Epigenetic regulation of cardiac electrophysiology in atrial fibrillation: HDAC2 determines action potential duration and suppresses NRSF in cardiomyocytes.


Journal

Basic research in cardiology
ISSN: 1435-1803
Titre abrégé: Basic Res Cardiol
Pays: Germany
ID NLM: 0360342

Informations de publication

Date de publication:
25 02 2021
Historique:
received: 23 11 2020
accepted: 18 02 2021
entrez: 25 2 2021
pubmed: 26 2 2021
medline: 15 12 2021
Statut: epublish

Résumé

Atrial fibrillation (AF) is associated with electrical remodeling, leading to cellular electrophysiological dysfunction and arrhythmia perpetuation. Emerging evidence suggests a key role for epigenetic mechanisms in the regulation of ion channel expression. Histone deacetylases (HDACs) control gene expression through deacetylation of histone proteins. We hypothesized that class I HDACs in complex with neuron-restrictive silencer factor (NRSF) determine atrial K

Identifiants

pubmed: 33630168
doi: 10.1007/s00395-021-00855-x
pii: 10.1007/s00395-021-00855-x
doi:

Substances chimiques

Potassium Channels 0
RE1-silencing transcription factor 0
Repressor Proteins 0
HDAC2 protein, human EC 3.5.1.98
Histone Deacetylase 2 EC 3.5.1.98

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

13

Subventions

Organisme : University of Heidelberg, Faculty of Medicine
ID : Postdoctoral Fellowships
Organisme : University of Heidelberg, Faculty of Medicine
ID : Postdoctoral Fellowship
Organisme : Deutsche Gesellschaft für Kardiologie-Herz und Kreislaufforschung.
ID : Fellowship
Organisme : Deutsche Gesellschaft für Kardiologie-Herz und Kreislaufforschung.
ID : Fellowship
Organisme : Deutsche Gesellschaft für Kardiologie-Herz und Kreislaufforschung.
ID : Otto-Hess-Promotionsstipendium
Organisme : Deutsche Stiftung für Herzforschung
ID : F/08/14
Organisme : Deutsche Stiftung für Herzforschung
ID : Fellowship
Organisme : Deutsche Stiftung für Herzforschung
ID : Kaltenbach-Promotionsstipendium
Organisme : Deutsche Stiftung für Herzforschung
ID : Kaltenbach-Promotionsstipendium
Organisme : Deutsche Stiftung für Herzforschung
ID : Kaltenbach-Promotionsstipendium
Organisme : German Internal Medicine Society
ID : Clinician-Scientist-Program
Organisme : Deutsche Forschungsgemeinschaft
ID : SCHW 1611/-1
Organisme : Deutsche Forschungsgemeinschaft
ID : TH 1120/7-1
Organisme : Deutsche Forschungsgemeinschaft
ID : TH 1120/8-1
Organisme : Ministerium für Wissenschaft, Forschung und Kunst Baden-Württemberg
ID : Sonderlinie Medizin
Organisme : Heidelberg Research Center for Molecular Medicine
ID : Senior Career Fellowship
Organisme : Department of Cardiology, University of Heidelberg
ID : Cardiology Career Program
Organisme : Department of Cardiology, University of Heidelberg
ID : Cardiology Career Program

