TY  - JOUR
A1  - Zebger-Gong, Hong
A1  - Mueller, Dominik
A1  - Diercke, Michaela
A1  - Haffner, Dieter
A1  - Hocher, Berthold
A1  - Verberckmoes, Steven
A1  - Schmidt, Sven
A1  - D'Haese, Patrick C.
A1  - Querfeld, Uwe
T1  - 1,25-Dihydroxyvitamin D-3-induced aortic calcifications in experimental uremia: up-regulation of osteoblast markers, calcium-transporting proteins and osterix
JF  - Journal of hypertension
N2  - Background and objective Whether treatment with vitamin D receptor activators contributes to cardiovascular disease in patients with chronic kidney disease is a matter of debate. We studied mechanisms involved in vitamin D-related vascular calcifications in vivo and in vitro.
 Methods Aortic calcifications were induced in subtotally nephrectomized (SNX) rats by treatment with a high dose (0.25 mu g/kg per day) of 1,25-dihydroxyvitamin D-3 (calcitriol) given for 6 weeks. Likewise, primary rat vascular smooth muscle cells (VSMCs) were incubated with calcitriol at concentrations ranging from 10(-11) to 10(-7) mol/l. Immunohistochemistry revealed that the aortic expression of osteopontin, osteocalcin and bone sialoprotein was significantly increased in calcitriol-treated SNX rats compared to untreated SNX controls. In addition, aortic expression of the transient receptor potential vanilloid calcium channel 6 (TRPV6) and calbindin D9k was significantly up-regulated by treatment with calcitriol. Furthermore, calcitriol significantly increased expression of the osteogenic transcription factor osterix. In-vitro studies showed similar results, confirming that these effects could be attributed to treatment with calcitriol.
 Conclusions High-dose calcitriol treatment induces an osteoblastic phenotype in VSMC both in SNX rats and in vitro, associated with up-regulation of proteins regulating mineralization and calcium transport, and of the osteogenic transcription factor osterix.
KW  - calbindin D9k
KW  - calcitriol
KW  - calcium transport
KW  - osteoblast
KW  - osterix
KW  - TRPV5
KW  - TRPV6
KW  - vascular calcification
Y1  - 2011
U6  - https://doi.org/10.1097/HJH.0b013e328340aa30
SN  - 0263-6352
VL  - 29
IS  - 2
SP  - 339
EP  - 348
PB  - Lippincott Williams & Wilkins
CY  - Philadelphia
ER  - 
TY  - JOUR
A1  - Wiesner-Reinhold, Melanie
A1  - Barknowitz, Gitte
A1  - Florian, Simone
A1  - Mewis, Inga
A1  - Schumacher, Fabian
A1  - Schreiner, Monika
A1  - Glatt, Hansruedi
T1  - 1-Methoxy-3-indolylmethyl DNA adducts in six tissues, and blood protein adducts, in mice under pak choi diet: time course and persistence
JF  - Archives of toxicology : official journal of EUROTOX
N2  - We previously showed that purified 1-methoxy-3-indolylmethyl (1-MIM) glucosinolate, a secondary plant metabolite in Brassica species, is mutagenic in various in vitro systems and forms DNA and protein adducts in mouse models. In the present study, we administered 1-MIM glucosinolate in a natural matrix to mice, by feeding a diet containing pak choi powder and extract. Groups of animals were killed after 1, 2, 4 and 8 days of pak choi diet, directly or, in the case of the 8-day treatment, after 0, 8 and 16 days of recovery with pak choi-free diet. DNA adducts [N-2-(1-MIM)-dG, N-6-(1-MIM)-dA] in six tissues, as well as protein adducts [tau N-(1-MIM)-His] in serum albumin (SA) and hemoglobin (Hb) were determined using UPLC-MS/MS with isotopically labeled internal standards. None of the samples from the 12 control animals under standard diet contained any 1-MIM adducts. All groups receiving pak choi diet showed DNA adducts in all six tissues (exception: lung of mice treated for a single day) as well as SA and Hb adducts. During the feeding period, all adduct levels continuously increased until day 8 (in the jejunum until day 4). During the 14-day recovery period, N-2-(1-MIM)-dG in liver, kidney, lung, jejunum, cecum and colon decreased to 52, 41, 59, 11, 7 and 2%, respectively, of the peak level. The time course of N-6-(1-MIM)-dA was similar. Immunohistochemical analyses indicated that cell turnover is a major mechanism of DNA adduct elimination in the intestine. In the same recovery period, protein adducts decreased more rapidly in SA than in Hb, to 0.7 and 37%, respectively, of the peak level, consistent with the differential turnover of these proteins. In conclusion, the pak choi diet lead to the formation of high levels of adducts in mice. Cell and protein turnover was a major mechanism of adduct elimination, at least in gut and blood.
