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- Algal–bacterial bioflm (1)
Institute
- Fachbereich Chemie und Biotechnologie (534) (remove)
Investigation of TRPV1 loss-of-function phenotypes in transgenic shRNA expressing and knockout mice
(2008)
Thomas Christoph
; Gregor Bahrenberg
; Jean de Vry
; Werner Englberger
; Volker A. Erdmann
; Moritz Frech
; Babette Kögel
; Thomas Röhl
; Klaus Schiene
; Wolfgang Schröder
; Jost Seibler
; Jens Kurreck
Shannon Dallas
; Laurent Salphati
; David Gomez-Zepeda
; Thomas Wanek
; Liangfu Chen
; Xiaoyan Chu
; Jeevan Kunta
; Mario Mezler
; Marie-Claude Menet
; Stephanie Chasseigneaux
; Xavier Declèves
; Oliver Langer
; Esaie Pierre
; Karen DiLoreto
; Carolin Hoft
; Loic Laplanche
; Jodie Pang
; Tony Pereira
; Clara Andonian
; Damir Simic
; Anja Rode
; Jocelyn Yabut
; Xiaolin Zhang
; Nico Scheer
Breast cancer resistance protein (BCRP) is expressed in various tissues, such as the gut, liver, kidney and blood brain barrier (BBB), where it mediates the unidirectional transport of substrates to the apical/luminal side of polarized cells. Thereby BCRP acts as an efflux pump, mediating the elimination or restricting the entry of endogenous compounds or xenobiotics into tissues and it plays important roles in drug disposition, efficacy and safety. Bcrp knockout mice (Bcrp−/−) have been used widely to study the role of this transporter in limiting intestinal absorption and brain penetration of substrate compounds. Here we describe the first generation and characterization of a mouse line humanized for BCRP (hBCRP), in which the mouse coding sequence from the start to stop codon was replaced with the corresponding human genomic region, such that the human transporter is expressed under control of the murine Bcrp promoter. We demonstrate robust human and loss of mouse BCRP/Bcrp mRNA and protein expression in the hBCRP mice and the absence of major compensatory changes in the expression of other genes involved in drug metabolism and disposition. Pharmacokinetic and brain distribution studies with several BCRP probe substrates confirmed the functional activity of the human transporter in these mice. Furthermore, we provide practical examples for the use of hBCRP mice to study drug-drug interactions (DDIs). The hBCRP mouse is a promising model to study the in vivo role of human BCRP in limiting absorption and BBB penetration of substrate compounds and to investigate clinically relevant DDIs involving BCRP.
Christian Degering
; Thorsten Eggert
; Michael Puls
; Johannes Bongaerts
; Stefan Evers
; Karl-Heinz Maurer
; Karl-Erich Jaeger
Bacillus subtilis and Bacillus licheniformis are widely used for the large-scale industrial production of proteins. These strains can efficiently secrete proteins into the culture medium using the general secretion (Sec) pathway. A characteristic feature of all secreted proteins is their N-terminal signal peptides, which are recognized by the secretion machinery. Here, we have studied the production of an industrially important secreted protease, namely, subtilisin BPN′ from Bacillus amyloliquefaciens. One hundred seventy-three signal peptides originating from B. subtilis and 220 signal peptides from the B. licheniformis type strain were fused to this secretion target and expressed in B. subtilis, and the resulting library was analyzed by high-throughput screening for extracellular proteolytic activity. We have identified a number of signal peptides originating from both organisms which produced significantly increased yield of the secreted protease. Interestingly, we observed that levels of extracellular protease were improved not only in B. subtilis, which was used as the screening host, but also in two different B. licheniformis strains. To date, it is impossible to predict which signal peptide will result in better secretion and thus an improved yield of a given extracellular target protein. Our data show that screening a library consisting of homologous and heterologous signal peptides fused to a target protein can identify more-effective signal peptides, resulting in improved protein export not only in the original screening host but also in different production strains.
