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3. Physioxia rewires mitochondrial complex composition to protect stem cell viability

Author

Raabe, Janice, Wittig, Ilka, Laurette, Patrick, Stathopoulou, Konstantina, Brand, Theresa, Schulze, Thomas, Klampe, Birgit, Orthey, Ellen, Cabrera-Orefice, Alfredo, Meisterknecht, Jana, Thiemann, Ellen, Laufer, Sandra D., Shibamiya, Aya, Reinsch, Marina, Fuchs, Sigrid, Kaiser, Jennifer, Yang, Jiaqi, Zehr, Simonida, Wrona, Kinga M., Lorenz, Kristina, Lukowski, Robert, Hansen, Arne, Gilsbach, Ralf, Brandes, Ralf P., Ulmer, Bärbel M., Eschenhagen, Thomas, and Cuello, Friederike

Published
2024
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4. An arrhythmogenic metabolite in atrial fibrillation

Author

Krause, Julia, Nickel, Alexander, Madsen, Alexandra, Aitken-Buck, Hamish M., Stoter, A. M. Stella, Schrapers, Jessica, Ojeda, Francisco, Geiger, Kira, Kern, Melanie, Kohlhaas, Michael, Bertero, Edoardo, Hofmockel, Patrick, Hübner, Florian, Assum, Ines, Heinig, Matthias, Müller, Christian, Hansen, Arne, Krause, Tobias, Park, Deung-Dae, Just, Steffen, Aïssi, Dylan, Börnigen, Daniela, Lindner, Diana, Friedrich, Nele, Alhussini, Khaled, Bening, Constanze, Schnabel, Renate B., Karakas, Mahir, Iacoviello, Licia, Salomaa, Veikko, Linneberg, Allan, Tunstall-Pedoe, Hugh, Kuulasmaa, Kari, Kirchhof, Paulus, Blankenberg, Stefan, Christ, Torsten, Eschenhagen, Thomas, Lamberts, Regis R., Maack, Christoph, Stenzig, Justus, and Zeller, Tanja

Published
2023
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6. Human model of primary carnitine deficiency cardiomyopathy reveals ferroptosis as a novel mechanism

Author

Loos, Malte, Klampe, Birgit, Schulze, Thomas, Yin, Xiaoke, Theofilatos, Konstantinos, Ulmer, Bärbel Maria, Schulz, Carl, Behrens, Charlotta S., van Bergen, Tessa Diana, Adami, Eleonora, Maatz, Henrike, Schweizer, Michaela, Brodesser, Susanne, Skryabin, Boris V., Rozhdestvensky, Timofey S., Bodbin, Sara, Stathopoulou, Konstantina, Christ, Torsten, Denning, Chris, Hübner, Norbert, Mayr, Manuel, Cuello, Friederike, Eschenhagen, Thomas, and Hansen, Arne

Published
2023
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14. Bundesbank-Verluste: Bilanzierungspraxis und etwaige Nachschusspflicht des Bundes.

Author

Hansen, Arne

Subjects
BUSINESS losses, FINANCIAL statements, BONDS (Finance)
Abstract

The Bundesbank's balance sheet and those of other central banks in the eurozone are currently showing high "operating" losses due to the discrepancy between the low interest bearing securities holdings from bond purchases and the now higher interest bearing commercial bank deposits. However, the current accounting practice does not reflect the associated losses in value anywhere near the market level – even though, according to the PSPP ruling of the German Federal Constitutional Court, the sale of securities before final maturity should be the rule. Even under the current valuation practice, an equity gap cannot be ruled out in the future, which is generally seen as unproblematic for central banks. However, there are risks in the context of recapitalisation by the state. Within the eurozone, national and European requirements could make such capital injections necessary. [ABSTRACT FROM AUTHOR]

Published
2024
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15. Human induced pluripotent stem cell–derived atrial cardiomyocytes recapitulate contribution of the slowly activating delayed rectifier currents IKs to repolarization in the human atrium.

