Die Forschungen von K. Holl (1896 und 1899) und M. Richard (1962 und 1976) haben gezeigt, dass die von M. Lequien 1712 (PG 95–96) publizierten Sacra Parallela nur Auszüge eines sehr viel ...umfangreicheren, in drei Bücher unterteilten Florilegs sind, das in seiner ursprünglichen Form verloren ist, aber mit Hilfe der aus ihm überlieferten sogenannten "damaszenischen" Florilegien rekonstruiert werden kann. Spätestens seit dem 10. Jh. wurden die Sacra Johannes von Damaskos zugeschrieben, wohl zu Unrecht, da gute Gründe für eine Datierung des Werkes in das erste Viertel des 7. Jh.s sprechen. Das zweite Buch, das dem Menschen gewidmet ist, ist in zwei Rezensionen überliefert, deren große Unterschiede eine separate Edition erfordern, die in den Bänden VIII / 4-5 und VIII / 6-7 vorliegen. Der Band VIII / 8 enthält drei Supplemente zur Textedition, drei Appendices zum Kompilator und zur Entstehung der Sacra und zur handschriftlichen Überlieferung des Buches II, eine Konkordanz der Titloi beider Rezensionen sowie zwei Indices (Quellen und Parallelstellen) und ein Initienregister, die den Gesamtbestand an Texten erschließen, die in Sacra II überliefert werden.
Since 1963 the series Patristische Texte und Studien has been publishing research findings coordinated by the Patristics Commission, which today is a joint venture of all the German Academies. The ...series is presenting editions, commentaries and monographs on the writings and teachings of the Church Fathers.
Since 1963 the series Patristische Texte und Studien has been publishing research findings coordinated by the Patristics Commission, which today is a joint venture of all the German Academies. The ...series is presenting editions, commentaries and monographs on the writings and teachings of the Church Fathers.
Der vorliegende Band bietet eine vollständige neue Übersetzung und Kommentierung der Politischen Ratschläge ( Praecepta gerendae rei publicae) Plutarchs von Chaironeia (Provinz Achaea), die sich als ...ein Sendschreiben an einen jungen Hellenen aus Sardeis (Provinz Asia) vorstellen, der in die Stadtpolitik seiner Heimat unter den Bedingungen der römischen Oberhoheit eintreten will. Die interpretierenden Essays erläutern, vor allem anhand relevanter Inschriften-Zeugnisse, die politischen Rahmenbedingungen in Achaea und Asia und würdigen den spezifisch literarischen Charakter der Denkschrift.
Abstract Background Long noncoding ribonucleic acids (lncRNAs) are a subclass of regulatory noncoding ribonucleic acids for which expression and function in human endothelial cells and angiogenic ...processes is not well studied. Objectives The authors discovered hypoxia-sensitive human lncRNAs via next-generation ribonucleic acid sequencing and microarray approaches. To address their functional importance in angiogenic processes, several endothelial lncRNAs were characterized for their angiogenic characteristics in vitro and ex vivo. Methods Ribonucleic acid sequencing and microarray-derived data showed specific endothelial lncRNA expression changes after hypoxia. Validation experiments confirmed strong hypoxia-dependent activation of 2 intergenic lncRNAs: LINC00323 and MIR503HG. Results Silencing of these lncRNA transcripts led to angiogenic defects, including repression of growth factor signaling and/or the key endothelial transcription factor GATA2. Endothelial loss of these hypoxia-driven lncRNAs impaired cell-cycle control and inhibited capillary formation. The potential clinical importance of these endothelial lncRNAs to vascular structural integrity was demonstrated in an ex vivo model of human induced pluripotent stem cell–based engineered heart tissue. Conclusions The authors report an expression atlas of human hypoxia-sensitive lncRNAs and identified 2 lncRNAs with important functions to sustain endothelial cell biology. LncRNAs hold great promise to serve as important future therapeutic targets of cardiovascular disease.