KW  - 1-Methoxy-3-indolylmethyl glucosinolate
KW  - Neoglucobrassicin
KW  - DNA adducts
KW  - Blood protein adducts
KW  - Pak choi
Y1  - 2019
U6  - https://doi.org/10.1007/s00204-019-02452-3
SN  - 0340-5761
SN  - 1432-0738
VL  - 93
IS  - 6
SP  - 1515
EP  - 1527
PB  - Springer
CY  - Heidelberg
ER  - 
TY  - THES
A1  - Bendadani, Carolin
T1  - 1-Methylpyren: Biotransformation und Gentoxizität
Y1  - 2015
ER  - 
TY  - JOUR
A1  - Sammoud, Senda
A1  - Nevill, Alan Michael
A1  - Negra, Yassine
A1  - Bouguezzi, Raja
A1  - Chaabene, Helmi
A1  - Hachana, Younes
T1  - 100-m Breaststroke Swimming Performance in Youth Swimmers
BT  - the predictive value of anthropometrics
JF  - Pediatric exercise science
N2  - This study aimed to estimate the optimal body size, limb segment length, and girth or breadth ratios of 100-m breaststroke performance in youth swimmers. In total, 59 swimmers [male: n= 39, age = 11.5 (1.3) y; female: n= 20, age = 12.0 (1.0) y] participated in this study. To identify size/shape characteristics associated with 100-m breaststroke swimming performance, we computed a multiplicative allometric log-linear regression model, which was refined using backward elimination. Results showed that the 100-m breaststroke performance revealed a significant negative association with fat mass and a significant positive association with the segment length ratio (arm ratio = hand length/forearm length) and limb girth ratio (girth ratio = forearm girth/wrist girth). In addition, leg length, biacromial breadth, and biiliocristal breadth revealed significant positive associations with the 100-m breaststroke performance. However, height and body mass did not contribute to the model, suggesting that the advantage of longer levers was limb-specific rather than a general whole-body advantage. In fact, it is only by adopting multiplicative allometric models that the previously mentioned ratios could have been derived. These results highlighted the importance of considering anthropometric characteristics of youth breaststroke swimmers for talent identification and/or athlete monitoring purposes. In addition, these findings may assist orienting swimmers to the appropriate stroke based on their anthropometric characteristics.
KW  - allometric model
KW  - maturity
KW  - limb lengths
KW  - girths and breadths
Y1  - 2018
U6  - https://doi.org/10.1123/pes.2017-0220
SN  - 0899-8493
SN  - 1543-2920
VL  - 30
IS  - 3
SP  - 393
EP  - 401
PB  - Human Kinetics Publ.
CY  - Champaign
ER  - 
TY  - THES
A1  - Hollnagel, Heli Miriam
T1  - 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridin : Bioaktivierung und DNA-Adduktbildung in V79-Zelllinien und verschiedenen Rattengeweben
Y1  - 2004
ER  - 
TY  - THES
A1  - Sommer, Yasmin
T1  - 5-(Hydroxymethyl)-2-furfural: Sulfokonjugation und ihre Bedeutung für die Genotoxizität
Y1  - 2006
ER  - 
TY  - JOUR
A1  - Christakoudi, Sofa
A1  - Tsilidis, Konstantinos K.
A1  - Muller, David C.
A1  - Freisling, Heinz
A1  - Weiderpass, Elisabete
A1  - Overvad, Kim
A1  - Söderberg, Stefan
A1  - Häggström, Christel
A1  - Pischon, Tobias
A1  - Dahm, Christina C.
