@misc{SendGillesCoddetal.2018, author = {Send, T. S. and Gilles, M. and Codd, V. and Wolf, I. A. C. and Bardtke, S. and Streit, Fabian and Strohmaier, Jana and Frank, Josef and Schendel, D. and Sutterlin, M. W. and Denniff, M. and Laucht, Manfred and Samani, N. J. and Deuschle, Michael and Rietschel, Marcella and Witt, Stephanie H.}, title = {Telomere length in newborns is related to maternal stress during pregnancy Response}, series = {Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology}, volume = {43}, journal = {Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology}, number = {11}, publisher = {Nature Publ. Group}, address = {London}, issn = {0893-133X}, doi = {10.1038/s41386-018-0079-8}, pages = {2164 -- 2164}, year = {2018}, language = {en} } @article{WittFrankGillesetal.2018, author = {Witt, Stephanie H. and Frank, Josef and Gilles, Maria and Lang, Maren and Treutlein, Jens and Streit, Fabian and Wolf, Isabell A. C. and Peus, Verena and Scharnholz, Barbara and Send, Tabea S. and Heilmann-Heimbach, Stefanie and Sivalingam, Sugirthan and Dukal, Helene and Strohmaier, Jana and S{\"u}tterlin, Marc and Arloth, Janine and Laucht, Manfred and N{\"o}then, Markus M. and Deuschle, Michael and Rietschel, Marcella}, title = {Impact on birth weight of maternal smoking throughout pregnancy mediated by DNA methylation}, series = {BMC genomics}, volume = {19}, journal = {BMC genomics}, publisher = {BMC}, address = {London}, issn = {1471-2164}, doi = {10.1186/s12864-018-4652-7}, pages = {10}, year = {2018}, abstract = {Background: Cigarette smoking has severe adverse health consequences in adults and in the offspring of mothers who smoke during pregnancy. One of the most widely reported effects of smoking during pregnancy is reduced birth weight which is in turn associated with chronic disease in adulthood. Epigenome-wide association studies have revealed that smokers show a characteristic "smoking methylation pattern", and recent authors have proposed that DNA methylation mediates the impact of maternal smoking on birth weight. The aims of the present study were to replicate previous reports that methylation mediates the effect of maternal smoking on birth weight, and for the first time to investigate whether the observed mediation effects are sex-specific in order to account for known sex-specific differences in methylation levels. Methods: Methylation levels in the cord blood of 313 newborns were determined using the Illumina HumanMethylation450K Beadchip. A total of 5,527 CpG sites selected on the basis of evidence from the literature were tested. To determine whether the observed association between maternal smoking and birth weight was attributable to methylation, mediation analyses were performed for significant CpG sites. Separate analyses were then performed in males and females. Results: Following quality control, 282 newborns eventually remained in the analysis. A total of 25 mothers had smoked consistently throughout the pregnancy. The birthweigt of newborns whose mothers had smoked throughout pregnancy was reduced by >200g. After correction for multiple testing, 30 CpGs showed differential methylation in the maternal smoking subgroup including top "smoking methylation pattern" genes AHRR, MYO1G, GFI1, CYP1A1, and CNTNAP2. The effect of maternal smoking on birth weight was partly mediated by the methylation of cg25325512 (PIM1); cg25949550 (CNTNAP2); and cg08699196 (ITGB7). Sex-specific analyses revealed a mediating effect for cg25949550 (CNTNAP2) in male newborns. Conclusion: The present data replicate previous findings that methylation can mediate the effect of maternal smoking on birth weight. The analysis of sex-dependent mediation effects suggests that the sex of the newborn may have an influence. Larger studies are warranted to investigate the role of both the identified differentially methylated loci and the sex of the newborn in mediating the association between maternal smoking during pregnancy and birth weight.