Références

Allessie M, Ausma J, Schotten U (2002) Electrical, contractile and structural remodeling during atrial fibrillation. Cardiovasc Res 54:230–246. https://doi.org/10.1016/s0008-6363(02)00258-4
doi: 10.1016/s0008-6363(02)00258-4 pubmed: 12062329
Backs J, Olson EN (2006) Control of cardiac growth by histone acetylation/deacetylation. Circ Res 98:15–24. https://doi.org/10.1161/01.RES.0000197782.21444.8f
doi: 10.1161/01.RES.0000197782.21444.8f pubmed: 16397154
Burstein B, Nattel S (2008) Atrial fibrosis: mechanisms and clinical relevance in atrial fibrillation. J Am Coll Cardiol 51:802–809. https://doi.org/10.1016/j.jacc.2007.09.064
doi: 10.1016/j.jacc.2007.09.064 pubmed: 18294563
Campbell K, Calvo CJ, Mironov S, Herron T, Berenfeld O, Jalife J (2012) Spatial gradients in action potential duration created by regional magnetofection of hERG are a substrate for wavebreak and turbulent propagation in cardiomyocyte monolayers. J Physiol 590:6363–6379. https://doi.org/10.1113/jphysiol.2012.238758
doi: 10.1113/jphysiol.2012.238758 pubmed: 23090949 pmcid: 3533198
Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M (2009) Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science 325:834–840. https://doi.org/10.1126/science.1175371
doi: 10.1126/science.1175371 pubmed: 19608861
Dobrev D, Ravens U (2003) Remodeling of cardiomyocyte ion channels in human atrial fibrillation. Basic Res Cardiol 98:137–148. https://doi.org/10.1007/s00395-003-0409-8
doi: 10.1007/s00395-003-0409-8 pubmed: 12883831
Formisano L, Guida N, Valsecchi V, Cantile M, Cuomo O, Vinciguerra A, Laudati G, Pignataro G, Sirabella R, Di Renzo G, Annunziato L (2015) Sp3/REST/HDAC1/HDAC2 complex represses and Sp1/HIF-1/p300 complex activates ncx1 gene transcription, in brain ischemia and in ischemic brain preconditioning, by epigenetic mechanism. J Neurosci 35:7332–7348. https://doi.org/10.1523/JNEUROSCI.2174-14.2015
doi: 10.1523/JNEUROSCI.2174-14.2015 pubmed: 25972164 pmcid: 6705442
Glozak MA, Sengupta N, Zhang X, Seto E (2005) Acetylation and deacetylation of non-histone proteins. Gene 363:15–23. https://doi.org/10.1016/j.gene.2005.09.010
doi: 10.1016/j.gene.2005.09.010 pubmed: 16289629
Gregoretti IV, Lee YM, Goodson HV (2004) Molecular evolution of the histone deacetylase family: functional implications of phylogenetic analysis. J Mol Biol 338:17–31. https://doi.org/10.1016/j.jmb.2004.02.006
doi: 10.1016/j.jmb.2004.02.006 pubmed: 15050820
Kee HJ, Bae EH, Park S, Lee KE, Suh SH, Kim SW, Jeong MH (2013) HDAC inhibition suppresses cardiac hypertrophy and fibrosis in DOCA-salt hypertensive rats via regulation of HDAC6/HDAC8 enzyme activity. Kidney Blood Press Res 37:229–239. https://doi.org/10.1159/000350148
doi: 10.1159/000350148 pubmed: 23868068
Kong Y, Tannous P, Lu G, Berenji K, Rothermel BA, Olson EN, Hill JA (2006) Suppression of class I and II histone deacetylases blunts pressure-overload cardiac hypertrophy. Circulation 113:2579–2588. https://doi.org/10.1161/CIRCULATIONAHA.106.625467
doi: 10.1161/CIRCULATIONAHA.106.625467 pubmed: 16735673 pmcid: 4105979
Kook H, Lepore JJ, Gitler AD, Lu MM, Wing-Man Yung W, Mackay J, Zhou R, Ferrari V, Gruber P, Epstein JA (2003) Cardiac hypertrophy and histone deacetylase-dependent transcriptional repression mediated by the atypical homeodomain protein Hop. J Clin Invest 112:863–871. https://doi.org/10.1172/JCI19137
doi: 10.1172/JCI19137 pubmed: 12975471 pmcid: 193673
