@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{WildeTreitzKeppleretal.2016, author = {Wilde, Sandra Catharina and Treitz, Christian and Keppler, Julia Katharina and Koudelka, Tomas and Palani, Kalpana and Tholey, Andreas and Rawel, Harshadrai Manilal and Schwarz, Karin}, title = {beta-Lactoglobulin as nanotransporter - Part II: Characterization of the covalent protein modification by allicin and diallyl disulfide}, series = {Food chemistry}, volume = {197}, journal = {Food chemistry}, publisher = {Elsevier}, address = {Oxford}, issn = {0308-8146}, doi = {10.1016/j.foodchem.2015.11.011}, pages = {1022 -- 1029}, year = {2016}, abstract = {The whey protein beta-lactoglobulin has been proposed as a transporter for covalent bound bioactive compounds in order to enhance their stability and reduce their sensory perception. The garlic derived compounds allicin and diallyl disulfide were bound covalently to the native and heat denatured protein. The binding site and the influence of the modification on the digestibility were determined by mass spectrometric analysis of the modified beta-lactoglobulin. Further, the conformation of the modified protein was assessed by circular dichroism and dynamic light scattering. The free thiol group of Cys(121) turned out to be the major binding site. After proteolysis with trypsin at pH 7 but not with pepsin at pH 2, a limited transfer to other cysteinyl residues was observed. The covalently bound ligands did not mask any proteolytic cleavage sites of pepsin, trypsin or chymotrypsin. The modified beta-lactoglobulin showed a native like conformation, besides a moderate loosening of protein folding. The covalent binding of organosulfur compounds to beta-lactoglobulin provides a bioactive ingredient without impairing the digestibility and functional properties of the protein. (C) 2015 Elsevier Ltd. All rights reserved.}, language = {en} } @article{WalterCollenburgJaptoketal.2016, author = {Walter, T. and Collenburg, Lena and Japtok, Lukasz and Kleuser, Burkhard and Schneider-Schaulies, Sibylle and Mueller, N. and Becam, Jerome and Schubert-Unkmeir, A. and Kong, J. N. and Bieberich, Erhard and Seibel, J.}, title = {Incorporation and visualization of azido-functionalized N-oleoyl serinol in Jurkat cells, mouse brain astrocytes, 3T3 fibroblasts and human brain microvascular endothelial cells}, series = {Chemical communications}, volume = {52}, journal = {Chemical communications}, publisher = {Royal Society of Chemistry}, address = {Cambridge}, issn = {1359-7345}, doi = {10.1039/c6cc02879a}, pages = {8612 -- 8614}, year = {2016}, abstract = {The synthesis and biological evaluation of azido-N-oleoyl serinol is reported. It mimicks biofunctional lipid ceramides and has shown to be capable of click reactions for cell membrane imaging in Jurkat and human brain microvascular endothelial cells.}, language = {en} } @article{UhrWielandHomannetal.2016, author = {Uhr, Linda and Wieland, Phillis and Homann, Thomas and Huschek, Gerd and Rawel, Harshadrai Manilal}, title = {Identification and LC-MS/MS-based analyses of technical enzymes in wheat flour and baked products}, series = {European food research and technology : official organ of the EuCheMS, Division of Food Chemistry}, volume = {242}, journal = {European food research and technology : official organ of the EuCheMS, Division of Food Chemistry}, publisher = {Springer}, address = {New York}, issn = {1438-2377}, doi = {10.1007/s00217-015-2536-5}, pages = {247 -- 257}, year = {2016}, abstract = {The use of technical enzymes in bakery industry is necessary for a consistent and good quality of baked products. Since the cultivation of cereals leads to low amounts of endogenous enzymes being present, a need of their commercial alternatives is becoming a routine process in order to meet the consumer quality demands. Targeted quantification proteomics-based methods are necessary for their detection to meet the regulatory criteria. Here, we initially report on the identification of Lipase FE-01, a lipase from fungus Thermomyces lanuginosus, as analyzed by SDS-PAGE, in-Gel digestion, and MALDI-TOF-MS. In further experiments, the focus of the study was directed toward an extensive use and optimization of in-solution enzymatic digestion in combination with LC-MS/MS techniques in identification of specific peptide markers and finally in utilization of the latter in delivering reproducible quantification data for several different technical enzymes (alpha-amylases, xylanase, and lipases from microbial origin) in complex matrices such as baked bread and wheat flour. Two digestion protocols (a fast option using thermocycler program and the well-established overnight method) were tested, and both of these can be successfully applied. The application of isotopically labeled analogs of the MRM targeted peptides as internal standards and the addition of an internal protein standard during the extraction/digestion experiment were compared to determine the optimal quantification algorithm of the recovered enzyme concentrations. Thus, a standardized sensitive LC-MS/MS method could be developed to determine technical enzymes as forthcoming ingredients in the prefabricated food formulations in concentrations lower than 10 ppm.}, language = {en} } @article{TsuprykovAndoReichetzederetal.2016, author = {Tsuprykov, Oleg and Ando, Ryotaro and Reichetzeder, Christoph and von Websky, Karoline and Antonenko, Viktoriia and Sharkovska, Yuliya and Chaykovska, Lyubov and Rahnenfuehrer, Jan and Hasan, Ahmed Abdallah Abdalrahman Mohamed and Tammen, Harald and Alter, Markus L. and Klein, Thomas and Ueda, Seiji and Yamagishi, Sho-ichi and Okuda, Seiya and Hocher, Berthold}, title = {The dipeptidyl peptidase inhibitor linagliptin and the angiotensin II receptor blocker telmisartan show renal benefit by different pathways in rats with 5/6 nephrectomy}, series = {Kidney international : official journal of the International Society of Nephrology}, volume = {89}, journal = {Kidney international : official journal of the International Society of Nephrology}, publisher = {Nature Publ. Group}, address = {New York}, issn = {0085-2538}, doi = {10.1016/j.kint.2016.01.016}, pages = {1049 -- 1061}, year = {2016}, abstract = {Dipeptidyl peptidase (DPP)-4 inhibitors delay chronic kidney disease (CKD) progression in experimental diabetic nephropathy in a glucose-independent manner. Here we compared the effects of the DPP-4 inhibitor linagliptin versus telmisartan in preventing CKD progression in non-diabetic rats with 5/6 nephrectomy. Animals were allocated to 1 of 4 groups: sham operated plus placebo; 5/6 nephrectomy plus placebo; 5/6 nephrectomy plus linagliptin; and 5/6 nephrectomy plus telmisartan. Interstitial fibrosis was significantly decreased by 48\% with linagliptin but a non-significant 24\% with telmisartan versus placebo. The urine albumin-to-creatinine ratio was significantly decreased by 66\% with linagliptin and 92\% with telmisartan versus placebo. Blood pressure was significantly lowered by telmisartan, but it was not affected by linagliptin. As shown by mass spectrometry, the number of altered peptide signals for linagliptin in plasma was 552 and 320 in the kidney. For telmisartan, there were 108 peptide changes in plasma and 363 in the kidney versus placebo. Linagliptin up-regulated peptides derived from collagen type I, apolipoprotein C1, and heterogeneous nuclear ribonucleoproteins A2/B1, a potential downstream target of atrial natriuretic peptide, whereas telmisartan up-regulated angiotensin II. A second study was conducted to confirm these findings in 5/6 nephrectomy wild-type and genetically deficient DPP-4 rats treated with linagliptin or placebo. Linagliptin therapy in wild-type rats was as effective as DPP-4 genetic deficiency in terms of albuminuria reduction. Thus, linagliptin showed comparable efficacy to telmisartan in preventing CKD progression in non-diabetic rats with 5/6 nephrectomy. However, the underlying pathways seem to be different. Copyright (C) 2016, International Society of Nephrology. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).}, language = {en} } @article{SwidsinskiLoeningBauckeSchulzetal.2016, author = {Swidsinski, Alexander and Loening-Baucke, Vera and Schulz, Stefan and Manowsky, Julia and Verstraelen, Hans and Swidsinski, Sonja}, title = {Functional anatomy of the colonic bioreactor: Impact of antibiotics and Saccharomyces boulardii on bacterial composition in human fecal cylinders}, series = {Systematic and Applied Microbiology}, volume = {39}, journal = {Systematic and Applied Microbiology}, publisher = {Nature Publ. Group}, address = {Jena}, issn = {0723-2020}, doi = {10.1016/j.syapm.2015.11.002}, pages = {67 -- 75}, year = {2016}, abstract = {Sections of fecal cylinders were analyzed using fluorescence in situ hybridization targeting 180 bacterial groups. Samples were collected from three groups of women (N = 20 each) treated for bacterial vaginosis with ciprofloxacin + metronidazole. Group A only received the combined antibiotic regimen, whereas the A/Sb group received concomitant Saccharomyces boulardii CNCM I-745 treatment, and the A.Sb group received S. boulardii prophylaxis following the 14-day antibiotic course. The number of stool cylinders analyzed was 188 out of 228 in group A, 170 out of 228 in group A/Sb, and 172 out of 216 in group Ash. The colonic biomass was organized into a separate mucus layer with no bacteria, a 10-30 mu m broad unstirred transitional layer enriched with bacteria, and a patchy fermentative area that mixed digestive leftovers with bacteria. The antibiotics suppressed bacteria mainly in the fermentative area, whereas abundant bacterial clades retreated to the transitional mucus and survived. As a result, the total concentration of bacteria decreased only by one order. These effects were lasting, since the overall recovery of the microbial mass, bacterial diversity and concentrations were still below pre-antibiotic values 4 months after the end of antibiotic treatment. Sb-prophylaxis markedly reduced antibiotic effects and improved the recovery rates. Since the colon is a sophisticated bioreactor, the study indicated that the spatial anatomy of its biomass was crucial for its function. (C) 2015 The Authors. Published by Elsevier GmbH. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).