A1  - Zhang, Jie
A1  - Tjønneland, Anne
A1  - Schulze, Matthias Bernd
T1  - A Body Shape Index (ABSI) achieves better mortality risk stratification than alternative indices of abdominal obesity: results from a large European cohort
JF  - Scientific Reports
N2  - Abdominal and general adiposity are independently associated with mortality, but there is no consensus on how best to assess abdominal adiposity. We compared the ability of alternative waist indices to complement body mass index (BMI) when assessing all-cause mortality. We used data from 352,985 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) and Cox proportional hazards models adjusted for other risk factors. During a mean follow-up of 16.1 years, 38,178 participants died. Combining in one model BMI and a strongly correlated waist index altered the association patterns with mortality, to a predominantly negative association for BMI and a stronger positive association for the waist index, while combining BMI with the uncorrelated A Body Shape Index (ABSI) preserved the association patterns. Sex-specific cohort-wide quartiles of waist indices correlated with BMI could not separate high-risk from low-risk individuals within underweight (BMI<18.5 kg/m(2)) or obese (BMI30 kg/m(2)) categories, while the highest quartile of ABSI separated 18-39% of the individuals within each BMI category, which had 22-55% higher risk of death. In conclusion, only a waist index independent of BMI by design, such as ABSI, complements BMI and enables efficient risk stratification, which could facilitate personalisation of screening, treatment and monitoring.
KW  - all-cause mortality
KW  - anthropometric measures
KW  - mass index
KW  - overweight
KW  - cancer
KW  - prediction
KW  - adiposity
KW  - size
Y1  - 2020
VL  - 10
IS  - 1
PB  - Springer Nature
CY  - Berlin
ER  - 
TY  - GEN
A1  - Christakoudi, Sofa
A1  - Tsilidis, Konstantinos K.
A1  - Muller, David C.
A1  - Freisling, Heinz
A1  - Weiderpass, Elisabete
A1  - Overvad, Kim
A1  - Söderberg, Stefan
A1  - Häggström, Christel
A1  - Pischon, Tobias
A1  - Dahm, Christina C.
A1  - Zhang, Jie
A1  - Tjønneland, Anne
A1  - Schulze, Matthias Bernd
T1  - A Body Shape Index (ABSI) achieves better mortality risk stratification than alternative indices of abdominal obesity: results from a large European cohort
T2  - Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe
N2  - Abdominal and general adiposity are independently associated with mortality, but there is no consensus on how best to assess abdominal adiposity. We compared the ability of alternative waist indices to complement body mass index (BMI) when assessing all-cause mortality. We used data from 352,985 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) and Cox proportional hazards models adjusted for other risk factors. During a mean follow-up of 16.1 years, 38,178 participants died. Combining in one model BMI and a strongly correlated waist index altered the association patterns with mortality, to a predominantly negative association for BMI and a stronger positive association for the waist index, while combining BMI with the uncorrelated A Body Shape Index (ABSI) preserved the association patterns. Sex-specific cohort-wide quartiles of waist indices correlated with BMI could not separate high-risk from low-risk individuals within underweight (BMI<18.5 kg/m(2)) or obese (BMI30 kg/m(2)) categories, while the highest quartile of ABSI separated 18-39% of the individuals within each BMI category, which had 22-55% higher risk of death. In conclusion, only a waist index independent of BMI by design, such as ABSI, complements BMI and enables efficient risk stratification, which could facilitate personalisation of screening, treatment and monitoring.
T3  - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 1200 
KW  - all-cause mortality
KW  - anthropometric measures
KW  - mass index
KW  - overweight
KW  - cancer
KW  - prediction
KW  - adiposity
KW  - size
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-525827
SN  - 1866-8372
IS  - 1
ER  - 
TY  - JOUR
A1  - Vogel, Heike
A1  - Kamitz, Anne
A1  - Hallahan, Nicole
A1  - Lebek, Sandra
A1  - Schallschmidt, Tanja
A1  - Jonas, Wenke
A1  - Jähnert, Markus
A1  - Gottmann, Pascal
A1  - Zellner, Lisa
A1  - Kanzleiter, Timo
A1  - Damen, Mareike
A1  - Altenhofen, Delsi
A1  - Burkhardt, Ralph
A1  - Renner, Simone
A1  - Dahlhoff, Maik
A1  - Wolf, Eckhard
A1  - Müller, Timo Dirk
A1  - Blüher, Matthias
A1  - Joost, Hans-Georg
A1  - Chadt, Alexandra
A1  - Al-Hasani, Hadi
A1  - Schürmann, Annette
T1  - A collective diabetes cross in combination with a computational framework to dissect the genetics of human obesity and Type 2 diabetes
JF  - Human molecular genetics
N2  - 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.
