TY  - JOUR
A1  - Bousquet, J.
A1  - Farrell, J.
A1  - Crooks, G.
A1  - Hellings, P.
A1  - Bel, E. H.
A1  - Bewick, M.
A1  - Chavannes, N. H.
A1  - Correia de Sousa, J.
A1  - Cruz, A. A.
A1  - Haahtela, T.
A1  - Joos, G.
A1  - Khaltaev, N.
A1  - Malva, J.
A1  - Muraro, A.
A1  - Nogues, M.
A1  - Palkonen, S.
A1  - Pedersen, S.
A1  - Robalo-Cordeiro, C.
A1  - Samolinski, B.
A1  - Strandberg, T.
A1  - Valiulis, A.
A1  - Yorgancioglu, A.
A1  - Zuberbier, T.
A1  - Bedbrook, A.
A1  - Aberer, W.
A1  - Adachi, M.
A1  - Agusti, A.
A1  - Akdis, C. A.
A1  - Akdis, M.
A1  - Ankri, J.
A1  - Alonso, A.
A1  - Annesi-Maesano, I.
A1  - Ansotegui, I. J.
A1  - Anto, J. M.
A1  - Arnavielhe, S.
A1  - Arshad, H.
A1  - Bai, C.
A1  - Baiardini, I.
A1  - Bachert, C.
A1  - Baigenzhin, A. K.
A1  - Barbara, C.
A1  - Bateman, E. D.
A1  - Beghé, B.
A1  - Ben Kheder, A.
A1  - Bennoor, K. S.
A1  - Benson, M.
A1  - Bergmann, K. C.
A1  - Bieber, T.
A1  - Bindslev-Jensen, C.
A1  - Bjermer, L.
A1  - Blain, H.
A1  - Blasi, F.
A1  - Boner, A. L.
A1  - Bonini, M.
A1  - Bonini, S.
A1  - Bosnic-Anticevitch, S.
A1  - Boulet, L. P.
A1  - Bourret, R.
A1  - Bousquet, P. J.
A1  - Braido, F.
A1  - Briggs, A. H.
A1  - Brightling, C. E.
A1  - Brozek, J.
A1  - Buhl, R.
A1  - Burney, P. G.
A1  - Bush, A.
A1  - Caballero-Fonseca, F.
A1  - Caimmi, D.
A1  - Calderon, M. A.
A1  - Calverley, P. M.
A1  - Camargos, P. A. M.
A1  - Canonica, G. W.
A1  - Camuzat, T.
A1  - Carlsen, K. H.
A1  - Carr, W.
A1  - Carriazo, A.
A1  - Casale, T.
A1  - Cepeda Sarabia, A. M.
A1  - Chatzi, L.
A1  - Chen, Y. Z.
A1  - Chiron, R.
A1  - Chkhartishvili, E.
A1  - Chuchalin, A. G.
A1  - Chung, K. F.
A1  - Ciprandi, G.
A1  - Cirule, I.
A1  - Cox, L.
A1  - Costa, D. J.
A1  - Custovic, A.
A1  - Dahl, R.
A1  - Dahlen, S. E.
A1  - Darsow, U.
A1  - De Carlo, G.
A1  - De Blay, F.
A1  - Dedeu, T.
A1  - Deleanu, D.
A1  - De Manuel Keenoy, E.
A1  - Demoly, P.
A1  - Denburg, J. A.
A1  - Devillier, P.
A1  - Didier, A.
A1  - Dinh-Xuan, A. T.
A1  - Djukanovic, R.
A1  - Dokic, D.
A1  - Douagui, H.
A1  - Dray, G.
A1  - Dubakiene, R.
A1  - Durham, S. R.
A1  - Dykewicz, M. S.
A1  - El-Gamal, Y.
A1  - Emuzyte, R.
A1  - Fabbri, L. M.
A1  - Fletcher, M.
A1  - Fiocchi, A.
A1  - Fink Wagner, A.
A1  - Fonseca, J.
A1  - Fokkens, W. J.
A1  - Forastiere, F.
A1  - Frith, P.
A1  - Gaga, M.
A1  - Gamkrelidze, A.
A1  - Garces, J.
A1  - Garcia-Aymerich, J.
A1  - Gemicioğlu, B.
A1  - Gereda, J. E.
A1  - González Diaz, S.
A1  - Gotua, M.
A1  - Grisle, I.
A1  - Grouse, L.
A1  - Gutter, Z.
A1  - Guzmán, M. A.
A1  - Heaney, L. G.
A1  - Hellquist-Dahl, B.
A1  - Henderson, D.
A1  - Hendry, A.
A1  - Heinrich, J.
A1  - Heve, D.
A1  - Horak, F.
A1  - Hourihane, J. O’. B.
A1  - Howarth, P.
A1  - Humbert, M.
A1  - Hyland, M. E.
A1  - Illario, M.
A1  - Ivancevich, J. C.
A1  - Jardim, J. R.
A1  - Jares, E. J.
A1  - Jeandel, C.
A1  - Jenkins, C.
A1  - Johnston, S. L.
A1  - Jonquet, O.
A1  - Julge, K.
A1  - Jung, K. S.
A1  - Just, J.
A1  - Kaidashev, I.
A1  - Kaitov, M. R.
A1  - Kalayci, O.
A1  - Kalyoncu, A. F.
A1  - Keil, T.
A1  - Keith, P. K.
A1  - Klimek, L.
A1  - Koffi N’Goran, B.
A1  - Kolek, V.
A1  - Koppelman, G. H.
A1  - Kowalski, M. L.
A1  - Kull, I.
A1  - Kuna, P.
A1  - Kvedariene, V.
A1  - Lambrecht, B.
A1  - Lau, S.
A1  - Larenas‑Linnemann, D.
A1  - Laune, D.
A1  - Le, L. T. T.
A1  - Lieberman, P.
A1  - Lipworth, B.
A1  - Li, J.
A1  - Lodrup Carlsen, K.
A1  - Louis, R.
A1  - MacNee, W.
A1  - Magard, Y.
A1  - Magnan, A.
A1  - Mahboub, B.
A1  - Mair, A.
A1  - Majer, I.
A1  - Makela, M. J.
A1  - Manning, P.
A1  - Mara, S.
A1  - Marshall, G. D.
A1  - Masjedi, M. R.
A1  - Matignon, P.
A1  - Maurer, M.
A1  - Mavale‑Manuel, S.
A1  - Melén, E.
A1  - Melo‑Gomes, E.
A1  - Meltzer, E. O.
A1  - Menzies‑Gow, A.
A1  - Merk, H.
A1  - Michel, J. P.
A1  - Miculinic, N.
A1  - Mihaltan, F.
A1  - Milenkovic, B.
A1  - Mohammad, G. M. Y.
A1  - Molimard, M.
A1  - Momas, I.
A1  - Montilla‑Santana, A.
A1  - Morais‑Almeida, M.
A1  - Morgan, M.
A1  - Mösges, R.
A1  - Mullol, J.
A1  - Nafti, S.
A1  - Namazova‑Baranova, L.
A1  - Naclerio, R.
A1  - Neou, A.
A1  - Neffen, H.
A1  - Nekam, K.
A1  - Niggemann, B.
A1  - Ninot, G.
A1  - Nyembue, T. D.
A1  - O’Hehir, R. E.
A1  - Ohta, K.
A1  - Okamoto, Y.
A1  - Okubo, K.
A1  - Ouedraogo, S.
A1  - Paggiaro, P.
A1  - Pali‑Schöll, I.
A1  - Panzner, P.
A1  - Papadopoulos, N.
A1  - Papi, A.
A1  - Park, H. S.
A1  - Passalacqua, G.
A1  - Pavord, I.
A1  - Pawankar, R.
A1  - Pengelly, R.
A1  - Pfaar, O.
A1  - Picard, R.
A1  - Pigearias, B.
A1  - Pin, I.
A1  - Plavec, D.
A1  - Poethig, D.
A1  - Pohl, W.
A1  - Popov, T. A.
A1  - Portejoie, F.
A1  - Potter, P.
A1  - Postma, D.
A1  - Price, D.
A1  - Rabe, K. F.
A1  - Raciborski, F.
A1  - Radier Pontal, F.
A1  - Repka‑Ramirez, S.
A1  - Reitamo, S.
A1  - Rennard, S.
A1  - Rodenas, F.
A1  - Roberts, J.
A1  - Roca, J.
A1  - Rodriguez Mañas, L.
A1  - et al, 
T1  - Scaling up strategies of the chronic respiratory disease programme of the European Innovation Partnership on Active and Healthy Ageing (Action Plan B3: Area 5)
JF  - Clinical and Translational Allergy
N2  - Action Plan B3 of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) focuses on the integrated care of chronic diseases. Area 5 (Care Pathways) was initiated using chronic respiratory diseases as a model. The chronic respiratory disease action plan includes (1) AIRWAYS integrated care pathways (ICPs), (2) the joint initiative between the Reference site MACVIA-LR (Contre les MAladies Chroniques pour un VIeillissement Actif) and ARIA (Allergic Rhinitis and its Impact on Asthma), (3) Commitments for Action to the European Innovation Partnership on Active and Healthy Ageing and the AIRWAYS ICPs network. It is deployed in collaboration with the World Health Organization Global Alliance against Chronic Respiratory Diseases (GARD). The European Innovation Partnership on Active and Healthy Ageing has proposed a 5-step framework for developing an individual scaling up strategy: (1) what to scale up: (1-a) databases of good practices, (1-b) assessment of viability of the scaling up of good practices, (1-c) classification of good practices for local replication and (2) how to scale up: (2-a) facilitating partnerships for scaling up, (2-b) implementation of key success factors and lessons learnt, including emerging technologies for individualised and predictive medicine. This strategy has already been applied to the chronic respiratory disease action plan of the European Innovation Partnership on Active and Healthy Ageing.
KW  - EIP on AHA
KW  - European Innovation Partnership on Active and Healthy Ageing
KW  - AIRWAYS ICPs
KW  - MACVIA
KW  - Scaling up
KW  - Chronic respiratory diseases
KW  - ARIA
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-166874
VL  - 6
IS  - 29
ER  - 
TY  - JOUR
A1  - Galluzzi, L.
A1  - Bravo-San Pedro, J. M.
A1  - Vitale, I.
A1  - Aaronson, S. A.
A1  - Abrams, J. M.
A1  - Adam, D.
A1  - Alnemri, E. S.
A1  - Altucci, L.
A1  - Andrews, D.
A1  - Annicchiarico-Petruzelli, M.
A1  - Baehrecke, E. H.
A1  - Bazan, N. G.
A1  - Bertrand, M. J.
A1  - Bianchi, K.
A1  - Blagosklonny, M. V.
A1  - Blomgren, K.
A1  - Borner, C.
A1  - Bredesen, D. E.
A1  - Brenner, C.
A1  - Campanella, M.
A1  - Candi, E.
A1  - Cecconi, F.
A1  - Chan, F. K.
A1  - Chandel, N. S.
A1  - Cheng, E. H.
A1  - Chipuk, J. E.
A1  - Cidlowski, J. A.