}, language = {en} } @article{SieversRawelRingeletal.2016, author = {Sievers, Steven and Rawel, Harshadrai Manilal and Ringel, Karl Peter and Niggemann, Bodo and Beyer, Kirsten}, title = {Wheat protein recognition pattern in tolerant and allergic children}, series = {Pediatric Allergy and Immunology}, volume = {27}, journal = {Pediatric Allergy and Immunology}, publisher = {Wiley-Blackwell}, address = {Hoboken}, issn = {0905-6157}, doi = {10.1111/pai.12502}, pages = {147 -- 155}, year = {2016}, abstract = {BackgroundWheat is one of the most common food allergens in early childhood. In contrast to other food allergies, wheat-specific IgE correlates badly with clinical symptoms and relevant components have been identified mostly for wheat-depended exercise-induced anaphylaxis. Moreover, a high percentage of patients present with immediate type symptoms but wheat-specific IgE cannot be detected with commercial available systems. ObjectiveWe addressed the question whether the IgE recognition pattern between wheat allergic (WA) and clinically tolerant (WT) children differs in order to identify individual proteins useful for component-resolved diagnostics. MethodsSera of 106 children with suspected wheat allergy, of whom 44 children had clinical relevant wheat allergy and 62 were tolerant upon oral food challenge, were analyzed for wheat-specific IgE using the ImmunoCap system as well as immunoblots against water and salt soluble, and water-insoluble protein fractions. 40 randomly selected sera were analyzed for specific IgE to 5-gliadin. ResultsSixty-three percent of the WT and 86\% of the WA children were sensitized to wheat with >0.35 kU(A)/l in ImmunoCAP analysis. We could confirm the role of -, ss-, -, and -gliadins, and LMW glutenin subunits as major allergens and found also IgE binding to a broad spectrum of water- and salt-soluble protein bands. It is of great importance that wheat allergic and tolerant patients showed IgE binding to the same protein bands. WT and WA did not significantly differ in levels of 5-gliadin-specific IgE. Conclusions \& Clinical RelevanceChildren with challenge proven clinical relevant food allergy and tolerant ones had a similar spectrum of IgE binding to the same protein bands. These findings imply that component-resolved diagnostics might not be helpful in the diagnostic work-up of wheat allergy.}, language = {en} } @article{SchmiedchenLongardtLouietal.2016, author = {Schmiedchen, Bettina and Longardt, Ann Carolin and Loui, Andrea and Buehrer, Christoph and Raila, Jens and Schweigert, Florian J.}, title = {Effect of vitamin A supplementation on the urinary retinol excretion in very low birth weight infants}, series = {European journal of pediatrics : official organ of the Belgian Pediatric Association}, volume = {175}, journal = {European journal of pediatrics : official organ of the Belgian Pediatric Association}, publisher = {Springer}, address = {New York}, issn = {0340-6199}, doi = {10.1007/s00431-015-2647-9}, pages = {365 -- 372}, year = {2016}, abstract = {Despite high-dose vitamin A supplementation of very low birth weight infants (VLBW, <1500 g), their vitamin A status does not improve substantially. Unknown is the impact of urinary retinol excretion on the serum retinol concentration in these infants. Therefore, the effect of high-dose vitamin A supplementation on the urinary vitamin A excretion in VLBW infants was investigated. Sixty-three VLBW infants were treated with vitamin A (5000 IU intramuscular, 3 times/week for 4 weeks); 38 untreated infants were classified as control group. On days 3 and 28 of life, retinol, retinol-binding protein 4 (RBP4), glomerular filtration rate, proteinuria, and Tamm-Horsfall protein were quantified in urine. On day 3 of life, substantial retinol and RBP4 losses were found in both groups, which significantly decreased until day 28. Notwithstanding, the retinol excretion was higher (P<0.01) under vitamin A supplementation as compared to infants of the control group. On day 28 of life, the urinary retinol concentrations were predictive for serum retinol concentrations in the vitamin A treated (P<0.01), but not in the control group (P=0.570). Conclusion: High urinary retinol excretion may limit the vitamin A supplementation efficacy in VLBW infants. Advanced age and thus postnatal kidney maturation seems to be an important contributor in the prevention of urinary retinol losses.}, language = {en} } @misc{SchernthanerGroopCooperetal.2016, author = {Schernthaner, G. and Groop, P. and Cooper, M. and Perkovic, V and Hocher, Berthold and Kanasaki, K. and Sharma, K. and Stanton, R. and Toto, R. and Cescutti, Jessica and Gordat, M. and Meinicke, T. and Koitka-Weber, A. and Woerle, H. and Eynatten, M.}, title = {EFFECTS OF LINAGLIPTIN ON GLYCAEMIC CONTROL AND ALBUMINURIA IN TYPE 2 DIABETES - THE MARLINA-T2D (TM) TRIAL}, series = {Nephrology}, volume = {21}, journal = {Nephrology}, publisher = {Wiley-Blackwell}, address = {Hoboken}, issn = {1320-5358}, doi = {10.1111/nep.12887}, pages = {60 -- 60}, year = {2016}, language = {en} } @article{SandmannGarzMenzel2016, author = {Sandmann, Michael and Garz, Andreas and Menzel, Ralf}, title = {Physiological response of two different Chlamydomonas reinhardtii strains to light-dark rhythms}, series = {Botany}, volume = {94}, journal = {Botany}, publisher = {NRC Research Press}, address = {Ottawa}, issn = {1916-2790}, doi = {10.1139/cjb-2015-0144}, pages = {53 -- 64}, year = {2016}, abstract = {Cells of a cell-wall deficient line (cw15-type) of Chlamydomonas reinhardtii and of the corresponding wild type were grown during repetitive light-dark cycles. In a direct comparison, both lines showed approximately the same relative biomass increase during light phase but the cw-line produced significantly more, and smaller, daughter cells. Throughout the light period the average cellular starch content, the cellular chlorophyll content, the cellular rate of dark respiration, and the cellular rate of photosynthesis of the cw-line was lower. Despite this, several non-cell volume related parameters like the development of starch content per cell volume were clearly different over time between the strains. Additionally, the chlorophyll-based photosynthesis rates were 2-fold higher in the mutant than in the wild-type cells, and the ratio of chlorophyll a to chlorophyll b as well as the light-saturation index were also consistently higher in the mutant cells. Differences in the starch content were also confirmed by single cell analyses using a sensitive SHG-based microscopy approach. In summary, the cw15-type mutant deviates from its genetic background in the entire cell physiology. Both lines should be used in further studies in comparative systems biology with focus on the detailed relation between cell volume increase, photosynthesis, starch metabolism, and daughter cell productivity.}, language = {en} } @article{SahleBalzusGereckeetal.2016, author = {Sahle, Fitsum Feleke and Balzus, Benjamin and Gerecke, Christian and Kleuser, Burkhard and Bodmeier, Roland}, title = {Formulation and in vitro evaluation of polymeric enteric nanoparticles as dermal carriers with pH-dependent targeting potential}, series = {European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences, EUFEPS}, volume = {92}, journal = {European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences, EUFEPS}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0928-0987}, doi = {10.1016/j.ejps.2016.07.004}, pages = {98 -- 109}, year = {2016}, abstract = {pH-sensitive nanoparticles which release in a controlled fashion on the skin or dissolve in the hair follicle could significantly improve treatment effectiveness and make transfollicular drug delivery a success. Dexamethasone-loaded Eudragit L 100 nanoparticles were prepared by nanoprecipitation from an organic drug-polymer solution. Their toxicity potential was assessed using isolated human fibroblasts. pH-dependent swelling and erosion kinetics of the nanoparticles were investigated by dynamic light scattering and viscosity measurements and its effect on drug release was assessed in vitro with Franz diffusion cells. Stable, 100-550 nm-sized dexamethasone-loaded Eudragit L 100 nanoparticles with drug loading capacity and entrapment efficiency as high as 83\% and 85\%, respectively, were obtained by using polyvinyl alcohol as a stabilizer and ethanol as organic solvent The nanoparticles showed little or no toxicity on isolated normal human fibroblasts. Dexamethasone existed in the nanoparticles as solid solution or in amorphous form. The nanoparticles underwent extensive swelling and slow drug release in media with a low buffer capacity (as low as 10 mM) and a higher pH or at a pH close to the dissolution pH of the polymer (pH 6) and a higher buffer capacity. In 40 mM buffer and above pH 6.8, the nanoparticles eroded fast or dissolved completely and thus released the drug rapidly. pH-sensitive nanoparticles which potentially release in a controlled manner on the stratum corneum but dissolve in the hair follicle could be prepared. (C) 2016 Elsevier B.V. All rights reserved.}, language = {en} } @article{RosenkranzMaywaldHilgersetal.2016, author = {Rosenkranz, Eva and Maywald, Martina and Hilgers, Ralf-Dieter and Brieger, Anne and Clarner, Tim and Kipp, Markus and Pluemaekers, Birgit and Meyer, S{\"o}ren and Schwerdtle, Tanja and Rink, Lothar}, title = {Induction of regulatory T cells in Th1-/Th17-driven experimental autoimmune encephalomyelitis by zinc administration}, series = {The journal of nutritional biochemistry}, volume = {29}, journal = {The journal of nutritional biochemistry}, publisher = {Elsevier}, address = {New York}, issn = {0955-2863}, doi = {10.1016/j.jnutbio.2015.11.010}, pages = {116 -- 123}, year = {2016}, abstract = {The essential trace element zinc is indispensable for proper immune function as zinc deficiency accompanies immune defects and dysregulations like allergies, autoimmunity and an increased presence of transplant rejection. This point to the importance of the physiological and dietary control of zinc levels for a functioning immune system. This study investigates the capacity of zinc to induce immune tolerance. The beneficial impact of physiological zinc supplementation of 6 mu g/day (0.3 mg/kg body weight) or 30 mu g/day (1.5 mg/kg body weight) on murine experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis with a Th1/Th17 (Th, T helper) cell-dominated immunopathogenesis, was analyzed. Zinc administration diminished EAE scores in C57BL/6 mice in vivo (P<.05), reduced Th17 ROR gamma T+ cells (P<.05) and significantly increased inducible iTreg cells (P<.05). While Th17 cells decreased systemically, iTreg cells accumulated in the central nervous system. Cumulatively, zinc supplementation seems to be capable to induce tolerance in unwanted immune reactions by increasing iTreg cells. This makes zinc a promising future tool for treating autoimmune diseases without suppressing the immune system. (C) 2015 Elsevier Inc. All rights reserved.