Author

Sönmez, Muhammed Ikbal, Goldack, Silvana, Nurkkala, Elina, Schulz, Carl, Klampe, Birgit, Schulze, Thomas, Hansen, Arne, Eschenhagen, Thomas, Koivumäki, Jussi, and Christ, Torsten

Abstract

Aims Human induced pluripotent stem cell–derived atrial cardiomyocytes (hiPSC-aCM) could be a helpful tool to study the physiology and diseases of the human atrium. To fulfil this expectation, the electrophysiology of hiPSC-aCM should closely resemble the situation in the human atrium. Data on the contribution of the slowly activating delayed rectifier currents (I Ks) to repolarization are lacking for both human atrium and hiPSC-aCM. Methods and results Human atrial tissues were obtained from patients with sinus rhythm (SR) or atrial fibrillation (AF). Currents were measured in human atrial cardiomyocytes (aCM) and compared with hiPSC-aCM and used to model I Ks contribution to action potential (AP) shape. Action potential was recorded by sharp microelectrodes. HMR-1556 (1 µM) was used to identify I Ks and to estimate I Ks contribution to repolarization. Less than 50% of hiPSC-aCM and aCM possessed I Ks. Frequency of occurrence, current densities, activation/deactivation kinetics, and voltage dependency of I Ks did not differ significantly between hiPSC-aCM and aCM, neither in SR nor AF. β-Adrenoceptor stimulation with isoprenaline did not increase I Ks neither in aCM nor in hiPSC-aCM. In tissue from SR, block of I Ks with HMR-1556 did not lengthen the action potential duration, even when repolarization reserve was reduced by block of the ultra-rapid repolarizing current with 4-aminopyridine or the rapidly activating delayed rectifier potassium outward current with E-4031. Conclusion I Ks exists in hiPSC-aCM with biophysics not different from aCM. As in adult human atrium (SR and AF), I Ks does not appear to relevantly contribute to repolarization in hiPSC-aCM. [ABSTRACT FROM AUTHOR]

Published
2024
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20. Human induced pluripotent stem cell-derived cardiomyocytes as an electrophysiological model : Opportunities and challenges—The Hamburg perspective

Author

Ismaili, Djemail, Schulz, Carl, Horváth, András, Koivumäki, Jussi T., Mika, Delphine, Hansen, Arne, Eschenhagen, Thomas, Christ, Torsten, Tampere University, and BioMediTech

Subjects
318 Medical biotechnology
Abstract

Models based on human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) are proposed in almost any field of physiology and pharmacology. The development of human induced pluripotent stem cell-derived cardiomyocytes is expected to become a step forward to increase the translational power of cardiovascular research. Importantly they should allow to study genetic effects on an electrophysiological background close to the human situation. However, biological and methodological issues revealed when human induced pluripotent stem cell-derived cardiomyocytes were used in experimental electrophysiology. We will discuss some of the challenges that should be considered when human induced pluripotent stem cell-derived cardiomyocytes will be used as a physiological model. publishedVersion

Published
2023

23. A retrospective study of physical fitness and mental health among police students in Sweden.

Author

Krugly, Sandra, Bjärsholm, Daniel, Jansson, Alexander, Rosendal Hansen, Arne, Hansson, Olof, Brehm, Kajsa, Datmo, Angelica, Hafsteinsson Östenberg, Anna, and Vikman, Jenny

Subjects
PHYSICAL fitness, MENTAL health, POLICE education, POLICE, GENDER differences (Psychology), AEROBIC exercises
Abstract

Little is known about the physical and mental health among police students. Based on data on Swedish police students' physical fitness (N = 1736) and mental health (N = 407), the results show that: (a) there are gender differences; (b) the physical fitness changes during police education; in general, the students get stronger but less flexible, and the aerobic endurance increases for women but decreases for men; and (c) students' self-reported physical activity and mental health affect their perceived police ability differently in relation to gender. Consequently, this study questions if the Swedish police education is preparing the students adequately for their future profession. [ABSTRACT FROM AUTHOR]

Published
2023
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24. Neuer Verhaltenskodex für EZB-Ratsmitglieder erzeugt Klärungsbedarf.

