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Stefan Alexander Tennigkeit Raziye Karapinar Till Rudack Max-Aylmer Dreier Philipp Althoff Dennis Eickelbeck Tatjana Surdin Michelle Grömmke Melanie D. Mark Katharina Spoida Mathias Lübben Udo Höweler Prof. Dr. Stefan Herlitze Prof. Dr. Klaus Gerwert 《Chembiochem : a European journal of chemical biology》2019,20(14):1766-1771
The primary goal of optogenetics is the light-controlled noninvasive and specific manipulation of various cellular processes. Herein, we present a hybrid strategy for targeted protein engineering combining computational techniques with electrophysiological and UV/visible spectroscopic experiments. We validated our concept for channelrhodopsin-2 and applied it to modify the less-well-studied vertebrate opsin melanopsin. Melanopsin is a promising optogenetic tool that functions as a selective molecular light switch for G protein-coupled receptor pathways. Thus, we constructed a model of the melanopsin Gq protein complex and predicted an absorption maximum shift of the Y211F variant. This variant displays a narrow blue-shifted action spectrum and twofold faster deactivation kinetics compared to wild-type melanopsin on G protein-coupled inward rectifying K+ (GIRK) channels in HEK293 cells. Furthermore, we verified the in vivo activity and optogenetic potential for the variant in mice. Thus, we propose that our developed concept will be generally applicable to designing optogenetic tools. 相似文献
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L. Antonio González-Grajales Laura Pieper Stefan Görner Philipp Görner Rudolf Staufenbiel 《Journal of dairy science》2019,102(4):3609-3614
Few studies have compared individual variability of an intravenous glucose tolerance test (ivGTT) obtained daily in young cattle. The objective of this study was to evaluate the repeatability of glucose traits and insulin responses derived from ivGTT during 3 consecutive days in Holstein-Friesian cattle (bulls: n = 4, steers: n = 3, heifers: n = 3). Blood collections were performed from min 0 (basal concentrations) to min 63 (last measurement). Additional estimates included maximal concentration for glucose and insulin, glucose half-life time (GHLT), and glucose and insulin area under the curve. Glucose traits showed higher repeatability when compared with insulin responses. On average, the glucose trait and insulin response with the lowest coefficient of variation was GHLT (0.7%) and insulin area under the curve (21.3%), respectively. In addition, a general linear model with repeated measures was used to test for significant differences in glucose and insulin concentrations over time at different trial days. Both glucose and insulin concentrations were influenced by time point but not by trial day or time point × trial day. The results from this study showed that individual insulin responses were more variable than glucose traits. The high repeatability of GHLT evidenced the strict regulatory glucose disposal mechanisms occurring in young Holstein-Friesian cattle, whereas insulin responses showed high variability despite controlled management and nutritional practices. 相似文献
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Norgauer Philipp Grunewald Laura Priester Lena Heilemann Jens Hein Michael Stahl Karsten 《Forschung im Ingenieurwesen》2020,84(2):141-150
Forschung im Ingenieurwesen - Schneckengetriebe finden sich in verschiedenen Anwendungen als Stell- und Leistungsgetriebe. Aufgrund der Realisierbarkeit einer hohen Übersetzung bei kleinem... 相似文献
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Moritz Riebisch Philipp Weiß Clemens Cremer Ibrahim Aboulkhair Andreas Bührig-Polaczek 《Materials Science & Technology》2018,34(6):725-730
Solid solution-strengthened ductile iron (DI) exhibits outstanding mechanical properties due to the high silicon content. The strengthening by silicon addition is limited since additions above 4.3?wt-% lead to embrittlement. For a further improvement of mechanical properties, other alloying elements need to be considered. In the present work, the effect of various copper additions on the microstructure and the mechanical properties of solid solution-strengthened DI were investigated. The results show that no appreciable strengthening can be achieved by copper addition without the formation of pearlite in the matrix. The pearlite content increases considerably for Cu-additions above 0.23?wt-% and is independent of the cooling rate for the cooling conditions analysed. 相似文献
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