}, language = {en} } @article{ReyesVazquezZeidaetal.2016, author = {Reyes, Anibal M. and Vazquez, Diego S. and Zeida, Ari and Hugo, Martin and Dolores Pineyro, M. and Ines De Armas, Maria and Estrin, Dario and Radi, Rafael and Santos, Javier and Trujillo, Madia}, title = {PrxQ B from Mycobacterium tuberculosis is a monomeric, thioredoxin-dependent and highly efficient fatty acid hydroperoxide reductase}, 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 = {101}, 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.2016.10.005}, pages = {249 -- 260}, year = {2016}, abstract = {Mycobacterium tuberculosis (M. tuberculosis) is the intracellular bacterium responsible for tuberculosis disease (TD). Inside the phagosomes of activated macrophages, M. tuberculosis is exposed to cytotoxic hydroperoxides such as hydrogen peroxide, fatty acid hydroperoxides and peroxynitrite. Thus, the characterization of the bacterial antioxidant systems could facilitate novel drug developments. In this work, we characterized the product of the gene Rv1608c from M. tuberculosis, which according to sequence homology had been annotated as a putative peroxiredoxin of the peroxiredoxin Q subfamily (PrxQ B from M. tuberculosis or MtPrxQ B). The protein has been reported to be essential for M. tuberculosis growth in cholesterol-rich medium. We demonstrated the M. tuberculosis thioredoxin B/C-dependent peroxidase activity of MtPrxQ B, which acted as a two-cysteine peroxiredoxin that could function, although less efficiently, using a one-cysteine mechanism. Through steady-state and competition kinetic analysis, we proved that the net forward rate constant of MtPrxQ B reaction was 3 orders of magnitude faster for fatty acid hydroperoxides than for hydrogen peroxide (3x10(6) vs 6x10(3) M-1 s(-1), respectively), while the rate constant of peroxynitrite reduction was (0.6-1.4) x10(6) M-1 s(-1) at pH 7.4. The enzyme lacked activity towards cholesterol hydroperoxides solubilized in sodium deoxycholate. Both thioredoxin B and C rapidly reduced the oxidized form of MtPrxQ B, with rates constants of 0.5x10(6) and 1x10(6) M-1 s(-1), respectively. Our data indicated that MtPrxQ B is monomeric in solution both under reduced and oxidized states. In spite of the similar hydrodynamic behavior the reduced and oxidized forms of the protein showed important structural differences that were reflected in the protein circular dichroism spectra.}, language = {en} } @article{ReinkensmeierSteinbrennerHomannetal.2016, author = {Reinkensmeier, Annika and Steinbrenner, Katrin and Homann, Thomas and Bussler, Sara and Rohn, Sascha and Rawel, Harshadrai Manilal}, title = {Monitoring the apple polyphenol oxidase-modulated adduct formation of phenolic and amino compounds}, series = {Food chemistry}, volume = {194}, journal = {Food chemistry}, publisher = {Elsevier}, address = {Oxford}, issn = {0308-8146}, doi = {10.1016/j.foodchem.2015.07.145}, pages = {76 -- 85}, year = {2016}, abstract = {Minimally processed fruit products such as smoothies are increasingly coming into demand. However, they are often combined with dairy ingredients. In this combination, phenolic compounds, polyphenoloxidases, and amino compounds could interact. In this work, a model approach is presented where apple serves as a source for a high polyphenoloxidase activity for modulating the reactions. The polyphenoloxidase activity ranged from 128 to 333 nakt/mL in different apple varieties. From these, 'Braeburn' was found to provide the highest enzymatic activity. The formation and stability of resulting chromogenic conjugates was investigated. The results show that such adducts are not stable and possible degradation mechanisms leading to follow-up products formed are proposed. Finally, apple extracts were used to modify proteins and their functional properties characterized. There were retaining antioxidant properties inherent to phenolic compounds after adduct formation. Consequently, such interactions may also be utilized to improve the textural quality of food products.}, 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} } @misc{ReichetzederPutraLietal.2016, author = {Reichetzeder, Christoph and Putra, Sulistyo Emantoko Dwi and Li, Jian and Hocher, Berthold}, title = {Developmental Origins of Disease - Crisis Precipitates Change}, series = {Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry and pharmacology}, volume = {39}, journal = {Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry and pharmacology}, publisher = {Karger}, address = {Basel}, issn = {1015-8987}, doi = {10.1159/000447801}, pages = {919 -- 938}, year = {2016}, abstract = {The concept of developmental origins of diseases has gained a huge interest in recent years and is a constantly emerging scientific field. First observations hereof originated from epidemiological studies, linking impaired birth outcomes to adult chronic, noncommunicable disease. By now there is a considerable amount of both epidemiological and experimental evidence highlighting the impact of early life events on later life disease susceptibility. Albeit far from being completely understood, more recent studies managed to elucidate underlying mechanisms, with epigenetics having become almost synonymous with developmental programming. The aim of this review was to give a comprehensive overview of various aspects and mechanisms of developmental origins of diseases. Starting from initial research foci mainly centered on a nutritionally impaired intrauterine environment, more recent findings such as postnatal nutrition, preterm birth, paternal programming and putative interventional approaches are summarized. The review outlines general underlying mechanisms and particularly discusses mechanistic explanations for sexual dimorphism in developmental programming. Furthermore, novel hypotheses are presented emphasizing a non-mendelian impact of parental genes on the offspring's phenotype.}, language = {en} } @article{ReichetzederPutraPfabetal.2016, author = {Reichetzeder, Christoph and Putra, S. E. Dwi and Pfab, T. and Slowinski, T. and Neuber, Corinna and Kleuser, Burkhard and Hocher, Berthold}, title = {Increased global placental DNA methylation levels are associated with gestational diabetes}, series = {Clinical epigenetics}, volume = {8}, journal = {Clinical epigenetics}, publisher = {BioMed Central}, address = {London}, issn = {1868-7083}, doi = {10.1186/s13148-016-0247-9}, pages = {10}, year = {2016}, abstract = {Background: Gestational diabetes mellitus (GDM) is associated with adverse pregnancy outcomes. It is known that GDM is associated with an altered placental function and changes in placental gene regulation. More recent studies demonstrated an involvement of epigenetic mechanisms. So far, the focus regarding placental epigenetic changes in GDM was set on gene-specific DNA methylation analyses. Studies that robustly investigated placental global DNA methylation are lacking. However, several studies showed that tissue-specific alterations in global DNA methylation are independently associated with type 2 diabetes. Thus, the aim of this study was to characterize global placental DNA methylation by robustly measuring placental DNA 5-methylcytosine (5mC) content and to examine whether differences in placental global DNA methylation are associated with GDM. Methods: Global DNA methylation was quantified by the current gold standard method, LC-MS/MS. In total, 1030 placental samples were analyzed in this single-center birth cohort study. Results: Mothers with GDM displayed a significantly increased global placental DNA methylation (3.22 +/- 0.63 vs. 3.00 +/- 0.46 \%; p = 0.013; +/- SD). Bivariate logistic regression showed a highly significant positive correlation between global placental DNA methylation and the presence of GDM (p = 0.0009). Quintile stratification according to placental DNA 5mC levels revealed that the frequency of GDM was evenly distributed in quintiles 1-4 (2.9-5.3 \%), whereas the frequency in the fifth quintile was significantly higher (10.7 \%; p = 0.003). Bivariate logistic models adjusted for maternal age, BMI, ethnicity, recurrent miscarriages, and familiar diabetes predisposition clearly demonstrated an independent association between global placental DNA hypermethylation and GDM. Furthermore, an ANCOVA model considering known predictors of DNA methylation substantiated an independent association between GDM and placental DNA methylation. Conclusions: This is the first study that employed a robust quantitative assessment of placental global DNA methylation in over a thousand placental samples. The study provides large scale evidence that placental global DNA hypermethylation is associated with GDM, independent of established risk factors.