A1  - Ciechanover, A.
A1  - Dawson, T. M.
A1  - Dawson, V. L.
A1  - De Laurenzi, V.
A1  - De Maria, R.
A1  - Debatin, K. M.
A1  - Di Daniele, N.
A1  - Dixit, V. M.
A1  - Dynlacht, B. D.
A1  - El-Deiry, W. S.
A1  - Fimia, G. M.
A1  - Flavell, R. A.
A1  - Fulda, S.
A1  - Garrido, C.
A1  - Gougeon, M. L.
A1  - Green, D. R.
A1  - Gronemeyer, H.
A1  - Hajnoczky, G.
A1  - Hardwick, J. M.
A1  - Hengartner, M. O.
A1  - Ichijo, H.
A1  - Joseph, B.
A1  - Jost, P. J.
A1  - Kaufmann, T.
A1  - Kepp, O.
A1  - Klionsky, D. J.
A1  - Knight, R. A.
A1  - Kumar, S.
A1  - Lemasters, J. J.
A1  - Levine, B.
A1  - Linkermann, A.
A1  - Lipton, S. A.
A1  - Lockshin, R. A.
A1  - López-Otín, C.
A1  - Lugli, E.
A1  - Madeo, F.
A1  - Malorni, W.
A1  - Marine, J. C.
A1  - Martin, S. J.
A1  - Martinou, J. C.
A1  - Medema, J. P.
A1  - Meier, P.
A1  - Melino, S.
A1  - Mizushima, N.
A1  - Moll, U.
A1  - Muñoz-Pinedo, C.
A1  - Nuñez, G.
A1  - Oberst, A.
A1  - Panaretakis, T.
A1  - Penninger, J. M.
A1  - Peter, M. E.
A1  - Piacentini, M.
A1  - Pinton, P.
A1  - Prehn, J. H.
A1  - Puthalakath, H.
A1  - Rabinovich, G. A.
A1  - Ravichandran, K. S.
A1  - Rizzuto, R.
A1  - Rodrigues, C. M.
A1  - Rubinsztein, D. C.
A1  - Rudel, T.
A1  - Shi, Y.
A1  - Simon, H. U.
A1  - Stockwell, B. R.
A1  - Szabadkai, G.
A1  - Tait, S. W.
A1  - Tang, H. L.
A1  - Tavernarakis, N.
A1  - Tsujimoto, Y.
A1  - Vanden Berghe, T.
A1  - Vandenabeele, P.
A1  - Villunger, A.
A1  - Wagner, E. F.
A1  - Walczak, H.
A1  - White, E.
A1  - Wood, W. G.
A1  - Yuan, J.
A1  - Zakeri, Z.
A1  - Zhivotovsky, B.
A1  - Melino, G.
A1  - Kroemer, G.
T1  - Essential versus accessory aspects of cell death: recommendations of the NCCD 2015
JF  - Cell Death and Differentiation
N2  - Cells exposed to extreme physicochemical or mechanical stimuli die in an uncontrollable manner, as a result of their immediate structural breakdown. Such an unavoidable variant of cellular demise is generally referred to as 'accidental cell death' (ACD). In most settings, however, cell death is initiated by a genetically encoded apparatus, correlating with the fact that its course can be altered by pharmacologic or genetic interventions. 'Regulated cell death' (RCD) can occur as part of physiologic programs or can be activated once adaptive responses to perturbations of the extracellular or intracellular microenvironment fail. The biochemical phenomena that accompany RCD may be harnessed to classify it into a few subtypes, which often (but not always) exhibit stereotyped morphologic features. Nonetheless, efficiently inhibiting the processes that are commonly thought to cause RCD, such as the activation of executioner caspases in the course of apoptosis, does not exert true cytoprotective effects in the mammalian system, but simply alters the kinetics of cellular demise as it shifts its morphologic and biochemical correlates. Conversely, bona fide cytoprotection can be achieved by inhibiting the transduction of lethal signals in the early phases of the process, when adaptive responses are still operational. Thus, the mechanisms that truly execute RCD may be less understood, less inhibitable and perhaps more homogeneous than previously thought. Here, the Nomenclature Committee on Cell Death formulates a set of recommendations to help scientists and researchers to discriminate between essential and accessory aspects of cell death.
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-121207
VL  - 22
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  - 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  - Davis, Lea K.
A1  - Yu, Dongmei
A1  - Keenan, Clare L.
A1  - Gamazon, Eric R.
A1  - Konkashbaev, Anuar I.
A1  - Derks, Eske M.
A1  - Neale, Benjamin M.
A1  - Yang, Jian
A1  - Lee, S. Hong
A1  - Evans, Patrick
A1  - Barr, Cathy L.
A1  - Bellodi, Laura
A1  - Benarroch, Fortu
A1  - Berrio, Gabriel Bedoya
A1  - Bienvenu, Oscar J.
A1  - Bloch, Michael H.
A1  - Blom, Rianne M.
A1  - Bruun, Ruth D.
A1  - Budman, Cathy L.
A1  - Camarena, Beatriz
A1  - Campbell, Desmond
A1  - Cappi, Carolina
A1  - Cardona Silgado, Julio C.
A1  - Cath, Danielle C.
A1  - Cavallini, Maria C.
A1  - Chavira, Denise A.
A1  - Chouinard, Sylvian
A1  - Conti, David V.
A1  - Cook, Edwin H.
A1  - Coric, Vladimir
A1  - Cullen, Bernadette A.
A1  - Deforce, Dieter
A1  - Delorme, Richard
A1  - Dion, Yves
A1  - Edlund, Christopher K.
A1  - Egberts, Karin
A1  - Falkai, Peter
A1  - Fernandez, Thomas V.
A1  - Gallagher, Patience J.
A1  - Garrido, Helena
A1  - Geller, Daniel
A1  - Girard, Simon L.
A1  - Grabe, Hans J.
A1  - Grados, Marco A.
A1  - Greenberg, Benjamin D.
A1  - Gross-Tsur, Varda
A1  - Haddad, Stephen
A1  - Heiman, Gary A.
A1  - Hemmings, Sian M. J.
A1  - Hounie, Ana G.
A1  - Illmann, Cornelia
A1  - Jankovic, Joseph
A1  - Jenike, Micheal A.
A1  - Kennedy, James L.
A1  - King, Robert A.
A1  - Kremeyer, Barbara
A1  - Kurlan, Roger
A1  - Lanzagorta, Nuria
A1  - Leboyer, Marion
A1  - Leckman, James F.
A1  - Lennertz, Leonhard
A1  - Liu, Chunyu
A1  - Lochner, Christine
A1  - Lowe, Thomas L.
A1  - Macciardi, Fabio
A1  - McCracken, James T.
A1  - McGrath, Lauren M.
A1  - Restrepo, Sandra C. Mesa
A1  - Moessner, Rainald
A1  - Morgan, Jubel
A1  - Muller, Heike
A1  - Murphy, Dennis L.
A1  - Naarden, Allan L.
A1  - Ochoa, William Cornejo
A1  - Ophoff, Roel A.
A1  - Osiecki, Lisa
A1  - Pakstis, Andrew J.
A1  - Pato, Michele T.
A1  - Pato, Carlos N.
A1  - Piacentini, John
A1  - Pittenger, Christopher
A1  - Pollak, Yehunda
A1  - Rauch, Scott L.
A1  - Renner, Tobias J.
A1  - Reus, Victor I.
A1  - Richter, Margaret A.
A1  - Riddle, Mark A.
A1  - Robertson, Mary M.
A1  - Romero, Roxana
A1  - Rosàrio, Maria C.
A1  - Rosenberg, David
A1  - Rouleau, Guy A.
A1  - Ruhrmann, Stephan
A1  - Ruiz-Linares, Andreas
A1  - Sampaio, Aline S.
A1  - Samuels, Jack
A1  - Sandor, Paul
A1  - Sheppard, Broke
A1  - Singer, Harvey S.
A1  - Smit, Jan H.
A1  - Stein, Dan J.
A1  - Strengman, E.
A1  - Tischfield, Jay A.
A1  - Valencia Duarte, Ana V.
A1  - Vallada, Homero
A1  - Van Nieuwerburgh, Flip
A1  - Veenstra-VanderWeele, Jeremy
A1  - Walitza, Susanne
A1  - Wang, Ying
A1  - Wendland, Jens R.
A1  - Westenberg, Herman G. M.
A1  - Shugart, Yin Yao
A1  - Miguel, Euripedes C.
A1  - McMahon, William
A1  - Wagner, Michael
A1  - Nicolini, Humberto
A1  - Posthuma, Danielle
A1  - Hanna, Gregory L.
A1  - Heutink, Peter
A1  - Denys, Damiaan
A1  - Arnold, Paul D.
A1  - Oostra, Ben A.
A1  - Nestadt, Gerald
A1  - Freimer, Nelson B.
A1  - Pauls, David L.
A1  - Wray, Naomi R.
A1  - Stewart, S. Evelyn
A1  - Mathews, Carol A.
A1  - Knowles, James A.
A1  - Cox, Nancy J.
A1  - Scharf, Jeremiah M.
T1  - Partitioning the Heritability of Tourette Syndrome and Obsessive Compulsive Disorder Reveals Differences in Genetic Architecture
JF  - PLoS Genetics
N2  - The direct estimation of heritability from genome-wide common variant data as implemented in the program Genome-wide Complex Trait Analysis (GCTA) has provided a means to quantify heritability attributable to all interrogated variants. We have quantified the variance in liability to disease explained by all SNPs for two phenotypically-related neurobehavioral disorders, obsessive-compulsive disorder (OCD) and Tourette Syndrome (TS), using GCTA. Our analysis yielded a heritability point estimate of 0.58 (se = 0.09, p = 5.64e-12) for TS, and 0.37 (se = 0.07, p = 1.5e-07) for OCD. In addition, we conducted multiple genomic partitioning analyses to identify genomic elements that concentrate this heritability. We examined genomic architectures of TS and OCD by chromosome, MAF bin, and functional annotations. In addition, we assessed heritability for early onset and adult onset OCD. Among other notable results, we found that SNPs with a minor allele frequency of less than 5% accounted for 21% of the TS heritability and 0% of the OCD heritability. Additionally, we identified a significant contribution to TS and OCD heritability by variants significantly associated with gene expression in two regions of the brain (parietal cortex and cerebellum) for which we had available expression quantitative trait loci (eQTLs). Finally we analyzed the genetic correlation between TS and OCD, revealing a genetic correlation of 0.41 (se = 0.15, p = 0.002). These results are very close to previous heritability estimates for TS and OCD based on twin and family studies, suggesting that very little, if any, heritability is truly missing (i.e., unassayed) from TS and OCD GWAS studies of common variation. The results also indicate that there is some genetic overlap between these two phenotypically-related neuropsychiatric disorders, but suggest that the two disorders have distinct genetic architectures.
KW  - TIC disorders
KW  - missing heritability
KW  - complex diseases
KW  - neuropsychiatric disorders
KW  - common SNPS
KW  - gilles
KW  - family
KW  - brain
KW  - expression
KW  - autism
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-127377
SN  - 1553-7390
VL  - 9
IS  - 10
ER  - 
TY  - JOUR
A1  - Bousquet, Jean
A1  - Anto, Josep M.
