TY  - JOUR
A1  - Edgecock, T. R.
A1  - Caretta, O.
A1  - Davenne, T.
A1  - Densam, C.
A1  - Fitton, M.
A1  - Kelliher, D.
A1  - Loveridge, P.
A1  - Machida, S.
A1  - Prior, C.
A1  - Rogers, C.
A1  - Rooney, M.
A1  - Thomason, J.
A1  - Wilcox, D.
A1  - Wildner, E.
A1  - Efthymiopoulos, I.
A1  - Garoby, R.
A1  - Gilardoni, S.
A1  - Hansen, C.
A1  - Benedetto, E.
A1  - Jensen, E.
A1  - Kosmicki, A.
A1  - Martini, M.
A1  - Osborne, J.
A1  - Prior, G.
A1  - Stora, T.
A1  - Melo Mendonca, T.
A1  - Vlachoudis, V.
A1  - Waaijer, C.
A1  - Cupial, P.
A1  - Chancé, A.
A1  - Longhin, A.
A1  - Payet, J.
A1  - Zito, M.
A1  - Baussan, E.
A1  - Bobeth, C.
A1  - Bouquerel, E.
A1  - Dracos, M.
A1  - Gaudiot, G.
A1  - Lepers, B.
A1  - Osswald, F.
A1  - Poussot, P.
A1  - Vassilopoulos, N.
A1  - Wurtz, J.
A1  - Zeter, V.
A1  - Bielski, J.
A1  - Kozien, M.
A1  - Lacny, L.
A1  - Skoczen, B.
A1  - Szybinski, B.
A1  - Ustrycka, A.
A1  - Wroblewski, A.
A1  - Marie-Jeanne, M.
A1  - Balint, P.
A1  - Fourel, C.
A1  - Giraud, J.
A1  - Jacob, J.
A1  - Lamy, T.
A1  - Latrasse, L.
A1  - Sortais, P.
A1  - Thuillier, T.
A1  - Mitrofanov, S.
A1  - Loiselet, M.
A1  - Keutgen, Th.
A1  - Delbar, Th.
A1  - Debray, F.
A1  - Trophine, C.
A1  - Veys, S.
A1  - Daversin, C.
A1  - Zorin, V.
A1  - Izotov, I.
A1  - Skalyga, V.
A1  - Burt, G.
A1  - Dexter, A. C.
A1  - Kravchuk, V. L.
A1  - Marchi, T.
A1  - Cinausero, M.
A1  - Gramegna, F.
A1  - De Angelis, G.
A1  - Prete, G.
A1  - Collazuol, G.
A1  - Laveder, M.
A1  - Mazzocco, M.
A1  - Mezzetto, M.
A1  - Signorini, C.
A1  - Vardaci, E.
A1  - Di Nitto, A.
A1  - Brondi, A.
A1  - La Rana, G.
A1  - Migliozzi, P.
A1  - Moro, R.
A1  - Palladino, V.
A1  - Gelli, N.
A1  - Berkovits, D.
A1  - Hass, M.
A1  - Hirsh, T. Y.
A1  - Schuhmann, M.
A1  - Stahl, A.
A1  - Wehner, J.
A1  - Bross, A.
A1  - Kopp, J.
A1  - Neuffer, D.
A1  - Wands, R.
A1  - Bayes, R.
A1  - Laing, A.
A1  - Soler, P.
A1  - Agarwalla, S. K.
A1  - Cervera Villanueva, A.
A1  - Donini, A.
A1  - Ghosh, T.
A1  - Gómez Cadenas, J. J.
A1  - Hernández, P.
A1  - Martín-Albo, J.
A1  - Mena, O.
A1  - Burguet-Castell, J.
A1  - Agostino, L.
A1  - Buizza-Avanzini, M.
A1  - Marafini, M.
A1  - Patzak, T.
A1  - Tonazzo, A.
A1  - Duchesneau, D.
A1  - Mosca, L.
A1  - Bogomilov, M.
A1  - Karadzhov, Y.
A1  - Matev, R.
A1  - Tsenov, R.
A1  - Akhmedov, E.
A1  - Blennow, M.
A1  - Lindner, M.
A1  - Schwetz, T.
A1  - Fernández Martinez, E.
A1  - Maltoni, M.
A1  - Menéndez, J.
A1  - Giunti, C.
A1  - González García, M. C.