}, 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} } @phdthesis{Reeg2016, author = {Reeg, Sandra}, title = {Degradation of oxidized proteins by the proteasome - Involvement of chaperones and the ubiquitin-system}, school = {Universit{\"a}t Potsdam}, pages = {117}, year = {2016}, language = {en} } @article{RakersSchumacherMeinletal.2016, author = {Rakers, Christin and Schumacher, Fabian and Meinl, Walter and Glatt, Hansruedi and Kleuser, Burkhard and Wolber, Gerhard}, title = {In Silico Prediction of Human Sulfotransferase 1E1 Activity Guided by Pharmacophores from Molecular Dynamics Simulations}, series = {The journal of biological chemistry}, volume = {291}, journal = {The journal of biological chemistry}, publisher = {American Society for Biochemistry and Molecular Biology}, address = {Bethesda}, issn = {0021-9258}, doi = {10.1074/jbc.M115.685610}, pages = {58 -- 71}, year = {2016}, abstract = {Acting during phase II metabolism, sulfotransferases (SULTs) serve detoxification by transforming a broad spectrum of compounds from pharmaceutical, nutritional, or environmental sources into more easily excretable metabolites. However, SULT activity has also been shown to promote formation of reactive metabolites that may have genotoxic effects. SULT subtype 1E1 (SULT1E1) was identified as a key player in estrogen homeostasis, which is involved in many physiological processes and the pathogenesis of breast and endometrial cancer. The development of an in silico prediction model for SULT1E1 ligands would therefore support the development of metabolically inert drugs and help to assess health risks related to hormonal imbalances. Here, we report on a novel approach to develop a model that enables prediction of substrates and inhibitors of SULT1E1. Molecular dynamics simulations were performed to investigate enzyme flexibility and sample protein conformations. Pharmacophores were developed that served as a cornerstone of the model, and machine learning techniques were applied for prediction refinement. The prediction model was used to screen the DrugBank (a database of experimental and approved drugs): 28\% of the predicted hits were reported in literature as ligands of SULT1E1. From the remaining hits, a selection of nine molecules was subjected to biochemical assay validation and experimental results were in accordance with the in silico prediction of SULT1E1 inhibitors and substrates, thus affirming our prediction hypotheses.}, language = {en} } @article{PasslackSchmiedchenRailaetal.2016, author = {Passlack, Nadine and Schmiedchen, Bettina and Raila, Jens and Schweigert, Florian J. and Stumpff, Friederike and Kohn, Barbara and Neumann, Konrad and Zentek, Juergen}, title = {Impact of Increasing Dietary Calcium Levels on Calcium Excretion and Vitamin D Metabolites in the Blood of Healthy Adult Cats}, series = {PLoS one}, volume = {11}, journal = {PLoS one}, publisher = {PLoS}, address = {San Fransisco}, issn = {1932-6203}, doi = {10.1371/journal.pone.0149190}, pages = {47 -- 67}, year = {2016}, abstract = {Background Dietary calcium (Ca) concentrations might affect regulatory pathways within the Ca and vitamin D metabolism and consequently excretory mechanisms. Considering large variations in Ca concentrations of feline diets, the physiological impact on Ca homeostasis has not been evaluated to date. In the present study, diets with increasing concentrations of dicalcium phosphate were offered to ten healthy adult cats (Ca/phosphorus (P): 6.23/6.02, 7.77/7.56, 15.0/12.7, 19.0/17.3, 22.2/19.9, 24.3/21.6 g/kg dry matter). Each feeding period was divided into a 10-day adaptation and an 8-day sampling period in order to collect urine and faeces. On the last day of each feeding period, blood samples were taken. Results Urinary Ca concentrations remained unaffected, but faecal Ca concentrations increased (P < 0.001) with increasing dietary Ca levels. No effect on whole and intact parathyroid hormone levels, fibroblast growth factor 23 and calcitriol concentrations in the blood of the cats were observed. However, the calcitriol precursors 25(OH)D-2 and 25(OH)D-3, which are considered the most useful indicators for the vitamin D status, decreased with higher dietary Ca levels (P = 0.013 and P = 0.033). Increasing dietary levels of dicalcium phosphate revealed an acidifying effect on urinary fasting pH (6.02) and postprandial pH (6.01) (P < 0.001), possibly mediated by an increase of urinary phosphorus (P) concentrations (P < 0.001). Conclusions In conclusion, calcitriol precursors were linearly affected by increasing dietary Ca concentrations. The increase in faecal Ca excretion indicates that Ca homeostasis of cats is mainly regulated in the intestine and not by the kidneys. Long-term studies should investigate the physiological relevance of the acidifying effect observed when feeding diets high in Ca and P.}, language = {en} } @misc{NojimaKonishiJaptoketal.2016, author = {Nojima, Hiroyuki and Konishi, Takanori and Japtok, Lukasz and Kleuser, Burkhard and Edwards, Michael J. and Gulbins, Erich and Lentsch, Alex B.}, title = {Chemokine receptors, CXCR1 and CXCR2, differentially regulate exosome release in hepatocytes}, series = {Hepatology : official journal of the American Association for the Study of Liver Diseases}, volume = {64}, journal = {Hepatology : official journal of the American Association for the Study of Liver Diseases}, publisher = {Wiley-Blackwell}, address = {Hoboken}, issn = {0270-9139}, pages = {165A -- 165A}, year = {2016}, language = {en} } @article{NojimaKonishiFreemanetal.2016, author = {Nojima, Hiroyuki and Konishi, Takanori and Freeman, Christopher M. and Schuster, Rebecca M. and Japtok, Lukasz and Kleuser, Burkhard and Edwards, Michael J. and Gulbins, Erich and Lentsch, Alex B.}, title = {Chemokine Receptors, CXCR1 and CXCR2, Differentially Regulate Exosome Release in Hepatocytes}, series = {PLoS one}, volume = {11}, journal = {PLoS one}, publisher = {PLoS}, address = {San Fransisco}, issn = {1932-6203}, doi = {10.1371/journal.pone.0161443}, pages = {6900 -- +}, year = {2016}, abstract = {Exosomes are small membrane vesicles released by different cell types, including hepatocytes, that play important roles in intercellular communication. We have previously demonstrated that hepatocyte-derived exosomes contain the synthetic machinery to form sphingosine-1-phosphate (S1P) in target hepatocytes resulting in proliferation and liver regeneration after ischemia/reperfusion (I/R) injury. We also demonstrated that the chemokine receptors, CXCR1 and CXCR2, regulate liver recovery and regeneration after I/R injury. In the current study, we sought to determine if the regulatory effects of CXCR1 and CXCR2 on liver recovery and regeneration might occur via altered release of hepatocyte exosomes. We found that hepatocyte release of exosomes was dependent upon CXCR1 and CXCR2. CXCR1-deficient hepatocytes produced fewer exosomes, whereas CXCR2-deficient hepatocytes produced more exosomes compared to their wild-type controls. In CXCR2-deficient hepatocytes, there was increased activity of neutral sphingomyelinase (Nsm) and intracellular ceramide. CXCR1-deficient hepatocytes had no alterations in Nsm activity or ceramide production. Interestingly, exosomes from CXCR1-deficient hepatocytes had no effect on hepatocyte proliferation, due to a lack of neutral ceramidase and sphingosine kinase. The data demonstrate that CXCR1 and CXCR2 regulate hepatocyte exosome release. The mechanism utilized by CXCR1 remains elusive, but CXCR2 appears to modulate Nsm activity and resultant production of ceramide to control exosome release. CXCR1 is required for packaging of enzymes into exosomes that mediate their hepatocyte proliferative effect.}, language = {en} } @article{NojimaFreemanSchusteretal.2016, author = {Nojima, Hiroyuki and Freeman, Christopher M. and Schuster, Rebecca M. and Japtok, Lukasz and Kleuser, Burkhard and Edwards, Michael J. and Gulbins, Erich and Lentsch, Alex B.}, title = {Hepatocyte exosomes mediate liver repair and regeneration via sphingosine-1-phosphate}, series = {Journal of hepatology}, volume = {64}, journal = {Journal of hepatology}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0168-8278}, doi = {10.1016/j.jhep.2015.07.030}, pages = {60 -- 68}, year = {2016}, abstract = {Background \& Aims: Exosomes are small membrane vesicles involved in intercellular communication. Hepatocytes are known to release exosomes, but little is known about their biological function. We sought to determine if exosomes derived from hepatocytes contribute to liver repair and regeneration after injury. Methods: Exosomes derived from primary murine hepatocytes were isolated and characterized biochemically and biophysically. Using cultures of primary hepatocytes, we tested whether hepatocyte exosomes induced proliferation of hepatocytes in vitro. Using models of ischemia/reperfusion injury and partial hepatectomy, we evaluated whether hepatocyte exosomes promote hepatocyte proliferation and liver regeneration in vivo. Results: Hepatocyte exosomes, but not exosomes from other liver cell types, induce dose-dependent hepatocyte proliferation in vitro and in vivo. Mechanistically, hepatocyte exosomes directly fuse with target hepatocytes and transfer neutral ceramidase and sphingosine kinase 2 (SK2) causing increased synthesis of sphingosine-1-phosphate (S1P) within target hepatocytes. Ablation of exosomal SK prevents the proliferative effect of exosomes. After ischemia/reperfusion injury, the number of circulating exosomes with proliferative effects increases. Conclusions: Our data shows that hepatocyte-derived exosomes deliver the synthetic machinery to form S1P in target hepatocytes resulting in cell proliferation and liver regeneration after ischemia/reperfusion injury or partial hepatectomy. These findings represent a potentially novel new contributing mechanism of liver regeneration and have important implications for new therapeutic approaches to acute and chronic liver disease. (C) 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.}, language = {en} } @article{NiehoffSchulzSoltwischetal.2016, author = {Niehoff, Ann-Christin and Schulz, Jacqueline and Soltwisch, Jens and Meyer, Soren and Kettling, Hans and Sperling, Michael and Jeibmann, Astrid and Dreisewerd, Klaus and Francesconi, Kevin A. and Schwerdtle, Tanja and Karst, Uwe}, title = {Imaging by Elemental and Molecular Mass Spectrometry Reveals the Uptake of an Arsenolipid in the Brain of Drosophila melanogaster}, series = {Analytical chemistry}, volume = {88}, journal = {Analytical chemistry}, publisher = {American Chemical Society}, address = {Washington}, issn = {0003-2700}, doi = {10.1021/acs.analchem.6b00333}, pages = {5258 -- 5263}, year = {2016}, abstract = {Arsenic-containing lipids (arsenolipids) are natural products of marine organisms such as fish, invertebrates, and algae, many of which are important seafoods. A major group of arsenolipids, namely, the arsenic-containing hydrocarbons (AsHC), have recently been shown to be cytotoxic to human liver and bladder cells, a result that has stimulated interest in the chemistry and toxicology of these compounds. In this study, elemental laser ablation-inductively coupled plasma mass spectrometry (LA-ICPMS) and molecular matrix-assisted laser desorption/ionization (MALDI-)MS were used to image and quantify the uptake of an AsHC in the model organism Drosophila melanogaster. Using these two complementary methods, both an enrichment of arsenic and the presence of the AsHC in the brain were revealed, indicating that the intact arsenolipid had crossed the blood-brain barrier. Simultaneous acquisition of quantitative elemental concentrations and molecular distributions could allow new insight into organ-specific enrichment and possible transportation processes of arsenic-containing bioactive compounds in living organisms.