TY - JOUR A1 - Hansmann, T. A1 - Heinzmann, J. A1 - Wrenzycki, C. A1 - Zechner, U. A1 - Niemann, H. A1 - Haaf, T. T1 - Characterization of Differentially Methylated Regions in 3 Bovine Imprinted Genes: A Model for Studying Human Germ-Cell and Embryo Development JF - Cytogenetic and Genome Research N2 - Correct imprinting is crucial for normal fetal and placental development in mammals. Experimental evidence in animal models and epidemiological studies in humans suggest that assisted reproductive technologies (ARTs) can interfere with imprinted gene regulation in gametogenesis and early embryogenesis. Bos taurus is an agriculturally important species in which ARTs are commonly employed. Because this species exhibits a similar preimplantation development and gestation length as humans, it is increasingly being used as a model for human germ-cell and embryo development. However, in contrast to humans and mice, there is relatively little information on bovine imprinted genes. Here, we characterized the bovine intergenic IGF2-H19 imprinting control region (ICR) spanning approximately 3 kb. We identified a 300-bp differentially methylated region (DMR) approximately 6 kb upstream of the H19 promoter, containing a CpG island with CTCF-binding site and high sequence similarity with the human intergenic ICR. Additional differentially methylated CpG islands lie –6 kb to –3 kb upstream of the promoter, however these are less conserved. Both classical bisulfite sequencing and bisulfite pyrosequencing demonstrated complete methylation of the IGF2-H19 ICR in sperm, complete demethylation in parthenogenetic embryos having only the female genome, and differential methylation in placental and somatic tissues. In addition, we established pyrosequencing assays for the previously reported bovine SNRPN and PEG3 DMRs. The observed methylation patterns were consistent with genomic imprinting in all analyzed tissues/cell types. The identified IGF2-H19 ICR and the developed quantitative methylation assays may prove useful for further studies on the relationship between ARTs and imprinting defects in the bovine model. KW - bovine KW - differentially methylated region KW - IGF2-H19 KW - imprinting control region Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-199051 SN - 1424-8581 SN - 1424-859X N1 - This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively. VL - 132 IS - 4 ER - TY - JOUR A1 - Waaga, AM A1 - Ulrichs, Karin A1 - Krzymanski, M. A1 - Treumer, J. A1 - Hansmann, ML A1 - Rommel, T. A1 - Müller-Ruchholz, W. T1 - The immunosuppressive agent 15-deoxyspergualin induces tolerance and modulates MHC-antigen expression and interleukin-1 production in the early phase of rat allograft responses N2 - No abstract available KW - Chirurgie Y1 - 1990 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-45253 ER - TY - JOUR A1 - Alepee, Natalie A1 - Bahinski, Anthony A1 - Daneshian, Mardas A1 - De Weyer, Bart A1 - Fritsche, Ellen A1 - Goldberg, Alan A1 - Hansmann, Jan A1 - Hartung, Thomas A1 - Haycock, John A1 - Hogberg, Helena T. A1 - Hoelting, Lisa A1 - Kelm, Jens M. A1 - Kadereit, Suzanne A1 - McVey, Emily A1 - Landsiedel, Robert A1 - Leist, Marcel A1 - Lübberstedt, Marc A1 - Noor, Fozia A1 - Pellevoisin, Christian A1 - Petersohn, Dirk A1 - Pfannenbecker, Uwe A1 - Reisinger, Kerstin A1 - Ramirez, Tzutzuy A1 - Rothen-Rutishauser, Barbara A1 - Schäfer-Korting, Monika A1 - Zeilinger, Katrin A1 - Zurich, Marie-Gabriele T1 - State-of-the-Art of 3D Cultures (Organs-on-a-Chip) in Safety Testing and Pathophysiology JF - ALTEX - Alternatives to Animal Experimentation N2 - Integrated approaches using different in vitro methods in combination with bioinformatics can (i) increase the success rate and speed of drug development; (ii) improve the accuracy of toxicological risk assessment; and (iii) increase our understanding of disease. Three-dimensional (3D) cell culture models are important building blocks of this strategy which has emerged during the last years. The majority of these models are organotypic, i.e., they aim to reproduce major functions of an organ or organ system. This implies in many cases that more than one cell type forms the 3D structure, and often matrix elements play an important role. This review summarizes the state of the art concerning commonalities of the different models. For instance, the theory of mass transport/metabolite exchange in 3D systems and the special analytical requirements for test endpoints in organotypic cultures are discussed in detail. In the next part, 3D model systems for selected organs liver, lung, skin, brain are presented and characterized in dedicated chapters. Also, 3D approaches