Kuwahara K, Saito Y, Takano M, Arai Y, Yasuno S, Nakagawa Y, Takahashi N, Adachi Y, Takemura G, Horie M, Miyamoto Y, Morisaki T, Kuratomi S, Noma A, Fujiwara H, Yoshimasa Y, Kinoshita H, Kawakami R, Kishimoto I, Nakanishi M, Usami S, Saito Y, Harada M, Nakao K (2003) NRSF regulates the fetal cardiac gene program and maintains normal cardiac structure and function. EMBO J 22:6310–6321. https://doi.org/10.1093/emboj/cdg601
doi: 10.1093/emboj/cdg601 pubmed: 14633990 pmcid: 291842
Li P, Kurata Y, Endang M, Ninomiya H, Higaki K, Taufiq F, Morikawa K, Shirayoshi Y, Horie M, Hisatome I (2018) Restoration of mutant hERG stability by inhibition of HDAC6. J Mol Cell Cardiol 115:158–169. https://doi.org/10.1016/j.yjmcc.2018.01.009
doi: 10.1016/j.yjmcc.2018.01.009 pubmed: 29355491
Li Z, Guo Y, Ren X, Rong L, Huang M, Cao J, Zang W (2019) HDAC2, but not HDAC1, regulates K
doi: 10.1016/j.neuroscience.2019.03.033 pubmed: 31022463
Liu F, Levin MD, Petrenko NB, Lu MM, Wang T, Yuan LJ, Stout AL, Epstein JA, Patel VV (2008) Histone-deacetylase inhibition reverses atrial arrhythmia inducibility and fibrosis in cardiac hypertrophy independent of angiotensin. J Mol Cell Cardiol 45:715–723. https://doi.org/10.1016/j.yjmcc.2008.08.015
doi: 10.1016/j.yjmcc.2008.08.015 pubmed: 18926829 pmcid: 2630487
Lkhagva B, Chang SL, Chen YC, Kao YH, Lin YK, Chiu CT, Chen SA, Chen YJ (2014) Histone deacetylase inhibition reduces pulmonary vein arrhythmogenesis through calcium regulation. Int J Cardiol 177:982–989. https://doi.org/10.1016/j.ijcard.2014.09.175
doi: 10.1016/j.ijcard.2014.09.175 pubmed: 25449511
Lkhagva B, Kao YH, Chen YC, Chao TF, Chen SA, Chen YJ (2016) Targeting histone deacetylases: a novel therapeutic strategy for atrial fibrillation. Eur J Pharmacol 781:250–257. https://doi.org/10.1016/j.ejphar.2016.04.034
doi: 10.1016/j.ejphar.2016.04.034 pubmed: 27089819
Lugenbiel P, Govorov K, Rahm AK, Wieder T, Gramlich D, Syren P, Weiberg N, Seyler C, Katus HA, Thomas D (2018) Inhibition of histone deacetylases induces K
doi: 10.1159/000492840 pubmed: 30134221
Lugenbiel P, Wenz F, Govorov K, Schweizer PA, Katus HA, Thomas D (2015) Atrial fibrillation complicated by heart failure induces distinct remodeling of calcium cycling proteins. PLoS ONE 10:e0116395. https://doi.org/10.1371/journal.pone.0116395
doi: 10.1371/journal.pone.0116395 pubmed: 25775120 pmcid: 4361185
Lugenbiel P, Wenz F, Syren P, Geschwill P, Govorov K, Seyler C, Frank D, Schweizer PA, Franke J, Weis T, Bruehl C, Schmack B, Ruhparwar A, Karck M, Frey N, Katus HA, Thomas D (2017) TREK-1 (K
doi: 10.1007/s00395-016-0597-7 pubmed: 28005193
Montgomery RL, Davis CA, Potthoff MJ, Haberland M, Fielitz J, Qi X, Hill JA, Richardson JA, Olson EN (2007) Histone deacetylases 1 and 2 redundantly regulate cardiac morphogenesis, growth, and contractility. Genes Dev 21:1790–1802. https://doi.org/10.1101/gad.1563807
doi: 10.1101/gad.1563807 pubmed: 17639084 pmcid: 1920173
Nattel S, Maguy A, Le Bouter S, Yeh YH (2007) Arrhythmogenic ion-channel remodeling in the heart: heart failure, myocardial infarction, and atrial fibrillation. Physiol Rev 87:425–456. https://doi.org/10.1152/physrev.00014.2006
doi: 10.1152/physrev.00014.2006 pubmed: 17429037
Nural-Guvener HF, Zakharova L, Nimlos J, Popovic S, Mastroeni D, Gaballa MA (2014) HDAC class I inhibitor, mocetinostat, reverses cardiac fibrosis in heart failure and diminishes CD90+ cardiac myofibroblast activation. Fibrogenesis Tissue Repair 7:10. https://doi.org/10.1186/1755-1536-7-10