}, language = {en} } @article{MarschallBornhorstKuehneltetal.2016, author = {Marschall, Talke Anu and Bornhorst, Julia and Kuehnelt, Doris and Schwerdtle, Tanja}, title = {Differing cytotoxicity and bioavailability of selenite, methylselenocysteine, selenomethionine, selenosugar 1 and trimethylselenonium ion and their underlying metabolic transformations in human cells}, series = {Applied computing review : the publication of the ACM Special Interest Group on Applied Computing}, volume = {60}, journal = {Applied computing review : the publication of the ACM Special Interest Group on Applied Computing}, publisher = {Wiley-Blackwell}, address = {Hoboken}, issn = {1613-4125}, doi = {10.1002/mnfr.201600422}, pages = {2622 -- 2632}, year = {2016}, abstract = {Scope: The trace element selenium (Se) is an integral component of our diet. However, its metabolism and toxicity following elevated uptake are not fully understood. Since the either adverse or beneficial health effects strongly depend on the ingested Se species, five low molecular weight species were investigated regarding their toxicological effects, cellular bioavailability and species-specific metabolism in human cells. Methods and results: For the first time, the urinary metabolites methyl-2-acetamido-2-deoxy1- seleno-beta-D-galactopyranoside (selenosugar 1) and trimethylselenonium ion (TMSe) were toxicologically characterised in comparison to the food relevant species methylselenocysteine (MeSeCys), selenomethionine (SeMet) and selenite in human urothelial, astrocytoma and hepatoma cells. In all cell lines selenosugar 1 and TMSe showed no cytotoxicity. Selenite, MeSeCys and SeMet exerted substantial cytotoxicity, which was strongest in the urothelial cells. There was no correlation between the potencies of the respective toxic effects and the measured cellular Se concentrations. Se speciation indicated that metabolism of the respective species is likely to affect cellular toxicity. Conclusion: Despite being taken up, selenosugar 1 and TMSe are non-cytotoxic to urothelial cells, most likely because they are not metabolically activated. The absent cytotoxicity of selenosugar 1 and TMSe up to supra-physiological concentrations, support their importance as metabolites for Se detoxification.}, language = {en} } @article{ManowskyCamargoKippetal.2016, author = {Manowsky, Julia and Camargo, Rodolfo Gonzalez and Kipp, Anna Patricia and Henkel, Janin and P{\"u}schel, Gerhard Paul}, title = {Insulin-induced cytokine production in macrophages causes insulin resistance in hepatocytes}, series = {American journal of physiology : Endocrinology and metabolism}, volume = {310}, journal = {American journal of physiology : Endocrinology and metabolism}, publisher = {American Chemical Society}, address = {Bethesda}, issn = {0193-1849}, doi = {10.1152/ajpendo.00427.2015}, pages = {E938 -- E946}, year = {2016}, abstract = {Overweight and obesity are associated with hyperinsulinemia, insulin resistance, and a low-grade inflammation. Although hyperinsulinemia is generally thought to result from an attempt of the beta-cell to compensate for insulin resistance, there is evidence that hyperinsulinaemia itself may contribute to the development of insulin resistance and possibly the low-grade inflammation. To test this hypothesis, U937 macrophages were exposed to insulin. In these cells, insulin induced expression of the proinflammatory cytokines IL-1 beta, IL-8, CCL2, and OSM. The insulin-elicited induction of IL-1 beta was independent of the presence of endotoxin and most likely mediated by an insulin-dependent activation of NF-kappa B. Supernatants of the insulin-treated U937 macrophages rendered primary cultures of rat hepatocytes insulin resistant; they attenuated the insulin-dependent induction of glucokinase by 50\%. The cytokines contained in the supernatants of insulin-treated U937 macrophages activated ERK1/2 and IKK beta, resulting in an inhibitory serine phosphorylation of the insulin receptor substrate. In addition, STAT3 was activated and SOCS3 induced, further contributing to the interruption of the insulin receptor signal chain in hepatocytes. These results indicate that hyperinsulinemia per se might contribute to the low-grade inflammation prevailing in overweight and obese patients and thereby promote the development of insulin resistance particularly in the liver, because the insulin concentration in the portal circulation is much higher than in all other tissues.}, language = {en} } @article{MageneyBaldermannAlbach2016, author = {Mageney, Vera and Baldermann, Susanne and Albach, Dirk C.}, title = {Intraspecific Variation in Carotenoids of Brassica oleracea var. sabellica}, series = {Journal of agricultural and food chemistry : a publication of the American Chemical Society}, volume = {64}, journal = {Journal of agricultural and food chemistry : a publication of the American Chemical Society}, publisher = {American Chemical Society}, address = {Washington}, issn = {0021-8561}, doi = {10.1021/acs.jafc.6b00268}, pages = {3251 -- 3257}, year = {2016}, abstract = {Carotenoids are best known as a source of natural antioxidants. Physiologically, carotenoids are part of the photoprotection in plants as they act as scavengers of reactive oxygen species (ROS). An important source of carotenoids in European food is Brassica oleracea. Focusing on the most abundant carotenoids, we estimated the contents of beta-carotene, (9Z)-neoxanthin, zeaxanthin, and lutein as well as those of chlorophylls a and b to assess their variability in Brassica oleracea var. sabellica. Our analyses included more than 30 cultivars categorized in five distinct sets grouped according to morphological characteristics or geographical origin. Our results demonstrated specific carotenoid patterns characteristic for American, Italian, and red-colored kale cultivars. Moreover, we demonstrated a tendency of high zeaxanthin proportions under traditional harvest conditions, which accord to low-temperature regimes. We also compared the carotenoid patterns of self-generated hybrid lines. Corresponding findings indicated that crossbreeding has a high potential for carotenoid content optimization in kale.}, language = {en} } @article{LuTsuprykovVignonZellwegeretal.2016, author = {Lu, Yong Ping and Tsuprykov, Oleg and Vignon-Zellweger, Nicolas and Heiden, Susi and Hocher, Berthold}, title = {Global Overexpression of ET-1 Decreases Blood Pressure - A Systematic Review and Meta-Analysis of ET-1 Transgenic Mice}, series = {Naunyn-Schmiedeberg's archives of pharmacology}, volume = {41}, journal = {Naunyn-Schmiedeberg's archives of pharmacology}, publisher = {Karger}, address = {Basel}, issn = {1420-4096}, doi = {10.1159/000450567}, pages = {770 -- 780}, year = {2016}, abstract = {Background/Aims: ET-1 has independent effects on blood pressure regulation in vivo, it is involved in tubular water and salt excretion, promotes constriction of smooth muscle cells, modulates sympathetic nerve activity, and activates the liberation of nitric oxide. To determine the net effect of these partially counteracting mechanisms on blood pressure, a systematic meta-analysis was performed. Methods: Based on the principles of Cochrane systematic reviews, we searched in major literature databases - MEDLINE (PubMed), Embase, Google Scholar, and the China Biological Medicine Database (CBM-disc) - for articles relevant to the topic of the blood pressure phenotype of endothelin-1 transgenic (ET-1+/+) mice from January 1, 1988 to March 31, 2016. Review Manager Version 5.0 (Rev-Man 5.0) software was applied for statistical analysis. In total thirteen studies reported blood pressure data. Results: The meta-analysis of blood pressure data showed that homozygous ET-1 transgenic mice (ET-1+/+ mice) had a significantly lower blood pressure as compared to WT mice (mean difference:-2.57 mmHg, 95\% CI: -4.98 similar to -0.16, P = 0.04), with minimal heterogeneity (P = 0.86). A subgroup analysis of mice older than 6 months revealed that the blood pressure difference between ET-1+/+ mice and WT mice was even more pronounced (mean difference: -6.19 mmHg, 95\% CI: -10.76 similar to -1.62, P = 0.008), with minimal heterogeneity (P = 0.91). Conclusion: This meta-analysis provides robust evidence that global ET-1 overexpression in mice lowers blood pressure in an age-dependent manner. Older ET-1+/+ mice have a somewhat more pronounced reduction of blood pressure. (C) 2016 The Author(s) Published by S. Karger AG, Basel}, language = {en} } @article{LohrenBornhorstFitkauetal.2016, author = {Lohren, Hanna and Bornhorst, Julia and Fitkau, Romy and Pohl, Gabriele and Galla, Hans-Joachim and Schwerdtle, Tanja}, title = {Effects on and transfer across the blood-brain barrier in vitro-Comparison of organic and inorganic mercury species}, series = {BMC pharmacology \& toxicology}, volume = {17}, journal = {BMC pharmacology \& toxicology}, publisher = {BioMed Central}, address = {London}, issn = {2050-6511}, doi = {10.1186/s40360-016-0106-5}, pages = {422 -- 433}, year = {2016}, abstract = {Background: Transport of methylmercury (MeHg) across the blood-brain barrier towards the brain side is well discussed in literature, while ethylmercury (EtHg) and inorganic mercury are not adequately characterized regarding their entry into the brain. Studies investigating a possible efflux out of the brain are not described to our knowledge. Methods: This study compares, for the first time, effects of organic methylmercury chloride (MeHgCl), EtHg-containing thiomersal and inorganic Hg chloride (HgCl2) on as well as their transfer across a primary porcine in vitro model of the blood-brain barrier. Results: With respect to the barrier integrity, the barrier model exhibited a much higher sensitivity towards HgCl2 following basolateral incubation (brain-facing side) as compared to apical application (blood-facing side). These HgCl2 induced effects on the barrier integrity after brain side incubation are comparable to that of the organic species, although MeHgCl and thiomersal exerted much higher cytotoxic effects in the barrier building cells. Hg transfer rates following exposure to organic species in both directions argue for diffusion as transfer mechanism. Inorganic Hg application surprisingly resulted in a Hg transfer out of the brain-facing compartment. Conclusions: In case of MeHgCl and thiomersal incubation, mercury crossed the barrier in both directions, with a slight accumulation in the basolateral, brain-facing compartment, after simultaneous incubation in both compartments. For HgCl2, our data provide first evidence that the blood-brain barrier transfers mercury out of the brain.