Y1  - 2018
U6  - https://doi.org/10.1093/hmg/ddy217
SN  - 0964-6906
SN  - 1460-2083
VL  - 27
IS  - 17
SP  - 3099
EP  - 3112
PB  - Oxford Univ. Press
CY  - Oxford
ER  - 
TY  - JOUR
A1  - Hoie, Lars H.
A1  - Morgenstern, E. C. A.
A1  - Grünwald, Jörg
A1  - Graubaum, Hans-Joachim
A1  - Busch, R.
A1  - Luder, W.
A1  - Zunft, Hans-Joachim Franz
T1  - A double-blind placebo-controlled clinical trial compares the cholesterollowering effects of two different soy protein preparations in hypercholesterolemic subjects
N2  - Background Soy protein is effective in lowering plasma cholesterol, LDL cholesterol and triglyceride concentrations. It has not been conclusively answered, whether and to what extent other soy constituents may also contribute to this effect. Objective To investigate the change in blood lipid levels after application of two soy-based supplements containing soy protein either without (SuproSoy(R)) or with (Abacor(R)) soy fiber and phospholipids in a randomized placebo-controlled triple-armed study. Methods 121 hypercholesterolemic adults ( 66 females, 55 males) were recruited and randomly assigned to one of three treatments. Over 8 weeks they received daily either 25 g soy protein ( as a component of the supplements Abacor(R) or SuproSoy(R)) or 25 g milk protein ( as a component of placebo). Serum lipids were measured at baseline and after 4, 6 and 8 weeks. Results After 8 weeks of supplementation total cholesterol levels were reduced by 8.0 +/- 9.6% (Abacor(R)) and 3.4 +/- 8.3% (SuproSoy(R)); LDL cholesterol levels by 9.7 +/- 11.7% ( Abacor(R)) and 5.4 +/- 11.6% ( SuproSoy(R)); and Apolipoprotein B levels by 6.9 +/- 14.6% (Abacor(R)) and 4.0 +/- 12.4 % (SuproSoy(R)). Serum levels of HDL cholesterol and triglycerides remained unchanged. Conclusions A preparation combining isolated soy protein with soy fibers and phospholipids showed twice the lipid-lowering effect of a preparation containing isolated soy protein alone. Therefore, such soy-based supplements can be useful in reducing the cardiovascular risk
Y1  - 2005
SN  - 1436-6207
ER  - 
TY  - JOUR
A1  - Li, Jian
A1  - Chen, You-Peng
A1  - Wang, Zi-Neng
A1  - Liu, Tie-Bin
A1  - Chen, Dan
A1  - Dong, Yun-Peng
A1  - Hocher, Berthold
T1  - A functional fetal HSD11B2[CA]n microsatellite polymorphism is associated with maternal serum cortisol concentrations in pregnant women
JF  - Kidney & blood pressure research : official organ of the Gesellschaft für Nephrologie
N2  - Background/Aims: Cortisol plays an important role during pregnancy. It controls maternal glucose metabolism and fetal development. Cortisol metabolism is partially controlled by the 11b-HSD2. This enzyme is expressed in the kidney and human placenta. The activity of the enzyme is partially controlled by functional polymorphisms: the HSD11B2[CA]n microsatellite polymorphism. The impact of this functional gene polymorphism on cortisol metabolism and potential effects on the newborn's is unknown so far. Methods: In the current prospective birth cohort study in southern Asia, we analyzed the association of the HSD11B2[CA]n microsatellite polymorphisms in 187 mothers and their newborn's on maternal and newborn's serum cortisol concentrations. Results: Using multivariable regression analyses considering known confounding ( gestational age, newborn's gender, the labor uterine contraction states and the timing during the day of blood taking), we showed that the fetal HSD11B2[CA]n microsatellite polymorphisms in the first intron was related to maternal cortisol concentration ( R2=0.26, B=96.27, p=0.007), whereas as the newborn's cortisol concentrations were independent of fetal and maternal HSD11B2[CA] n microsatellite polymorphism. Conclusions: Our study showed for the first time that the fetal HSD11B2[CA]n microsatellite polymorphism of the HSD11B2 gene in healthy uncomplicated human pregnancy is associated with maternal cortisol concentration. This indicates that fetal genes controlling cortisol metabolism may affect maternal cortisol concentration and hence physiology in healthy pregnant women.
