TY  - JOUR
A1  - Adrián-Martínez, S.
A1  - Albert, A.
A1  - André, M.
A1  - Anton, G.
A1  - Ardid, M.
A1  - Aubert, J.-J.
A1  - Avgitas, T.
A1  - Baret, B.
A1  - Barrios-Martí, J.
A1  - Basa, S.
A1  - Bertin, V.
A1  - Biagi, S.
A1  - Bormuth, R.
A1  - Bou-Cabo, M.
A1  - Bouwhuis, M.C.
A1  - Bruijn, R.
A1  - Brunner, J.
A1  - Busto, J.
A1  - Capone, A.
A1  - Caramete, L.
A1  - Carr, J.
A1  - Celli, S.
A1  - Chiarusi, T.
A1  - Circella, M.
A1  - Coleiro, A.
A1  - Coniglione, R.
A1  - Costantini, H.
A1  - Coyle, P.
A1  - Creusot, A.
A1  - Deschamps, A.
A1  - De Bonis, G.
A1  - Distefano, C.
A1  - Donzaud, C.
A1  - Dornic, D.
A1  - Drouhin, D.
A1  - Eberl, T.
A1  - El Bojaddaini, I.
A1  - Elsässer, D.
A1  - Enzenhöfer, A.
A1  - Fehn, K.
A1  - Felis, I.
A1  - Fusco, L.A.
A1  - Galatà, S.
A1  - Gay, P.
A1  - Geißelsöder, S.
A1  - Geyer, K.
A1  - Giordano, V.
A1  - Gleixner, A.
A1  - Glotin, H.
A1  - Gracia-Ruiz, R.
A1  - Graf, K.
A1  - Hallmann, S.
A1  - van Haren, H.
A1  - Heijboer, A.J.
A1  - Hello, Y.
A1  - Hernández-Rey, J.-J.
A1  - Hößl, J.
A1  - Hofestädt, J.
A1  - Hugon, C.
A1  - Illuminati, G.
A1  - James, C.W.
A1  - de Jong, M.
A1  - Kadler, M.
A1  - Kalekin, O.
A1  - Katz, U.
A1  - Kießling, D.
A1  - Kouchner, A.
A1  - Kreter, M.
A1  - Kreykenbohm, I.
A1  - Kulikovskiy, V.
A1  - Lachaud, C.
A1  - Lahmann, R.
A1  - Lefèvre, D.
A1  - Leonora, E.
A1  - Loucatos, S.
A1  - Marcelin, M.
A1  - Margiotta, A.
A1  - Marinelli, A.
A1  - Martínez-Mora, J.A.
A1  - Mathieu, A.
A1  - Michael, T.
A1  - Migliozzi, P.
A1  - Moussa, A.
A1  - Mueller, C.
A1  - Nezri, E.
A1  - Păvălaș, G.E.
A1  - Pellegrino, C.
A1  - Perrina, C.
A1  - Piattelli, P.
A1  - Popa, V.
A1  - Pradier, T.
A1  - Racca, C.
A1  - Riccobene, G.
A1  - Roensch, K.
A1  - Saldaña, M.
A1  - Samtleben, D.F.E.
A1  - Sanguineti, M.
A1  - Sapienza, P.
A1  - Schnabel, J.
A1  - Schüssler, F.
A1  - Seitz, T.
A1  - Sieger, C.
A1  - Spurio, M.
A1  - Stolarczyk, Th.
A1  - Sánchez-Losa, A.
A1  - Taiuti, M.
A1  - Trovato, A.
A1  - Tselengidou, M.
A1  - Turpin, D.
A1  - Tönnis, C.
A1  - Vallage, B.
A1  - Vallée, C.
A1  - Van Elewyck, V.
A1  - Vivolo, D.
A1  - Wagner, S.
A1  - Wilms, J.
A1  - Zornoza, J.D.
A1  - Zúñiga, J.
T1  - A search for Secluded Dark Matter in the Sun with the ANTARES neutrino telescope
JF  - Journal of Cosmology and Astroparticle Physics
N2  - A search for Secluded Dark Matter annihilation in the Sun using 2007-2012 data of the ANTARES neutrino telescope is presented. Three different cases are considered: a) detection of dimuons that result from the decay of the mediator, or neutrino detection from: b) mediator that decays into a dimuon and, in turn, into neutrinos, and c) mediator that decays directly into neutrinos. As no significant excess over background is observed, constraints are derived on the dark matter mass and the lifetime of the mediator.
