Thus far, there is little knowledge on bacterial species that promote or prevent metabolic disease. Clostridium ramosum and Enterococcus cloacae were demonstrated to promote obesity in gnotobiotic mouse models, whereas bifidobacteria and Akkermansia muciniphila were associated with favorable phenotypes in conventional mice, especially when oligofructose was fed. How diet modulates the gut microbiota towards a beneficial or harmful composition needs further research. Gnotobiotic animals are a valuable tool to elucidate mechanisms underlying diet-host-microbe interactions.},
  language  = {en}
}
@article{DuenkelbergMaywaldSchmittetal.2020,
  author    = {D{\"u}nkelberg, Sophie and Maywald, Martina and Schmitt, Anne Kristina and Schwerdtle, Tanja and Meyer, S{\"o}ren and Rink, Lothar},
  title     = {The interaction of sodium and zinc in the priming of T cell subpopulations regarding Th17 and Treg cells},
  series = {Molecular nutrition \& food research : bioactivity, chemistry, immunology, microbiology, safety, technology},
  volume    = {64},
  journal   = {Molecular nutrition \& food research : bioactivity, chemistry, immunology, microbiology, safety, technology},
  number    = {2},
  publisher = {Wiley-VCH},
  address   = {Weinheim},
  issn      = {1613-4133},
  doi       = {10.1002/mnfr.201900245},
  pages     = {10},
  year      = {2020},
  abstract  = {Scope: Nutrition is a critical determinant of a functional immune system. The aim of this study is to investigate the molecular mechanisms by which immune cells are influenced by zinc and sodium. Methods and Results: Mixed lymphocyte cultures and Jurkat cells are generated and incubated with zinc, sodium, or a combination of both for further tests. Zinc induces the number of regulatory T cells (Treg) and decreases T helper 17 cells (Th17), and sodium has the opposite effect. The transforming growth factor beta receptor signaling pathway is also enhanced by zinc and reduced by sodium as indicated by contrary phosphoSmad 2/3 induction. Antagonistic effects can also be seen on zinc transporter and metallothionein-1 (MT-1) mRNA expression: zinc declines Zip10 mRNA expression while sodium induces it, whereas MT-1 mRNA expression is induced by zinc while it is reduced by sodium. Conclusion: This data indicate that zinc and sodium display opposite effects regarding Treg and Th17 induction in MLC, respectively, resulting in a contrary effect on the immune system. Additionally, it reveals a direct interaction of zinc and sodium in the priming of T cell subpopulations and shows that Zip10 and MT-1 play a significant role in those differentiation pathways.},
  language  = {en}
}
@article{CramerTackeBornhorstetal.2014,
  author    = {Cramer, Sandra and Tacke, Sebastian and Bornhorst, Julia and Klingauf, J{\"u}rgen and Schwerdtle, Tanja and Galla, Hans-Joachim},
  title     = {The Influence of Silver Nanoparticles on the Blood-Brain and the Blood-Cerebrospinal Fluid Barrier in vitro},
  series = {Journal of Nanomedicine \& Nanotechnology},
  volume    = {5},
  journal   = {Journal of Nanomedicine \& Nanotechnology},
  number    = {5},
  issn      = {2157-7439},
  doi       = {10.4172/2157-7439.1000225},
  pages     = {12},
  year      = {2014},
  abstract  = {The use of silver nanoparticles in medical and consumer products such as wound dressings, clothing and cosmetic has increased significantly in recent years. Still, the influence of these particles on our health and especially on our brain, has not been examined adequately up to now. We studied the influence of AgEO- (Ethylene Oxide) and AgCitrate-Nanoparticles (NPs) on the protective barriers of the brain, namely the blood-brain barrier (BBB) and the blood-cerebrospinal fluid (blood-CSF) barrier in vitro. The NPs toxicity was evaluated by examining changes in membrane integrity, cell morphology, barrier properties, oxidative stress and inflammatory reactions. AgNPs decreased cell viability, disturbed barrier integrity and tight junctions and triggered oxidative stress and DNA strand breaks. However, all mentioned effects were, at least partly, suppressed by a Citrate-coating and were most pronounced in the cells of the BBB as compared to the epithelial cells representing the blood-CSF barrier. AgEO- but not AgCitrate-NPs also triggered an inflammatory reaction in porcine brain capillary endothelial cells (PBCEC), which represent the BBB. Our data indicate that AgNPs may cause adverse effects within the barriers of the brain, but their toxicity can be reduced by choosing an appropriate coating material.},