to the modeling of tumors are presented and discussed. All chapters give a historical background, illustrate the large variety of approaches, and highlight up- and downsides as well as specific requirements. Moreover, they refer to the application in disease modeling, drug discovery and safety assessment. Finally, consensus recommendations indicate a roadmap for the successful implementation of 3D models in routine screening. It is expected that the use of such models will accelerate progress by reducing error rates and wrong predictions from compound testing. KW - 3D models KW - organotypic KW - organ-on-a-chip KW - multicellular tumor spheroids KW - primary human hepatocytes KW - embryonic stem cell KW - reconstructed human epidermis KW - in-vitro models KW - full thickness skin KW - necrosis-factor-alpha KW - metabolic flux analysis KW - long-term KW - human liver cells Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-117826 VL - 31 IS - 4 ER - TY - JOUR A1 - Radakovic, D. A1 - Reboredo, J. A1 - Helm, M. A1 - Weigel, T. A1 - Schürlein, S. A1 - Kupczyk, E. A1 - Leyh, R. G. A1 - Walles, H. A1 - Hansmann, J. T1 - A multilayered electrospun graft as vascular access for hemodialysis JF - PLoS ONE N2 - Despite medical achievements, the number of patients with end-stage kidney disease keeps steadily raising, thereby entailing a high number of surgical and interventional procedures to establish and maintain arteriovenous vascular access for hemodialysis. Due to vascular disease, aneurysms or infection, the preferred access—an autogenous arteriovenous fistula—is not always available and appropriate. Moreover, when replacing small diameter blood vessels, synthetic vascular grafts possess well-known disadvantages. A continuous multilayered gradient electrospinning was used to produce vascular grafts made of collagen type I nanofibers on luminal and adventitial graft side, and poly-ɛ-caprolactone as medial layer. Therefore, a custom-made electrospinner with robust environmental control was developed. The morphology of electrospun grafts was characterized by scanning electron microscopy and measurement of mechanical properties. Human microvascular endothelial cells were cultured in the graft under static culture conditions and compared to cultures obtained from dynamic continuous flow bioreactors. Immunofluorescent analysis showed that endothelial cells form a continuous luminal layer and functional characteristics were confirmed by uptake of acetylated low-density-lipoprotein. Incorporation of vancomycin and gentamicin to the medial graft layer allowed antimicrobial inhibition without exhibiting an adverse impact on cell viability. Most striking a physiological hemocompatibility was achieved for the multilayered grafts. KW - collagens KW - polymers KW - vascular surgery KW - endothelial cells KW - cell cultures KW - blood KW - antibiotics KW - scanning electron microscopy Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-159102 VL - 12 IS - 10 ER - TY - JOUR A1 - Wagner, N. A1 - Crippa, L. A1 - Amaricci, A. A1 - Hansmann, P. A1 - Klett, M. A1 - König, E. J. A1 - Schäfer, T. A1 - Di Sante, D. A1 - Cano, J. A1 - Millis, A. J. A1 - Georges, A. A1 - Sangiovanni, G. T1 - Mott insulators with boundary zeros JF - Nature Communications N2 - The topological classification of electronic band structures is based on symmetry properties of Bloch eigenstates of single-particle Hamiltonians. In parallel, topological field theory has opened the doors to the formulation and characterization of non-trivial phases of matter driven by strong electron-electron interaction. Even though important examples of topological Mott insulators have been constructed, the relevance of the underlying non-interacting band topology to the physics of the Mott phase has remained unexplored. Here, we show that the momentum structure of the Green’s function zeros defining the “Luttinger surface" provides a topological characterization of the Mott phase related, in the simplest description, to the one of the single-particle electronic dispersion. Considerations on the zeros lead to the prediction of new phenomena: a topological Mott insulator with an inverted gap for the bulk zeros must possess gapless zeros at the boundary, which behave as a form of “topological antimatter” annihilating conventional edge states. Placing band and Mott topological insulators in contact produces distinctive observable signatures at the interface, revealing the otherwise spectroscopically elusive Green’s function zeros. KW - electronic properties and materials KW - topological insulators Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-358150 VL - 14 ER -