KW  - dark matter experiments
KW  - neutrino detectors
KW  - dark matter detectors
KW  - neutrino astronomy
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-189035
VL  - 2016
IS  - 5
ER  - 
TY  - JOUR
A1  - Adrián-Martínez, S.
A1  - Albert, A.
A1  - André, M.
A1  - Anton, G.
A1  - Ardid, M.
A1  - Aubert, J.-J.
A1  - Avgitas, T.
A1  - Baret, B.
A1  - Barrios-Martí, J.
A1  - Basa, S.
A1  - Bertin, V.
A1  - Biagi, S.
A1  - Bormuth, R.
A1  - Bouwhuis, M.C.
A1  - Bruijn, R.
A1  - Brunner, J.
A1  - Busto, J.
A1  - Capone, A.
A1  - Caramete, L.
A1  - Carr, J.
A1  - Celli, S.
A1  - Chiarusi, T.
A1  - Circella, M.
A1  - Coleiro, A.
A1  - Coniglione, R.
A1  - Costantini, H.
A1  - Coyle, P.
A1  - Creusot, A.
A1  - Deschamps, A.
A1  - De Bonis, G.
A1  - Distefano, C.
A1  - Donzaud, C.
A1  - Dornic, D.
A1  - Drouhin, D.
A1  - Eberl, T.
A1  - El Bojaddaini, I.
A1  - Elsässer, D.
A1  - Enzenhöfer, A.
A1  - Fehn, K.
A1  - Felis, I.
A1  - Fusco, L.A.
A1  - Galatà, S.
A1  - Gay, P.
A1  - Geißelsöder, S.
A1  - Geyer, K.
A1  - Giordano, V.
A1  - Gleixner, A.
A1  - Glotin, H.
A1  - Gracia-Ruiz, R.
A1  - Graf, K.
A1  - Hallmann, S.
A1  - van Haren, H.
A1  - Heijboer, A.J.
A1  - Hello, Y.
A1  - Hernández-Rey, J.J.
A1  - Hößl, J.
A1  - Hofestädt, J.
A1  - Hugon, C.
A1  - Illuminati, G.
A1  - James, C.W.
A1  - de Jong, M.
A1  - Jongen, M.
A1  - Kadler, M.
A1  - Kalekin, O.
A1  - Katz, U.
A1  - Kießling, D.
A1  - Kouchner, A.
A1  - Kreter, M.
A1  - Kreykenbohm, I.
A1  - Kulikovskiy, V.
A1  - Lachaud, C.
A1  - Lahmann, R.
A1  - Lefèvre, D.
A1  - Leonora, E.
A1  - Loucatos, S.
A1  - Marcelin, M.
A1  - Margiotta, A.
A1  - Marinelli, A.
A1  - Martínez-Mora, J.A.
A1  - Mathieu, A.
A1  - Melis, K.
A1  - Michael, T.
A1  - Migliozzi, P.
A1  - Moussa, A.
A1  - Mueller, C.
A1  - Nezri, E.
A1  - Pavalas, G.E.
A1  - Pellegrino, C.
A1  - Perrina, C.
A1  - Piattelli, P.
A1  - Popa, V.
A1  - Pradier, T.
A1  - Racca, C.
A1  - Riccobene, G.
A1  - Roensch, K.
A1  - Saldaña, M.
A1  - Samtleben, D.F.E.
A1  - Sánchez-Losa, A.
A1  - Sanguineti, M.
A1  - Sapienza, P.
A1  - Schnabel, J.
A1  - Schüssler, F.
A1  - Seitz, T.
A1  - Sieger, C.
A1  - Spurio, M.
A1  - Stolarczyk, Th.
A1  - Taiuti, M.
A1  - Tönnis, C.
A1  - Trovato, A.
A1  - Tselengidou, M.
A1  - Turpin, D.
A1  - Vallage, B.
A1  - Vallée, C.