A1  - Bachert, Claus
A1  - Haahtela, Tari
A1  - Zuberbier, Torsten
A1  - Czarlewski, Wienczyslawa
A1  - Bedbrook, Anna
A1  - Bosnic‐Anticevich, Sinthia
A1  - Walter Canonica, G.
A1  - Cardona, Victoria
A1  - Costa, Elisio
A1  - Cruz, Alvaro A.
A1  - Erhola, Marina
A1  - Fokkens, Wytske J.
A1  - Fonseca, Joao A.
A1  - Illario, Maddalena
A1  - Ivancevich, Juan‐Carlos
A1  - Jutel, Marek
A1  - Klimek, Ludger
A1  - Kuna, Piotr
A1  - Kvedariene, Violeta
A1  - Le, LTT
A1  - Larenas‐Linnemann, Désirée E.
A1  - Laune, Daniel
A1  - Lourenço, Olga M.
A1  - Melén, Erik
A1  - Mullol, Joaquim
A1  - Niedoszytko, Marek
A1  - Odemyr, Mikaëla
A1  - Okamoto, Yoshitaka
A1  - Papadopoulos, Nikos G.
A1  - Patella, Vincenzo
A1  - Pfaar, Oliver
A1  - Pham‐Thi, Nhân
A1  - Rolland, Christine
A1  - Samolinski, Boleslaw
A1  - Sheikh, Aziz
A1  - Sofiev, Mikhail
A1  - Suppli Ulrik, Charlotte
A1  - Todo‐Bom, Ana
A1  - Tomazic, Peter‐Valentin
A1  - Toppila‐Salmi, Sanna
A1  - Tsiligianni, Ioanna
A1  - Valiulis, Arunas
A1  - Valovirta, Erkka
A1  - Ventura, Maria‐Teresa
A1  - Walker, Samantha
A1  - Williams, Sian
A1  - Yorgancioglu, Arzu
A1  - Agache, Ioana
A1  - Akdis, Cezmi A.
A1  - Almeida, Rute
A1  - Ansotegui, Ignacio J.
A1  - Annesi‐Maesano, Isabella
A1  - Arnavielhe, Sylvie
A1  - Basagaña, Xavier
A1  - D. Bateman, Eric
A1  - Bédard, Annabelle
A1  - Bedolla‐Barajas, Martin
A1  - Becker, Sven
A1  - Bennoor, Kazi S.
A1  - Benveniste, Samuel
A1  - Bergmann, Karl C.
A1  - Bewick, Michael
A1  - Bialek, Slawomir
A1  - E. Billo, Nils
A1  - Bindslev‐Jensen, Carsten
A1  - Bjermer, Leif
A1  - Blain, Hubert
A1  - Bonini, Matteo
A1  - Bonniaud, Philippe
A1  - Bosse, Isabelle
A1  - Bouchard, Jacques
A1  - Boulet, Louis‐Philippe
A1  - Bourret, Rodolphe
A1  - Boussery, Koen
A1  - Braido, Fluvio
A1  - Briedis, Vitalis
A1  - Briggs, Andrew
A1  - Brightling, Christopher E.
A1  - Brozek, Jan
A1  - Brusselle, Guy
A1  - Brussino, Luisa
A1  - Buhl, Roland
A1  - Buonaiuto, Roland
A1  - Calderon, Moises A.
A1  - Camargos, Paulo
A1  - Camuzat, Thierry
A1  - Caraballo, Luis
A1  - Carriazo, Ana‐Maria
A1  - Carr, Warner
A1  - Cartier, Christine
A1  - Casale, Thomas
A1  - Cecchi, Lorenzo
A1  - Cepeda Sarabia, Alfonso M.
A1  - H. Chavannes, Niels
A1  - Chkhartishvili, Ekaterine
A1  - Chu, Derek K.
A1  - Cingi, Cemal
A1  - Correia de Sousa, Jaime
A1  - Costa, David J.
A1  - Courbis, Anne‐Lise
A1  - Custovic, Adnan
A1  - Cvetkosvki, Biljana
A1  - D'Amato, Gennaro
A1  - da Silva, Jane
A1  - Dantas, Carina
A1  - Dokic, Dejan
A1  - Dauvilliers, Yves
A1  - De Feo, Giulia
A1  - De Vries, Govert
A1  - Devillier, Philippe
A1  - Di Capua, Stefania
A1  - Dray, Gerard
A1  - Dubakiene, Ruta
A1  - Durham, Stephen R.
A1  - Dykewicz, Mark
A1  - Ebisawa, Motohiro
A1  - Gaga, Mina
A1  - El‐Gamal, Yehia
A1  - Heffler, Enrico
A1  - Emuzyte, Regina
A1  - Farrell, John
A1  - Fauquert, Jean‐Luc
A1  - Fiocchi, Alessandro
A1  - Fink‐Wagner, Antje
A1  - Fontaine, Jean‐François
A1  - Fuentes Perez, José M.
A1  - Gemicioğlu, Bilun
A1  - Gamkrelidze, Amiran
A1  - Garcia‐Aymerich, Judith
A1  - Gevaert, Philippe
A1  - Gomez, René Maximiliano
A1  - González Diaz, Sandra
A1  - Gotua, Maia
A1  - Guldemond, Nick A.
A1  - Guzmán, Maria‐Antonieta
A1  - Hajjam, Jawad
A1  - Huerta Villalobos, Yunuen R.
A1  - Humbert, Marc
A1  - Iaccarino, Guido
A1  - Ierodiakonou, Despo
A1  - Iinuma, Tomohisa
A1  - Jassem, Ewa
A1  - Joos, Guy
A1  - Jung, Ki‐Suck
A1  - Kaidashev, Igor
A1  - Kalayci, Omer
A1  - Kardas, Przemyslaw
A1  - Keil, Thomas
A1  - Khaitov, Musa
A1  - Khaltaev, Nikolai
A1  - Kleine‐Tebbe, Jorg
A1  - Kouznetsov, Rostislav
A1  - Kowalski, Marek L.
A1  - Kritikos, Vicky
A1  - Kull, Inger
A1  - La Grutta, Stefania
A1  - Leonardini, Lisa
A1  - Ljungberg, Henrik
A1  - Lieberman, Philip
A1  - Lipworth, Brian
A1  - Lodrup Carlsen, Karin C.
A1  - Lopes‐Pereira, Catarina
A1  - Loureiro, Claudia C.
A1  - Louis, Renaud
A1  - Mair, Alpana
A1  - Mahboub, Bassam
A1  - Makris, Michaël
A1  - Malva, Joao
A1  - Manning, Patrick
A1  - Marshall, Gailen D.
A1  - Masjedi, Mohamed R.
A1  - Maspero, Jorge F.
A1  - Carreiro‐Martins, Pedro
A1  - Makela, Mika
A1  - Mathieu‐Dupas, Eve
A1  - Maurer, Marcus
A1  - De Manuel Keenoy, Esteban
A1  - Melo‐Gomes, Elisabete
A1  - Meltzer, Eli O.
A1  - Menditto, Enrica
A1  - Mercier, Jacques
A1  - Micheli, Yann
A1  - Miculinic, Neven
A1  - Mihaltan, Florin
A1  - Milenkovic, Branislava
A1  - Mitsias, Dimitirios I.
A1  - Moda, Giuliana
A1  - Mogica‐Martinez, Maria‐Dolores
A1  - Mohammad, Yousser
A1  - Montefort, Steve
A1  - Monti, Ricardo
A1  - Morais‐Almeida, Mario
A1  - Mösges, Ralph
A1  - Münter, Lars
A1  - Muraro, Antonella
A1  - Murray, Ruth
A1  - Naclerio, Robert
A1  - Napoli, Luigi
A1  - Namazova‐Baranova, Leyla
A1  - Neffen, Hugo
A1  - Nekam, Kristoff
A1  - Neou, Angelo
A1  - Nordlund, Björn
A1  - Novellino, Ettore
A1  - Nyembue, Dieudonné
A1  - O'Hehir, Robyn
A1  - Ohta, Ken
A1  - Okubo, Kimi
A1  - Onorato, Gabrielle L.
A1  - Orlando, Valentina
A1  - Ouedraogo, Solange
A1  - Palamarchuk, Julia
A1  - Pali‐Schöll, Isabella
A1  - Panzner, Peter
A1  - Park, Hae‐Sim
A1  - Passalacqua, Gianni
A1  - Pépin, Jean‐Louis
A1  - Paulino, Ema
A1  - Pawankar, Ruby
A1  - Phillips, Jim
A1  - Picard, Robert
A1  - Pinnock, Hilary
A1  - Plavec, Davor
A1  - Popov, Todor A.
A1  - Portejoie, Fabienne
A1  - Price, David
A1  - Prokopakis, Emmanuel P.
A1  - Psarros, Fotis
A1  - Pugin, Benoit
A1  - Puggioni, Francesca
A1  - Quinones‐Delgado, Pablo
A1  - Raciborski, Filip
A1  - Rajabian‐Söderlund, Rojin
A1  - Regateiro, Frederico S.
A1  - Reitsma, Sietze
A1  - Rivero‐Yeverino, Daniela
A1  - Roberts, Graham
A1  - Roche, Nicolas
A1  - Rodriguez‐Zagal, Erendira
A1  - Rolland, Christine
A1  - Roller‐Wirnsberger, Regina E.
A1  - Rosario, Nelson
A1  - Romano, Antonino
A1  - Rottem, Menachem
A1  - Ryan, Dermot
A1  - Salimäki, Johanna
A1  - Sanchez‐Borges, Mario M.
A1  - Sastre, Joaquin
A1  - Scadding, Glenis K.
A1  - Scheire, Sophie
A1  - Schmid‐Grendelmeier, Peter
A1  - Schünemann, Holger J.
A1  - Sarquis Serpa, Faradiba
A1  - Shamji, Mohamed
A1  - Sisul, Juan‐Carlos
A1  - Sofiev, Mikhail
A1  - Solé, Dirceu
A1  - Somekh, David
A1  - Sooronbaev, Talant
A1  - Sova, Milan
A1  - Spertini, François
A1  - Spranger, Otto
A1  - Stellato, Cristiana
A1  - Stelmach, Rafael
A1  - Thibaudon, Michel
A1  - To, Teresa
A1  - Toumi, Mondher
A1  - Usmani, Omar
A1  - Valero, Antonio A.
A1  - Valenta, Rudolph
A1  - Valentin‐Rostan, Marylin
A1  - Pereira, Marilyn Urrutia
A1  - van der Kleij, Rianne
A1  - Van Eerd, Michiel
A1  - Vandenplas, Olivier
A1  - Vasankari, Tuula
A1  - Vaz Carneiro, Antonio
A1  - Vezzani, Giorgio
A1  - Viart, Frédéric
A1  - Viegi, Giovanni
A1  - Wallace, Dana
A1  - Wagenmann, Martin
A1  - Wang, De Yun
A1  - Waserman, Susan
A1  - Wickman, Magnus
A1  - Williams, Dennis M.