doi: 10.1186/1755-1536-7-10 pubmed: 25024745 pmcid: 4094898
Ohya S, Kanatsuka S, Hatano N, Kito H, Matsui A, Fujimoto M, Matsuba S, Niwa S, Zhan P, Suzuki T, Muraki K (2016) Downregulation of the Ca
doi: 10.1002/prp2.228 pubmed: 27069638 pmcid: 4804315
Rahm AK, Wieder T, Gramlich D, Müller ME, Wunsch MN, El Tahry FA, Heimberger T, Weis T, Most P, Katus HA, Thomas D, Lugenbiel P (2021) HDAC2-dependent remodeling of K
doi: 10.1016/j.lfs.2020.11889 pubmed: 33310041
Schmidt C, Wiedmann F, Zhou XB, Heijman J, Voigt N, Ratte A, Lang S, Kallenberger SM, Campana C, Weymann A, De Simone R, Szabo G, Ruhparwar A, Kallenbach K, Karck M, Ehrlich JR, Baczko I, Borggrefe M, Ravens U, Dobrev D, Katus HA, Thomas D (2017) Inverse remodelling of K
doi: 10.1093/eurheartj/ehw559 pubmed: 28057773
Schmitt N, Grunnet M, Olesen SP (2014) Cardiac potassium channel subtypes: new roles in repolarization and arrhythmia. Physiol Rev 94:609–653. https://doi.org/10.1152/physrev.00022.2013
doi: 10.1152/physrev.00022.2013 pubmed: 24692356
Scholz B, Schulte JS, Hamer S, Himmler K, Pluteanu F, Seidl MD, Stein J, Wardelmann E, Hammer E, Volker U, Muller FU (2019) HDAC (histone deacetylase) inhibitor valproic acid attenuates atrial remodeling and delays the onset of atrial fibrillation in mice. Circ Arrhythm Electrophysiol 12:e007071. https://doi.org/10.1161/CIRCEP.118.007071
doi: 10.1161/CIRCEP.118.007071 pubmed: 30879335 pmcid: 6426346
Schweizer PA, Yampolsky P, Malik R, Thomas D, Zehelein J, Katus HA, Koenen M (2009) Transcription profiling of HCN-channel isotypes throughout mouse cardiac development. Basic Res Cardiol 104:621–629. https://doi.org/10.1007/s00395-009-0031-5
doi: 10.1007/s00395-009-0031-5 pubmed: 19421833 pmcid: 2758203
Seki M, LaCanna R, Powers JC, Vrakas C, Liu F, Berretta R, Chacko G, Holten J, Jadiya P, Wang T, Arkles JS, Copper JM, Houser SR, Huang J, Patel VV, Recchia FA (2016) Class I histone deacetylase inhibition for the treatment of sustained atrial fibrillation. J Pharmacol Exp Ther 358:441–449. https://doi.org/10.1124/jpet.116.234591
doi: 10.1124/jpet.116.234591 pubmed: 27353074 pmcid: 4998670
Shultz MD, Cao X, Chen CH, Cho YS, Davis NR, Eckman J, Fan J, Fekete A, Firestone B, Flynn J, Green J, Growney JD, Holmqvist M, Hsu M, Jansson D, Jiang L, Kwon P, Liu G, Lombardo F, Lu Q, Majumdar D, Meta C, Perez L, Pu M, Ramsey T, Remiszewski S, Skolnik S, Traebert M, Urban L, Uttamsingh V, Wang P, Whitebread S, Whitehead L, Yan-Neale Y, Yao YM, Zhou L, Atadja P (2011) Optimization of the in vitro cardiac safety of hydroxamate-based histone deacetylase inhibitors. J Med Chem 54:4752–4772. https://doi.org/10.1021/jm200388e
doi: 10.1021/jm200388e pubmed: 21650221
Tsai FC, Lin YC, Chang SH, Chang GJ, Hsu YJ, Lin YM, Lee YS, Wang CL, Yeh YH (2016) Differential left-to-right atria gene expression ratio in human sinus rhythm and atrial fibrillation: implications for arrhythmogenesis and thrombogenesis. Int J Cardiol 222:104–112. https://doi.org/10.1016/j.ijcard.2016.07.103
doi: 10.1016/j.ijcard.2016.07.103 pubmed: 27494721
Zhang D, Wu CT, Qi X, Meijering RA, Hoogstra-Berends F, Tadevosyan A, Cubukcuoglu Deniz G, Durdu S, Akar AR, Sibon OC, Nattel S, Henning RH, Brundel BJ (2014) Activation of histone deacetylase-6 induces contractile dysfunction through derailment of alpha-tubulin proteostasis in experimental and human atrial fibrillation. Circulation 129:346–358. https://doi.org/10.1161/CIRCULATIONAHA.113.005300
doi: 10.1161/CIRCULATIONAHA.113.005300 pubmed: 24146251