A1  - Van Elewyck, V.
A1  - Vivolo, D.
A1  - Wagner, S.
A1  - Wilms, J.
A1  - Zornoza, J.D.
A1  - Zúñiga, J.
T1  - Limits on dark matter annihilation in the sun using the ANTARES neutrino telescope
JF  - Physics Letters B
N2  - A search for muon neutrinos originating from dark matter annihilations in the Sun is performed using the data recorded by the ANTARES neutrino telescope from 2007 to 2012. In order to obtain the best possible sensitivities to dark matter signals, an optimisation of the event selection criteria is performed taking into account the background of atmospheric muons, atmospheric neutrinos and the energy spectra of the expected neutrino signals. No significant excess over the background is observed and 90% C.L. upper limits on the neutrino flux, the spin-dependent and spin-independent WIMP-nucleon cross-sections are derived for WIMP masses ranging from 50 GeV to 5 TeV for the annihilation channels WIMP + WIMP→ b\(\overline{b}\), W\(^{+}\)W\(^{−}\) and τ\(^{+}\)τ\(^{−}\).
KW  - dark matter
KW  - WIMP
KW  - neutralino
KW  - indirect detection
KW  - neutrino telescope
KW  - sun
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-166642
VL  - 759
ER  - 
TY  - JOUR
A1  - Adrián-Martínez, S.
A1  - Albert, A.
A1  - André, M.
A1  - Anghinolfi, M.
A1  - Anton, G.
A1  - Ardid, M.
A1  - Aubert, J.-J.
A1  - Avgitas, T.
A1  - Baret, B.
A1  - Barrios-Martí, J.
A1  - Basa, S.
A1  - Bertin, V.
A1  - Biagi, S.
A1  - Bormuth, R.
A1  - Bouwhuis, M.C.
A1  - Bruijn, R.
A1  - Brunner, J.
A1  - Busto, J.
A1  - Capone, A.
A1  - Caramete, L.
A1  - Carr, J.
A1  - Celli, S.
A1  - Chiarusi, T.
A1  - Circella, M.
A1  - Coleiro, A.
A1  - Coniglione, R.
A1  - Constantini, H.
A1  - Coyle, P.
A1  - Creusot, A.
A1  - Deschamps, A.
A1  - De Bonis, G.
A1  - Distefano, C.
A1  - Donzaud, C.
A1  - Dornic, D.
A1  - Drouhin, D.
A1  - Eberl, T.
A1  - El Bojaddaini, I.
A1  - Elsässer, D.
A1  - Enzenhöfer, A.
A1  - Fehn, K.
A1  - Felis, I.
A1  - Fusco, L.A.
A1  - Galatà, S.
A1  - Gay, P.
A1  - Geißelsöder, S.
A1  - Geyer, K.
A1  - Giordano, V.
A1  - Gleixner, A.
A1  - Glotin, H.
A1  - Gracia-Ruiz, R.
A1  - Graf, K.
A1  - Hallmann, S.
A1  - van Haren, H.
A1  - Heijboer, A.J.
A1  - Hello, Y.
A1  - Hernández-Rey, J.J.
A1  - Hößl, J.
A1  - Hofestädt, J.
A1  - Hugon, C.
A1  - Illuminati, G.
A1  - James, C.W.
A1  - de Jong, M.
A1  - Kadler, M.
A1  - Kalekin, O.
A1  - Katz, U.
A1  - Kießling, D.
A1  - Kouchner, A.
A1  - Kreter, M.
A1  - Kreykenbohm, I.
A1  - Kulikovskiy, V.
A1  - Lachaud, C.
A1  - Lahmann, R.
A1  - Lefèvre, D.
A1  - Leonora, E.
A1  - Loucatos, S.
A1  - Marcelin, M.
A1  - Margiotta, A.
A1  - Marinelli, A.
A1  - Martínez-Mora, J.A.
A1  - Mathieu, A.
A1  - Michael, T.
A1  - Migliozzi, P.
A1  - Moussa, A.
A1  - Mueller, C.
A1  - Nezri, E.
A1  - Pavalas, G.E.
A1  - Pellegrino, C.
A1  - Perrina, C.
A1  - Piattelli, P.