  language  = {en}
}
@article{KanaSopGouadoAchuetal.2015,
  author    = {Kana-Sop, Marie Modestine and Gouado, Inocent and Achu, Mercy Bih and Van Camp, John and Zollo, Paul Henri Amvam and Schweigert, Florian J. and Oberleas, Donald and Ekoe, Tetanye},
  title     = {The Influence of Iron and Zinc Supplementation on the Bioavailability of Provitamin A Carotenoids from Papaya Following Consumption of a Vitamin A-Deficient Diet},
  series = {Journal of nutritional science and vitaminology},
  volume    = {61},
  journal   = {Journal of nutritional science and vitaminology},
  number    = {3},
  publisher = {Univ. of Tokyo Pr.},
  address   = {Tokyo},
  issn      = {0301-4800},
  pages     = {205 -- 214},
  year      = {2015},
  abstract  = {Iron deficiency anemia, zinc and vitamin A deficiencies are serious public health problems in Cameroon, as in many developing countries. Local vegetables which are sources of provitamin A carotenoids (PACs) can be used to improve vitamin A intakes. However, traditional meals are often unable to cover zinc and iron needs. The aim of this study was to determine the bioavailability of 3 PACs (alpha-carotene, beta-carotene, and beta-cryptoxanthin) in young men, who were fed with a vitamin A-free diet and received iron and zinc supplementation. Twelve healthy participants were divided into three groups and were supplemented with elemental iron (20 mg of iron fumarate), 20 mg of zinc sulfate or iron + zinc (20 mg of iron in the morning and 20 mg of zinc in the evening) for 11 d. They were given a vitamin A- and PAC-free diet from the 6th to the 11th day, followed by a test meal containing 0.55 kg of freshly peeled papaya as a source of PACs. Blood samples were collected four times successively on the 11th day (the test meal day), at TO (just after the test meal), after 2 h (T2), after 4 h (T4) and after 7 h (T7). Ultracentrifugation was used to isolate serum chylomicrons. Retinol appearance and PAC postprandial concentrations were determined. The supplementation with zinc, iron and iron+zinc influenced the chylomicron appearance of retinol and PACs differently as reflected by retention times and maximum absorption peaks. Iron led to highest retinol levels in the chylomicron. Zinc and iron+zinc supplements were best for optimal intact appearance of alpha-carotene, beta-carotene and beta-cryptoxanthin respectively. Supplementation with iron led to the greatest bioavailability of PACs from papaya and its conversion to retinol.},
  language  = {en}
}
@article{LiChenDongetal.2014,
  author    = {Li, Jian and Chen, You-Peng and Dong, Yun-Peng and Yu, Cal-Hong and Lu, Yong-Ping and Xiao, Xiao-Min and Hocher, Berthold},
  title     = {The impact of umbilical blood flow regulation on fetal development differs in diabetic and non-diabetic pregnancy},
  series = {Kidney \& blood pressure research : official organ of the Gesellschaft f{\"u}r Nephrologie},
  volume    = {39},
  journal   = {Kidney \& blood pressure research : official organ of the Gesellschaft f{\"u}r Nephrologie},
  number    = {4},
  publisher = {Karger},
  address   = {Basel},
  issn      = {1420-4096},
  doi       = {10.1159/000355815},
  pages     = {369 -- 377},
  year      = {2014},
  abstract  = {Background/Aims: Diabetes is well-known to influence endothelial function. Endothelial function and blood flow regulation might be different in diabetic and non-diabetic pregnancy. However, the impact of umbilical blood flow regulation in gestational diabetes on fetal development is unknown so far. Methods: In a prospective birth cohort study, we analyzed the association of the umbilical artery Doppler indices (pulsatility index, resistance index and systolic/diastolic ratio) and fetal size measures (biparietal diameter, head circumference, abdominal circumference, femur length and birth weight) in 519 non-gestational diabetes mellitus pregnancies (controls) and 226 gestational diabetes mellitus pregnancies in middle (day 160.32 +/- 16.29 of gestation) and late (day 268.12 +/- 13.04 of