Auteurs

Patrick Lugenbiel (P)

Department of Cardiology, University of Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany.
HCR (Heidelberg Center for Heart Rhythm Disorders), Heidelberg, Germany.

Katharina Govorov (K)

Department of Cardiology, University of Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany.
HCR (Heidelberg Center for Heart Rhythm Disorders), Heidelberg, Germany.

Pascal Syren (P)

Department of Cardiology, University of Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany.
HCR (Heidelberg Center for Heart Rhythm Disorders), Heidelberg, Germany.

Ann-Kathrin Rahm (AK)

Department of Cardiology, University of Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany.
HCR (Heidelberg Center for Heart Rhythm Disorders), Heidelberg, Germany.
DZHK (German Centre for Cardiovascular Research), partner site Heidelberg/Mannheim, University of Heidelberg, Heidelberg, Germany.

Teresa Wieder (T)

Department of Cardiology, University of Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany.
HCR (Heidelberg Center for Heart Rhythm Disorders), Heidelberg, Germany.

Maximilian Wunsch (M)

Department of Cardiology, University of Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany.
HCR (Heidelberg Center for Heart Rhythm Disorders), Heidelberg, Germany.
DZHK (German Centre for Cardiovascular Research), partner site Heidelberg/Mannheim, University of Heidelberg, Heidelberg, Germany.

Nadine Weiberg (N)

Department of Cardiology, University of Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany.
HCR (Heidelberg Center for Heart Rhythm Disorders), Heidelberg, Germany.

Emili Manolova (E)

Department of Cardiology, University of Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany.
HCR (Heidelberg Center for Heart Rhythm Disorders), Heidelberg, Germany.

Dominik Gramlich (D)

Department of Cardiology, University of Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany.
HCR (Heidelberg Center for Heart Rhythm Disorders), Heidelberg, Germany.
DZHK (German Centre for Cardiovascular Research), partner site Heidelberg/Mannheim, University of Heidelberg, Heidelberg, Germany.

Rasmus Rivinius (R)

Department of Cardiology, University of Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany.
HCR (Heidelberg Center for Heart Rhythm Disorders), Heidelberg, Germany.
DZHK (German Centre for Cardiovascular Research), partner site Heidelberg/Mannheim, University of Heidelberg, Heidelberg, Germany.

Daniel Finke (D)

Department of Cardiology, University of Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany.
HCR (Heidelberg Center for Heart Rhythm Disorders), Heidelberg, Germany.
Department of Molecular Cardiology and Epigenetics, University Hospital Heidelberg, Heidelberg, Germany.