A1  - Popa, V.
A1  - Pradier, T.
A1  - Racca, C.
A1  - Riccobene, G.
A1  - Roensch, K.
A1  - Saldaña, M.
A1  - Samtleben, D.F.E.
A1  - Sánchez-Losa, A.
A1  - Sanguineti, M.
A1  - Sapienza, P.
A1  - Schnabel, J.
A1  - Schüssler, F.
A1  - Seitz, T.
A1  - Sieger, C.
A1  - Spurio, M.
A1  - Stolarczyk, Th.
A1  - Taiuti, M.
A1  - Trovato, A.
A1  - Tselengidou, M.
A1  - Turpin, D.
A1  - Tönnis, C.
A1  - Vallage, B.
A1  - Vallée, C.
A1  - Van Elewyck, V.
A1  - Visser, E.
A1  - Vivolo, D.
A1  - Wagner, S.
A1  - Wilms, J.
A1  - Zornoza, J.D.
A1  - Zúñiga, J.
T1  - Constraints on the neutrino emission from the Galactic Ridge with the ANTARES telescope
JF  - Physics Letters B
N2  - A highly significant excess of high-energy astrophysical neutrinos has been reported by the IceCube Collaboration. Some features of the energy and declination distributions of IceCube events hint at a North/South asymmetry of the neutrino flux. This could be due to the presence of the bulk of our Galaxy in the Southern hemisphere. The ANTARES neutrino telescope, located in the Mediterranean Sea, has been taking data since 2007. It offers the best sensitivity to muon neutrinos produced by galactic cosmic ray interactions in this region of the sky. In this letter a search for an extended neutrino flux from the Galactic Ridge region is presented. Different models of neutrino production by cosmic ray propagation are tested. No excess of events is observed and upper limits for different neutrino flux spectral indices Γ are set. For Γ=2.4 the 90% confidence level flux upper limit at 100 TeV for one neutrino flavour corresponds to Φ\(^{1f}_{0}\) (100 TeV) = 2.0 · 10\(^{−17}\) GeV\(^{−1}\) cm\(^{−2}\)s\(^{−1}\)sr\(^{−1}\). Under this assumption, at most two events of the IceCube cosmic candidates can originate from the Galactic Ridge. A simple power-law extrapolation of the Fermi-LAT flux to account for IceCube High Energy Starting Events is excluded at 90% confidence level.
KW  - neutrino emission
KW  - Galactic Ridge
KW  - ANTARES telescope
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-166608
VL  - 760
ER  - 
TY  - JOUR
A1  - Boschert, V.
A1  - Frisch, C.
A1  - Back, J. W.
A1  - van Pee,, K.
A1  - Weidauer, S. E.
A1  - Muth, E.-M.
A1  - Schmieder, P.
A1  - Beerbaum, M.
A1  - Knappik, A.
A1  - Timmerman, P.
A1  - Mueller, T. D.
T1  - The sclerostin-neutralizing antibody AbD09097 recognizes an epitope adjacent to sclerostin's binding site for the Wnt co-receptor LRP6
JF  - Open Biology
N2  - The glycoprotein sclerostin has been identified as a negative regulator of bone growth. It exerts its function by interacting with the Wnt co-receptor LRP5/6, blocks the binding of Wnt factors and thereby inhibits Wnt signalling. Neutralizing anti-sclerostin antibodies are able to restore Wnt activity and enhance bone growth thereby presenting a new osteoanabolic therapy approach for diseases such as osteoporosis. We have generated various Fab antibodies against human and murine sclerostin using a phage display set-up. Biochemical analyses have identified one Fab developed against murine sclerostin, AbD09097 that efficiently neutralizes sclerostin's Wnt inhibitory activity. In vitro interaction analysis using sclerostin variants revealed that this neutralizing Fab binds to sclerostin's flexible second loop, which has been shown to harbour the LRP5/6 binding motif. Affinity maturation was then applied to AbD09097, providing a set of improved neutralizing Fab antibodies which particularly bind human sclerostin with enhanced affinity. Determining the crystal structure of AbD09097 provides first insights into how this antibody might recognize and neutralize sclerostin. Together with the structure–function relationship derived from affinity maturation these new data will foster the rational design of new and highly efficient anti-sclerostin antibodies for the therapy of bone loss diseases such as osteoporosis.
