@article{DallasSalphatiGomezZepedaetal.2016, author = {Dallas, Shannon and Salphati, Laurent and Gomez-Zepeda, David and Wanek, Thomas and Chen, Liangfu and Chu, Xiaoyan and Kunta, Jeevan and Mezler, Mario and Menet, Marie-Claude and Chasseigneaux, Stephanie and Decl{\`e}ves, Xavier and Langer, Oliver and Pierre, Esaie and DiLoreto, Karen and Hoft, Carolin and Laplanche, Loic and Pang, Jodie and Pereira, Tony and Andonian, Clara and Simic, Damir and Rode, Anja and Yabut, Jocelyn and Zhang, Xiaolin and Scheer, Nico}, title = {Generation and Characterization of a Breast Cancer Resistance Protein Humanized Mouse Model}, series = {Molecular Pharmacology}, volume = {89}, journal = {Molecular Pharmacology}, number = {5}, publisher = {ASPET}, address = {Bethesda, Md.}, issn = {1521-0111}, doi = {10.1124/mol.115.102079}, pages = {492 -- 504}, year = {2016}, abstract = {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.}, language = {en} } @inproceedings{CapitainHeringTippkoetteretal.2016, author = {Capitain, C. and Hering, T. and Tippk{\"o}tter, Nils and Ulber, R.}, title = {Enzymatic polymerization of lignin model compounds and solubilized lignin in an aqueous ethanol extract}, series = {New frontiers of biotech-processes (Himmelfahrtstagung) : 02-04 May 2016, Rhein-Mosel-Halle, Koblenz/Germany}, booktitle = {New frontiers of biotech-processes (Himmelfahrtstagung) : 02-04 May 2016, Rhein-Mosel-Halle, Koblenz/Germany}, publisher = {DECHEMA}, address = {Frankfurt am Main}, pages = {151 -- 152}, year = {2016}, language = {en} } @article{BreuerRaueStrobeletal.2016, author = {Breuer, Lars and Raue, Markus and Strobel, M. and Mang, Thomas and Sch{\"o}ning, Michael Josef and Thoelen, R. and Wagner, Torsten}, title = {Hydrogels with incorporated graphene oxide as light-addressable actuator materials for cell culture environments in lab-on-chip systems}, series = {Physica status solidi (a)}, volume = {213}, journal = {Physica status solidi (a)}, number = {6}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {1862-6300}, doi = {10.1002/pssa.201533056}, pages = {1520 -- 1525}, year = {2016}, abstract = {Abstractauthoren Graphene oxide (GO) nanoparticles were incorporated in temperature-sensitive Poly(N-isopropylacrylamide) (PNIPAAm) hydrogels. The nanoparticles increase the light absorption and convert light energy into heat efficiently. Thus, the hydrogels with GO can be stimulated spatially resolved by illumination as it was demonstrated by IR thermography. The temporal progression of the temperature maximum was detected for different concentrations of GO within the polymer network. Furthermore, the compatibility of PNIPAAm hydrogels with GO and cell cultures was investigated. For this purpose, culture medium was incubated with hydrogels containing GO and the viability and morphology of chinese hamster ovary (CHO) cells was examined after several days of culturing in presence of this medium.}, language = {en} } @misc{AlKaidyTippkoetterUlber2016, author = {Al-Kaidy, Huschyar and Tippk{\"o}tter, Nils and Ulber, Roland}, title = {Vorrichtung und Verfahren zur Bestimmung des Kontaktwinkels eines Fl{\"u}ssigk{\"o}rpers mit einer Festk{\"o}rperoberfl{\"a}che}, year = {2016}, abstract = {Die vorliegende Erfindung betrifft eine Vorrichtung und ein Verfahren zur Bestimmung des Kontaktwinkels eines fl{\"u}ssigen oder mit Fl{\"u}ssigkeit gef{\"u}llten K{\"o}rpers. Dieser besteht aus einem Tr{\"a}ger (1) und einer damit verbundenen, in einem Winkelbereich von mehr als 0 ° bis maximal 90 ° neigbaren Ebene (8) mit einer darin ausgebildeten Abrollbahn (9) f{\"u}r den fl{\"u}ssigen oder mit Fl{\"u}ssigkeit gef{\"u}llten K{\"o}rper. An der Ebene (8) sind mehrere Sensoren (11,12) zur Erfassung der Rolldauer des K{\"o}rpers entlang der Rollstrecke angeordnet. Erfindungsgem{\"a}ß ist vorgesehen, dass die Einstellung des Neigungswinkels der Ebene (8) {\"u}ber ein Winkelmessger{\"a}t (10) erfolgt, wodurch ein Abrollwinkel erfassbar ist, bei dem der K{\"o}rper in Bewegung ger{\"a}t. Aus der Rolldauer, der Rollstrecke und dem Abrollwinkel wird der Kontaktwinkel des K{\"o}rpers ermittelt.