A1  - Wong, Gary
A1  - Wroczynski, Piotr
A1  - Yiallouros, Panayiotis K.
A1  - Yusuf, Osman M.
A1  - Zar, Heather J.
A1  - Zeng, Stéphane
A1  - Zernotti, Mario E.
A1  - Zhang, Luo
A1  - Shan Zhong, Nan
A1  - Zidarn, Mihaela
T1  - ARIA digital anamorphosis: Digital transformation of health and care in airway diseases from research to practice
JF  - Allergy
N2  - Digital anamorphosis is used to define a distorted image of health and care that may be viewed correctly using digital tools and strategies. MASK digital anamorphosis represents the process used by MASK to develop the digital transformation of health and care in rhinitis. It strengthens the ARIA change management strategy in the prevention and management of airway disease. The MASK strategy is based on validated digital tools. Using the MASK digital tool and the CARAT online enhanced clinical framework, solutions for practical steps of digital enhancement of care are proposed.
KW  - ARIA
KW  - asthma
KW  - CARAT
KW  - digital transformation of health and care
KW  - MASK
KW  - rhinitis
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-228339
VL  - 76
IS  - 1
SP  - 168
EP  - 190
ER  - 
TY  - JOUR
A1  - Dumont, Martine
A1  - Weber-Lassalle, Nana
A1  - Joly-Beauparlant, Charles
A1  - Ernst, Corinna
A1  - Droit, Arnaud
A1  - Feng, Bing-Jian
A1  - Dubois, Stéphane
A1  - Collin-Deschesnes, Annie-Claude
A1  - Soucy, Penny
A1  - Vallée, Maxime
A1  - Fournier, Frédéric
A1  - Lemaçon, Audrey
A1  - Adank, Muriel A.
A1  - Allen, Jamie
A1  - Altmüller, Janine
A1  - Arnold, Norbert
A1  - Ausems, Margreet G. E. M.
A1  - Berutti, Riccardo
A1  - Bolla, Manjeet K.
A1  - Bull, Shelley
A1  - Carvalho, Sara
A1  - Cornelissen, Sten
A1  - Dufault, Michael R.
A1  - Dunning, Alison M.
A1  - Engel, Christoph
A1  - Gehrig, Andrea
A1  - Geurts-Giele, Willemina R. R.
A1  - Gieger, Christian
A1  - Green, Jessica
A1  - Hackmann, Karl
A1  - Helmy, Mohamed
A1  - Hentschel, Julia
A1  - Hogervorst, Frans B. L.
A1  - Hollestelle, Antoinette
A1  - Hooning, Maartje J.
A1  - Horváth, Judit
A1  - Ikram, M. Arfan
A1  - Kaulfuß, Silke
A1  - Keeman, Renske
A1  - Kuang, Da
A1  - Luccarini, Craig
A1  - Maier, Wolfgang
A1  - Martens, John W. M.
A1  - Niederacher, Dieter
A1  - Nürnberg, Peter
A1  - Ott, Claus-Eric
A1  - Peters, Annette
A1  - Pharoah, Paul D. P.
A1  - Ramirez, Alfredo
A1  - Ramser, Juliane
A1  - Riedel-Heller, Steffi
A1  - Schmidt, Gunnar
A1  - Shah, Mitul
A1  - Scherer, Martin
A1  - Stäbler, Antje
A1  - Strom, Tim M.
A1  - Sutter, Christian
A1  - Thiele, Holger
A1  - van Asperen, Christi J.
A1  - van der Kolk, Lizet
A1  - van der Luijt, Rob B.
A1  - Volk, Alexander E.
A1  - Wagner, Michael
A1  - Waisfisz, Quinten
A1  - Wang, Qin
A1  - Wang-Gohrke, Shan
A1  - Weber, Bernhard H. F.
A1  - Devilee, Peter
A1  - Tavtigian, Sean
A1  - Bader, Gary D.
A1  - Meindl, Alfons
A1  - Goldgar, David E.
A1  - Andrulis, Irene L.
A1  - Schmutzler, Rita K.
A1  - Easton, Douglas F.
A1  - Schmidt, Marjanka K.
A1  - Hahnen, Eric
A1  - Simard, Jacques
T1  - Uncovering the contribution of moderate-penetrance susceptibility genes to breast cancer by whole-exome sequencing and targeted enrichment sequencing of candidate genes in women of European ancestry
JF  - Cancers
N2  - Rare variants in at least 10 genes, including BRCA1, BRCA2, PALB2, ATM, and CHEK2, are associated with increased risk of breast cancer; however, these variants, in combination with common variants identified through genome-wide association studies, explain only a fraction of the familial aggregation of the disease. To identify further susceptibility genes, we performed a two-stage whole-exome sequencing study. In the discovery stage, samples from 1528 breast cancer cases enriched for breast cancer susceptibility and 3733 geographically matched unaffected controls were sequenced. Using five different filtering and gene prioritization strategies, 198 genes were selected for further validation. These genes, and a panel of 32 known or suspected breast cancer susceptibility genes, were assessed in a validation set of 6211 cases and 6019 controls for their association with risk of breast cancer overall, and by estrogen receptor (ER) disease subtypes, using gene burden tests applied to loss-of-function and rare missense variants. Twenty genes showed nominal evidence of association (p-value < 0.05) with either overall or subtype-specific breast cancer. Our study had the statistical power to detect susceptibility genes with effect sizes similar to ATM, CHEK2, and PALB2, however, it was underpowered to identify genes in which susceptibility variants are rarer or confer smaller effect sizes. Larger sample sizes would be required in order to identify such genes.
KW  - breast cancer
KW  - genetic susceptibility
KW  - whole-exome sequencing
KW  - moderate-penetrance genes
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-281768
SN  - 2072-6694
VL  - 14
IS  - 14
ER  - 
TY  - JOUR
A1  - El-Helou, Sabine M.
A1  - Biegner, Anika-Kerstin
A1  - Bode, Sebastian
A1  - Ehl, Stephan R.
A1  - Heeg, Maximilian
A1  - Maccari, Maria E.
A1  - Ritterbusch, Henrike
A1  - Speckmann, Carsten
A1  - Rusch, Stephan
A1  - Scheible, Raphael
A1  - Warnatz, Klaus
A1  - Atschekzei, Faranaz
A1  - Beider, Renata
A1  - Ernst, Diana
A1  - Gerschmann, Stev
A1  - Jablonka, Alexandra
A1  - Mielke, Gudrun
A1  - Schmidt, Reinhold E.
A1  - Schürmann, Gesine
A1  - Sogkas, Georgios
A1  - Baumann, Ulrich H.
A1  - Klemann, Christian
A1  - Viemann, Dorothee
A1  - Bernuth, Horst von
A1  - Krüger, Renate
A1  - Hanitsch, Leif G.
A1  - Scheibenbogen, Carmen M.
A1  - Wittke, Kirsten
A1  - Albert, Michael H.
A1  - Eichinger, Anna
A1  - Hauck, Fabian
A1  - Klein, Christoph
A1  - Rack-Hoch, Anita
A1  - Sollinger, Franz M.
A1  - Avila, Anne
A1  - Borte, Michael
A1  - Borte, Stephan
A1  - Fasshauer, Maria
A1  - Hauenherm, Anja
A1  - Kellner, Nils
A1  - Müller, Anna H.
A1  - Ülzen, Anett
A1  - Bader, Peter
A1  - Bakhtiar, Shahrzad
A1  - Lee, Jae-Yun
A1  - Heß, Ursula
A1  - Schubert, Ralf
A1  - Wölke, Sandra
A1  - Zielen, Stefan
A1  - Ghosh, Sujal
A1  - Laws, Hans-Juergen
A1  - Neubert, Jennifer
A1  - Oommen, Prasad T.
A1  - Hönig, Manfred
A1  - Schulz, Ansgar
A1  - Steinmann, Sandra
A1  - Klaus, Schwarz
A1  - Dückers, Gregor
A1  - Lamers, Beate
A1  - Langemeyer, Vanessa
A1  - Niehues, Tim
A1  - Shai, Sonu
A1  - Graf, Dagmar
A1  - Müglich, Carmen
A1  - Schmalzing, Marc T.
A1  - Schwaneck, Eva C.
A1  - Tony, Hans-Peter
A1  - Dirks, Johannes
A1  - Haase, Gabriele
A1  - Liese, Johannes G.
A1  - Morbach, Henner
A1  - Foell, Dirk
A1  - Hellige, Antje
A1  - Wittkowski, Helmut
A1  - Masjosthusmann, Katja
A1  - Mohr, Michael
A1  - Geberzahn, Linda
A1  - Hedrich, Christian M.
A1  - Müller, Christiane
A1  - Rösen-Wolff, Angela
A1  - Roesler, Joachim
A1  - Zimmermann, Antje
A1  - Behrends, Uta
A1  - Rieber, Nikolaus
A1  - Schauer, Uwe
A1  - Handgretinger, Rupert
A1  - Holzer, Ursula
A1  - Henes, Jörg
A1  - Kanz, Lothar
A1  - Boesecke, Christoph
A1  - Rockstroh, Jürgen K.
A1  - Schwarze-Zander, Carolynne
A1  - Wasmuth, Jan-Christian
A1  - Dilloo, Dagmar
A1  - Hülsmann, Brigitte
A1  - Schönberger, Stefan
A1  - Schreiber, Stefan
A1  - Zeuner, Rainald
A1  - Ankermann, Tobias
A1  - Bismarck, Philipp von
A1  - Huppertz, Hans-Iko
A1  - Kaiser-Labusch, Petra
A1  - Greil, Johann
A1  - Jakoby, Donate
A1  - Kulozik, Andreas E.
A1  - Metzler, Markus
A1  - Naumann-Bartsch, Nora
A1  - Sobik, Bettina
A1  - Graf, Norbert
A1  - Heine, Sabine
A1  - Kobbe, Robin
A1  - Lehmberg, Kai
A1  - Müller, Ingo
A1  - Herrmann, Friedrich
A1  - Horneff, Gerd
A1  - Klein, Ariane
A1  - Peitz, Joachim
A1  - Schmidt, Nadine
A1  - Bielack, Stefan
A1  - Groß-Wieltsch, Ute
A1  - Classen, Carl F.
A1  - Klasen, Jessica
A1  - Deutz, Peter
A1  - Kamitz, Dirk
A1  - Lassy, Lisa
A1  - Tenbrock, Klaus
A1  - Wagner, Norbert
A1  - Bernbeck, Benedikt
A1  - Brummel, Bastian
A1  - Lara-Villacanas, Eusebia
A1  - Münstermann, Esther
A1  - Schneider, Dominik T.
A1  - Tietsch, Nadine
A1  - Westkemper, Marco
A1  - Weiß, Michael
A1  - Kramm, Christof
A1  - Kühnle, Ingrid
A1  - Kullmann, Silke
A1  - Girschick, Hermann
A1  - Specker, Christof
A1  - Vinnemeier-Laubenthal, Elisabeth
A1  - Haenicke, Henriette
A1  - Schulz, Claudia
A1  - Schweigerer, Lothar
A1  - Müller, Thomas G.