}, language = {en} } @misc{LiTsuprykovYangetal.2016, author = {Li, Jian and Tsuprykov, Oleg and Yang, Xiaoping and Hocher, Berthold}, title = {Paternal programming of offspring cardiometabolic diseases in later life}, series = {Journal of hypertension}, volume = {34}, journal = {Journal of hypertension}, publisher = {Wiley-Blackwell}, address = {Philadelphia}, issn = {0263-6352}, doi = {10.1097/HJH.0000000000001051}, pages = {2111 -- 2126}, year = {2016}, language = {en} } @article{LiLuReichetzederetal.2016, author = {Li, Jian and Lu, Yong Ping and Reichetzeder, Christoph and Kalk, Philipp and Kleuser, Burkhard and Adamski, Jerzy and Hocher, Berthold}, title = {Maternal PCaaC38:6 is Associated With Preterm Birth - a Risk Factor for Early and Late Adverse Outcome of the Offspring}, series = {Journal of European public policy}, volume = {41}, journal = {Journal of European public policy}, publisher = {Karger}, address = {Basel}, issn = {1420-4096}, doi = {10.1159/000443428}, pages = {250 -- 257}, year = {2016}, abstract = {Background/Aims: Preterm birth (PTB) and low birth weight (LBW) significantly influence mortality and morbidity of the offspring in early life and also have long-term consequences in later life. A better understanding of the molecular mechanisms of preterm birth could provide new insights regarding putative preventive strategies. Metabolomics provides a powerful analytic tool to readout complex interactions between genetics, environment and health and may serve to identify relevant biomarkers. In this study, the association between 163 targeted maternal blood metabolites and gestational age was investigated in order to find candidate biomarkers for PTB. Methods: Five hundred twenty-three women were included into this observational study. Maternal blood was obtained before delivery. The concentration of 163 maternal serum metabolites was measured by flow injection tandem mass spectrometry. To find putative biomarkers for preterm birth, a three-step analysis was designed: bivariate correlation analysis followed by multivariable regression analysis and a comparison of mean values among gestational age groups. Results: Bivariate correlation analysis showed that 2 acylcarnitines (C16:2, C2), 1 amino acids (xLeu), 8 diacyl-PCs (PCaaC36:4, PCaaC38:4, PCaaC38:5, PCaaC38:6, PCaaC40:4, PCaaC40:5, PCaaC40:6, PCaaC42:4), and 1 Acylalkyl-PCs (PCaeC40:5) were inversely correlated with gestational age. Multivariable regression analysis confounded for PTB history, maternal body mass index (BMI) before pregnancy, systolic blood pressure at the third trimester, and maternal body weight at the third trimester, showed that the diacyl-PC PCaaC38:6 was the only metabolite inversely correlated with gestational age. Conclusions: Maternal blood concentrations of PCaaC38:6 are independently associated with gestational age. (C) 2016 The Author(s) Published by S. Karger AG, Basel}, language = {en} } @phdthesis{Kamitz2016, author = {Kamitz, Anne}, title = {Identification and positional cloning of Ltg/NZO; a novel susceptibility locus associated with fatty liver disease}, school = {Universit{\"a}t Potsdam}, pages = {102}, year = {2016}, language = {en} } @phdthesis{Jaeger2016, author = {J{\"a}ger, Susanne}, title = {Genetic variants and metabolic pathways of type 2 diabetes within the EPIC-Potsdam study}, school = {Universit{\"a}t Potsdam}, pages = {139, XXVII}, year = {2016}, language = {en} } @article{IslamKhalilMaenneretal.2016, author = {Islam, Khan Shaiful and Khalil, Mahmoud and M{\"a}nner, K. and Raila, Jens and Rawel, Harshadrai Manilal and Zentek, J. and Schweigert, Florian J.}, title = {Effect of dietary alpha-tocopherol on the bioavailability of lutein in laying hen}, series = {Journal of animal physiology and animal nutrition}, volume = {100}, journal = {Journal of animal physiology and animal nutrition}, publisher = {Wiley-Blackwell}, address = {Hoboken}, issn = {0931-2439}, doi = {10.1111/jpn.12464}, pages = {868 -- 875}, year = {2016}, abstract = {Lutein and its isomer zeaxanthin have gained considerable interest as possible nutritional ingredient in the prevention of age-related macular degeneration (AMD) in humans. Egg yolk is a rich source of these carotenoids. As an oxidative sensitive component, antioxidants such as -tocopherol (T) might contribute to an improved accumulation in egg yolk. To test this, chickens were fed lutein esters (LE) with and without -tocopherol as an antioxidant. After depletion on a wheat-soya bean-based lutein-poor diet for 21days, laying hens (n=42) were equally divided into three groups and fed the following diets for 21days: control (basal diet), a LE group (40mg LE/kg feed) and LE+T group (40mg LE plus 100mg T/kg feed). Eggs and blood were collected periodically. Carotenoids and -tocopherol in yolk and blood plasma were determined by HPLC. Egg yolk was also analysed for total carotenoids using a one-step spectrophotometric method (iCheck(())). Lutein, zeaxanthin, -tocopherol and total carotenoids in egg yolk were highest after 14days of feeding and decreased slightly afterwards. At the end of the trial, eggs of LE+T group contained higher amount of lutein (13.72), zeaxanthin (0.65), -tocopherol (297.40) and total carotenoids (21.6) compared to the LE group (10.96, 0.55, 205.20 and 18.0mg/kg, respectively, p<0.05). Blood plasma values of LE+T group contain higher lutein (1.3), zeaxanthin (0.06) and tocopherol (20.1) compared to LE group (1.02, 0.04 and 14.90mg/l, respectively, p<0.05). In conclusion, dietary -tocopherol enhances bioavailability of lutein reflecting higher content in egg yolk and blood plasma. Improved bioavailability might be due to increased absorption of lutein in the presence of tocopherol and/or a greater stability of lutein/zeaxanthin due to the presence of -tocopherol as an antioxidant.}, language = {en} } @article{HoenzkeGereckeElpeltetal.2016, author = {H{\"o}nzke, Stefan and Gerecke, Christian and Elpelt, Anja and Zhang, Nan and Unbehauen, Michael and Kral, Vivian and Fleige, Emanuel and Paulus, Florian and Haag, Rainer and Sch{\"a}fer-Korting, Monika and Kleuser, Burkhard and Hedtrich, Sarah}, title = {Tailored dendritic core-multishell nanocarriers for efficient dermal drug delivery: A systematic top-down approach from synthesis to preclinical testing}, series = {Journal of controlled release}, volume = {242}, journal = {Journal of controlled release}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0168-3659}, doi = {10.1016/j.jconrel.2016.06.030}, pages = {50 -- 63}, year = {2016}, abstract = {Drug loaded dendritic core-multishell (CMS) nanocarriers are of especial interest for the treatment of skin diseases, owing to their striking dermal delivery efficiencies following topical applications. CMS nanocarriers are composed of a polyglycerol core, connected by amide-bonds to an inner alkyl shell and an outer methoxy poly(ethylene glycol) shell. Since topically applied nanocarriers are subjected to biodegradation, the application of conventional amide-based CMS nanocarriers (10-A-18-350) has been limited by the potential production of toxic polyglycerol amines. To circumvent this issue, three tailored ester-based CMS nanocarriers (10-E-12-350, 10-E-15-350, 10-E-18-350) of varying inner alkyl chain length were synthesized and comprehensively characterized in terms of particle size, drug loading, biodegradation and dermal drug delivery efficiency. Dexamethasone (DXM), a potent drug widely used for the treatment of inflammatory skin diseases, was chosen as a therapeutically relevant test compound for the present study. Ester-and amide-based CMS nanocarriers delivered DXM more efficiently into human skin than a commercially available DXM cream. Subsequent in vitro and in vivo toxicity studies identified CMS (10-E-15-350) as the most biocompatible carrier system. The anti-inflammatory potency of DXM-loaded CMS (10-E-15-350) nanocarriers was assessed in TNF alpha supplemented skin models, where a significant reduction of the pro-inflammatory cytokine IL-8 was seen, with markedly greater efficacy than commercial DXM cream. In summary, we report the rational design and characterization of tailored, biodegradable, ester-based CMS nanocarriers, and their subsequent stepwise screening for biocompatibility, dermal delivery efficiency and therapeutic efficacy in a top-down approach yielding the best carrier system for topical applications. (C) 2016 Elsevier B.V. All rights reserved.}, language = {en} } @article{HustonKornhuberMuehleetal.2016, author = {Huston, Joseph P. and Kornhuber, Johannes and Muehle, Christiane and Japtok, Lukasz and Komorowski, Mara and Mattern, Claudia and Reichel, Martin and Gulbins, Erich and Kleuser, Burkhard and Topic, Bianca and Silva, Maria A. De Souza and Mueller, Christian P.