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G-protein coupled receptors (GPCRs) are encoded by nonabundant mRNAs, and it is difficult to detect them reliably with the highly parallel methods that are in general use. Because of this, we developed and validated a sensitive, specific, semi-quantitative method for detecting these transcripts. We have used the method to profile GPCR transcripts in white blood cells (WBCs)–B, CD4, CD8, NK, and dendritic cells; monocytes, and macrophage-like monocytes treated with granulocyte-macrophage colony-stimulating factor–as well as platelets. On average, the white cells studied expressed 160 receptor mRNAs (range, 123–206). Platelets made 69. Some, but far from all, of the receptors we found have been detected earlier. We believe our data should stimulate studies of receptor function and contribute to drug development. [ABSTRACT FROM AUTHOR]

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]

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]

UnlabelledDifferent tissue-engineering approaches have been developed to induce and promote cardiac regeneration; however, the impact of the immune system and its responses to the various scaffold components of the engineered grafts remains unclear. Fibrin-based engineered heart tissue (EHT) was generated from neonatal Lewis (Lew) rat heart cells and transplanted onto the left ventricular surface of three different rat strains: syngeneic Lew, allogeneic Brown Norway, and immunodeficient Rowett Nude rats. Interferon spot frequency assay results showed similar degrees of systemic immune activation in the syngeneic and allogeneic groups, whereas no systemic immune response was detectable in the immunodeficient group (p < .001 vs. syngeneic and allogeneic). Histological analysis revealed much higher local infiltration of CD3- and CD68-positive cells in syngeneic and allogeneic rats than in immunodeficient animals. Enzyme-linked immunospot and immunofluorescence experiments revealed matrix-directed TH1-based rejection in syngeneic recipients without collateral impairment of heart cell survival. Bioluminescence imaging was used for in vivo longitudinal monitoring of transplanted luciferase-positive EHT constructs. Survival was documented in syngeneic and immunodeficient recipients for a period of up to 110 days after transplant, whereas in the allogeneic setting, graft survival was limited to only 14 ± 1 days. EHT strategies using autologous cells are promising approaches for cardiac repair applications. Although fibrin-based scaffold components elicited an immune response in our studies, syngeneic cells carried in the EHT were relatively unaffected.SignificanceAn initial insight into immunological consequences after transplantation of engineered heart tissue was gained through this study. Most important, this study was able to demonstrate cell survival despite rejection of matrix components. Generation of syngeneic human engineered heart tissue, possibly using human induced pluripotent stem cell technology with subsequent directed rejection of matrix components, may be a potential future approach to replace diseased myocardium.