}, language = {en} } @misc{HartungBenaryWolfetal.2017, author = {Hartung, Niklas and Benary, Uwe and Wolf, Jana and Kofahl, Bente}, title = {Paracrine and autocrine regulation of gene expression by Wnt-inhibitor Dickkopf in wild-type and mutant hepatocytes}, series = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe}, journal = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe}, number = {886}, issn = {1866-8372}, doi = {10.25932/publishup-43077}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-430778}, pages = {18}, year = {2017}, abstract = {Background Cells are able to communicate and coordinate their function within tissues via secreted factors. Aberrant secretion by cancer cells can modulate this intercellular communication, in particular in highly organised tissues such as the liver. Hepatocytes, the major cell type of the liver, secrete Dickkopf (Dkk), which inhibits Wnt/ β-catenin signalling in an autocrine and paracrine manner. Consequently, Dkk modulates the expression of Wnt/ β-catenin target genes. We present a mathematical model that describes the autocrine and paracrine regulation of hepatic gene expression by Dkk under wild-type conditions as well as in the presence of mutant cells. Results Our spatial model describes the competition of Dkk and Wnt at receptor level, intra-cellular Wnt/ β-catenin signalling, and the regulation of target gene expression for 21 individual hepatocytes. Autocrine and paracrine regulation is mediated through a feedback mechanism via Dkk and Dkk diffusion along the porto-central axis. Along this axis an APC concentration gradient is modelled as experimentally detected in liver. Simulations of mutant cells demonstrate that already a single mutant cell increases overall Dkk concentration. The influence of the mutant cell on gene expression of surrounding wild-type hepatocytes is limited in magnitude and restricted to hepatocytes in close proximity. To explore the underlying molecular mechanisms, we perform a comprehensive analysis of the model parameters such as diffusion coefficient, mutation strength and feedback strength. Conclusions Our simulations show that Dkk concentration is elevated in the presence of a mutant cell. However, the impact of these elevated Dkk levels on wild-type hepatocytes is confined in space and magnitude. The combination of inter- and intracellular processes, such as Dkk feedback, diffusion and Wnt/ β-catenin signal transduction, allow wild-type hepatocytes to largely maintain their gene expression.}, language = {en} } @article{DschietzigKrauseRelleHennequinetal.2015, author = {Dschietzig, Thomas Bernd and Krause-Relle, Katharina and Hennequin, Maud and von Websky, Karoline and Rahnenfuhrer, Jan and Ruppert, Jana and Groena, Hans Juergen and Armbruster, Franz Paul and Bathgate, Ross A. D. and Aschenbach, Joerg R. and Forssmann, Wolf-Georg and Hocher, Berthold}, title = {Relaxin-2 does not Ameliorate Nephropathy in an experimental model of Type-1 Diabetes}, series = {Kidney \& blood pressure research : official organ of the Gesellschaft f{\"u}r Nephrologie}, volume = {40}, journal = {Kidney \& blood pressure research : official organ of the Gesellschaft f{\"u}r Nephrologie}, number = {1}, publisher = {Karger}, address = {Basel}, issn = {1420-4096}, doi = {10.1159/000368484}, pages = {77 -- 88}, year = {2015}, abstract = {Background/Aims: In diabetic nephropathy (DN), the current angiotensin-II-blocking pharmacotherapy is frequently failing. For diabetic cardiomyopathy (DC), there is no specific remedy available. Relaxin-2 (Rlx) - an anti-fibrotic, anti-inflammatory, and vasoprotecting peptide - is a candidate drug for both. Methods: Low-dose (32 mu g/kg/day) and high-dose (320 mu g/kg/day) Rlx were tested against vehicle (n = 20 each) and non-diabetic controls (n = 14) for 12 weeks in a model of type-1 diabetes induced in endothelial nitric oxide synthase knock-out (eNOS-KO) mice by intraperitoneal injection of streptozotocin. Results: Diabetic animals showed normal plasma creatinine, markedly increased albuminuria and urinary malonyldialdehyde, elevated relative kidney weight, glomerulosclerosis, and increased glomerular size, but no relevant interstitial fibrosis. Neither dose of Rlx affected these changes although the drug was active and targeted plasma levels were achieved. Of note, we found no activation of the renal TGF-beta pathway in this model. In the hearts of diabetic animals, no fibrotic alterations indicative of DC could be determined which precluded testing of the initial hypothesis. Conclusions: We investigated a model showing early DN without overt tubulo-interstitial fibrosis and activation of the TGF-beta-Smad-2/3 pathway. In this model, Rlx proved ineffective; however, the same may not apply to other models and types of diabetes.