Lorenz H Lehmann (LH)

Department of Cardiology, University of Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany.
HCR (Heidelberg Center for Heart Rhythm Disorders), Heidelberg, Germany.
Department of Molecular Cardiology and Epigenetics, University Hospital Heidelberg, Heidelberg, Germany.

Patrick A Schweizer (PA)

Department of Cardiology, University of Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany.
HCR (Heidelberg Center for Heart Rhythm Disorders), Heidelberg, Germany.
DZHK (German Centre for Cardiovascular Research), partner site Heidelberg/Mannheim, University of Heidelberg, Heidelberg, Germany.

Derk Frank (D)

Department of Internal Medicine III, Cardiology and Angiology, University Medical Center Schleswig-Holstein, Kiel, Germany.
DZHK (German Centre for Cardiovascular Research), partner site Hamburg/Kiel/Lübeck, University Medical Center Schleswig-Holstein, Kiel, Germany.

Fadwa A El Tahry (FA)

Department of Cardiology, University of Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany.
DZHK (German Centre for Cardiovascular Research), partner site Heidelberg/Mannheim, University of Heidelberg, Heidelberg, Germany.

Claus Bruehl (C)

Institute for Physiology and Pathophysiology, Heidelberg, Germany.

Tanja Heimberger (T)

Department of Cardiology, University of Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany.
DZHK (German Centre for Cardiovascular Research), partner site Heidelberg/Mannheim, University of Heidelberg, Heidelberg, Germany.

Steffi Sandke (S)

Department of Cardiology, University of Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany.
DZHK (German Centre for Cardiovascular Research), partner site Heidelberg/Mannheim, University of Heidelberg, Heidelberg, Germany.

Tanja Weis (T)

Department of Cardiology, University of Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany.
DZHK (German Centre for Cardiovascular Research), partner site Heidelberg/Mannheim, University of Heidelberg, Heidelberg, Germany.

Patrick Most (P)

Department of Cardiology, University of Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany.
DZHK (German Centre for Cardiovascular Research), partner site Heidelberg/Mannheim, University of Heidelberg, Heidelberg, Germany.

Bastian Schmack (B)

Department of Cardiac Surgery, University Hospital Heidelberg, Heidelberg, Germany.

Arjang Ruhparwar (A)

Department of Cardiac Surgery, University Hospital Heidelberg, Heidelberg, Germany.

Matthias Karck (M)

Department of Cardiac Surgery, University Hospital Heidelberg, Heidelberg, Germany.

Norbert Frey (N)

Department of Cardiology, University of Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany.
HCR (Heidelberg Center for Heart Rhythm Disorders), Heidelberg, Germany.
DZHK (German Centre for Cardiovascular Research), partner site Heidelberg/Mannheim, University of Heidelberg, Heidelberg, Germany.
Department of Internal Medicine III, Cardiology and Angiology, University Medical Center Schleswig-Holstein, Kiel, Germany.
DZHK (German Centre for Cardiovascular Research), partner site Hamburg/Kiel/Lübeck, University Medical Center Schleswig-Holstein, Kiel, Germany.

Hugo A Katus (HA)

Department of Cardiology, University of Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany.
HCR (Heidelberg Center for Heart Rhythm Disorders), Heidelberg, Germany.
DZHK (German Centre for Cardiovascular Research), partner site Heidelberg/Mannheim, University of Heidelberg, Heidelberg, Germany.

Dierk Thomas (D)

Department of Cardiology, University of Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany. dierk.thomas@med.uni-heidelberg.de.
HCR (Heidelberg Center for Heart Rhythm Disorders), Heidelberg, Germany. dierk.thomas@med.uni-heidelberg.de.
DZHK (German Centre for Cardiovascular Research), partner site Heidelberg/Mannheim, University of Heidelberg, Heidelberg, Germany. dierk.thomas@med.uni-heidelberg.de.

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