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51.
52.
Frank Lennartz Karen Bayer Nadine Czerwonka Yinghui Lu Kristine Kehr Manuela Hirz Torsten Steinmetzer Wolfgang Garten Christiane Herden 《Cellular microbiology》2016,18(3):340-354
Borna disease virus (BDV) is a non‐segmented negative‐stranded RNA virus that maintains a strictly neurotropic and persistent infection in affected end hosts. The primary target cells for BDV infection are brain cells, e.g. neurons and astrocytes. The exact mechanism of how infection is propagated between these cells and especially the role of the viral glycoprotein (GP) for cell–cell transmission, however, are still incompletely understood. Here, we use different cell culture systems, including rat primary astrocytes and mixed cultures of rat brain cells, to show that BDV primarily spreads through cell–cell contacts. We employ a highly stable and efficient peptidomimetic inhibitor to inhibit the furin‐mediated processing of GP and demonstrate that cleaved and fusion‐active GP is strictly necessary for the cell‐to‐cell spread of BDV. Together, our quantitative observations clarify the role of Borna disease virus‐glycoprotein for viral dissemination and highlight the regulation of GP expression as a potential mechanism to limit viral spread and maintain persistence. These findings furthermore indicate that targeting host cell proteases might be a promising approach to inhibit viral GP activation and spread of infection. 相似文献
53.
Erzsebet Pászti-Gere Réka Fanni Barna Gabriella Ujhelyi Torsten Steinmetzer 《Journal of enzyme inhibition and medicinal chemistry》2016,31(5):736-741
The type II trypsin-like transmembrane serine protease matriptase, is mainly expressed in epithelial cells and one of the key regulators in the formation and maintenance of epithelial barrier integrity. Therefore, we have studied the inhibition of matriptase in a non-transformed porcine intestinal IPEC-J2 cell monolayer cultured on polyester membrane inserts by the non-selective 4-(2-aminoethyl)-benzosulphonylfluoride (AEBSF) and four more selective 3-amidinophenylalanine-derived matriptase inhibitors. It was found that suppression of matriptase activity by MI-432 and MI-460 led to decreased transepithelial electrical resistance (TER) of the cell monolayer and to an enhanced transport of fluorescently labelled dextran, a marker for paracellular transport between apical and basolateral compartments. To this date this is the first report in which the inhibition of matriptase activity by synthetic inhibitors has been correlated to a reduced barrier integrity of a non-cancerous IPEC-J2 epithelial cell monolayer in order to describe interaction between matriptase activity and intestinal epithelium in vitro. 相似文献
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Torsten Schubert Stephan H. von Reuß Cindy Kunze Christian Paetz Stefan Kruse Peggy Brand-Schön Anita Mac Nelly Jörg Nüske Gabriele Diekert 《Microbial biotechnology》2019,12(2):346-359
Cobamides (Cbas) are essential cofactors of reductive dehalogenases (RDases) in organohalide-respiring bacteria (OHRB). Changes in the Cba structure can influence RDase function. Here, we report on the cofactor versatility or selectivity of Desulfitobacterium RDases produced either in the native organism or heterologously. The susceptibility of Desulfitobacterium hafniense strain DCB-2 to guided Cba biosynthesis (i.e. incorporation of exogenous Cba lower ligand base precursors) was analysed. Exogenous benzimidazoles, azabenzimidazoles and 4,5-dimethylimidazole were incorporated by the organism into Cbas. When the type of Cba changed, no effect on the turnover rate of the 3-chloro-4-hydroxy-phenylacetate-converting enzyme RdhA6 and the 3,5-dichlorophenol-dehalogenating enzyme RdhA3 was observed. The impact of the amendment of Cba lower ligand precursors on RDase function was also investigated in Shimwellia blattae, the Cba producer used for the heterologous production of Desulfitobacterium RDases. The recombinant tetrachloroethene RDase (PceAY51) appeared to be non-selective towards different Cbas. However, the functional production of the 1,2-dichloroethane-dihaloeliminating enzyme (DcaA) of Desulfitobacterium dichloroeliminans was completely prevented in cells producing 5,6-dimethylbenzimidazolyl-Cba, but substantially enhanced in cells that incorporated 5-methoxybenzimidazole into the Cba cofactor. The results of the study indicate the utilization of a range of different Cbas by Desulfitobacterium RDases with selected representatives apparently preferring distinct Cbas. 相似文献
56.