Author

Hansen, Arne

Abstract

The trust placed in a central back is considered its most important asset – especially in turbulent times for monetary policy. In order to avoid any appearance of conflicts of interest, the European Central Bank (ECB) felt motivated to tighten its Code of Conduct for high-level officials at the beginning of 2023. However, an analysis of current self-disclosures by the members of the ECB's Governing Council on their financial investments indicates a lack of clarity in the new investment rules, which seems to result in inconsistent and partly contradictory disclosures – especially with regard to "legacy assets". The clarity and comprehensibility of the rules as well as their consistent implementation should therefore be reviewed in order to prevent an erosion of confidence in the ECB. [ABSTRACT FROM AUTHOR]

Published
2023
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25. Vasopressin stimulates the proliferation and differentiation of red blood cell precursors and improves recovery from anemia

Author

Mayer, Balázs, Németh, Krisztián, Krepuska, Miklós, Myneni, Vamsee D., Maric, Dragan, Tisdale, John F., Hsieh, Matthew M., Uchida, Naoya, Lee, Heon-Jin, Nemeth, Michael J., Holmbeck, Kenn, Noguchi, Constance Tom, Rogers, Heather, Dey, Soumyadeep, Hansen, Arne, Hong, Jeffrey, Chow, Ian, Key, Sharon, Szalayova, Ildikó, Pagani, Jerome, Markó, Károly, McClain-Caldwell, Ian, Vitale-Cross, Lynn, Young, W. Scott, Brownstein, Michael J., and Mezey, Éva

Published
2017
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30. MUSCLEMOTION: A Versatile Open Software Tool to Quantify Cardiomyocyte and Cardiac Muscle Contraction In Vitro and In Vivo

Author

Sala, Luca, van Meer, Berend J., Tertoolen, Leon G.J., Bakkers, Jeroen, Bellin, Milena, Davis, Richard P., Denning, Chris, Dieben, Michel A.E., Eschenhagen, Thomas, Giacomelli, Elisa, Grandela, Catarina, Hansen, Arne, Holman, Eduard R., Jongbloed, Monique R.M., Kamel, Sarah M., Koopman, Charlotte D., Lachaud, Quentin, Mannhardt, Ingra, Mol, Mervyn P.H., Mosqueira, Diogo, Orlova, Valeria V., Passier, Robert, Ribeiro, Marcelo C., Saleem, Umber, Smith, Godfrey L., Burton, Francis L., and Mummery, Christine L.

Published
2018
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34. Author Correction: Differentiation of cardiomyocytes and generation of human engineered heart tissue

Author

Breckwoldt, Kaja, Brenière-Letuffe, David, Mannhardt, Ingra, Schulze, Thomas, Ulmer, Bärbel, Werner, Tessa, Benzin, Anika, Klampe, Birgit, Reinsch, Marina C, Laufer, Sandra, Shibamiya, Aya, Prondzynski, Maksymilian, Mearini, Giulia, Schade, Dennis, Fuchs, Sigrid, Neuber, Christiane, Krämer, Elisabeth, Saleem, Umber, Schulze, Mirja L, Rodriguez, Marita L, Eschenhagen, Thomas, and Hansen, Arne

Published
2019
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35. Regulation of APD and Force by the Na + /Ca 2+ Exchanger in Human-Induced Pluripotent Stem Cell-Derived Engineered Heart Tissue.

Author

Ismaili, Djemail, Gurr, Katrin, Horváth, András, Yuan, Lei, Lemoine, Marc D., Schulz, Carl, Sani, Jascha, Petersen, Johannes, Reichenspurner, Hermann, Kirchhof, Paulus, Jespersen, Thomas, Eschenhagen, Thomas, Hansen, Arne, Koivumäki, Jussi T., and Christ, Torsten

Subjects
ACTION potentials, TISSUE engineering, SPATIAL arrangement, HEART
Abstract