A1  - Stiefel, Martina
A1  - Belohradsky, Bernd H.
A1  - Soetedjo, Veronika
A1  - Kindle, Gerhard
A1  - Grimbacher, Bodo
T1  - The German national registry of primary immunodeficiencies (2012-2017)
JF  - Frontiers in Immunology
N2  - Introduction: The German PID-NET registry was founded in 2009, serving as the first national registry of patients with primary immunodeficiencies (PID) in Germany. It is part of the European Society for Immunodeficiencies (ESID) registry. The primary purpose of the registry is to gather data on the epidemiology, diagnostic delay, diagnosis, and treatment of PIDs. 

Methods: Clinical and laboratory data was collected from 2,453 patients from 36 German PID centres in an online registry. Data was analysed with the software Stata® and Excel. 

Results: The minimum prevalence of PID in Germany is 2.72 per 100,000 inhabitants. Among patients aged 1-25, there was a clear predominance of males. The median age of living patients ranged between 7 and 40 years, depending on the respective PID. Predominantly antibody disorders were the most prevalent group with 57% of all 2,453 PID patients (including 728 CVID patients). A gene defect was identified in 36% of patients. Familial cases were observed in 21% of patients. The age of onset for presenting symptoms ranged from birth to late adulthood (range 0-88 years). Presenting symptoms comprised infections (74%) and immune dysregulation (22%). Ninety-three patients were diagnosed without prior clinical symptoms. Regarding the general and clinical diagnostic delay, no PID had undergone a slight decrease within the last decade. However, both, SCID and hyper IgE-syndrome showed a substantial improvement in shortening the time between onset of symptoms and genetic diagnosis. Regarding treatment, 49% of all patients received immunoglobulin G (IgG) substitution (70%-subcutaneous; 29%-intravenous; 1%-unknown). Three-hundred patients underwent at least one hematopoietic stem cell transplantation (HSCT). Five patients had gene therapy. 

Conclusion: The German PID-NET registry is a precious tool for physicians, researchers, the pharmaceutical industry, politicians, and ultimately the patients, for whom the outcomes will eventually lead to a more timely diagnosis and better treatment.
KW  - registry for primary immunodeficiency
KW  - primary immunodeficiency (PID)
KW  - German PID-NET registry
KW  - PID prevalence
KW  - European Society for Immunodeficiencies (ESID)
KW  - IgG substitution therapy
KW  - CVID
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-226629
VL  - 10
ER  - 
TY  - JOUR
A1  - Benz, Peter M.
A1  - Merkel, Carla J.
A1  - Offner, Kristin
A1  - Abeßer, Marco
A1  - Ullrich, Melanie
A1  - Fischer, Tobias
A1  - Bayer, Barbara
A1  - Wagner, Helga
A1  - Gambaryan, Stepan
A1  - Ursitti, Jeanine A.
A1  - Adham, Ibrahim M.
A1  - Linke, Wolfgang A.
A1  - Feller, Stephan M.
A1  - Fleming, Ingrid
A1  - Renné, Thomas
A1  - Frantz, Stefan
A1  - Unger, Andreas
A1  - Schuh, Kai
T1  - Mena/VASP and alphaII-Spectrin complexes regulate cytoplasmic actin networks in cardiomyocytes and protect from conduction abnormalities and dilated cardiomyopathy
JF  - Cell Communication and Signaling
N2  - Background: In the heart, cytoplasmic actin networks are thought to have important roles in mechanical support, myofibrillogenesis, and ion channel function. However, subcellular localization of cytoplasmic actin isoforms and proteins involved in the modulation of the cytoplasmic actin networks are elusive. Mena and VASP are important regulators of actin dynamics. Due to the lethal phenotype of mice with combined deficiency in Mena and VASP, however, distinct cardiac roles of the proteins remain speculative. In the present study, we analyzed the physiological functions of Mena and VASP in the heart and also investigated the role of the proteins in the organization of cytoplasmic actin networks.
Results: We generated a mouse model, which simultaneously lacks Mena and VASP in the heart. Mena/VASP double-deficiency induced dilated cardiomyopathy and conduction abnormalities. In wild-type mice, Mena and VASP specifically interacted with a distinct αII-Spectrin splice variant (SH3i), which is in cardiomyocytes exclusively localized at Z- and intercalated discs. At Z- and intercalated discs, Mena and β-actin localized to the edges of the sarcomeres, where the thin filaments are anchored. In Mena/VASP double-deficient mice, β-actin networks were disrupted and the integrity of Z- and intercalated discs was markedly impaired.
Conclusions: Together, our data suggest that Mena, VASP, and αII-Spectrin assemble cardiac multi-protein complexes, which regulate cytoplasmic actin networks. Conversely, Mena/VASP deficiency results in disrupted β-actin assembly, Z- and intercalated disc malformation, and induces dilated cardiomyopathy and conduction abnormalities.
KW  - Mena/VASP
KW  - dilated cardiomyopathy
KW  - actin
KW  - heart
KW  - spectrin
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-128760
VL  - 11
IS  - 56
ER  - 
TY  - JOUR
A1  - Lambrecht, G.
A1  - Feifel, R.
A1  - Wagner-Röder, M.
A1  - Strohmann, C.
A1  - Zilch, H.
A1  - Tacke, Reinhold
A1  - Waelbroeck, M.
A1  - Christophe, J.
A1  - Boddeke, H.
A1  - Mutschler, E.
T1  - Affinity profiles of hexahydro-sila-difenidol analogues at muscarinic receptor subtypes
N2  - In an attempt to assess the structural requirements of hexahydro-sila-difenidol for potency and selectivity, a series of analogues modified in the amino group and the phenyl ring were investigated for their affinity to muscarinic M1- (rabbit vas deferens), Mr (guinea-pig atria) and Mr (guinea-pig ileum) receptors. All compounds were competitive antagonists in the three tissues. Their affinities to the three muscarinic receptor subtypes differed by more than two orders of magnitude and the observed receptor selectivities were not associated with high affinity. The pyrrolidino and hexamethyleneimino analogues, compounds substituted in the phenylring with a methoxy group or a chlorine atom as weil as p-fluoro-hexahydro-difenidol displayed the same affinity profile as the parent compound, hexahydro-sila-difenidol: M1 = M3 > M2 • A different selectivity patternwas observed for p-fluoro-hexahydro-sila-difenidol: M3 > M1 > M2 • This compound exhibited its highest affinity for M3-receptors in guinea-pig ileum (pA 2 = 7.84), intermediate affinity for M1-receptors in rabbit vas deferens (pA 2 = 6.68) and lowest affinity for the Mrreceptors in guinea-pig atria (pA 2 = 6.01). This receptor selectivity profile of p-fluoro-hexahydro-sila-difenidol was confirmed in ganglia (M1), atria (M2 ) and ileum (M 3 ) of the rat. Furthermore, dose ratios obtained with either pirenzepine (Mt) or hexahydrosila- difenidol (M2 and M3) and the p-fluoro analogue used in combination suggested that the antagonism was additive, implying mutual competition with a single population of muscarinic receptor subtypes. These results indicate that p-fluoro-hexahydro-sila-difenidol represents a valuable tool for characterization of muscarinic receptor subtypes.
KW  - Anorganische Chemie
KW  - Muscarinic receptor subtypes
KW  - Muscarinic M3selective antagonists
KW  - Hexahydro-sila-difenidol analogues
Y1  - 1989
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-63979
ER  - 
TY  - JOUR
A1  - Feifel, R.
A1  - Wagner-Röder, M.
A1  - Strohmann, C.
A1  - Tacke, Reinhold
A1  - Waelbroeck, M.
A1  - Christophe, J.
A1  - Mutschler, E.
A1  - Lambrecht, G.
T1  - Stereoselective inhibition of muscarinic receptor subtypes by the enantiomers of hexahydro-difenidol and acetylenic analogues
N2  - 1 Tbc affinities of the (R)- and (S)-enantiomers of hexahydro-difenidol (1) and its acetylenie analogues hexbutinol (2), hexbutinol methiodide (3) and p-fluoro-hexbutinol (4) (stereochemieal purity > 99.8%) for musearlnie receptors in rabbit vas deferens (M1), guinea-pig atria (M2) and guinea-pig ileum (M3) were measured by dose-ratio experiments. 2 The (R)-enantiomers consistently showed higher aßinities than the (S)-isomers. The stereosclectivity ratios [(R)/(S)] wcrc greatest with thc enantiomers of 1 (vas deferens: 550; ilcum: 191; atria: 17) and least with thosc ofthc p-Fluoro-analogue 4 (vas defercns: 34; ileum: 8.5; atria: 1.7). 3 The enantiomerie potency ratios for compounds 1-4 were highest in rabbit vas deferens, intermediate in guinea-pig ileum and much less in guinea-pig atria. Thus, these ratios may serve as a predietor of muscarinic receptor subtype identity. 4 (S)-p-Fluoro-hexbutinol [(S)-4] showed a novel receptor selectivity profile with preference for M\(_3\) receptors: M\(_3\) > M\(_2\) \(\geq\) M\(_1\)• 5 These results do not conform to Pfeiffer's rule that aetivity differences between enantiomers are greater with more potent compounds.
KW  - Anorganische Chemie
Y1  - 1990
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-64002
ER  - 
TY  - JOUR
A1  - Niemann, Axel
A1  - Huber, Nina
A1  - Wagner, Konstanze M.
A1  - Somandin, Christian
A1  - Horn, Michael
A1  - Lebrun-Julien, Frédéric
A1  - Angst, Brigitte
A1  - Pereira, Jorge A.
A1  - Halfter, Hartmut
A1  - Welzl, Hans
A1  - Feltri, M. Laura
A1  - Wrabetz, Lawrence
A1  - Young, Peter
A1  - Wessig, Carsten
A1  - Toyka, Klaus V.
A1  - Suter, Ueli
T1  - The Gdap1 knockout mouse mechanistically links redox control to Charcot–Marie–Tooth disease
JF  - Brain
N2  - The ganglioside-induced differentiation-associated protein 1 (GDAP1) is a mitochondrial fission factor and mutations in GDAP1 cause Charcot–Marie–Tooth disease. We found that Gdap1 knockout mice (\(Gdap1^{−/−}\)), mimicking genetic alterations of patients suffering from severe forms of Charcot–Marie–Tooth disease, develop an age-related, hypomyelinating peripheral neuropathy. Ablation of Gdap1 expression in Schwann cells recapitulates this phenotype. Additionally, intra-axonal mitochondria of peripheral neurons are larger in \(Gdap1^{−/−}\) mice and mitochondrial transport is impaired in cultured sensory neurons of \(Gdap1^{−/−}\) mice compared with controls. These changes in mitochondrial morphology and dynamics also influence mitochondrial biogenesis. We demonstrate that mitochondrial DNA biogenesis and content is increased in the peripheral nervous system but not in the central nervous system of \(Gdap1^{−/−}\) mice compared with control littermates. In search for a molecular mechanism we turned to the paralogue of GDAP1, GDAP1L1, which is mainly expressed in the unaffected central nervous system. GDAP1L1 responds to elevated levels of oxidized glutathione by translocating from the cytosol to mitochondria, where it inserts into the mitochondrial outer membrane. This translocation is necessary to substitute for loss of GDAP1 expression. Accordingly, more GDAP1L1 was associated with mitochondria in the spinal cord of aged \(Gdap1^{−/−}\) mice compared with controls. Our findings demonstrate that Charcot–Marie–Tooth disease caused by mutations in GDAP1 leads to mild, persistent oxidative stress in the peripheral nervous system, which can be compensated by GDAP1L1 in the unaffected central nervous system. We conclude that members of the GDAP1 family are responsive and protective against stress associated with increased levels of oxidized glutathione.