}, language = {de} } @article{AlKaidyTippkoetter2016, author = {Al-Kaidy, Huschyar and Tippk{\"o}tter, Nils}, title = {Superparamagnetic hydrophobic particles as shell material for digital microfluidic droplets and proof-of-principle reaction assessments with immobilized laccase}, series = {Engineering in Life Sciences}, volume = {16}, journal = {Engineering in Life Sciences}, number = {3}, publisher = {Wiley-VCH}, address = {Weinheim}, doi = {10.1002/elsc.201400124}, pages = {222 -- 230}, year = {2016}, abstract = {In the field of biotechnology and molecular biology, the use of small liquid volumes has significant advantages. In particular, screening and optimization runs with acceptable amounts of expensive and hardly available catalysts, reagents, or biomolecules are feasible with microfluidic technologies. The presented new microfluidic system is based on the inclusion of small liquid volumes by a protective shell of magnetizable microparticles. Hereby, discrete aqueous microreactor drops with volumes of 1-30 μL can be formed on a simple planar surface. A digital movement and manipulation of the microreactor is performed by overlapping magnetic forces. The magnetic forces are generated by an electrical coil matrix positioned below a glass plate. With the new platform technology, several discrete reaction compartments can be moved simultaneously on one surface. Due to the magnetic fields, the reactors can even be merged to initiate reactions by mixing or positioned above surface-immobilized catalysts and then opened by magnetic force. Comparative synthesis routes of the magnetizable shell particles and superhydrophobic glass slides including their performance and stability with the reaction platform are described. The influence of diffusive mass transport during the catalyzed reaction is discussed by evaluation finite element model of the microreactor. Furthermore, a first model dye reaction of the enzyme laccase has been established.}, language = {en} } @article{AlKaidyKuthanHeringetal.2016, author = {Al-Kaidy, Huschyar and Kuthan, Kai and Hering, Thomas and Tippk{\"o}tter, Nils}, title = {Aqueous droplets used as enzymatic microreactors and their electromagnetic actuation}, series = {Journal of Visualized Experiments}, journal = {Journal of Visualized Experiments}, number = {Issue 126}, issn = {1940-087X}, doi = {10.3791/54643}, year = {2016}, abstract = {For the successful implementation of microfluidic reaction systems, such as PCR and electrophoresis, the movement of small liquid volumes is essential. In conventional lab-on-a-chip-platforms, solvents and samples are passed through defined microfluidic channels with complex flow control installations. The droplet actuation platform presented here is a promising alternative. With it, it is possible to move a liquid drop (microreactor) on a planar surface of a reaction platform (lab-in-a-drop). The actuation of microreactors on the hydrophobic surface of the platform is based on the use of magnetic forces acting on the outer shell of the liquid drops which is made of a thin layer of superhydrophobic magnetite particles. The hydrophobic surface of the platform is needed to avoid any contact between the liquid core and the surface to allow a smooth movement of the microreactor. On the platform, one or more microreactors with volumes of 10 µL can be positioned and moved simultaneously. The platform itself consists of a 3 x 3 matrix of electrical double coils which accommodate either neodymium or iron cores. The magnetic field gradients are automatically controlled. By variation of the magnetic field gradients, the microreactors' magnetic hydrophobic shell can be manipulated automatically to move the microreactor or open the shell reversibly. Reactions of substrates and corresponding enzymes can be initiated by merging the microreactors or bringing them into contact with surface immobilized catalysts.}, language = {en} }