The physiological importance of NCX in human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) is not well characterized but may depend on the relative strength of the current, compared to adult cardiomyocytes, and on the exact spatial arrangement of proteins involved in Ca2+ extrusion. Here, we determined NCX currents and its contribution to action potential and force in hiPSC-CMs cultured in engineered heart tissue (EHT). The results were compared with data from rat and human left ventricular tissue. The NCX currents in hiPSC-CMs were larger than in ventricular cardiomyocytes isolated from human left ventricles (1.3 ± 0.2 pA/pF and 3.2 ± 0.2 pA/pF for human ventricle and EHT, respectively, p < 0.05). SEA0400 (10 µM) markedly shortened the APD90 in EHT (by 26.6 ± 5%, p < 0.05) and, to a lesser extent, in rat ventricular tissue (by 10.7 ± 1.6%, p < 0.05). Shortening in human left ventricular preparations was small and not different from time-matched controls (TMCs; p > 0.05). Force was increased by the NCX block in rat ventricle (by 31 ± 5.4%, p < 0.05) and EHT (by 20.8 ± 3.9%, p < 0.05), but not in human left ventricular preparations. In conclusion, hiPSC-CMs possess NCX currents not smaller than human left ventricular tissue. Robust NCX block-induced APD shortening and inotropy makes EHT an attractive pharmacological model. [ABSTRACT FROM AUTHOR]

Published
2022
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36. A biallelic loss-of-function variant in MYZAP is associated with a recessive form of severe dilated cardiomyopathy.

Author

Maver, Aleš, Žigman, Tamara, Rangrez, Ashraf Yusuf, Ćorić, Marijana, Homolak, Jan, Šarić, Dalibor, Škifić, Iva, Udovičić, Mario, Zekušić, Marija, Saleem, Umber, Laufer, Sandra D., Hansen, Arne, Frey, Norbert, Barić, Ivo, and Peterlin, Borut

Subjects
DILATED cardiomyopathy, MYOCARDIUM, EXOMES, CONTRACTILE proteins, HEART cells
Abstract

Dilated cardiomyopathy (DCM) is a primary disorder of the cardiac muscle, characterized by dilatation of the left ventricle and contractile dysfunction. About 50% of DCM cases can be attributed to monogenic causes, whereas the etiology in the remaining patients remains unexplained. We report a family with two brothers affected by severe DCM with onset in the adolescent period. Using exome sequencing, we identified a homozygous premature termination variant in the MYZAP gene in both affected sibs. MYZAP encodes for myocardial zonula adherens protein—a conserved cardiac protein in the intercalated disc structure of cardiomyocytes. The effect of the variant was demonstrated by light and electron microscopy of the heart muscle and immunohistochemical and western blot analysis of the MYZAP protein in the heart tissue of the proband. Functional characterization using patient-derived induced pluripotent stem cell cardiomyocytes revealed significantly lower force and longer time to peak contraction and relaxation consistent with severe contractile dysfunction. Weprovide independent support for the role of biallelic loss-of-function MYZAP variants in dilated cardiomyopathy. This report extends the spectrum of cardiac disease associated with dysfunction of cardiac intercalated disc junction and sheds light on the mechanisms leading to DCM. [ABSTRACT FROM AUTHOR]

Published
2022
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39. Perspectives on the measurement problem: perspectives from the measurement problem

Author

Hansen, Arne and Wolf, Stefan

Abstract

In quantum mechanics, the measurement problem is commonly regarded as reason for deep concern. It seems that, either, the problem can be solved and there is hope for quantum mechanics, or the theory better be left behind in search of another one. We investigate the prospect of finding a solution to the measurement problem—within quantum mechanics, as well as in theoretical frameworks beyond it. As we do so, there emerges a perspective on doing physics drawing from considerations in the philosophy of language and in epistemology. Developing this perspective for further aspects in physics reveals: The notion of a system is similarly problematic. Eventually, the question arises whether these are problems of specific physical theories, or rather of specific stances towards physics. In this regard, we examine in particular the role and understanding of assumptions.

