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Cardiomyocytes are permanently exposed to mechanical stimulation due to cardiac contractility. Passive myocardial stiffness is a crucial factor, which defines the physiological ventricular compliance and volume of diastolic filling with blood. Heart diseases often present with increased myocardial stiffness, for instance when fibrotic changes modify the composition of the cardiac extracellular matrix (ECM). Consequently, the ventricle loses its compliance, and the diastolic blood volume is reduced. Recent advances in the field of cardiac mechanobiology revealed that disease-related environmental stiffness changes cause severe alterations in cardiomyocyte cellular behavior and function. Here, we review the molecular mechanotransduction pathways that enable cardiomyocytes to sense stiffness changes and translate those into an altered gene expression. We will also summarize current knowledge about when myocardial stiffness increases in the diseased heart. Sophisticated in vitro studies revealed functional changes, when cardiomyocytes faced a stiffer matrix. Finally, we will highlight recent studies that described modulations of cardiac stiffness and thus myocardial performance in vivo. Mechanobiology research is just at the cusp of systematic investigations related to mechanical changes in the diseased heart but what is known already makes way for new therapeutic approaches in regenerative biology., Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe; 1234

Cardiogenesis is a complex developmental process involving multiple overlapping stages of cell fate specification, proliferation, differentiation, and morphogenesis. Precise spatiotemporal coordination between the different cardiogenic processes is ensured by intercellular signalling crosstalk and tissue-tissue interactions. Notch is an intercellular signalling pathway crucial for cell fate decisions during multicellular organismal development and is aptly positioned to coordinate the complex signalling crosstalk required for progressive cell lineage restriction during cardiogenesis. In this Review, we describe the role of Notch signalling and the crosstalk with other signalling pathways during the differentiation and patterning of the different cardiac tissues and in cardiac valve and ventricular chamber development. We examine how perturbation of Notch signalling activity is linked to congenital heart diseases affecting the neonate and adult, and discuss studies that shed light on the role of Notch signalling in heart regeneration and repair after injury.

The epicardium, the outer mesothelial layer enclosing the myocardium, plays key roles in heart development and regeneration. During embryogenesis it arises from the proepicardium (PE), a cell cluster that appears in the dorsal pericardium close to the venous pole of the heart. Little is known about how the PE emerges from the pericardial mesothelium. Using the zebrafish model and a combination of genetic tools, pharmacological agents and quantitativein vivoimaging we reveal that a coordinated collective movement of the dorsal pericardium drives PE formation. We found that PE cells are apically extruded in response to actomyosin activity. Our results reveal that the coordinated action of Notch/Bmp pathways is critically needed for apical extrusion of PE cells. More generally, by comparison to cell extrusion for the elimination of unfit cells from epithelia, our results describe a unique mechanism where extruded cell viability is maintained.

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Biología Molecular. Fecha de lectura: 18-12-2015, Esta tesis tiene embargado el acceso al texto completo hasta el 18-06-2017, Juliane Münch holds a PhD fellowship linked to grant FP7-ITN 215761 (NotchIT)

Macroscopic social and economic changes in the last few years are forcing business companies and public institutions to redefine their approach to social intervention, focusing on local and highly individualised solutions. This change is also calling for a new design approach. The challenge for designers is not only to be able to provide local and highly individualised solutions, but also to propose strategies to transfer and reproduce the solutions, or part of them, into different local contexts, thus creating economy of scope. This would be possible by using forms of codification and modularisation of the most relevant components in local solutions. The code refers to the organisational knowledge included in local components and the way each component interacts with the others. Like software systems, local product-service systems can be built upon a source code. This paper will illustrate how this process was developed in a concrete case. Through this case the authors analyse the possibility to build something similar to a source code for initiatives based on social interaction and investigate the process of construction of such a code Furthermore, the author discuss differences and analogies between design intervention in a social context and in the normal business context. The question of codification suggests a methodological approach for supporting transferability both in the problem space (dealing with complexity) and in the solution space (dealing with contingency). The analysis of differences and similarities between business- and socially-oriented processes suggests a new role for designers and new opportunities for innovation. Keywords: Product Service Systems, Methodology, Design and Morality, Codification, Transferability

Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz 64(12), 1522-1532 (2021). doi:10.1007/s00103-021-03455-1 special issue: "COVID-19 und Public Health: Gesundheit von Kindern und Jugendlichen", Published by Springer, Heidelberg