KW  - Pregnancy
KW  - Placenta
KW  - Cortisol vertical bar metabolism
KW  - 11 beta-hydroxysteroid dehydrogenase 2
KW  - HSD11B2[CA]n polymorphism
Y1  - 2013
U6  - https://doi.org/10.1159/000355761
SN  - 1420-4096
SN  - 1423-0143
VL  - 38
IS  - 1
SP  - 132
EP  - 141
PB  - Karger
CY  - Basel
ER  - 
TY  - JOUR
A1  - Collenburg, Lena
A1  - Walter, Tim
A1  - Burgert, Anne
A1  - Mueller, Nora
A1  - Seibel, Juergen
A1  - Japtok, Lukasz
A1  - Kleuser, Burkhard
A1  - Sauer, Markus
A1  - Schneider-Schaulies, Sibylle
T1  - A Functionalized Sphingolipid Analogue for Studying Redistribution during Activation in Living T Cells
JF  - The journal of immunology
N2  - Sphingolipids are major components of the plasma membrane. In particular, ceramide serves as an essential building hub for complex sphingolipids, but also as an organizer of membrane domains segregating receptors and signalosomes. Sphingomyelin breakdown as a result of sphingomyelinase activation after ligation of a variety of receptors is the predominant source of ceramides released at the plasma membrane. This especially applies to T lymphocytes where formation of ceramide-enriched membrane microdomains modulates TCR signaling. Because ceramide release and redistribution occur very rapidly in response to receptor ligation, novel tools to further study these processes in living T cells are urgently needed. To meet this demand, we synthesized nontoxic, azido-functionalized ceramides allowing for bio-orthogonal click-reactions to fluorescently label incorporated ceramides, and thus investigate formation of ceramide-enriched domains. Azido-functionalized C-6-ceramides were incorporated into and localized within plasma membrane microdomains and proximal vesicles in T cells. They segregated into clusters after TCR, and especially CD28 ligation, indicating efficient sorting into plasma membrane domains associated with T cell activation; this was abolished upon sphingomyelinase inhibition. Importantly, T cell activation was not abrogated upon incorporation of the compound, which was efficiently excluded from the immune synapse center as has previously been seen in Ab-based studies using fixed cells. Therefore, the functionalized ceramides are novel, highly potent tools to study the subcellular redistribution of ceramides in the course of T cell activation. Moreover, they will certainly also be generally applicable to studies addressing rapid stimulation-mediated ceramide release in living cells.
Y1  - 2016
U6  - https://doi.org/10.4049/jimmunol.1502447
SN  - 0022-1767
SN  - 1550-6606
VL  - 196
SP  - 3951
EP  - 3962
PB  - American Assoc. of Immunologists
CY  - Bethesda
ER  - 
TY  - GEN
A1  - Scholtka, Bettina
A1  - Schneider, Mandy
A1  - Melcher, Ralph
A1  - Katzenberger, Tiemo
A1  - Friedrich, Daniela
A1  - Berghof-Jäger, Kornelia
A1  - Scheppach, Wolfgang
A1  - Steinberg, Pablo
T1  - A gene marker panel covering the Wnt and the Ras-Raf-MEK-MAPK signalling pathways allows to detect gene mutations in 80% of early (UICC I) colon cancer stages in humans
N2  - Background: Very recently a gene marker panel that allows the mutational analysis of APC, CTNNB1, B-RAF and K-RAS was conceived. The aim of the present study was to use the 4-gene marker panel covering the Wnt and Ras-Raf-MEK-MAPK signalling pathways to determine the percentage of sporadic colorectal carcinomas (CRC) carrying at least one of the four above-mentioned genes in a mutated form alone and/or in combination with microsatellite instability (MSI) and to compare the sensitivity of the gene marker panel used in this study with that of gene marker panels previously reported in the scientific literature. Methods: CTNNB1 and B-RAF were screened by PCR-single-strand conformation polymorphism analysis and K-RAS gene mutations by restriction fragment length polymorphism analysis. For the mutational analysis of the APC gene mutation cluster region (codons 1243–1567) direct DNA sequencing was performed. The U.S. National Cancer Institute microsatellite panel (BAT25, BAT26, D2S123, D5S346 and D17S250) was used for MSI analysis. Results: It could be shown that about 80% of early stage CRC (UICC stages I and II) and over 90% of CRC in the UICC stage IV carried at least one mutated gene and/or showed MSI. No significant increase in the gene mutation frequencies could be determined when comparing tumours in the UICC stage I with those in UICC stage IV. Conclusions: When compared with previously published gene marker panels the 4-gene marker panel used in the present study shows an excellent performance, allowing to detect genetic alterations in 80–90% of human sporadic CRC samples analyzed.