KW  - phage display
KW  - Wnt signalling
KW  - sclerostin
KW  - neutralizing antibody
KW  - osteoporosis
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-177925
VL  - 6
ER  - 
TY  - JOUR
A1  - Böhm, J.
A1  - Scherzer, S.
A1  - Shabala, S.
A1  - Krol, E.
A1  - Neher, E.
A1  - Mueller, T. D.
A1  - Hedrich, R.
T1  - Venus flytrap HKT1-type channel provides for prey sodium uptake into carnivorous plant without conflicting with electrical excitability
JF  - Molecular Plant
N2  - The animal diet of the carnivorous Venus flytrap, Dionaea muscipula, contains a sodium load that enters the capture organ via an HKT1-type sodium channel, expressed in special epithelia cells on the inner trap lobe surface. DmHKT1 expression and sodium uptake activity is induced upon prey contact. Here, we analyzed the HKT1 properties required for prey sodium osmolyte management of carnivorous Dionaea. Analyses were based on homology modeling, generation of model-derived point mutants, and their functional testing in Xenopus oocytes. We showed that the wild-type HKT1 and its Na\(^+\)- and K\(^+\)-permeable mutants function as ion channels rather than K\(^+\) transporters driven by proton or sodium gradients. These structural and biophysical features of a high-capacity, Na\(^+\)-selective ion channel enable Dionaea glands to manage prey-derived sodium loads without confounding the action potential-based information management of the flytrap.
KW  - sodium channel
KW  - HKT1
KW  - Dionaea muscipula
KW  - action potential
KW  - glands
KW  - sodium uptake
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-189803
VL  - 9
IS  - 3
ER  - 
TY  - JOUR
A1  - Stange, Katja
A1  - Désir, Julie
A1  - Kakar, Naseebullah
A1  - Mueller, Thomas D.
A1  - Budde, Birgit S.
A1  - Gordon, Christopher T.
A1  - Horn, Denise
A1  - Seemann, Petra
A1  - Borck, Guntram
T1  - A hypomorphic BMPR1B mutation causes du Pan acromesomelic dysplasia
JF  - Orphanet Journal of Rare Diseases
N2  - Background: 
Grebe dysplasia, Hunter-Thompson dysplasia, and du Pan dysplasia constitute a spectrum of skeletal dysplasias inherited as an autosomal recessive trait characterized by short stature, severe acromesomelic shortening of the limbs, and normal axial skeleton. The majority of patients with these disorders have biallelic loss-of-function mutations of GDF5. In single instances, Grebe dysplasia and a Grebe dysplasia-like phenotype with genital anomalies have been shown to be caused by mutations in BMPR1B, encoding a GDF5 receptor. 

Methods: 
We clinically and radiologically characterised an acromesomelic chondrodysplasia in an adult woman born to consanguineous parents. We sequenced GDF5 and BMPR1B on DNA of the proposita. We performed 3D structural analysis and luciferase reporter assays to functionally investigate the identified BMPR1B mutation. 

Results: 
We extend the genotype-phenotype correlation in the acromesomelic chondrodysplasias by showing that the milder du Pan dysplasia can be caused by a hypomorphic BMPR1B mutation. We show that the homozygous c.91C>T, p.(Arg31Cys) mutation causing du Pan dysplasia leads to a significant loss of BMPR1B function, but to a lesser extent than the previously reported p.Cys53Arg mutation that results in the more severe Grebe dysplasia. 

Conclusions: 
The phenotypic severity gradient of the clinically and radiologically related acromesomelic chondrodysplasia spectrum of skeletal disorders may be due to the extent of functional impairment of the ligand-receptor pair GDF5-BMPR1B.
KW  - linkage analysis
KW  - chondrodysplasia
KW  - specificity
KW  - Grebe dysplasia
KW  - BMPR1B
KW  - du Pan dysplasia
KW  - tool
KW  - missense
KW  - grebe
KW  - protein-1 CDMP1 gene
KW  - Acromesomelic dysplasias
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-151650
VL  - 10
IS  - 84
ER  -