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1.
Biopreserv Biobank ; 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33646019

RESUMO

Cryopreservation of genetically modified mouse lines prevents the loss of specific mutants that are of enormous scientific value for both basic and applied research. Cryopreservation of spermatozoa or preimplantation embryos enables discontinuation of breeding as well as archiving of specific lines for future studies. Regarding active inter-laboratory exchange of mutants, cryopreserved material is more advantageous to transport than live animals. However, transportation stress should not be trivialized. Security scanning of transport boxes at airports and customs, in particular, as well as additional cosmic radiation, pose a threat to undefined dosages of irradiation exposure. To simulate this, cryopreserved samples of mouse spermatozoa and preimplantation embryos were exposed to an X-ray dosage of 1 mGy in an X-ray machine. For subsequent investigation of the cell integrity of irradiated spermatozoa and embryos, spermatozoa forward motility as well as embryo developmental capacity and apoptosis values were examined and compared with nonirradiated control samples. The percentage of forward-moving spermatozoa per sample appears to be significantly reduced after irradiation exposure. The in vitro developmental capacity of preimplantation embryos as well as their relative share of apoptotic cells do not seem to be influenced by irradiation exposure. This leads to the assumption that, at least in preimplantation embryos, X-ray dosages of 1 mGy do not induce sudden severe cellular harm. Nevertheless, stochastic effects of ionizing irradiation, such as mutations, do not have a dosage threshold and always represent the potential danger of alterations to cells and cellular components, especially the DNA. This could lead to undefined mutations inducing genetic drift, in the worst case to the loss of a mutant line. We therefore strongly recommend minimizing "transportation stress," in particular by irradiation exposure, to keep its potential consequences in mind, and to standardize shipping procedures.

2.
Biofabrication ; 12(4): 045016, 2020 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-32598334

RESUMO

Understanding the pathophysiological processes of cartilage degradation requires adequate model systems to develop therapeutic strategies towards osteoarthritis (OA). Although different in vitro or in vivo models have been described, further comprehensive approaches are needed to study specific disease aspects. This study aimed to combine in vitro and in silico modeling based on a tissue-engineering approach using mesenchymal condensation to mimic cytokine-induced cellular and matrix-related changes during cartilage degradation. Thus, scaffold-free cartilage-like constructs (SFCCs) were produced based on self-organization of mesenchymal stromal cells (mesenchymal condensation) and (i) characterized regarding their cellular and matrix composition or secondly (ii) treated with interleukin-1ß (IL-1ß) and tumor necrosis factor α (TNFα) for 3 weeks to simulate OA-related matrix degradation. In addition, an existing mathematical model based on partial differential equations was optimized and transferred to the underlying settings to simulate the distribution of IL-1ß, type II collagen degradation and cell number reduction. By combining in vitro and in silico methods, we aimed to develop a valid, efficient alternative approach to examine and predict disease progression and effects of new therapeutics.

3.
J Chem Phys ; 142(10): 104105, 2015 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-25778906

RESUMO

Key parameters of a recently developed coarse-grained molecular dynamics-finite element coupling approach have been analyzed in the framework of uncertainty quantification (UQ). We have employed a polystyrene sample for the case study. The new hybrid approach contains several parameters which cannot be determined on the basis of simple physical arguments. Among others, this includes the so-called anchor points as information transmitters between the particle-based molecular dynamics (MD) domain and the surrounding finite element continuum, the force constant between polymer beads and anchor points, the number of anchor points, and the relative sizes of the MD core domain and the surrounding dissipative particle dynamics domain. Polymer properties such as density, radius of gyration, end-to-end distance, and radial distribution functions are calculated as a function of the above model parameters. The influence of these input parameters on the resulting polymer properties is studied by UQ. Our analysis shows that the hybrid method is highly robust. The variation of polymer properties of interest as a function of the input parameters is weak.

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