T3  - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - paper 120 
KW  - Colorectal carcinomas
KW  - K-RAS
KW  - Microsatellite instability
KW  - Oncogenes
KW  - Tumour suppressor genes
Y1  - 2009
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus-44587
ER  - 
TY  - JOUR
A1  - Kühnel, Dana
A1  - Steinberg, Pablo
A1  - Scholtka, Bettina
T1  - A human-relevant dose of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PHIP) can induce precancerous lesions in rat intestine after 6 months of exposure
Y1  - 2004
SN  - 0028-1298
ER  - 
TY  - JOUR
A1  - Winkelbeiner, Nicola Lisa
A1  - Wandt, Viktoria Klara Veronika
A1  - Ebert, Franziska
A1  - Lossow, Kristina
A1  - Bankoglu, Ezgi E.
A1  - Martin, Maximilian
A1  - Mangerich, Aswin
A1  - Stopper, Helga
A1  - Bornhorst, Julia
A1  - Kipp, Anna Patricia
A1  - Schwerdtle, Tanja
T1  - A Multi-Endpoint Approach to Base Excision Repair Incision Activity Augmented by PARylation and DNA Damage Levels in Mice
BT  - Impact of Sex and Age
JF  - International Journal of Molecular Sciences
N2  - Investigation of processes that contribute to the maintenance of genomic stability is one crucial factor in the attempt to understand mechanisms that facilitate ageing. The DNA damage response (DDR) and DNA repair mechanisms are crucial to safeguard the integrity of DNA and to prevent accumulation of persistent DNA damage. Among them, base excision repair (BER) plays a decisive role. BER is the major repair pathway for small oxidative base modifications and apurinic/apyrimidinic (AP) sites. We established a highly sensitive non-radioactive assay to measure BER incision activity in murine liver samples. Incision activity can be assessed towards the three DNA lesions 8-oxo-2’-deoxyguanosine (8-oxodG), 5-hydroxy-2’-deoxyuracil (5-OHdU), and an AP site analogue. We applied the established assay to murine livers of adult and old mice of both sexes. Furthermore, poly(ADP-ribosyl)ation (PARylation) was assessed, which is an important determinant in DDR and BER. Additionally, DNA damage levels were measured to examine the overall damage levels. No impact of ageing on the investigated endpoints in liver tissue were found. However, animal sex seems to be a significant impact factor, as evident by sex-dependent alterations in all endpoints investigated. Moreover, our results revealed interrelationships between the investigated endpoints indicative for the synergetic mode of action of the cellular DNA integrity maintaining machinery.
KW  - maintenance of genomic integrity
KW  - ageing
KW  - sex
KW  - DNA damage
KW  - base excision repair (incision activity)
KW  - DNA damage response
KW  - poly(ADP-ribosyl)ation
KW  - liver
Y1  - 2020
U6  - https://doi.org/10.3390/ijms21186600
SN  - 1422-0067
VL  - 21
IS  - 18
PB  - Molecular Diversity Preservation International
CY  - Basel
ER  - 
TY  - GEN
A1  - Winkelbeiner, Nicola Lisa
A1  - Wandt, Viktoria Klara Veronika
A1  - Ebert, Franziska
A1  - Lossow, Kristina
A1  - Bankoglu, Ezgi E.