KW  - animal models
KW  - Charcot-Marie-Tooth disease
KW  - mitochondria
KW  - axonal transport
KW  - demyelinating disease
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-120731
VL  - 137
IS  - 3
ER  - 
TY  - JOUR
A1  - Ungethüm, K.
A1  - Wiedmann, S.
A1  - Wagner, M.
A1  - Leyh, R.
A1  - Ertl, G.
A1  - Frantz, S.
A1  - Geisler, T.
A1  - Karmann, W.
A1  - Prondzinsky, R.
A1  - Herdeg, C.
A1  - Noutsias, M.
A1  - Ludwig, T.
A1  - Käs, J.
A1  - Klocke, B.
A1  - Krapp, J.
A1  - Wood, D.
A1  - Kotseva, K.
A1  - Störk, S.
A1  - Heuschmann, P. U.
T1  - Secondary prevention in diabetic and nondiabetic coronary heart disease patients: insights from the German subset of the hospital arm of the EUROASPIRE IV and V surveys
JF  - Clinical Research in Cardiology
N2  - Background
Patients with coronary heart disease (CHD) with and without diabetes mellitus have an increased risk of recurrent events requiring multifactorial secondary prevention of cardiovascular risk factors. We compared prevalences of cardiovascular risk factors and its determinants including lifestyle, pharmacotherapy and diabetes mellitus among patients with chronic CHD examined within the fourth and fifth EUROASPIRE surveys (EA-IV, 2012–13; and EA-V, 2016–17) in Germany.

Methods
The EA initiative iteratively conducts European-wide multicenter surveys investigating the quality of secondary prevention in chronic CHD patients aged 18 to 79 years. The data collection in Germany was performed during a comprehensive baseline visit at study centers in Würzburg (EA-IV, EA-V), Halle (EA-V), and Tübingen (EA-V).

Results
384 EA-V participants (median age 69.0 years, 81.3% male) and 536 EA-IV participants (median age 68.7 years, 82.3% male) were examined. Comparing EA-IV and EA-V, no relevant differences in risk factor prevalence and lifestyle changes were observed with the exception of lower LDL cholesterol levels in EA-V. Prevalence of unrecognized diabetes was significantly lower in EA-V as compared to EA-IV (11.8% vs. 19.6%) while the proportion of prediabetes was similarly high in the remaining population (62.1% vs. 61.0%).

Conclusion
Between 2012 and 2017, a modest decrease in LDL cholesterol levels was observed, while no differences in blood pressure control and body weight were apparent in chronic CHD patients in Germany. Although the prevalence of unrecognized diabetes decreased in the later study period, the proportion of normoglycemic patients was low. As pharmacotherapy appeared fairly well implemented, stronger efforts towards lifestyle interventions, mental health programs and cardiac rehabilitation might help to improve risk factor profiles in chronic CHD patients.
KW  - coronary heart disease
KW  - diabetes mellitus
KW  - secondary prevention
KW  - EUROASPIRE
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-324037
VL  - 112
IS  - 2
ER  - 
TY  - JOUR
A1  - Gotru, Sanjeev Kiran
A1  - van Geffen, Johanna P.
A1  - Nagy, Magdolna
A1  - Mammadova-Bach, Elmina
A1  - Eilenberger, Julia
A1  - Volz, Julia
A1  - Manukjan, Georgi
A1  - Schulze, Harald
A1  - Wagner, Leonard
A1  - Eber, Stefan
A1  - Schambeck, Christian
A1  - Deppermann, Carsten
A1  - Brouns, Sanne
A1  - Nurden, Paquita
A1  - Greinacher, Andreas
A1  - Sachs, Ulrich
A1  - Nieswandt, Bernhard
A1  - Hermanns, Heike M.
A1  - Heemskerk, Johan W. M.
A1  - Braun, Attila
T1  - Defective Zn2+ homeostasis in mouse and human platelets with α- and δ-storage pool diseases
JF  - Scientific Reports
N2  - Zinc (Zn2+) can modulate platelet and coagulation activation pathways, including fibrin formation. Here, we studied the (patho)physiological consequences of abnormal platelet Zn2+ storage and release. To visualize Zn2+ storage in human and mouse platelets, the Zn2+ specific fluorescent dye FluoZin3 was used. In resting platelets, the dye transiently accumulated into distinct cytosolic puncta, which were lost upon platelet activation. Platelets isolated from Unc13d−/− mice, characterized by combined defects of α/δ granular release, showed a markedly impaired Zn2+ release upon activation. Platelets from Nbeal2−/− mice mimicking Gray platelet syndrome (GPS), characterized by primarily loss of the α-granule content, had strongly reduced Zn2+ levels, which was also confirmed in primary megakaryocytes. In human platelets isolated from patients with GPS, Hermansky-Pudlak Syndrome (HPS) and Storage Pool Disease (SPD) altered Zn2+ homeostasis was detected. In turbidity and flow based assays, platelet-dependent fibrin formation was impaired in both Nbeal2−/− and Unc13d−/− mice, and the impairment could be partially restored by extracellular Zn2+. Altogether, we conclude that the release of ionic Zn2+ store from secretory granules upon platelet activation contributes to the procoagulant role of Zn2+ in platelet-dependent fibrin formation.
KW  - coagulation system
KW  - metals
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-227455
VL  - 9
ER  - 
TY  - JOUR
A1  - Hirche, T. O.
A1  - Knoop, C.
A1  - Hebestreit, H.
A1  - Shimmin, D.
A1  - Solé, A.
A1  - Elborn, J. S.
A1  - Ellemunter, H.
A1  - Aurora, P.
A1  - Hogardt, M.
A1  - Wagner, T. O. F.
T1  - Practical Guidelines: Lung Transplantation in Patients with Cystic Fibrosis
JF  - Pulmonary Medicine
N2  - There are no European recommendations on issues specifically related to lung transplantation (LTX) in cystic fibrosis (CF). The main goal of this paper is to provide CF care team members with clinically relevant CF-specific information on all aspects of LTX, highlighting areas of consensus and controversy throughout Europe. Bilateral lung transplantation has been shown to be an important therapeutic option for end-stage CF pulmonary disease. Transplant function and patient survival after transplantation are better than in most other indications for this procedure. Attention though has to be paid to pretransplant morbidity, time for referral, evaluation, indication, and contraindication in children and in adults. This review makes extensive use of specific evidence in the field of lung transplantation in CF patients and addresses all issues of practical importance. The requirements of pre-, peri-, and postoperative management are discussed in detail including bridging to transplant and postoperative complications, immune suppression, chronic allograft dysfunction, infection, and malignancies being the most important. Among the contributors to this guiding information are 19 members of the ECORN-CF project and other experts. The document is endorsed by the European Cystic Fibrosis Society and sponsored by the Christiane Herzog Foundation.
KW  - cystic fibrosis
KW  - lung transplantation
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-121569
SN  - 2090-1836
VL  - 2014
ER  - 
TY  - JOUR
A1  - Wagenbrenner, Mike
A1  - Heinz, Tizian
A1  - Horas, Konstantin
A1  - Jakuscheit, Axel
A1  - Arnholdt, Joerg
A1  - Mayer-Wagner, Susanne
A1  - Rudert, Maximilian
A1  - Holzapfel, Boris M.
A1  - Weißenberger, Manuel
T1  - Impact of Tranexamic Acid on Chondrocytes and Osteogenically Differentiated Human Mesenchymal Stromal Cells (hMSCs) In Vitro
JF  - Journal of Clinical Medicine
N2  - The topical application of tranexamic acid (TXA) helps to prevent post-operative blood loss in total joint replacements. Despite these findings, the effects on articular and periarticular tissues remain unclear. Therefore, this in vitro study examined the effects of varying exposure times and concentrations of TXA on proliferation rates, gene expression and differentiation capacity of chondrocytes and human mesenchymal stromal cells (hMSCs), which underwent osteogenic differentiation. Chondrocytes and hMSCs were isolated and multiplied in monolayer cell cultures. Osteogenic differentiation of hMSCs was induced for 21 days using a differentiation medium containing specific growth factors. Cell proliferation was analyzed using ATP assays. Effects of TXA on cell morphology were examined via light microscopy and histological staining, while expression levels of tissue-specific genes were measured using semiquantitative RT-PCR. After treatment with 50 mg/mL of TXA, a decrease in cell proliferation rates was observed. Furthermore, treatment with concentrations of 20 mg/mL of TXA for at least 48 h led to a visible detachment of chondrocytes. TXA treatment with 50 mg/mL for at least 24 h led to a decrease in the expression of specific marker genes in chondrocytes and osteogenically differentiated hMSCs. No significant effects were observed for concentrations beyond 20 mg/mL of TXA combined with exposure times of less than 24 h. This might therefore represent a safe limit for topical application in vivo. Further research regarding in vivo conditions and effects on hMSC functionality are necessary to fully determine the effects of TXA on articular and periarticular tissues.
KW  - tranexamic acid
KW  - hMSCs
KW  - chondrocytes
KW  - osteoarthritis
KW  - toxicity
KW  - differentiation capacity
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-219410
SN  - 2077-0383
VL  - 9
IS  - 12
ER  - 
TY  - JOUR
A1  - Wagner, Ines
A1  - Volkmer, Michael
A1  - Sharan, Malvika
A1  - Villaveces, Jose M.
A1  - Oswald, Felix
A1  - Surendranath, Vineeth
A1  - Habermann, Bianca H.
T1  - morFeus: a web-based program to detect remotely conserved orthologs using symmetrical best hits and orthology network scoring
JF  - BMC Bioinformatics
N2  - Background: Searching the orthologs of a given protein or DNA sequence is one of the most important and most commonly used Bioinformatics methods in Biology. Programs like BLAST or the orthology search engine Inparanoid can be used to find orthologs when the similarity between two sequences is sufficiently high. They however fail when the level of conservation is low. The detection of remotely conserved proteins oftentimes involves sophisticated manual intervention that is difficult to automate. 
Results: Here, we introduce morFeus, a search program to find remotely conserved orthologs. Based on relaxed sequence similarity searches, morFeus selects sequences based on the similarity of their alignments to the query, tests for orthology by iterative reciprocal BLAST searches and calculates a network score for the resulting network of orthologs that is a measure of orthology independent of the E-value. Detecting remotely conserved orthologs of a protein using morFeus thus requires no manual intervention. We demonstrate the performance of morFeus by comparing it to state-of-the-art orthology resources and methods. We provide an example of remotely conserved orthologs, which were experimentally shown to be functionally equivalent in the respective organisms and therefore meet the criteria of the orthology-function conjecture. 