Santini Nadia S. Lovelock Catherine E. Hua Quan Zawadzki Atun Mazumder Debashish Mercer Tim R. Muñoz-Rojas Miriam Hardwick Simon A. Madala Bindu Swapna Cornwell William Thomas Torsten Marzinelli Ezequiel M. Adam Paul Paul Swapan Vergés Adriana 《Ecosystems》2019,22(8):1803-1822
Ecosystems - Saltmarshes provide many valuable ecosystem services including storage of a large amount of ‘blue carbon’ within their soils. To date, up to 50% of the world’s... 相似文献
57.
Franziska S. Kemter Nadine Schallopp Theodor Sperlea Javier Serrania Patrick Sobetzko Georg Fritz Torsten Waldminghaus 《Molecular microbiology》2019,111(6):1617-1637
Vibrio cholerae is an aquatic bacterium with the potential to infect humans and cause the cholera disease. While most bacteria have single chromosomes, the V. cholerae genome is encoded on two replicons of different size. This study focuses on the DNA replication and cell division of this bi‐chromosomal bacterium during the stringent response induced by starvation stress. V. cholerae cells were found to initially shut DNA replication initiation down upon stringent response induction by the serine analog serine hydroxamate. Surprisingly, cells temporarily restart their DNA replication before finally reaching a state with fully replicated single chromosome sets. This division‐replication pattern is very different to that of the related single chromosome model bacterium Escherichia coli. Within the replication restart phase, both chromosomes of V. cholerae maintained their known order of replication timing to achieve termination synchrony. Using flow cytometry combined with mathematical modeling, we established that a phase of cellular regrowth be the reason for the observed restart of DNA replication after the initial shutdown. Our study shows that although the stringent response induction itself is widely conserved, bacteria developed different ways of how to react to the sensed nutrient limitation, potentially reflecting their individual lifestyle requirements. 相似文献
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59.
Ralf Müller-Rath Stefan Andereya Sascha Gravius Dieter Christian Wirtz Rudolf Marx Torsten Mumme 《Biomedizinische Technik》2007,52(6):391-397
Cemented femoral stems have shown decreased longevity compared to cementless implants in hip revision arthroplasty. The aim of this study was to evaluate the effect of an amphiphilic bonder on bone cement stability in a biomechanical femur expulsion test. A simplified hip simulator test setup with idealised femur stem specimens was carried out. The stems were implanted into bovine femurs (group 1: no bonder, n=10; group 2: bonder including glutaraldehyde, n=10; group 3: bonder without glutaraldehyde, n=10). A dynamic loading (maximum load: 800 N; minimum load: 100 N; frequency: 3 Hz; 105 cycles) was performed. Subsequently, the stem specimens were expulsed axially out of their implant beds and maximum load at failure was recorded. The static controls showed a mean maximum load to failure of 4123 N in group 1, 8357.5 N in group 2 and 5830.8 N in group 3. After dynamic loading, the specimens of group 2 reached the highest load to failure (8191.5 N), followed by group 3 (5649.5 N) and group 1 (3462 N), respectively. In group 2, we observed nine periprosthetic fractures at a load of 8400 N without signs of interface loosening. Application of an amphiphilic bonder led to a significant improvement of bonding stability, especially when glutaraldehyde was added to the bonder. This technique might offer an increased longevity of cemented femur revision stems in total hip replacement. 相似文献
60.
Schöneberg T Hermsdorf T Engemaier E Engel K Liebscher I Thor D Zierau K Römpler H Schulz A 《Purinergic signalling》2007,3(4):255-268
Metabotropic pyrimidine and purine nucleotide receptors (P2Y receptors) belong to the superfamily of G protein-coupled receptors
(GPCR). They are distinguishable from adenosine receptors (P1) as they bind adenine and/or uracil nucleotide triphosphates
or diphosphates depending on the subtype. Over the past decade, P2Y receptors have been cloned from a variety of tissues and
species, and as many as eight functional subtypes have been characterized. Most recently, several members of the P2Y12-like receptor group, which includes the clopidogrel-sensitive ADP receptor P2Y12, have been deorphanized. The P2Y12-like receptor group comprises several structurally related GPCR which, however, display heterogeneous agonist specificity
including nucleotides, their derivatives, and lipids. Besides the established function of P2Y12 in platelet activation, expression in macrophages, neuronal and glial cells as well as recent results from functional studies
implicate that several members of this group may have specific functions in neurotransmission, inflammation, chemotaxis, and
response to tissue injury. This review focuses specifically on the structure-function relation and shortly summarizes some
aspects of the physiological relevance of P2Y12-like receptor members. 相似文献