Variable Expression of Cre Recombinase Transgenes Precludes Reliable Prediction of Tissue-Specific Gene Disruption by Tail-Biopsy Genotyping

The Cre/loxP-system has become the system of choice for the generation of conditional so-called knockout mouse strains, i.e. the tissue-specific disruption of expression of a certain target gene. We here report the loss of expression of Cre recombinase in a transgenic mouse strain with increasing number of generations. This eventually led to the complete abrogation of gene expression of the inserted Cre cDNA while still being detectable at the genomic level. Conversely, loss of Cre expression caused an incomplete or even complete lack of disruption for the protein under investigation. As Cre expression in the tissue of interest in most cases cannot be addressed in vivo during the course of a study, our findings implicate the possibility that individual tail-biopsy genotypes may not necessarily indicate the presence or absence of gene disruption. This indicates that sustained post hoc analyses in regards to efficacy of disruption for every single study group member may be required

Mechanistic insights into p53‐regulated cytotoxicity of combined entinostat and irinotecan against colorectal cancer cells

Late‐stage colorectal cancer (CRC) is still a clinically challenging problem. The activity of the tumor suppressor p53 is regulated via post‐translational modifications (PTMs). While the relevance of p53 C‐terminal acetylation for transcriptional regulation is well defined, it is unknown whether this PTM controls mitochondrially mediated apoptosis directly. We used wild‐type p53 or p53‐negative human CRC cells, cells with acetylation‐defective p53, transformation assays, CRC organoids, and xenograft mouse models to assess how p53 acetylation determines cellular stress responses. The topoisomerase‐1 inhibitor irinotecan induces acetylation of several lysine residues within p53. Inhibition of histone deacetylases (HDACs) with the class I HDAC inhibitor entinostat synergistically triggers mitochondrial damage and apoptosis in irinotecan‐treated p53‐positive CRC cells. This specifically relies on the C‐terminal acetylation of p53 by CREB‐binding protein/p300 and the presence of C‐terminally acetylated p53 in complex with the proapoptotic BCL2 antagonist/killer protein. This control of C‐terminal acetylation by HDACs can mechanistically explain why combinations of irinotecan and entinostat represent clinically tractable agents for the therapy of p53‐proficient CRC

9. Vorlesung (25.08.2020): Kalorimetrie

Vorlesungsinhalt: Indirekte Kalorimetrie; Direkte Kalorimetrie; Bombenkalorimetrie; Gefriertrocknun

Development of KUKA robot programming standard for standardization of robot programs for the SITEC Automation GmbH

Ziel dieses Masterthesis ist es, in der Firma SITEC Automation GmbH einen firmeneigenen Programmierstandard für KUKA-Roboter zu erstellen. Anhand dieses Standards soll dem Anwender die Möglichkeit geboten werden, Roboterprogramme genormt zu erstellen und somit Projekte in kürzeren Zeiträumen zu erstellen. Für die Erzeugung des Programmierstandards ist es erforderlich, Dokumentationen bisheriger Roboter-Projekte zu studieren, die Erkenntnisse, sowie neue Ideen in einem Standard umzusetzen und dem Anwender in entsprechender Zusammenführung darzustellen. Zum Abschluss erfolgt eine Auswertung der Ergebnisse

2. Vorlesung (19.12.2020): Verdauungssystem

Vorlesungsinhalt: Verdauungssystem = Verdauungstrakt + Hilfsorgane; Darstellung und Erläuterung an einer Zeichnun

Errichtung eines teilautomatisierten Konzentrationsmessstandes

nicht vorhande