Conclusions: Based on our results, we conclude that morFeus is a powerful and specific search method for detecting remotely conserved orthologs.
KW  - reciprocal best hit
KW  - finder using symmetrical best hits
KW  - sequences
KW  - annotation
KW  - identification
KW  - database
KW  - genomes
KW  - proteins
KW  - homologs
KW  - hidden markov-models
KW  - phylogenetic trees
KW  - PSI-blast
KW  - eigenvector centrality
KW  - meta-analysis based orthology
KW  - orthology
KW  - remote sequence conservation
KW  - alignment clustering
KW  - orthology network
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-115590
VL  - 15
IS  - 263
ER  - 
TY  - JOUR
A1  - Leikam, C
A1  - Hufnagel, AL
A1  - Otto, C
A1  - Murphy, DJ
A1  - Mühling, B
A1  - Kneitz, S
A1  - Nanda, I
A1  - Schmid, M
A1  - Wagner, TU
A1  - Haferkamp, S
A1  - Bröcker, E-B
A1  - Schartl, M
A1  - Meierjohann, S
T1  - In vitro evidence for senescent multinucleated melanocytes as a source for tumor-initiating cells
JF  - Cell Death and Disease
N2  - Oncogenic signaling in melanocytes results in oncogene-induced senescence (OIS), a stable cell-cycle arrest frequently characterized by a bi-or multinuclear phenotype that is considered as a barrier to cancer progression. However, the long-sustained conviction that senescence is a truly irreversible process has recently been challenged. Still, it is not known whether cells driven into OIS can progress to cancer and thereby pose a potential threat. Here, we show that prolonged expression of the melanoma oncogene N-RAS\(^{61K}\) in pigment cells overcomes OIS by triggering the emergence of tumor-initiating mononucleated stem-like cells from senescent cells. This progeny is dedifferentiated, highly proliferative, anoikis-resistant and induces fast growing, metastatic tumors. Our data describe that differentiated cells, which are driven into senescence by an oncogene, use this senescence state as trigger for tumor transformation, giving rise to highly aggressive tumor-initiating cells. These observations provide the first experimental in vitro evidence for the evasion of OIS on the cellular level and ensuing transformation.
KW  - reactive oxygen
KW  - human melanoma
KW  - MITF
KW  - cancer
KW  - skin
KW  - DNA damage
KW  - kappa-B
KW  - oncogene-induced senescence
KW  - cellular senescence
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-148718
VL  - 6
IS  - e1711
ER  - 
TY  - JOUR
A1  - Schlecht, Anja
A1  - Vallon, Mario
A1  - Wagner, Nicole
A1  - Ergün, Süleyman
A1  - Braunger, Barbara M.
T1  - TGFβ-Neurotrophin Interactions in Heart, Retina, and Brain
JF  - Biomolecules
N2  - Ischemic insults to the heart and brain, i.e., myocardial and cerebral infarction, respectively, are amongst the leading causes of death worldwide. While there are therapeutic options to allow reperfusion of ischemic myocardial and brain tissue by reopening obstructed vessels, mitigating primary tissue damage, post-infarction inflammation and tissue remodeling can lead to secondary tissue damage. Similarly, ischemia in retinal tissue is the driving force in the progression of neovascular eye diseases such as diabetic retinopathy (DR) and age-related macular degeneration (AMD), which eventually lead to functional blindness, if left untreated. Intriguingly, the easily observable retinal blood vessels can be used as a window to the heart and brain to allow judgement of microvascular damages in diseases such as diabetes or hypertension. The complex neuronal and endocrine interactions between heart, retina and brain have also been appreciated in myocardial infarction, ischemic stroke, and retinal diseases. To describe the intimate relationship between the individual tissues, we use the terms heart-brain and brain-retina axis in this review and focus on the role of transforming growth factor β (TGFβ) and neurotrophins in regulation of these axes under physiologic and pathologic conditions. Moreover, we particularly discuss their roles in inflammation and repair following ischemic/neovascular insults. As there is evidence that TGFβ signaling has the potential to regulate expression of neurotrophins, it is tempting to speculate, and is discussed here, that cross-talk between TGFβ and neurotrophin signaling protects cells from harmful and/or damaging events in the heart, retina, and brain.
KW  - heart-brain axis
KW  - brain-retina axis
KW  - neurotrophins
KW  - TGFβ signaling
KW  - myocardial infarction
KW  - diabetic retinopathy
KW  - age-related macular degeneration
KW  - ischemic stroke
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-246159
SN  - 2218-273X
VL  - 11
IS  - 9
ER  - 
TY  - JOUR
A1  - Raselli, Tina
A1  - Hearn, Tom
A1  - Wyss, Annika
A1  - Atrott, Kirstin
A1  - Peter, Alain
A1  - Frey-Wagner, Isabelle
A1  - Spalinger, Marianne R.
A1  - Maggio, Ewerton M.
A1  - Sailer, Andreas W.
A1  - Schmitt, Johannes
A1  - Schreiner, Philipp
A1  - Moncsek, Anja
A1  - Mertens, Joachim
A1  - Scharl, Michael
A1  - Griffiths, William J.
A1  - Bueter, Marco
A1  - Geier, Andreas
A1  - Rogler, Gerhard
A1  - Wang, Yuqin
A1  - Misselwitz, Benjamin
T1  - Elevated oxysterol levels in human and mouse livers reflect nonalcoholic steatohepatitis
JF  - Journal of Lipid Research
N2  - Nonalcoholic steatohepatitis (NASH), a primary cause of liver disease, leads to complications such as fibrosis, cirrhosis, and carcinoma, but the pathophysiology of NASH is incompletely understood. Epstein-Barr virus-induced G protein-coupled receptor 2 (EBI2) and its oxysterol ligand 7 alpha,25-dihydroxycholesterol (7 alpha,25-diHC) are recently discovered immune regulators. Several lines of evidence suggest a role of oxysterols in NASH pathogenesis, but rigorous testing has not been performed. We measured oxysterol levels in the livers of NASH patients by LC-MS and tested the role of the EBI2-7 alpha,25-diHC system in a murine feeding model of NASH. Free oxysterol profiling in livers from NASH patients revealed a pronounced increase in 24- and 7-hydroxylated oxysterols in NASH compared with controls. Levels of 24- and 7-hydroxylated oxysterols correlated with histological NASH activity. Histological analysis of murine liver samples demonstrated ballooning and liver inflammation. No significant genotype-related differences were observed in Ebi2(-/-) mice and mice with defects in the 7 alpha,25-diHC synthesizing enzymes CH25H and CYP7B1 compared with wild-type littermate controls, arguing against an essential role of these genes in NASH pathogenesis. Elevated 24- and 7-hydroxylated oxysterol levels were confirmed in murine NASH liver samples. Our results suggest increased bile acid synthesis in NASH samples, as judged by the enhanced level of 7 alpha-hydroxycholest-4-en-3-one and impaired 24S-hydroxycholesterol metabolism as characteristic biochemical changes in livers affected by NASH.
KW  - nonalcoholic fatty liver disease
KW  - Epstein-Barr virus-induced gene 2
KW  - cholesterol 25 hydroxylase
KW  - 25-hydroxycholesterol 7 alpha-hydroxylase
KW  - mouse feeding model
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-225004
VL  - 60
IS  - 7
ER  - 
TY  - JOUR
A1  - Wagenbrenner, Mike
A1  - Poker, Konrad
A1  - Heinz, Tizian
A1  - Herrmann, Marietta
A1  - Horas, Konstantin
A1  - Ebert, Regina
A1  - Mayer-Wagner, Susanne
A1  - Holzapfel, Boris M.
A1  - Rudert, Maximilian
A1  - Steinert, Andre F.
A1  - Weißenberger, Manuel
T1  - Mesenchymal stromal cells (MSCs) isolated from various tissues of the human arthritic knee joint possess similar multipotent differentiation potential
JF  - Applied Sciences
N2  - (1) Background: The mesenchymal stromal cells (MSCs) of different tissue origins are applied in cell-based chondrogenic regeneration. However, there is a lack of comparability determining the most suitable cell source for the tissue engineering (TE) of cartilage. The purpose of this study was to compare the in vitro chondrogenic potential of MSC-like cells from different tissue sources (bone marrow, meniscus, anterior cruciate ligament, synovial membrane, and the infrapatellar fat pad removed during total knee arthroplasty (TKA)) and define which cell source is best suited for cartilage regeneration. (2) Methods: MSC-like cells were isolated from five donors and expanded using adherent monolayer cultures. Differentiation was induced by culture media containing specific growth factors. Transforming growth factor (TGF)-ß1 was used as the growth factor for chondrogenic differentiation. Osteogenesis and adipogenesis were induced in monolayer cultures for 27 days, while pellet cell cultures were used for chondrogenesis for 21 days. Control cultures were maintained under the same conditions. After, the differentiation period samples were analyzed, using histological and immunohistochemical staining, as well as molecularbiological analysis by RT-PCR, to assess the expression of specific marker genes. (3) Results: Plastic-adherent growth and in vitro trilineage differentiation capacity of all isolated cells were proven. Flow cytometry revealed the clear co-expression of surface markers CD44, CD73, CD90, and CD105 on all isolated cells. Adipogenesis was validated through the formation of lipid droplets, while osteogenesis was proven by the formation of calcium deposits within differentiated cell cultures. The formation of proteoglycans was observed during chondrogenesis in pellet cultures, with immunohistochemical staining revealing an increased relative gene expression of collagen type II. RT-PCR proved an elevated expression of specific marker genes after successful differentiation, with no significant differences regarding different cell source of native tissue. (4) Conclusions: Irrespective of the cell source of native tissue, all MSC-like cells showed multipotent differentiation potential in vitro. The multipotent differentiation capacity did not differ significantly, and chondrogenic differentiation was proven in all pellet cultures. Therefore, cell suitability for cell-based cartilage therapies and tissue engineering is given for various tissue origins that are routinely removed during total knee arthroplasty (TKA). This study might provide essential information for the clinical tool of cell harvesting, leading to more flexibility in cell availability.
KW  - knee joint
KW  - MSCs
KW  - cellular origin
KW  - cartilage regeneration
KW  - tissue engineering
KW  - cell-based therapies
KW  - osteoarthritis
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-262334
SN  - 2076-3417
VL  - 12
IS  - 4
ER  - 
TY  - JOUR
A1  - Mielich-Süss, Benjamin
A1  - Wagner, Rabea M.