A1  - Martin, Maximilian
A1  - Mangerich, Aswin
A1  - Stopper, Helga
A1  - Bornhorst, Julia
A1  - Kipp, Anna Patricia
A1  - Schwerdtle, Tanja
T1  - A Multi-Endpoint Approach to Base Excision Repair Incision Activity Augmented by PARylation and DNA Damage Levels in Mice
BT  - Impact of Sex and Age
T2  - Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe
N2  - Investigation of processes that contribute to the maintenance of genomic stability is one crucial factor in the attempt to understand mechanisms that facilitate ageing. The DNA damage response (DDR) and DNA repair mechanisms are crucial to safeguard the integrity of DNA and to prevent accumulation of persistent DNA damage. Among them, base excision repair (BER) plays a decisive role. BER is the major repair pathway for small oxidative base modifications and apurinic/apyrimidinic (AP) sites. We established a highly sensitive non-radioactive assay to measure BER incision activity in murine liver samples. Incision activity can be assessed towards the three DNA lesions 8-oxo-2’-deoxyguanosine (8-oxodG), 5-hydroxy-2’-deoxyuracil (5-OHdU), and an AP site analogue. We applied the established assay to murine livers of adult and old mice of both sexes. Furthermore, poly(ADP-ribosyl)ation (PARylation) was assessed, which is an important determinant in DDR and BER. Additionally, DNA damage levels were measured to examine the overall damage levels. No impact of ageing on the investigated endpoints in liver tissue were found. However, animal sex seems to be a significant impact factor, as evident by sex-dependent alterations in all endpoints investigated. Moreover, our results revealed interrelationships between the investigated endpoints indicative for the synergetic mode of action of the cellular DNA integrity maintaining machinery.
T3  - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 1021 
KW  - maintenance of genomic integrity
KW  - ageing
KW  - sex
KW  - DNA damage
KW  - base excision repair (incision activity)
KW  - DNA damage response
KW  - poly(ADP-ribosyl)ation
KW  - liver
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-484831
SN  - 1866-8372
IS  - 1021
ER  - 
TY  - GEN
A1  - Sagu Tchewonpi, Sorel
A1  - Huschek, Gerd
A1  - Bönick, Josephine
A1  - Homann, Thomas
A1  - Rawel, Harshadrai Manilal
T1  - A New Approach of Extraction of α-Amylase/trypsin Inhibitors from Wheat (Triticum aestivum L.), Based on Optimization Using Plackett–Burman and Box–Behnken Designs
T2  - Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe
N2  - Wheat is one of the most consumed foods in the world and unfortunately causes allergic reactions which have important health effects. The α-amylase/trypsin inhibitors (ATIs) have been identified as potentially allergen components of wheat. Due to a lack of data on optimization of ATI extraction, a new wheat ATIs extraction approach combining solvent extraction and selective precipitation is proposed in this work. Two types of wheat cultivars (Triticum aestivum L.), Julius and Ponticus were used and parameters such as solvent type, extraction time, temperature, stirring speed, salt type, salt concentration, buffer pH and centrifugation speed were analyzed using the Plackett-Burman design. Salt concentration, extraction time and pH appeared to have significant effects on the recovery of ATIs (p < 0.01). In both wheat cultivars, Julius and Ponticus, ammonium sulfate substantially reduced protein concentration and inhibition of amylase activity (IAA) compared to sodium chloride. The optimal conditions with desirability levels of 0.94 and 0.91 according to the Doehlert design were: salt concentrations of 1.67 and 1.22 M, extraction times of 53 and 118 min, and pHs of 7.1 and 7.9 for Julius and Ponticus, respectively. The corresponding responses were: protein concentrations of 0.31 and 0.35 mg and IAAs of 91.6 and 83.3%. Electrophoresis and MALDI-TOF/MS analysis showed that the extracted ATIs masses were between 10 and 20 kDa. Based on the initial LC-MS/MS analysis, up to 10 individual ATIs were identified in the extracted proteins under the optimal conditions. The positive implication of the present study lies in the quick assessment of their content in different varieties especially while considering their allergenic potential.
