@article{RohmerDobritzTuncbilekDereetal.2022, author = {Rohmer, Carina and Dobritz, Ronja and Tuncbilek-Dere, Dilek and Lehmann, Esther and Gerlach, David and George, Shilpa Elizabeth and Bae, Taeok and Nieselt, Kay and Wolz, Christiane}, title = {Influence of Staphylococcus aureus strain background on Sa3int phage life cycle switches}, series = {Viruses}, volume = {14}, journal = {Viruses}, number = {11}, issn = {1999-4915}, doi = {10.3390/v14112471}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-297209}, year = {2022}, abstract = {Staphylococcus aureus asymptomatically colonizes the nasal cavity of mammals, but it is also a leading cause of life-threatening infections. Most human nasal isolates carry Sa3 phages, which integrate into the bacterial hlb gene encoding a sphingomyelinase. The virulence factor-encoding genes carried by the Sa3-phages are highly human-specific, and most animal strains are Sa3 negative. Thus, both insertion and excision of the prophage could potentially confer a fitness advantage to S. aureus. Here, we analyzed the phage life cycle of two Sa3 phages, Φ13 and ΦN315, in different phage-cured S. aureus strains. Based on phage transfer experiments, strains could be classified into low (8325-4, SH1000, and USA300c) and high (MW2c and Newman-c) transfer strains. High-transfer strains promoted the replication of phages, whereas phage adsorption, integration, excision, or recA transcription was not significantly different between strains. RNASeq analyses of replication-deficient lysogens revealed no strain-specific differences in the CI/Mor regulatory switch. However, lytic genes were significantly upregulated in the high transfer strain MW2c Φ13 compared to strain 8325-4 Φ13. By transcriptional start site prediction, new promoter regions within the lytic modules were identified, which are likely targeted by specific host factors. Such host-phage interaction probably accounts for the strain-specific differences in phage replication and transfer frequency. Thus, the genetic makeup of the host strains may determine the rate of phage mobilization, a feature that might impact the speed at which certain strains can achieve host adaptation.}, language = {en} } @article{AgostonLiHaslingeretal.2012, author = {Agoston, Zsuzsa and Li, Naixin and Haslinger, Anja and Wizenmann, Andrea and Schulte, Dorothea}, title = {Genetic and physical interaction of Meis2, Pax3 and Pax7 during dorsal midbrain development}, series = {BMC Developmental Biology}, volume = {12}, journal = {BMC Developmental Biology}, number = {10}, doi = {10.1186/1471-213X-12-10}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-132626}, year = {2012}, abstract = {Background: During early stages of brain development, secreted molecules, components of intracellular signaling pathways and transcriptional regulators act in positive and negative feed-back or feed-forward loops at the mid-hindbrain boundary. These genetic interactions are of central importance for the specification and subsequent development of the adjacent mid-and hindbrain. Much less, however, is known about the regulatory relationship and functional interaction of molecules that are expressed in the tectal anlage after tectal fate specification has taken place and tectal development has commenced. Results: Here, we provide experimental evidence for reciprocal regulation and subsequent cooperation of the paired-type transcription factors Pax3, Pax7 and the TALE-homeodomain protein Meis2 in the tectal anlage. Using in ovo electroporation of the mesencephalic vesicle of chick embryos we show that (i) Pax3 and Pax7 mutually regulate each other's expression in the mesencephalic vesicle, (ii) Meis2 acts downstream of Pax3/7 and requires balanced expression levels of both proteins, and (iii) Meis2 physically interacts with Pax3 and Pax7. These results extend our previous observation that Meis2 cooperates with Otx2 in tectal development to include Pax3 and Pax7 as Meis2 interacting proteins in the tectal anlage. Conclusion: The results described here suggest a model in which interdependent regulatory loops involving Pax3 and Pax7 in the dorsal mesencephalic vesicle modulate Meis2 expression. Physical interaction with Meis2 may then confer tectal specificity to a wide range of otherwise broadly expressed transcriptional regulators, including Otx2, Pax3 and Pax7.}, language = {en} } @article{RamachandranSchirmerMuenstetal.2015, author = {Ramachandran, Sarada Devi and Schirmer, Katharina and M{\"u}nst, Bernhard and Heinz, Stefan and Ghafoory, Shahrouz and W{\"o}lfl, Stefan and Simon-Keller, Katja and Marx, Alexander and {\O}ie, Cristina Ionica and Ebert, Matthias P. and Walles, Heike and Braspenning, Joris and Breitkopf-Heinlein, Katja}, title = {In Vitro Generation of Functional Liver Organoid-Like Structures Using Adult Human Cells}, series = {PLoS One}, volume = {10}, journal = {PLoS One}, number = {10}, doi = {10.1371/journal.pone.0139345}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-139552}, pages = {e0139345}, year = {2015}, abstract = {In this study we used differentiated adult human upcyte (R) cells for the in vitro generation of liver organoids. Upcyte (R) cells are genetically engineered cell strains derived from primary human cells by lenti-viral transduction of genes or gene combinations inducing transient proliferation capacity (upcyte (R) process). Proliferating upcyte (R) cells undergo a finite number of cell divisions, i.e., 20 to 40 population doublings, but upon withdrawal of proliferation stimulating factors, they regain most of the cell specific characteristics of primary cells. When a defined mixture of differentiated human upcyte (R) cells (hepatocytes, liver sinusoidal endothelial cells (LSECs) and mesenchymal stem cells (MSCs)) was cultured in vitro on a thick layer of Matrigel\(^{TM}\), they self-organized to form liver organoid-like structures within 24 hours. When further cultured for 10 days in a bioreactor, these liver organoids show typical functional characteristics of liver parenchyma including activity of cytochromes P450, CYP3A4, CYP2B6 and CYP2C9 as well as mRNA expression of several marker genes and other enzymes. In summary, we hereby describe that 3D functional hepatic structures composed of primary human cell strains can be generated in vitro. They can be cultured for a prolonged period of time and are potentially useful ex vivo models to study liver functions.}, language = {en} } @article{SerflingRudolfBuschetal.2014, author = {Serfling, Edgar and Rudolf, Ronald and Busch, Rhoda and Patra, Amiya K. and Muhammad, Khalid and Avots, Andris and Andrau, Jean-Christophe and Klein-Hessling, Stefan}, title = {Architecture and expression of the Nfatc1 gene in lymphocytes}, doi = {10.3389/fimmu.2014.00021}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-112718}, year = {2014}, abstract = {In lymphocytes, the three NFAT factors NFATc1 (also designated as NFAT2), NFATc2 (NFAT1), and NFATc3 (NFAT4 or NFATx) are expressed and are the targets of immune receptor signals, which lead to a rapid rise of intracellular Ca++, the activation of phosphatase calcineurin, and to the activation of cytosolic NFATc proteins. In addition to rapid activation of NFAT factors, immune receptor signals lead to accumulation of the short NFATc1/αA isoform in lymphocytes which controls their proliferation and survival. In this mini-review, we summarize our current knowledge on the structure and transcription of the Nfatc1 gene in lymphocytes, which is controlled by two promoters, two poly A addition sites and a remote downstream enhancer. The Nfatc1 gene resembles numerous primary response genes (PRGs) induced by LPS in macrophages. Similar to the PRG promoters, the Nfatc1 promoter region is organized in CpG islands, forms DNase I hypersensitive sites, and is marked by histone tail modifications before induction. By studying gene induction in lymphocytes in detail, it will be important to elucidate whether the properties of the Nfatc1 induction are not only typical for the Nfatc1 gene but also for other transcription factor genes expressed in lymphocytes.}, language = {en} }