}, title = {A sphingolipid mechanism for behavioral extinction}, series = {Journal of neurochemistry}, volume = {137}, journal = {Journal of neurochemistry}, publisher = {Wiley-Blackwell}, address = {Hoboken}, issn = {0022-3042}, doi = {10.1111/jnc.13537}, pages = {589 -- 603}, year = {2016}, abstract = {Reward-dependent instrumental behavior must continuously be re-adjusted according to environmental conditions. Failure to adapt to changes in reward contingencies may incur psychiatric disorders like anxiety and depression. When an expected reward is omitted, behavior undergoes extinction. While extinction involves active re-learning, it is also accompanied by emotional behaviors indicative of frustration, anxiety, and despair (extinction-induced depression). Here, we report evidence for a sphingolipid mechanism in the extinction of behavior. Rapid extinction, indicating efficient re-learning, coincided with a decrease in the activity of the enzyme acid sphingomyelinase (ASM), which catalyzes turnover of sphingomyelin to ceramide, in the dorsal hippocampus of rats. The stronger the decline in ASM activity, the more rapid was the extinction. Sphingolipid-focused lipidomic analysis showed that this results in a decline of local ceramide species in the dorsal hippocampus. Ceramides shape the fluidity of lipid rafts in synaptic membranes and by that way can control neural plasticity. We also found that aging modifies activity of enzymes and ceramide levels in selective brain regions. Aging also changed how the chronic treatment with corticosterone (stress) or intranasal dopamine modified regional enzyme activity and ceramide levels, coinciding with rate of extinction. These data provide first evidence for a functional ASM-ceramide pathway in the brain involved in the extinction of learned behavior. This finding extends the known cellular mechanisms underlying behavioral plasticity to a new class of membrane-located molecules, the sphingolipids, and their regulatory enzymes, and may offer new treatment targets for extinction- and learning-related psychopathological conditions.}, language = {en} } @article{HuschekBoenickLoewensteinetal.2016, author = {Huschek, Gerd and Boenick, Josephine and Loewenstein, Yvonne and Sievers, Steven and Rawel, Harshadrai Manilal}, title = {Quantification of allergenic plant traces in baked products by targeted proteomics using isotope marked peptides}, 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 = {74}, 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.2016.07.057}, pages = {286 -- 293}, year = {2016}, abstract = {The right choice of analytical methods for plant allergen quantification is a deciding factor for the correct assessment and labeling of allergens in processed food in view of consumer protection. The aim of the present study was to develop a validated target peptide multi-method by LC/MS/MS providing high specificity and sensitivity for plant allergen protein detection, plant identification in vegan or vegetarian products using peptide markers for quantification. The methodical concept considers the selection of target peptides of thermostable allergenic plant proteins (Gly m6 soy, Ses i6 sesame and (beta-conglutin from white lupine) by data base research, BLAST and in silico digestion using Skyline software. Different allergenic concentration levels of these proteins were integrated into our own reference bakery products and quantified with. synthesized isotopically labeled peptides after in-solution digestion using LC/MS/MS. Recovery rates within the range of 70-113\% and LOQ of 10 ppm-50 ppm (mg allergenic food/kg) could be determined. The results are independent of thermal processing applied during baking and of epitope binding site for the tested allergens. (C) 2016 Elsevier Ltd. All rights reserved.}, language = {en} } @article{HollmannWernerAvotaetal.2016, author = {Hollmann, Claudia and Werner, Sandra and Avota, Elita and Reuter, Dajana and Japtok, Lukasz and Kleuser, Burkhard and Gulbins, Erich and Becker, Katrin Anne and Schneider-Schaulies, J{\"u}rgen and Beyersdorf, Niklas}, title = {Inhibition of Acid Sphingomyelinase Allows for Selective Targeting of CD4(+) Conventional versus Foxp3(+) Regulatory T Cells}, series = {The journal of immunology}, volume = {197}, journal = {The journal of immunology}, publisher = {American Assoc. of Immunologists}, address = {Bethesda}, issn = {0022-1767}, doi = {10.4049/jimmunol.1600691}, pages = {3130 -- 3141}, year = {2016}, abstract = {CD4(+) Foxp3(+) regulatory T cells (Tregs) depend on CD28 signaling for their survival and function, a receptor that has been previously shown to activate the acid sphingomyelinase (Asm)/ceramide system. In this article, we show that the basal and CD28-induced Asm activity is higher in Tregs than in conventional CD4(+) T cells (Tconvs) of wild-type (wt) mice. In Asm-deficient (Smpd1(-/-); Asm(-/-)) mice, as compared with wt mice, the frequency of Tregs among CD4(+) T cells, turnover of the effector molecule CTLA-4, and their suppressive activity in vitro were increased. The biological significance of these findings was confirmed in our Treg-sensitive mouse model of measles virus (MV) CNS infection, in which we observed more infected neurons and less MV-specific CD8(+) T cells in brains of Asm(-/-) mice compared with wt mice. In addition to genetic deficiency, treatment of wt mice with the Asm inhibitor amitriptyline recapitulated the phenotype of Asm-deficient mice because it also increased the frequency of Tregs among CD4(+) T cells. Reduced absolute cell numbers of Tconvs after inhibitor treatment in vivo and extensive in vitro experiments revealed that Tregs are more resistant toward Asm inhibitor-induced cell death than Tconvs. Mechanistically, IL-2 was capable of providing crucial survival signals to the Tregs upon inhibitor treatment in vitro, shifting the Treg/Tconv ratio to the Treg side. Thus, our data indicate that Asm-inhibiting drugs should be further evaluated for the therapy of inflammatory and autoimmune disorders.}, language = {en} } @misc{HollmannReuterWerneretal.2016, author = {Hollmann, C. and Reuter, D. and Werner, S. and Avota, Elita and Mueller, N. and Japtok, Lukasz and Kleuser, Burkhard and Becker, Katrin Anne and Gulbins, Erich and Schneider-Schaulies, J{\"u}rgen and Beyersdorf, Niklas}, title = {Pharmacological inhibition of acid sphingomyelinase or genetic ablation enhances CD4(+) Foxp3(+) regulatory T cell activity}, series = {European journal of immunology}, volume = {46}, journal = {European journal of immunology}, publisher = {Wiley-Blackwell}, address = {Hoboken}, issn = {0014-2980}, pages = {14 -- 14}, year = {2016}, language = {en} } @article{HocherHaumannRahnenfuehreretal.2016, author = {Hocher, Berthold and Haumann, Hannah and Rahnenf{\"u}hrer, Jan and Reichetzeder, Christoph and Kalk, Philipp and Pfab, Thiemo and Tsuprykov, Oleg and Winter, Stefan and Hofmann, Ute and Li, Jian and P{\"u}schel, Gerhard Paul and Lang, Florian and Schuppan, Detlef and Schwab, Matthias and Schaeffeler, Elke}, title = {Maternal eNOS deficiency determines a fatty liver phenotype of the offspring in a sex dependent manner}, series = {Epigenetics : the official journal of the DNA Methylation Society}, volume = {11}, journal = {Epigenetics : the official journal of the DNA Methylation Society}, publisher = {Routledge, Taylor \& Francis Group}, address = {Philadelphia}, issn = {1559-2294}, doi = {10.1080/15592294.2016.1184800}, pages = {539 -- 552}, year = {2016}, abstract = {Maternal environmental factors can impact on the phenotype of the offspring via the induction of epigenetic adaptive mechanisms. The advanced fetal programming hypothesis proposes that maternal genetic variants may influence the offspring's phenotype indirectly via epigenetic modification, despite the absence of a primary genetic defect. To test this hypothesis, heterozygous female eNOS knockout mice and wild type mice were bred with male wild type mice. We then assessed the impact of maternal eNOS deficiency on the liver phenotype of wild type offspring. Birth weight of male wild type offspring born to female heterozygous eNOS knockout mice was reduced compared to offspring of wild type mice. Moreover, the offspring displayed a sex specific liver phenotype, with an increased liver weight, due to steatosis. This was accompanied by sex specific differences in expression and DNA methylation of distinct genes. Liver global DNA methylation was significantly enhanced in both male and female offspring. Also, hepatic parameters of carbohydrate metabolism were reduced in male and female offspring. In addition, male mice displayed reductions in various amino acids in the liver. Maternal genetic alterations, such as partial deletion of the eNOS gene, can affect liver metabolism of wild type offspring without transmission of the intrinsic defect. This occurs in a sex specific way, with more detrimental effects in females. This finding demonstrates that a maternal genetic defect can epigenetically alter the phenotype of the offspring, without inheritance of the defect itself. Importantly, these acquired epigenetic phenotypic changes can persist into adulthood.}, language = {en} } @article{HenzeHomannRohnetal.2016, author = {Henze, Andrea and Homann, Thomas and Rohn, Isabelle and Aschner, Michael A. and Link, Christopher D. and Kleuser, Burkhard and Schweigert, Florian J. and Schwerdtle, Tanja and Bornhorst, Julia}, title = {Caenorhabditis elegans as a model system to study post-translational modifications of human transthyretin}, series = {Scientific reports}, volume = {6}, journal = {Scientific reports}, publisher = {Nature Publ. Group}, address = {London}, issn = {2045-2322}, doi = {10.1038/srep37346}, pages = {12}, year = {2016}, abstract = {The visceral protein transthyretin (TTR) is frequently affected by oxidative post-translational protein modifications (PTPMs) in various diseases. Thus, better insight into structure-function relationships due to oxidative PTPMs of TTR should contribute to the understanding of pathophysiologic mechanisms. While the in vivo analysis of TTR in mammalian models is complex, time-and resource-consuming, transgenic Caenorhabditis elegans expressing hTTR provide an optimal model for the in vivo identification and characterization of drug-mediated oxidative PTPMs of hTTR by means of matrix assisted laser desorption/ionization - time of flight - mass spectrometry (MALDI-TOF-MS). Herein, we demonstrated that hTTR is expressed in all developmental stages of Caenorhabditis elegans, enabling the analysis of hTTR metabolism during the whole life-cycle. The suitability of the applied model was verified by exposing worms to D-penicillamine and menadione. Both drugs induced substantial changes in the oxidative PTPM pattern of hTTR. Additionally, for the first time a covalent binding of both drugs with hTTR was identified and verified by molecular modelling.