@article{WirschingGrassmannEichelmannetal.2018, author = {Wirsching, Jan and Grassmann, Sophie and Eichelmann, Fabian and Harms, Laura Malin and Schenk, Matthew and Barth, Eva and Berndzen, Alide and Olalekan, Moses and Sarmini, Leen and Zuberer, Hedwig and Aleksandrova, Krasimira}, title = {Development and reliability assessment of a new quality appraisal tool for cross-sectional studies using biomarker data (BIOCROSS)}, series = {BMC Medical Research Methodology}, volume = {18}, journal = {BMC Medical Research Methodology}, publisher = {BMC}, address = {London}, issn = {1471-2288}, doi = {10.1186/s12874-018-0583-x}, pages = {8}, year = {2018}, abstract = {Background Biomarker-based analyses are commonly reported in observational epidemiological studies; however currently there are no specific study quality assessment tools to assist evaluation of conducted research. Accounting for study design and biomarker measurement would be important for deriving valid conclusions when conducting systematic data evaluation. Methods We developed a study quality assessment tool designed specifically to assess biomarker-based cross-sectional studies (BIOCROSS) and evaluated its inter-rater reliability. The tool includes 10-items covering 5 domains: 'Study rational', 'Design/Methods', 'Data analysis', 'Data interpretation' and 'Biomarker measurement', aiming to assess different quality features of biomarker cross-sectional studies. To evaluate the inter-rater reliability, 30 studies were distributed among 5 raters and intraclass correlation coefficients (ICC-s) were derived from respective ratings. Results The estimated overall ICC between the 5 raters was 0.57 (95\% Confidence Interval (CI): 0.38-0.74) indicating a good inter-rater reliability. The ICC-s ranged from 0.11 (95\% CI: 0.01-0.27) for the domain 'Study rational' to 0.56 (95\% CI: 0.40-0.72) for the domain 'Data interpretation'. Conclusion BIOCROSS is a new study quality assessment tool suitable for evaluation of reporting quality from cross-sectional epidemiological studies employing biomarker data. The tool proved to be reliable for use by biomedical scientists with diverse backgrounds and could facilitate comprehensive review of biomarker studies in human research.}, language = {en} } @article{WernoWilhelmiKuropkaetal.2018, author = {Werno, Martin Witold and Wilhelmi, Ilka and Kuropka, Benno and Ebert, Franziska and Freund, Christian and Sch{\"u}rmann, Annette}, title = {The GTPase ARFRP1 affects lipid droplet protein composition and triglyceride release from intracellular storage of intestinal Caco-2 cells}, series = {Biochemical and biophysical research communications}, volume = {506}, journal = {Biochemical and biophysical research communications}, number = {1}, publisher = {Elsevier}, address = {San Diego}, issn = {0006-291X}, doi = {10.1016/j.bbrc.2018.10.092}, pages = {259 -- 265}, year = {2018}, abstract = {Intestinal release of dietary triglycerides via chylomicrons is the major contributor to elevated postprandial triglyceride levels. Dietary lipids can be transiently stored in cytosolic lipid droplets (LDs) located in intestinal enterocytes for later release. ADP ribosylation factor-related protein 1 (ARFRP1) participates in processes of LD growth in adipocytes and in lipidation of lipoproteins in liver and intestine. This study aims to explore the impact of ARFRP1 on LD organization and its interplay with chylomicron-mediated triglyceride release in intestinal-like Caco-2 cells. Suppression of Arfrp1 reduced release of intracellularly derived triglycerides (0.69-fold) and increased the abundance of transitional endoplasmic reticulum ATPase TERA/VCP, fatty acid synthase-associated factor 2 (FAF2) and perilipin 2 (Plin2) at the LD surface. Furthermore, TERA/VCP and FAF2 co-occurred more frequently with ATGL at LDs, suggesting a reduced adipocyte triglyceride lipase (ATGL)-mediated lipolysis. Accordingly, inhibition of lipolysis reduced lipid release from intracellular storage pools by the same magnitude as Arfrp1 depletion. Thus, the lack of Arfrp1 increases the abundance of lipolysis-modulating enzymes TERA/VCP, FAF2 and Plin2 at LDs, which might decrease lipolysis and reduce availability of fatty acids for triglyceride synthesis and their release via chylomicrons. (C) 2018 The Authors. Published by Elsevier Inc.}, language = {en} } @phdthesis{Weiss2018, author = {Weiß, Stefanie}, title = {Contribution of bacterially synthesized folate vitamers to folate status and impact on crohn's Disease}, school = {Universit{\"a}t Potsdam}, pages = {148}, year = {2018}, language = {en} } @phdthesis{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} } @article{vonWebskyHasanReichetzederetal.2018, author = {von Websky, Karoline and Hasan, Ahmed Abdallah Abdalrahman Mohamed and Reichetzeder, Christoph and Tsuprykov, Oleg and Hocher, Berthold}, title = {Impact of vitamin D on pregnancy-related disorders and on offspring outcome}, series = {The Journal of Steroid Biochemistry and Molecular Biology}, volume = {180}, journal = {The Journal of Steroid Biochemistry and Molecular Biology}, publisher = {Elsevier}, address = {Oxford}, issn = {0960-0760}, doi = {10.1016/j.jsbmb.2017.11.008}, pages = {51 -- 64}, year = {2018}, abstract = {Observational studies from all over the world continue to find high prevalence rates of vitamin D insufficiency and deficiency in many populations, including pregnant women. Beyond its classical function as a regulator of calcium and phosphate metabolism, vitamin D elicits numerous effects in the human body. Current evidence highlights a vital role of vitamin D in mammalian gestation. During pregnancy, adaptations in maternal vitamin D metabolism lead to a physiologic increase of vitamin D levels, mainly because of an increased renal production, although other potential sources like the placenta are being discussed. A sufficient supply of mother and child with calcium and vitamin D during pregnancy ensures a healthy bone development of the fetus, whereas lack of either of these nutrients can lead to the development of rickets in the child. Moreover, vitamin D insufficiency during pregnancy has consistently been associated with adverse maternal and neonatal pregnancy outcomes. In multitudinous studies, low maternal vitamin D status was associated with a higher risk for pre-eclampsia, gestational diabetes mellitus and other gestational diseases. Likewise, several negative consequences for the fetus have been reported, including fetal growth restriction, increased risk of preterm birth and a changed susceptibility for later-life diseases. However, study results are diverging and causality has not been proven so far. Meta-analyses on the relationship between maternal vitamin D status and pregnancy outcomes revealed a wide heterogeneity of studied populations and the applied methodology in vitamin D assessment. Until today, clinical guidelines for supplementation cannot be based on high-quality evidence and it is not clear if the required intake for pregnant women differs from non-pregnant women. Long-term safety data of vitamin D supplementation in pregnant women has not been established and overdosing of vitamin D might have unfavorable effects, especially in mothers and newborns with mutations of genes involved in vitamin D metabolism. Reliable data from large observational and interventional randomized control trials are urgently needed as a basis for any detailed and safe recommendations for supplementation in the general population and, most importantly, in pregnant women. This is of utmost importance, as ensuring a sufficient vitamin D-supply of mother and child implies a great potential for the prevention of birth complications and development of diseases.}, language = {en} } @article{VogelKamitzHallahanetal.2018, author = {Vogel, Heike and Kamitz, Anne and Hallahan, Nicole and Lebek, Sandra and Schallschmidt, Tanja and Jonas, Wenke and J{\"a}hnert, Markus and Gottmann, Pascal and Zellner, Lisa and Kanzleiter, Timo and Damen, Mareike and Altenhofen, Delsi and Burkhardt, Ralph and Renner, Simone and Dahlhoff, Maik and Wolf, Eckhard and M{\"u}ller, Timo Dirk and Bl{\"u}her, Matthias and Joost, Hans-Georg and Chadt, Alexandra and Al-Hasani, Hadi and Sch{\"u}rmann, Annette}, title = {A collective diabetes cross in combination with a computational framework to dissect the genetics of human obesity and Type 2 diabetes}, series = {Human molecular genetics}, volume = {27}, journal = {Human molecular genetics}, number = {17}, publisher = {Oxford Univ. Press}, address = {Oxford}, issn = {0964-6906}, doi = {10.1093/hmg/ddy217}, pages = {3099 -- 3112}, year = {2018}, abstract = {To explore the genetic determinants of obesity and Type 2 diabetes (T2D), the German Center for Diabetes Research (DZD) conducted crossbreedings of the obese and diabetes-prone New Zealand Obese mouse strain with four different lean strains (B6, DBA, C3H, 129P2) that vary in their susceptibility to develop T2D. Genome-wide linkage analyses localized more than 290 quantitative trait loci (QTL) for obesity, 190 QTL for diabetes-related traits and 100 QTL for plasma metabolites in the out-cross populations. A computational framework was developed that allowed to refine critical regions and to nominate a small number of candidate genes by integrating reciprocal haplotype mapping and transcriptome data. The efficiency of the complex procedure was demonstrated for one obesity QTL. The genomic interval of 35 Mb with 502 annotated candidate genes was narrowed down to six candidates. Accordingly, congenic mice retained the obesity phenotype owing to an interval that contains three of the six candidate genes. Among these the phospholipase PLA2G4A exhibited an elevated expression in adipose tissue of obese human subjects and is therefore a critical regulator of the obesity locus. Together, our broad and complex approach demonstrates that combined- and comparative-cross analysis exhibits improved mapping resolution and represents a valid tool for the identification of disease genes.