Sophia Florence Dellmann
; J. Glorius
; Yu A. Litvinov
; R. Reifarth
; Kafa Al-Khasawneh
; M. Aliotta
; L. Bott
; Benjamin Brückner
; C. G. Bruno
; Ruijiu Chen
; T. Davinson
; T. Dickel
; Iris Dillmann
; D. Dmytriev
; P. Erbacher
; D. Freire-Fernández
; Oliver Forstner
; H. Geissel
; K. Göbel
; Christopher J. Griffin
; R. Grisenti
; Alexandre Gumberidze
; Emma Haettner
; Siegbert Hagmann
; M. Heil
; R. Heß
; P.-M. Hillenbrand
; R. Joseph
; B. Jurado
; Christophor Kozhuharov
; I. Kulikov
; Bastian Löher
; Christoph Langer
; Guy Leckenby
; C. Lederer-Woods
; M. Lestinsky
; S. A. Litvinov
; B. A. Lorenz
; E. Lorenz
; J. Marsh
; Esther Babette Menz
; T. Morgenroth
; N. Petridis
; Jerome Pibernat
; U. Popp
; Athanasios Psaltis
; Shahab Sanjari
; C. Scheidenberger
; M. Sguazzin
; Ragandeep Singh Sidhu
; Uwe Spillmann
; M. Steck
; T. Stöhlker
; A. Surzhykov
; J. A. Swartz
; H. Törnqvist
; L. Varga
; Diego Vescovi
; H. Weick
; M. Weigand
; P. Woods
; Y. Xing
; Taiyo Yamaguchi
Experimental determination of the cross sections of proton capture on radioactive nuclei is extremely difficult. Therefore, it is of substantial interest for the understanding of the production of the p-nuclei. For the first time, a direct measurement of proton-capture cross sections on stored, radioactive ions became possible in an energy range of interest for nuclear astrophysics. The experiment was performed at the Experimental Storage Ring (ESR) at GSI by making use of a sensitive method to measure (p,γ) and (p,n) reactions in inverse kinematics. These reaction channels are of high relevance for the nucleosyn-thesis processes in supernovae, which are among the most violent explosions in the universe and are not yet well understood. The cross section of the ¹¹⁸Te(p,γ) reaction has been measured at energies of 6 MeV/u and 7 MeV/u. The heavy ions interacted with a hydrogen gas jet target. The radiative recombination process of the fully stripped ¹¹⁸Te ions and electrons from the hydrogen target was used as a luminosity monitor. An overview of the experimental method and preliminary results from the ongoing analysis will be presented.
Veronika Maria Deppe
; Johannes Bongaerts
; Timothy O'Connell
; Karl-Heinz Maurer
; Friedhelm Meinhardt
Veronika Maria Deppe
; Stephanie Klatte
; Johannes Bongaerts
; Karl-Heinz Maurer
; Timothy O'Connell
; Friedhelm Meinhardt
Intensive poultry operation systems emit a considerable volume of inorganic and organic matter in the surrounding environment. Monitoring cleaning properties of exhaust air cleaning systems and to detect small but significant changes in emission characteristics during a fattening cycle is important for both emission and fattening process control. In the present study, we evaluated the potential of near-infrared spectroscopy (NIRS) combined with chemometric techniques as a monitoring tool of exhaust air from poultry operation systems. To generate a high-quality data set for evaluation, the exhaust air of two poultry houses was sampled by applying state-of-the-art filter sampling protocols. The two stables were identical except for one crucial difference, the presence or absence of an exhaust air cleaning system. In total, twenty-one exhaust air samples were collected at the two sites to monitor spectral differences caused by the cleaning device, and to follow changes in exhaust air characteristics during a fattening period. The total dust load was analyzed by gravimetric determination and included as a response variable in multivariate data analysis. The filter samples were directly measured with NIR spectroscopy. Principal component analysis (PCA), linear discriminant analysis (LDA), and factor analysis (FA) were effective in classifying the NIR exhaust air spectra according to fattening day and origin. The results indicate that the dust load and the composition of exhaust air (inorganic or organic matter) substantially influence the NIR spectral patterns. In conclusion, NIR spectroscopy as a tool is a promising and very rapid way to detect differences between exhaust air samples based on still not clearly defined circumstances triggered during a fattening period and the availability of an exhaust air cleaning system.