}, language = {en} } @article{SendGillesCoddetal.2017, author = {Send, Tabea Sarah and Gilles, Maria and Codd, Veryan and Wolf, Isabell and Bardtke, Svenja and Streit, Fabian and Strohmaier, Jana and Frank, Josef and Schendel, Darja and Suetterlin, Mark W. and Denniff, Matthew and Laucht, Manfred and Samani, Nilesh J. and Deuschle, Michael and Rietschel, Marcella and Witt, Stephanie H.}, title = {Telomere Length in Newborns is Related to Maternal Stress During Pregnancy}, series = {Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology}, volume = {42}, journal = {Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology}, publisher = {Nature Publ. Group}, address = {London}, issn = {0893-133X}, doi = {10.1038/npp.2017.73}, pages = {2407 -- 2413}, year = {2017}, abstract = {Telomere length (TL) is a marker of biological aging, and numerous studies have shown associations between TL and somatic or psychiatric disorders. Research also indicates an association between maternal stress during pregnancy and TL in the offspring. The present study investigated possible associations between TL and: (1) maternal perceived stress during pregnancy; (2) a maternal lifetime history of psychiatric disorder (lifetime PD); and (3) paternal age. TL was analyzed in 319 newborns and 318 mothers from a predominantly Caucasian sample (n= 273 Caucasian newborns and n= 274 Caucasian mothers). Two key findings were observed. First, maternal perceived stress during pregnancy was associated with shorter telomeres in newborns but not with maternal TL. Second, maternal lifetime PD was associated with shorter maternal telomeres, but not with TL in newborns. Paternal age was not associated with TL in newborns. The finding that maternal stress during pregnancy is associated with shorter telomeres in newborns supports the results of smaller previous studies. The fact that a relation between maternal prenatal stress and TL was observed in the offspring but not in mothers may be attributable to a high vulnerability to stress during intrauterine development of a maturing organism. To our knowledge, this is the largest study to date to show that maternal stress during pregnancy but not maternal lifetime PD is associated with shorter telomeres in the offspring.}, language = {en} } @article{HartungBenaryWolfetal.2017, author = {Hartung, Niklas and Benary, Uwe and Wolf, Jana and Kofahl, Bente}, title = {Paracrine and autocrine regulation of gene expression by Wnt-inhibitor Dickkopf in wild-type and mutant hepatocytes}, series = {BMC systems biology}, volume = {11}, journal = {BMC systems biology}, publisher = {BioMed Central}, address = {London}, issn = {1752-0509}, doi = {10.1186/s12918-017-0470-9}, pages = {16}, year = {2017}, abstract = {Background: Cells are able to communicate and coordinate their function within tissues via secreted factors. Aberrant secretion by cancer cells can modulate this intercellular communication, in particular in highly organised tissues such as the liver. Hepatocytes, the major cell type of the liver, secrete Dickkopf (Dkk), which inhibits Wnt/beta-catenin signalling in an autocrine and paracrine manner. Consequently, Dkk modulates the expression of Wnt/beta-catenin target genes. We present a mathematical model that describes the autocrine and paracrine regulation of hepatic gene expression by Dkk under wild-type conditions as well as in the presence of mutant cells. Results: Our spatial model describes the competition of Dkk and Wnt at receptor level, intra-cellular Wnt/beta-catenin signalling, and the regulation of target gene expression for 21 individual hepatocytes. Autocrine and paracrine regulation is mediated through a feedback mechanism via Dkk and Dkk diffusion along the porto-central axis. Along this axis an APC concentration gradient is modelled as experimentally detected in liver. Simulations of mutant cells demonstrate that already a single mutant cell increases overall Dkk concentration. The influence of the mutant cell on gene expression of surrounding wild-type hepatocytes is limited in magnitude and restricted to hepatocytes in close proximity. To explore the underlying molecular mechanisms, we perform a comprehensive analysis of the model parameters such as diffusion coefficient, mutation strength and feedback strength. Conclusions: Our simulations show that Dkk concentration is elevated in the presence of a mutant cell. However, the impact of these elevated Dkk levels on wild-type hepatocytes is confined in space and magnitude. The combination of inter-and intracellular processes, such as Dkk feedback, diffusion and Wnt/beta-catenin signal transduction, allow wild-type hepatocytes to largely maintain their gene expression.