}, language = {en} } @misc{UhligGehreKammereretal.2018, author = {Uhlig, Katja and Gehre, Christian P. and Kammerer, Sarah and K{\"u}pper, Jan-Heiner and Coleman, Charles Dominic and P{\"u}schel, Gerhard Paul and Duschl, Claus}, title = {Real-time monitoring of oxygen consumption of hepatocytes in a microbioreactor}, series = {Toxicology letters}, volume = {295}, journal = {Toxicology letters}, publisher = {Elsevier}, address = {Clare}, issn = {0378-4274}, doi = {10.1016/j.toxlet.2018.06.652}, pages = {S115 -- S115}, year = {2018}, language = {en} } @article{TsuprykovBuseSkobloetal.2018, author = {Tsuprykov, Oleg and Buse, Claudia and Skoblo, Roman and Haq, Afrozul and Hocher, Berthold}, title = {Reference intervals for measured and calculated free 25-hydroxyvitamin D in normal pregnancy}, series = {The Journal of Steroid Biochemistry and Molecular Biology}, volume = {181}, journal = {The Journal of Steroid Biochemistry and Molecular Biology}, publisher = {Elsevier}, address = {Oxford}, issn = {0960-0760}, doi = {10.1016/j.jsbmb.2018.03.005}, pages = {80 -- 87}, year = {2018}, abstract = {The determination of free 25-hydroxyvitamin D (25(OH)D) as compared to the analysis of total 25-hydroxyvitamin D might reflect better the vitamin D status during pregnancy, since vitamin D-binding protein (DBP) concentrations increase throughout pregnancy and the vast majority of 25(OH)D is tightly bound to DBP thus strongly influencing total 25(OH)D. The concentration of the biologically active free 25(OH)D - on the other hand - is much less dependent on the DBP concentrations. The study was conducted in May-June 2016 in 368 Caucasian pregnant healthy women - residents of Northeastern Germany. Free 25(OH)D was either measured directly by commercial ELISA kit or assessed by calculation via total 25(OH)D, DBP, and albumin serum concentrations. Regardless of the detection method, free 25(OH)D lowers in the 3rd trimester comparing to the 1st trimester (by 12\% and 21\%, p < 0.05 and p < 0.001, for measured and calculated free 25(OH)D, respectively), whereas total 25(OH)D was not decreased in late pregnancy. DBP rises with gestational age. Total 25(OH)D was not correlated with serum calcium (p = 0.251), whereas free 25(OH)D was significantly (p = 0.007 for measured free 25(OH)D and p < 0.001 for calculated free 25(OH)D) positively correlated with calcium. All 25(OH) D isoforms were significantly negatively correlated with bone-specific alkaline phosphatase (BSAP), however the correlation strength was the lowest with total 25(OH)D (rho = -0.108, p = 0.038), whereas both measured and calculated free 25(OH)D revealed better associations with BSAP (rho = -0.203 and rho = -0.211 for measured and calculated free 25(OH)D, respectively, p < 0.001 for both). We established pregnancy trimester specific reference intervals for free measured and calculated 25(OH)D and DBP. Both measured and calculated free 25(OH)D showed better correlations with parameters of the endocrine vitamin D system (calcium and BSAP). Both ways of measuring free 25(OH)D in pregnant women are suitable as novel laboratory parameter for vitamin D status monitoring during human pregnancy and might replace in the future the routine total 25(OH)D assessment.}, language = {en} } @article{TaoSuXuetal.2018, author = {Tao, Ting and Su, Qiongli and Xu, Simeng and Deng, Jun and Zhou, Sichun and Zhuang, Yu and Huang, Yanjun and He, Caimei and He, Shanping and Peng, Mei and Hocher, Berthold and Yang, Xiaoping}, title = {Down-regulation of PKM2 decreases FASN expression in bladder cancer cells through AKT/mTOR/SREBP-1c axis}, series = {Journal of cellular physiology}, volume = {234}, journal = {Journal of cellular physiology}, number = {3}, publisher = {Wiley}, address = {Hoboken}, issn = {0021-9541}, doi = {10.1002/jcp.27129}, pages = {3088 -- 3104}, year = {2018}, abstract = {Fatty acid synthase (FASN) catalyzing the terminal steps in the de novo biogenesis of fatty acids is correlated with low survival and high disease recurrence in patients with bladder cancer. Pyruvate kinase M2 (PKM2) regulates the final step of glycolysis levels and provides a growth advantage to tumors. However, it is unclear whether the change of PKM2 has an effect on FASN and what is the mechanisms underlying. Here we describe a novel function of PKM2 in control of lipid metabolism by mediating transcriptional activation of FASN, showing the reduced expression of sterol regulatory element binding protein 1c (SREBP-1c). We first discovered that PKM2 physically interacts with the SREBP-1c using biochemical approaches, and downregulation of PKM2 reduced the expression of SREBP-1c by inactivating the AKT/mTOR signaling pathway, which in turn directly suppressed the transcription of major lipogenic genes FASN to reduce tumor growths. Furthermore, either PKM2 inhibitor-Shikonin or FASN inhibitor-TVB-3166 alone induced a strong antiproliferative and anticolony forming effect in bladder cancer cell line. The combination of both inhibitors exhibits a super synergistic effect on blocking the bladder cancer cells growth. It provides a new target and scientific basis for the treatment of bladder cancer.}, language = {en} } @misc{Steinberg2018, author = {Steinberg, Pablo}, title = {Only one Component of a holistic Nutrition Policy}, series = {Fleischwirtschaft}, volume = {98}, journal = {Fleischwirtschaft}, number = {11}, publisher = {Deutscher Fachverlag GmbH}, address = {Frankfurt am Main}, issn = {0015-363X}, pages = {8 -- 9}, year = {2018}, language = {de} }