T3  - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 805 
KW  - wheat
KW  - α-amylase/trypsin inhibitors
KW  - extraction
KW  - Plackett–Burman design
KW  - Doehlert design
KW  - SDS-PAGE
KW  - MALDI-TOF/MS
KW  - LC-MS/MS
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-442229
SN  - 1866-8372
IS  - 805
ER  - 
TY  - JOUR
A1  - Sagu Tchewonpi, Sorel
A1  - Huschek, Gerd
A1  - Bönick, Josephine
A1  - Homann, Thomas
A1  - Rawel, Harshadrai Manilal
T1  - A New Approach of Extraction of α-Amylase/trypsin Inhibitors from Wheat (Triticum aestivum L.), Based on Optimization Using Plackett–Burman and Box–Behnken Designs
JF  - molecules
N2  - Wheat is one of the most consumed foods in the world and unfortunately causes allergic reactions which have important health effects. The α-amylase/trypsin inhibitors (ATIs) have been identified as potentially allergen components of wheat. Due to a lack of data on optimization of ATI extraction, a new wheat ATIs extraction approach combining solvent extraction and selective precipitation is proposed in this work. Two types of wheat cultivars (Triticum aestivum L.), Julius and Ponticus were used and parameters such as solvent type, extraction time, temperature, stirring speed, salt type, salt concentration, buffer pH and centrifugation speed were analyzed using the Plackett-Burman design. Salt concentration, extraction time and pH appeared to have significant effects on the recovery of ATIs (p < 0.01). In both wheat cultivars, Julius and Ponticus, ammonium sulfate substantially reduced protein concentration and inhibition of amylase activity (IAA) compared to sodium chloride. The optimal conditions with desirability levels of 0.94 and 0.91 according to the Doehlert design were: salt concentrations of 1.67 and 1.22 M, extraction times of 53 and 118 min, and pHs of 7.1 and 7.9 for Julius and Ponticus, respectively. The corresponding responses were: protein concentrations of 0.31 and 0.35 mg and IAAs of 91.6 and 83.3%. Electrophoresis and MALDI-TOF/MS analysis showed that the extracted ATIs masses were between 10 and 20 kDa. Based on the initial LC-MS/MS analysis, up to 10 individual ATIs were identified in the extracted proteins under the optimal conditions. The positive implication of the present study lies in the quick assessment of their content in different varieties especially while considering their allergenic potential.
KW  - wheat
KW  - α-amylase/trypsin inhibitors
KW  - extraction
KW  - Plackett–Burman design
KW  - Doehlert design
KW  - SDS-PAGE
KW  - MALDI-TOF/MS
KW  - LC-MS/MS
Y1  - 2019
U6  - https://doi.org/10.3390/molecules24193589
SN  - 1420-3049
VL  - 24
IS  - 19
PB  - MDPI
CY  - Basel
ER  - 
TY  - JOUR
A1  - Jannasch, Franziska
A1  - Nickel, Daniela V.
A1  - Bergmann, Manuela M.
A1  - Schulze, Matthias Bernd
T1  - A new evidence-based diet score to capture associations of food consumption and chronic disease risk
JF  - Nutrients / Molecular Diversity Preservation International (MDPI)
N2  - Previously, the attempt to compile German dietary guidelines into a diet score was predominantly not successful with regards to preventing chronic diseases in the EPIC-Potsdam study. Current guidelines were supplemented by the latest evidence from systematic reviews and expert papers published between 2010 and 2020 on the prevention potential of food groups on chronic diseases such as type 2 diabetes, cardiovascular diseases and cancer. A diet score was developed by scoring the food groups according to a recommended low, moderate or high intake. The relative validity and reliability of the diet score, assessed by a food frequency questionnaire, was investigated. The consideration of current evidence resulted in 10 key food groups being preventive of the chronic diseases of interest. They served as components in the diet score and were scored from 0 to 1 point, depending on their recommended intake, resulting in a maximum of 10 points. Both the reliability (r = 0.53) and relative validity (r = 0.43) were deemed sufficient to consider the diet score as a stable construct in future investigations. This new diet score can be a promising tool to investigate dietary intake in etiological research by concentrating on 10 key dietary determinants with evidence-based prevention potential for chronic diseases.
KW  - diet score
KW  - dietary guidelines
KW  - food groups
KW  - chronic disease
KW  - type 2
KW  - diabetes
KW  - cardiovascular disease
KW  - cancer
KW  - prevention
KW  - reliability;
KW  - validity
Y1  - 2022
U6  - https://doi.org/10.3390/nu14112359
SN  - 2072-6643
VL  - 14
IS  - 11
PB  - MDPI
CY  - Basel
ER  - 
TY  - JOUR
A1  - Graubaum, Hans-Joachim
A1  - Luder, W.
A1  - Zunft, Hans-Joachim Franz
T1  - A new isolated soy protein with high levels of nondenaturated protein shows twice the cholesterol-lowering effect of a commercial isolated soy protein
Y1  - 2004
SN  - 0022-3166
ER  -