}, language = {en} } @article{EccardWolf2009, author = {Eccard, Jana and Wolf, Jochen B. W.}, title = {Effects of brood size on multiple-paternity rates : a case for 'paternity share' as an offspring- based estimate}, issn = {0003-3472}, doi = {10.1016/j.anbehav.2009.04.008}, year = {2009}, language = {en} } @article{SchmidtSaxenhoferDrewesetal.2016, author = {Schmidt, Sabrina and Saxenhofer, Moritz and Drewes, Stephan and Schlegel, Mathias and Wanka, Konrad M. and Frank, Raphael and Klimpel, Sven and von Blanckenhagen, Felix and Maaz, Denny and Herden, Christiane and Freise, Jona and Wolf, Ronny and Stubbe, Michael and Borkenhagen, Peter and Ansorge, Hermann and Eccard, Jana and Lang, Johannes and Jourdain, Elsa and Jacob, Jens and Marianneau, Philippe and Heckel, Gerald and Ulrich, Rainer G{\"u}nter}, title = {High genetic structuring of Tula hantavirus}, series = {Archives of virology}, volume = {161}, journal = {Archives of virology}, publisher = {Springer}, address = {Wien}, issn = {0304-8608}, doi = {10.1007/s00705-016-2762-6}, pages = {1135 -- 1149}, year = {2016}, abstract = {Tula virus (TULV) is a vole-associated hantavirus with low or no pathogenicity to humans. In the present study, 686 common voles (Microtus arvalis), 249 field voles (Microtus agrestis) and 30 water voles (Arvicola spec.) were collected at 79 sites in Germany, Luxembourg and France and screened by RT-PCR and TULV-IgG ELISA. TULV-specific RNA and/or antibodies were detected at 43 of the sites, demonstrating a geographically widespread distribution of the virus in the studied area. The TULV prevalence in common voles (16.7 \%) was higher than that in field voles (9.2 \%) and water voles (10.0 \%). Time series data at ten trapping sites showed evidence of a lasting presence of TULV RNA within common vole populations for up to 34 months, although usually at low prevalence. Phylogenetic analysis demonstrated a strong genetic structuring of TULV sequences according to geography and independent of the rodent species, confirming the common vole as the preferential host, with spillover infections to co-occurring field and water voles. TULV phylogenetic clades showed a general association with evolutionary lineages in the common vole as assessed by mitochondrial DNA sequences on a large geographical scale, but with local-scale discrepancies in the contact areas.}, language = {en} } @article{HegerBernardVerdierGessleretal.2019, author = {Heger, Tina and Bernard-Verdier, Maud and Gessler, Arthur and Greenwood, Alex D. and Grossart, Hans-Peter and Hilker, Monika and Keinath, Silvia and Kowarik, Ingo and K{\"u}ffer, Christoph and Marquard, Elisabeth and Mueller, Johannes and Niemeier, Stephanie and Onandia, Gabriela and Petermann, Jana S. and Rillig, Matthias C. and Rodel, Mark-Oliver and Saul, Wolf-Christian and Schittko, Conrad and Tockner, Klement and Joshi, Jasmin Radha and Jeschke, Jonathan M.}, title = {Towards an Integrative, Eco-Evolutionary Understanding of Ecological Novelty: Studying and Communicating Interlinked Effects of Global Change}, series = {Bioscience}, volume = {69}, journal = {Bioscience}, number = {11}, publisher = {Oxford Univ. Press}, address = {Oxford}, issn = {0006-3568}, doi = {10.1093/biosci/biz095}, pages = {888 -- 899}, year = {2019}, abstract = {Global change has complex eco-evolutionary consequences for organisms and ecosystems, but related concepts (e.g., novel ecosystems) do not cover their full range. Here we propose an umbrella concept of "ecological novelty" comprising (1) a site-specific and (2) an organism-centered, eco-evolutionary perspective. Under this umbrella, complementary options for studying and communicating effects of global change on organisms, ecosystems, and landscapes can be included in a toolbox. This allows researchers to address ecological novelty from different perspectives, e.g., by defining it based on (a) categorical or continuous measures, (b) reference conditions related to sites or organisms, and (c) types of human activities. We suggest striving for a descriptive, non-normative usage of the term "ecological novelty" in science. Normative evaluations and decisions about conservation policies or management are important, but require additional societal processes and engagement with multiple stakeholders.}, language = {en} }