A1  - Salvado, J.
A1  - Coloma, P.
A1  - Huber, P.
A1  - Li, T.
A1  - López Pavón, J.
A1  - Orme, C.
A1  - Pascoli, S.
A1  - Meloni, D.
A1  - Tang, J.
A1  - Winter, W.
A1  - Ohlsson, T.
A1  - Zhang, H.
A1  - Scotto-Lavina, L.
A1  - Terranova, F.
A1  - Bonesini, M.
A1  - Tortora, L.
A1  - Alekou, A.
A1  - Aslaninejad, M.
A1  - Bontoiu, C.
A1  - Kurup, A.
A1  - Jenner, L. J.
A1  - Long, K.
A1  - Pasternak, J.
A1  - Pozimski, J.
A1  - Back, J. J.
A1  - Harrison, P.
A1  - Beard, K.
A1  - Bogacz, A.
A1  - Berg, J. S.
A1  - Stratakis, D.
A1  - Witte, H.
A1  - Snopok, P.
A1  - Bliss, N.
A1  - Cordwell, M.
A1  - Moss, A.
A1  - Pattalwar, S.
A1  - Apollonio, M.
T1  - High intensity neutrino oscillation facilities in Europe
JF  - Physical Review Special Topics-Accelerators and Beams
N2  - The EUROnu project has studied three possible options for future, high intensity neutrino oscillation facilities in Europe. The first is a Super Beam, in which the neutrinos come from the decay of pions created by bombarding targets with a 4 MW proton beam from the CERN High Power Superconducting Proton Linac. The far detector for this facility is the 500 kt MEMPHYS water Cherenkov, located in the Frejus tunnel. The second facility is the Neutrino Factory, in which the neutrinos come from the decay of mu(+) and mu(-) beams in a storage ring. The far detector in this case is a 100 kt magnetized iron neutrino detector at a baseline of 2000 km. The third option is a Beta Beam, in which the neutrinos come from the decay of beta emitting isotopes, in particular He-6 and Ne-18, also stored in a ring. The far detector is also the MEMPHYS detector in the Frejus tunnel. EUROnu has undertaken conceptual designs of these facilities and studied the performance of the detectors. Based on this, it has determined the physics reach of each facility, in particular for the measurement of CP violation in the lepton sector, and estimated the cost of construction. These have demonstrated that the best facility to build is the Neutrino Factory. However, if a powerful proton driver is constructed for another purpose or if the MEMPHYS detector is built for astroparticle physics, the Super Beam also becomes very attractive.
KW  - EMMA
KW  - beta-beam
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-126611
VL  - 16
IS  - 2
ER  - 
TY  - JOUR
A1  - Pfeiffer, A.
A1  - Hanack, C.
A1  - Kopp, R.
A1  - Tacke, R.
A1  - Moser, U.
A1  - Mutschler, E.
A1  - Lambrecht, G.
A1  - Herawi, M.
T1  - Human Gastric Mucosa Expresses Glandular M3 Subtype of Muscarinic Receptors
JF  - Digestive Diseases and Sciences
N2  - Five subtypes of muscarinic receptors have been distinguished by pharmacological and molecular biological methods. This report characterizes the muscarinic subtype present in human gastric mucosa by radioligand binding studies. The receptor density was 27 ± 6 fmol/mg protein and the tritiated ligand N-methylscopolamine had an affinity of (Kn) 0.39 ± 0.08 nM (n = 11). The M1 receptor selective antagonist pirenzepine and the M2 receptor selective ligand AF-DX 116 had low affinities of 148 ± 32 nM (n = 13) and 4043 ± 1011 nM (n = 3) K n , respectively. The glandular M3 antagonists hexahydrosiladifenidol and silahexocyclium had high affinities ofKn 78 ± 23 nM (n = 5) and 5.6 ± 1.8 nM (n = 3). The agonist carbachol interacted with a single low-affinity site and binding was insensitive to modulation by guanine nucleotides. Antagonist and agonist binding studies thus showed an affinity profile typical of M3 receptors of the glandular type.
KW  - glandular M3 receptor
KW  - acid secretion
KW  - muscarinic receptor subtype
KW  - human gastric mucosa
KW  - stomach
Y1  - 1990
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-128286
VL  - 35
IS  - 12
ER  - 
TY  - JOUR
A1  - Kopp, R.
A1  - Lambrecht, G.