gestation) pregnancy. Results: Multiple regression analysis considering confounding factors (gestational day of ultrasound examination, offspring sex, maternal body mess index before pregnancy, maternal age at delivery, maternal body weight at delivery and maternal hypertension) showed that umbilical artery Doppler indices (pulsatility index, resistance index and systolic/diastolic ratio) were associated with fetal head circumference and femur length in middle gestational diabetes mellitus pregnancy but not in non-gestational diabetes mellitus pregnancy. Head circumference, biparietal diameter, abdominal circumference and femur length in mid gestation were smaller in fetus of gestational diabetes mellitus pregnancy versus non-gestational diabetes mellitus pregnancy. In contrast to non-gestational diabetes mellitus pregnancy in late gestation, umbilical artery Doppler indices in gestational diabetes mellitus pregnancy were not associated with ultrasound measures of fetal growth. Birth weight was slightly increased in gestational diabetes mellitus pregnancy as compared to non-gestational diabetes mellitus pregnancy. Conclusions: The impact of umbilical blood flow on fetal growth is time dependent in human gestational diabetes mellitus and non-gestational diabetes mellitus pregnancy. In gestational diabetes mellitus pregnancy umbilical blood flow is critical for organ development in much earlier stages of pregnancy as compared to non-gestational diabetes mellitus pregnancy. The physiological and molecular pathways why there is a catch up growth in later times of gestational diabetes mellitus pregnancy resulting in larger gestational diabetes mellitus babies at birth needs to be addressed in further studies.},
  language  = {en}
}
@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{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{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{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}
}
@article{MaaresDumanKeiletal.2018,
  author    = {Maares, Maria and Duman, Ayse and Keil, Claudia and Schwerdtle, Tanja and Haase, Hajo},
  title     = {The impact of apical and basolateral albumin on intestinal zinc resorption in the Caco-2/HT-29-MTX co-culture model},
  series = {Metallomics : integrated biometal science},
  volume    = {10},
  journal   = {Metallomics : integrated biometal science},
  number    = {7},
  publisher = {Royal Society of Chemistry},
  address   = {Cambridge},
  issn      = {1756-5901},
  doi       = {10.1039/c8mt00064f},
  pages     = {979 -- 991},
  year      = {2018},
  abstract  = {The molecular mechanisms of intestinal zinc resorption and its regulation are still topics of ongoing research. To this end, the application of suitable in vitro intestinal models, optimized with regard to their cellular composition and medium constituents, is of crucial importance. As one vital aspect, the impact of cell culture media or buffer compounds, respectively, on the speciation and cellular availability of zinc has to be considered when investigating zinc resorption. Thus, the present study aims to investigate the impact of serum, and in particular its main constituent serum albumin, on zinc uptake and toxicity in the intestinal cell line Caco-2. Furthermore, the impact of serum albumin on zinc resorption is analyzed using a co-culture of Caco-2 cells and the mucin-producing goblet cell line HT-29-MTX. Apically added albumin significantly impaired zinc uptake into enterocytes and buffered its cytotoxicity. Yet, undigested albumin does not occur in the intestinal lumen in vivo and impairment of zinc uptake was abrogated by digestion of albumin. Interestingly, zinc uptake, as well as gene expression studies of mt1a and selected intestinal zinc transporters after zinc incubation for 24 h, did not show significant differences between 0 and 10\% serum. Importantly, the basolateral application of serum in a transport study significantly enhanced fractional apical zinc resorption, suggesting that the occurrence of a zinc acceptor in the plasma considerably affects intestinal zinc resorption. This study demonstrates that the apical and basolateral medium composition is crucial when investigating zinc, particularly its intestinal resorption, using in vitro cell culture.},
  language  = {en}
}