A1  - Mietrach, Nicole
A1  - Hertlein, Tobias
A1  - Marincola, Gabriella
A1  - Ohlsen, Knut
A1  - Geibel, Sebastian
A1  - Lopez, Daniel
T1  - Flotillin scaffold activity contributes to type VII secretion system assembly in Staphylococcus aureus
JF  - PLoS Pathogens
N2  - Scaffold proteins are ubiquitous chaperones that promote efficient interactions between partners of multi-enzymatic protein complexes; although they are well studied in eukaryotes, their role in prokaryotic systems is poorly understood. Bacterial membranes have functional membrane microdomains (FMM), a structure homologous to eukaryotic lipid rafts. Similar to their eukaryotic counterparts, bacterial FMM harbor a scaffold protein termed flotillin that is thought to promote interactions between proteins spatially confined to the FMM. Here we used biochemical approaches to define the scaffold activity of the flotillin homolog FloA of the human pathogen Staphylococcus aureus, using assembly of interacting protein partners of the type VII secretion system (T7SS) as a case study. Staphylococcus aureus cells that lacked FloA showed reduced T7SS function, and thus reduced secretion of T7SS-related effectors, probably due to the supporting scaffold activity of flotillin. We found that the presence of flotillin mediates intermolecular interactions of T7SS proteins. We tested several small molecules that interfere with flotillin scaffold activity, which perturbed T7SS activity in vitro and in vivo. Our results suggest that flotillin assists in the assembly of S. aureus membrane components that participate in infection and influences the infective potential of this pathogen.
KW  - flotillin
KW  - scaffold protein
KW  - Staphylococcus aureus
KW  - type VII secretion system
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170035
VL  - 13
IS  - 11
ER  - 
TY  - JOUR
A1  - Haake, Markus
A1  - Haack, Beatrice
A1  - Schäfer, Tina
A1  - Harter, Patrick N.
A1  - Mattavelli, Greta
A1  - Eiring, Patrick
A1  - Vashist, Neha
A1  - Wedekink, Florian
A1  - Genssler, Sabrina
A1  - Fischer, Birgitt
A1  - Dahlhoff, Julia
A1  - Mokhtari, Fatemeh
A1  - Kuzkina, Anastasia
A1  - Welters, Marij J. P.
A1  - Benz, Tamara M.
A1  - Sorger, Lena
A1  - Thiemann, Vincent
A1  - Almanzar, Giovanni
A1  - Selle, Martina
A1  - Thein, Klara
A1  - Späth, Jacob
A1  - Gonzalez, Maria Cecilia
A1  - Reitinger, Carmen
A1  - Ipsen-Escobedo, Andrea
A1  - Wistuba-Hamprecht, Kilian
A1  - Eichler, Kristin
A1  - Filipski, Katharina
A1  - Zeiner, Pia S.
A1  - Beschorner, Rudi
A1  - Goedemans, Renske
A1  - Gogolla, Falk Hagen
A1  - Hackl, Hubert
A1  - Rooswinkel, Rogier W.
A1  - Thiem, Alexander
A1  - Romer Roche, Paula
A1  - Joshi, Hemant
A1  - Pühringer, Dirk
A1  - Wöckel, Achim
A1  - Diessner, Joachim E.
A1  - Rüdiger, Manfred
A1  - Leo, Eugen
A1  - Cheng, Phil F.
A1  - Levesque, Mitchell P.
A1  - Goebeler, Matthias
A1  - Sauer, Markus
A1  - Nimmerjahn, Falk
A1  - Schuberth-Wagner, Christine
A1  - Felten, Stefanie von
A1  - Mittelbronn, Michel
A1  - Mehling, Matthias
A1  - Beilhack, Andreas
A1  - van der Burg, Sjoerd H.
A1  - Riedel, Angela
A1  - Weide, Benjamin
A1  - Dummer, Reinhard
A1  - Wischhusen, Jörg
T1  - Tumor-derived GDF-15 blocks LFA-1 dependent T cell recruitment and suppresses responses to anti-PD-1 treatment
JF  - Nature Communications
N2  - Immune checkpoint blockade therapy is beneficial and even curative for some cancer patients. However, the majority don’t respond to immune therapy. Across different tumor types, pre-existing T cell infiltrates predict response to checkpoint-based immunotherapy. Based on in vitro pharmacological studies, mouse models and analyses of human melanoma patients, we show that the cytokine GDF-15 impairs LFA-1/β2-integrin-mediated adhesion of T cells to activated endothelial cells, which is a pre-requisite of T cell extravasation. In melanoma patients, GDF-15 serum levels strongly correlate with failure of PD-1-based immune checkpoint blockade therapy. Neutralization of GDF-15 improves both T cell trafficking and therapy efficiency in murine tumor models. Thus GDF-15, beside its known role in cancer-related anorexia and cachexia, emerges as a regulator of T cell extravasation into the tumor microenvironment, which provides an even stronger rationale for therapeutic anti-GDF-15 antibody development.
KW  - cancer microenvironment
KW  - immunotherapy
KW  - T cells
KW  - tumour immunology
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-357333
VL  - 14
ER  - 
TY  - JOUR
A1  - Wagner, N.
A1  - Crippa, L.
A1  - Amaricci, A.
A1  - Hansmann, P.
A1  - Klett, M.
A1  - König, E. J.
A1  - Schäfer, T.
A1  - Di Sante, D.
A1  - Cano, J.
A1  - Millis, A. J.
A1  - Georges, A.
A1  - Sangiovanni, G.
T1  - Mott insulators with boundary zeros
JF  - Nature Communications
N2  - The topological classification of electronic band structures is based on symmetry properties of Bloch eigenstates of single-particle Hamiltonians. In parallel, topological field theory has opened the doors to the formulation and characterization of non-trivial phases of matter driven by strong electron-electron interaction. Even though important examples of topological Mott insulators have been constructed, the relevance of the underlying non-interacting band topology to the physics of the Mott phase has remained unexplored. Here, we show that the momentum structure of the Green’s function zeros defining the “Luttinger surface" provides a topological characterization of the Mott phase related, in the simplest description, to the one of the single-particle electronic dispersion. Considerations on the zeros lead to the prediction of new phenomena: a topological Mott insulator with an inverted gap for the bulk zeros must possess gapless zeros at the boundary, which behave as a form of “topological antimatter” annihilating conventional edge states. Placing band and Mott topological insulators in contact produces distinctive observable signatures at the interface, revealing the otherwise spectroscopically elusive Green’s function zeros.
KW  - electronic properties and materials
KW  - topological insulators
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-358150
VL  - 14
ER  - 
TY  - JOUR
A1  - Holländer, Olivia
A1  - Schwender, Kristina
A1  - Böhme, Petra
A1  - Fleckhaus, Jan
A1  - Haas, Cordula
A1  - Han, Yang
A1  - Heidorn, Frank
A1  - Klein-Unseld, Rachel
A1  - Lichtenwald, Julia
A1  - Naue, Jana
A1  - Neubauer, Jacqueline
A1  - Poetsch, Micaela
A1  - Schneider, Peter M.
A1  - Wagner, Wolfgang
A1  - Vennemann, Marielle
T1  - Forensische DNA-Methylierungsanalyse
T1  - Forensic DNA methylation analysis : First technical collaborative exercise by the working group on molecular age estimation of the German Society of Legal Medicine
BT  - Erster, technischer Ringversuch der Arbeitsgruppe „Molekulare Altersschätzung“ der Deutschen Gesellschaft für Rechtsmedizin
JF  - Rechtsmedizin
N2  - Die quantitative Analyse der relativen DNA-Methylierung gilt als eine der vielversprechendsten Methoden der molekularen Altersschätzung. Viele Studien der letzten Jahre identifizierten geeignete Positionen im Genom, deren DNA-Methylierung sich altersabhängig verändert. Für den Einsatz dieser Methode in der Routine- bzw. Fallarbeit ist es von großer Bedeutung, angewandte Analysetechniken zu validieren. Als ein Teilaspekt dieser Validierung sollte die Vergleichbarkeit der Analyseergebnisse zur DNA-Methylierung mithilfe der Mini- und Pyrosequenzierung zwischen verschiedenen Laboren evaluiert werden. Die Arbeitsgruppe „Molekulare Altersschätzung“ der Deutschen Gesellschaft für Rechtsmedizin (DGRM) führte hierzu den ersten, technischen Ringversuch durch, der 4 Positionen in den Genen PDE4C, EDARADD, SST und KLF14 umfasste. Diese Marker waren in vorangegangenen Studien als altersabhängige Biomarker charakterisiert worden. Am Ringversuch nahmen 12 Labore teil, wobei jedes die Wahl zwischen der Minisequenzierung und/oder der Pyrosequenzierung für die quantitative Methylierungsanalyse hatte. Jedem teilnehmenden Labor wurden Blut- und Speichelproben von 3 Personen unterschiedlichen Alters übersandt. Die Wahl der Reagenzien für die Probenbearbeitung wurde den Teilnehmern freigestellt.

Die Ergebnisse der Minisequenzierung zeigten systematische Abweichungen zwischen den Laboren, die am ehesten auf die Verwendung unterschiedlicher Reagenzien und Analyseplattformen zurückzuführen sein können. Die Resultate der Pyrosequenzierung hingegen wiesen nicht auf systematische Abweichungen zwischen den Laboren hin, hier zeigte sich jedoch die Tendenz einer markerabhängigen Abweichung. Darüber hinaus konnten Unterschiede hinsichtlich technischer Probleme zwischen Laboren mit mehr Erfahrung in der jeweiligen Sequenzierungsmethode und Laboren mit weniger Erfahrung festgestellt werden. Sowohl die Beobachtung von systematischen als auch die von markerabhängigen Abweichungen lässt den Schluss zu, dass eine Übertragung von Analysemethoden zwischen Laboren grundsätzlich möglich ist, eine Anpassung des jeweiligen Modells zur Altersschätzung jedoch notwendig sein kann.
N2  - Quantitative analysis of relative DNA methylation is currently one of the most promising methods of molecular age estimation. In recent years numerous studies identified potential DNA methylation markers showing age-dependent changes in their relative methylation state. For routine application of this method validation is an important prerequisite. One aspect of validation is the degree of comparability of analytical data between laboratories. The working group on molecular age estimation of the German Society for Legal Medicine (DGRM) conducted a first technical proficiency test comprising four age estimation markers within the genes PDE4C, EDARADD, SST and KLF14. These positions were previously characterized as age-dependent biomarkers. A total of 12 laboratories participated using pyrosequencing and/or minisequencing techniques for quantitative analysis of DNA methylation. Each laboratory received blood and buccal swab samples from three individuals of different ages. Laboratories were free in their choice of reagents and material for sequencing.

Minisequencing results showed systematic deviations between laboratories, which are believed to originate from differing reagents and sequencing platforms. The results of pyrosequencing did not show clear signs of systematic deviation but did show differences in the comparability between markers. Different levels of technical problems were reported, which correlated with the amount of experience with the sequencing technology.

Both systematic and specific differences between analytical data produced in different laboratory settings lead to the conclusion that while it is generally possible to transfer an age estimation method to another laboratory, a mathematical model for age estimation might need to be adjusted accordingly.
KW  - DNA-Methylierung
KW  - Pyrosequenzierung
KW  - Minisequenzierung
KW  - Ergebnisreproduzierbarkeit
KW  - Laborleistungstests
KW  - DNA methylation
KW  - minisequencing
KW  - pyrosequencing
KW  - reproducibility of results
KW  - laboratory proficiency testing
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-307131
SN  - 0937-9819
SN  - 1434-5196
VL  - 31
IS  - 3
ER  -