Purpose Dysregulated microRNAs are implicated in the pathogenesis and aggressiveness of acute myeloid leukemia (AML). We describe the effect of the hematopoietic stem-cell self-renewal regulating ...miR-193b on progression and prognosis of AML. Methods We profiled miR-193b-5p/3p expression in cytogenetically and clinically characterized de novo pediatric AML (n = 161) via quantitative real-time polymerase chain reaction and validated our findings in an independent cohort of 187 adult patients. We investigated the tumor suppressive function of miR-193b in human AML blasts, patient-derived xenografts, and miR-193b knockout mice in vitro and in vivo. Results miR-193b exerted important, endogenous, tumor-suppressive functions on the hematopoietic system. miR-193b-3p was downregulated in several cytogenetically defined subgroups of pediatric and adult AML, and low expression served as an independent indicator for poor prognosis in pediatric AML (risk ratio ± standard error, -0.56 ± 0.23; P = .016). miR-193b-3p expression improved the prognostic value of the European LeukemiaNet risk-group stratification or a 17-gene leukemic stemness score. In knockout mice, loss of miR-193b cooperated with Hoxa9/Meis1 during leukemogenesis, whereas restoring miR-193b expression impaired leukemic engraftment. Similarly, expression of miR-193b in AML blasts from patients diminished leukemic growth in vitro and in mouse xenografts. Mechanistically, miR-193b induced apoptosis and a G1/S-phase block in various human AML subgroups by targeting multiple factors of the KIT-RAS-RAF-MEK-ERK (MAPK) signaling cascade and the downstream cell cycle regulator CCND1. Conclusion The tumor-suppressive function is independent of patient age or genetics; therefore, restoring miR-193b would assure high antileukemic efficacy by blocking the entire MAPK signaling cascade while preventing the emergence of resistance mechanisms.
Pathological cardiac hypertrophy is a result of afterload-increasing pathologies including untreated hypertension and aortic stenosis. It features progressive adverse cardiac remodeling, myocardial ...dysfunction, capillary rarefaction, and interstitial fibrosis often leading to heart failure.
This study aimed to establish a novel porcine model of pressure-overload-induced heart failure and to determine the effect of inhibition of microribonucleic acid 132 (miR-132) on heart failure development in this model.
This study developed a novel porcine model of percutaneous aortic constriction by implantation of a percutaneous reduction stent in the thoracic aorta, inducing progressive remodeling at day 56 (d56) after pressure-overload induction. In this study, an antisense oligonucleotide specifically inhibiting miR-132 (antimiR-132), was regionally applied via intracoronary injection at d0 (percutaneous transverse aortic constriction induction) and d28.
At d56, antimiR-132 treatment diminished cardiomyocyte cross-sectional area (188.9 ± 2.8 vs. 258.4 ± 9.0 μm
in untreated hypertrophic hearts) and improved global cardiac function (ejection fraction 48.9 ± 1.0% vs. 36.1 ± 1.7% in control hearts). Moreover, at d56 antimiR-132-treated hearts displayed less increase of interstitial fibrosis compared with sham-operated hearts (Δsham 1.8 ± 0.5%) than control hearts (Δsham 10.8 ± 0.6%). Of note, cardiac platelet and endothelial cell adhesion molecule 1
capillary density was higher in the antimiR-132-treated hearts (647 ± 20 cells/mm
) compared with in the control group (485 ± 23 cells/mm
).
The inhibition of miR-132 is a valid strategy in prevention of heart failure progression in hypertrophic heart disease and may be developed as a treatment for heart failure of nonischemic origin.
Adhesion G-protein-coupled receptors (aGPCRs) form a large family of cell surface molecules with versatile tasks in organ development. Many aGPCRs still await their functional and pharmacological ...deorphanization. Here, we characterized the orphan aGPCR CG11318/mayo of Drosophila melanogaster and found it expressed in specific regions of the gastrointestinal canal and anal plates, epithelial specializations that control ion homeostasis. Genetic removal of mayo results in tachycardia, which is caused by hyperkalemia of the larval hemolymph. The hyperkalemic effect can be mimicked by a raise in ambient potassium concentration, while normal potassium levels in mayoKO mutants can be restored by pharmacological inhibition of potassium channels. Intriguingly, hyperkalemia and tachycardia are caused non-cell autonomously through mayo-dependent control of enterocyte proliferation in the larval midgut, which is the primary function of this aGPCR. These findings characterize the ancestral aGPCR Mayo as a homeostatic regulator of gut development.
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•The CG11318 locus encodes the adhesion GPCR mayo•mayo controls midgut size through enterocyte proliferation•mayo removal results in hyperkalemia•Loss of mayo causes tachycardia
Vieira Contreras et al. reveal how the Drosophila adhesion G-protein-coupled receptor mayo impacts midgut development through enterocyte proliferation. mayo contributes to the potassium homeostasis in the hemolymph and thereby non-cell-autonomously controls cardiac frequency.
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