Published
2020

43. Heterozygous LmnadelK32 mice develop dilated cardiomyopathy through a combined pathomechanism of haploinsufficiency and peptide toxicity

Author

Cattin, Marie-Elodie, Bertrand, Anne T., Schlossarek, Saskia, Le Bihan, Marie-Catherine, Skov Jensen, Søren, Neuber, Christiane, Crocini, Claudia, Maron, Sophia, Lainé, Jeanne, Mougenot, Nathalie, Varnous, Shaïda, Fromes, Yves, Hansen, Arne, Eschenhagen, Thomas, Decostre, Valérie, Carrier, Lucie, and Bonne, Gisèle

Published
2013
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47. Comprehensive analyses of the inotropic compound omecamtiv mecarbil in rat and human cardiac preparations.

Author

Rhoden, Alexandra, Schulze, Thomas, Pietsch, Niels, Christ, Torsten, Hansen, Arne, and Eschenhagen, Thomas

Subjects
INDUCED pluripotent stem cells, MYOSIN, RATS
Abstract

Omecamtiv mecarbil (OM), a myosin activator, was reported to induce complex concentration- and species-dependent effects on contractile function, and clinical studies indicated a low therapeutic index with diastolic dysfunction at concentrations above 1 mM. To further characterize effects of OM in a human context and under different preload conditions, we constructed a setup that allows isometric contractility analysis of human induced pluripotent stem cell (hiPSC)-derived engineered heart tissues (EHTs). The results were compared with effects of OM on the very same EHTs measured under auxotonic conditions. OM induced a sustained, concentration-dependent increase in time to peak under all conditions (maximally two- to threefold). Peak force, in contrast, was increased by OM only in human, but not rat EHTs and only under isometric conditions, varied between hiPSC lines and showed a biphasic concentration dependency with maximal effects at 1θmM. Relaxation time tended to fall under auxotonic and strongly increased under isometric conditions, again with biphasic concentration dependency. Diastolic tension concentration dependently increased under all conditions. The latter was reduced by an inhibitor of the mitochondrial sodium calcium exchanger (CGP-37157). OM induced increases in mitochondrial oxidation in isolated cardiomyocytes, indicating that OM, an inotrope that does not increase intracellular and mitochondrial Ca2+, can induce mismatch between an increase in ATP and ROS production and unstimulated mitochondrial redox capacity. Taken together, we developed a novel setup well suitable for isometric measurements of EHTs. The effects of OM on contractility and diastolic tension are complex with concentration-, time-, species- and loading-dependent differences. Effects on mitochondrial function require further studies. [ABSTRACT FROM AUTHOR]

Published
2022
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49. Evidence for FHL1 as a novel disease gene for isolated hypertrophic cardiomyopathy

Author

Friedrich, Felix W., Wilding, Brendan R., Reischmann, Silke, Crocini, Claudia, Lang, Patrick, Charron, Philippe, Müller, Oliver J., McGrath, Meagan J., Vollert, Ingra, Hansen, Arne, Linke, Wolfgang A., Hengstenberg, Christian, Bonne, Gisèle, Morner, Stellan, Wichter, Thomas, Madeira, Hugo, Arbustini, Eloisa, Eschenhagen, Thomas, Mitchell, Christina A., Isnard, Richard, and Carrier, Lucie

Published
2012
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50. EULAR Sjögrenʼs Syndrome Patient Reported Index (ESSPRI): development of a consensus patient index for primary Sjögrenʼs syndrome

Author

Seror, Raphaèle, Ravaud, Philippe, Mariette, Xavier, Bootsma, Hendrika, Theander, Elke, Hansen, Arne, Ramos-Casals, Manel, Dörner, Thomas, Bombardieri, Stefano, Hachulla, Eric, Brun, Johan G, Kruize, Aike A, Praprotnik, Sonja, Tomsic, Matija, Gottenberg, Jacques-Eric, Devauchelle, Valerie, Devita, Salvatore, Vollenweider, Cristina, Mandl, Thomas, Tzioufas, Athanasios, Carsons, Steven, Saraux, Alain, Sutcliffe, Nurhan, Vitali, Claudio, and Bowman, Simon J

Published
2011
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