A1  - Mutschler, E.
A1  - Moser, U.
A1  - Tacke, Reinhold
A1  - Pfeiffer, A.
T1  - Human HT-29 colon carcinoma cells contain mucarinic M\(_3\) receptors coupled to phosphoinositide metabolism
N2  - Five different musearlnie receptor subtypes ean be distinguished by the differenees in their amino aeid sequence, the eoupled signal transduetion system, pharmaeologieal binding properties and aetivation of ionie fluxes. The present study served to eharaeterize the binding profile of musearlnie receptors in human eolon eareinoma eells (HT-29) using seleetive musearlnie antagonists. The affinities of the compounds were eompared with their poteney to inhibit cholinergieally-aetivated phosphoinositide metabolism. Pirenzepine displaced [\(^3\)H]N-methyl-scopolamine binding and inhibited inositolphosphate (IP) release with potencies typieal of those of non-M\(_1\) receptors. The M\(_3\) subtype-selective antagonists sila-hexocyelium and hexahydro-sila-difenidol bad high affinity to the musearlnie reeeptors in HT-29 cells (K0 = 3.1 nM and 27 nM, respectively) and inhibited IP release at nanomolar concentrations. The M\(_2\) receptor antagonists, AF-DX 116 and methoctramine, had low antimusearinic poteneies. Our results demonstrate that HT-29 human colon earcinoma cells contain an apparently pure population of M\(_3\) receptors. These cells could serve as a model system for further investigations coneerning regulatory and signal transduction mechanisms associated with glandular muscarinic M\(_3\) receptors.
KW  - Anorganische Chemie
KW  - Muscarinic M3 receptor subtypes
KW  - HT-29 colon carcinoma cells
KW  - Phosphatidylinositol metabolism
KW  - AF-DX 116
Y1  - 1989
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-63989
ER  - 
TY  - JOUR
A1  - Pils, Stefan
A1  - Kopp, Kathrin
A1  - Peterson, Lisa
A1  - Tascon, Julia Delgado
A1  - Nyffenegger-Jann, Naja J.
A1  - Hauck, Christof R.
T1  - The Adaptor Molecule Nck Localizes the WAVE Complex to Promote Actin Polymerization during CEACAM3-Mediated Phagocytosis of Bacteria
JF  - PLoS One
N2  - Background: CEACAM3 is a granulocyte receptor mediating the opsonin-independent recognition and phagocytosis of human-restricted CEACAM-binding bacteria. CEACAM3 function depends on an intracellular immunoreceptor tyrosine-based activation motif (ITAM)-like sequence that is tyrosine phosphorylated by Src family kinases upon receptor engagement. The phosphorylated ITAM-like sequence triggers GTP-loading of Rac by directly associating with the guanine nucleotide exchange factor (GEF) Vav. Rac stimulation in turn is critical for actin cytoskeleton rearrangements that generate lamellipodial protrusions and lead to bacterial uptake. 
Principal Findings: In our present study we provide biochemical and microscopic evidence that the adaptor proteins Nck1 and Nck2, but not CrkL, Grb2 or SLP-76, bind to tyrosine phosphorylated CEACAM3. The association is phosphorylation-dependent and requires the Nck SH2 domain. Overexpression of the isolated Nck1 SH2 domain, RNAi-mediated knock-down of Nck1, or genetic deletion of Nck1 and Nck2 interfere with CEACAM3-mediated bacterial internalization and with the formation of lamellipodial protrusions. Nck is constitutively associated with WAVE2 and directs the actin nucleation promoting WAVE complex to tyrosine phosphorylated CEACAM3. In turn, dominant-negative WAVE2 as well as shRNA-mediated knock-down of WAVE2 or the WAVE-complex component Nap1 reduce internalization of bacteria. 
Conclusions: Our results provide novel mechanistic insight into CEACAM3-initiated phagocytosis. We suggest that the CEACAM3 ITAM-like sequence is optimized to co-ordinate a minimal set of cellular factors needed to efficiently trigger actin-based lamellipodial protrusions and rapid pathogen engulfment.
KW  - activation
KW  - neisseria gonorrhoeae
KW  - human pathogens
KW  - T cell
KW  - signal transduction
KW  - escherichia coli
KW  - epithelial cells
KW  - tyrosine kinase
KW  - receptor
KW  - adhesion
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-131747
VL  - 7
IS  - 3
ER  -