}, language = {en} } @article{HenzeHomannRohnetal.2016, author = {Henze, Andrea and Homann, Thomas and Rohn, Isabelle and Aschner, Michael A. and Link, Christopher D. and Kleuser, Burkhard and Schweigert, Florian J. and Schwerdtle, Tanja and Bornhorst, Julia}, title = {Caenorhabditis elegans as a model system to study post-translational modifications of human transthyretin}, series = {Scientific reports}, volume = {6}, journal = {Scientific reports}, publisher = {Nature Publishing Group}, address = {London}, issn = {2045-2322}, doi = {10.1038/srep37346}, pages = {12}, year = {2016}, abstract = {The visceral protein transthyretin (TTR) is frequently affected by oxidative post-translational protein modifications (PTPMs) in various diseases. Thus, better insight into structure-function relationships due to oxidative PTPMs of TTR should contribute to the understanding of pathophysiologic mechanisms. While the in vivo analysis of TTR in mammalian models is complex, time- and resource-consuming, transgenic Caenorhabditis elegans expressing hTTR provide an optimal model for the in vivo identification and characterization of drug-mediated oxidative PTPMs of hTTR by means of matrix assisted laser desorption/ionization - time of flight - mass spectrometry (MALDI-TOF-MS). Herein, we demonstrated that hTTR is expressed in all developmental stages of Caenorhabditis elegans, enabling the analysis of hTTR metabolism during the whole life-cycle. The suitability of the applied model was verified by exposing worms to D-penicillamine and menadione. Both drugs induced substantial changes in the oxidative PTPM pattern of hTTR. Additionally, for the first time a covalent binding of both drugs with hTTR was identified and verified by molecular modelling.}, 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} } @phdthesis{Hallahan2016, author = {Hallahan, Nicole}, title = {Identification and characterization of a T2D QTL arising from an NZO.DBA mouse cross}, school = {Universit{\"a}t Potsdam}, pages = {133}, year = {2016}, language = {en} } @article{GubertPuntelLehmenetal.2016, author = {Gubert, Priscila and Puntel, Bruna and Lehmen, Tassia and Bornhorst, Julia and Avila, Daiana Silva and Aschner, Michael A. and Soares, Felix A. A.}, title = {Reversible reprotoxic effects of manganese through DAF-16 transcription factor activation and vitellogenin downregulation in Caenorhabditis elegans}, series = {Life sciences : molecular, cellular and functional basis of therapy}, volume = {151}, journal = {Life sciences : molecular, cellular and functional basis of therapy}, publisher = {Elsevier}, address = {Oxford}, issn = {0024-3205}, doi = {10.1016/j.lfs.2016.03.016}, pages = {218 -- 223}, year = {2016}, abstract = {Aims Vitellogenesis is the yolk production process which provides the essential nutrients for the developing embryos. Yolk is a lipoprotein particle that presents lipids and lipid-binding proteins, referred to as vitellogenins (VIT). The Caenorhabditis elegans nematode has six genes encoding VIT lipoproteins. Several pathways are known to regulate vitellogenesis, including the DAF-16 transcription factor. Some reports have shown that heavy metals, such as manganese (Mn), impair brood size in C. elegans; however the mechanisms associated with this effect have yet to be identified. Our aim was to evaluate Mn\&\#8242;s effects on C. elegans reproduction and better understand the pathways related to these effects. Main methods. Young adult larval stage worms were treated for 4 h with Mn in 85 mM NaCl and Escherichia coli OP50 medium. Key findings. Mn reduced egg-production and egg-laying during the first 24 h after the treatment, although the total number of progenies were indistinguishable from the control group levels. This delay may have occurred due to DAF-16 activation, which was noted only after the treatment and was not apparent 24 h later. Moreover, the expression, protein levels and green fluorescent protein (GFP) fluorescence associated with VIT were decreased soon after Mn treatment and recovered after 24 h. Significance Combined, these data suggest that the delay in egg-production is likely regulated by DAF-16 and followed by the inhibition of VIT transport activity. Further studies are needed to clarify the mechanisms associated with Mn-induced DAF-16 activation.}, language = {en} } @article{ForssmannTillmannHocketal.2016, author = {Forssmann, Wolf-Georg and Tillmann, Hanns-Christian and Hock, Dieter and Forssmann, Kristin and Bernasconi, Corrado and Forssmann, Ulf and Richter, Rudolf and Hocher, Berthold and Pfuetzner, Andreas}, title = {Pharmacokinetic and Pharmacodynamic Characteristics of Subcutaneously Applied PTH-1-37}, series = {German politics}, volume = {41}, journal = {German politics}, publisher = {Karger}, address = {Basel}, issn = {1420-4096}, doi = {10.1159/000443453}, pages = {507 -- 518}, year = {2016}, abstract = {Background/Aims: Parathyroid hormone (PTH) derivatives exert pronounced renal and osteoanabolic properties when given intermittently. The current study was performed to assess the pharmacokinetic and pharmacodynamic properties as well as safety of subcutaneously applied PTH-1-37 after repeated dosing in healthy subjects. Methods: This randomized, double-blind, dose-escalating, placebo and active comparator controlled study was conducted in 33 healthy postmenopausal women. Subjects were allocated to one of five treatment options: 10, 20, or 40 mu g PTH-1-37, 20 mu g PTH-1-34 or placebo, administered as once daily subcutaneous doses for three days. Plasma drug concentrations and serum levels of endogenous PTH-1-84, and calcium as markers of biological activity were monitored during the treatment. Results: PTH was absorbed rapidly from the subcutaneous tissue with a median t(max) of 30 minutes for 20 and 40 mu g of PTH-1-37. t(max) was 45 minutes for 20 mu g PTH-1-34. Elimination half-lives were estimated as 76 +/- 34 min and 70 +/- 13 min for 20 mu g and 40 mu g PTH-1-37 (mean +/- SD), and 78 +/- 34 for 20 mu g PTH-1-34. Both PTH fragments (PTH-1-37 and PTH-1-34) increased serum calcium. For PTH-1-37 the effect on serum calcium was dose-dependent. Suppression of endogenous PTH-1-84 was seen after the application of both PTH-1-37 and PTH-1-34. During the study period, the subjects experienced no unexpected or serious adverse events. Conclusions: PTH-1-37 is rapidly absorbed after s.c. injection, has a short plasma elimination half-life, and does not accumulate during multiple dosing. Biological activity was demonstrated by rising serum calcium and decreasing endogenous PTH-1-84 in blood plasma. The study drugs were well tolerated and safe. Our investigation presents data that PTH-1-37 is an excellent drug candidate for intervening with syndromes of dysregulation of calcium metabolism. (C) 2016 The Author(s) Published by S. Karger AG, Basel}, language = {en} } @article{ErrardUlrichsKuehneetal.2016, author = {Errard, Audrey and Ulrichs, Christian and K{\"u}hne, Stefan and Mewis, Inga and Mishig, Narantuya and Maul, Ronald and Drungowski, Mario and Parolin, Pia and Schreiner, Monika and Baldermann, Susanne}, title = {Metabolite Profiling Reveals a Specific Response in Tomato to Predaceous Chrysoperla carnea Larvae and Herbivore(s)-Predator Interactions with the Generalist Pests Tetranychus urticae and Myzus persicae}, series = {Frontiers in plant science}, volume = {7}, journal = {Frontiers in plant science}, publisher = {Frontiers Research Foundation}, address = {Lausanne}, issn = {1664-462X}, doi = {10.3389/fpls.2016.01256}, pages = {456 -- +}, year = {2016}, abstract = {The spider mite Tetranychus urticae Koch and the aphid Myzus persicae (Sulzer) both infest a number of economically significant crops, including tomato (Solanurn lycopersicum). Although used for decades to control pests, the impact of green lacewing larvae Chrysoperla carnea (Stephens) on plant biochemistry was not investigated. Here, we used profiling methods and targeted analyses to explore the impact of the predator and herbivore(s)-predator interactions on tomato biochemistry. Each pest and pest -predator combination induced a characteristic metabolite signature in the leaf and the fruit thus, the plant exhibited a systemic response. The treatments had a stronger impact on non-volatile metabolites including abscisic acid and amino acids in the leaves in comparison with the fruits. In contrast, the various biotic factors had a greater impact on the carotenoids in the fruits. We identified volatiles such as myrcene and alpha-terpinene which were induced by pest -predator interactions but not by single species, and we demonstrated the involvement of the phytohormone abscisic acid in tritrophic interactions for the first time. More importantly, C. carnea larvae alone impacted the plant metabolome, but the predator did not appear to elicit particular defense pathways on its own. Since the presence of both C. carnea larvae and pest individuals elicited volatiles which were shown to contribute to plant defense, C. carnea larvae could therefore contribute to the reduction of pest infestation, not only by its preying activity, but also by priming responses to generalist herbivores such as T urticae and M. persicae. On the other hand, the use of C. carnea larvae alone did not impact carotenoids thus, was not prejudicial to the fruit quality. The present piece of research highlights the specific impact of predator and tritrophic interactions with green lacewing larvae, spider mites, and aphids on different components of the tomato primary and secondary metabolism for the first time, and provides cues for further in-depth studies aiming to integrate entomological approaches and plant biochemistry.}, language = {en} } @phdthesis{Errard2016, author = {Errard, Audrey}, title = {Multiple-pest infestations: impact on tomato Solanum lycopersicum biochemistry in the presence/absence of predator, and on pest biology}, school = {Universit{\"a}t Potsdam}, pages = {83}, year = {2016}, language = {en} } @phdthesis{EmantokoDwiPutra2016, author = {Emantoko Dwi Putra, Sulistyo}, title = {Placental DNA Methylation in Association with Maternal Heath and Birth Outcomes}, school = {Universit{\"a}t Potsdam}, year = {2016}, language = {en} }