The FgfrL1 receptor is required for development of slow muscle fibers.

FgfrL1, which interacts with Fgf ligands and heparin, is a member of the fibroblast growth factor receptor (Fgfr) family. FgfrL1-deficient mice show two significant alterations when compared to wildtype mice: They die at birth due to a malformed diaphragm and they lack metanephric kidneys. Utilizing gene arrays, qPCR and in situ hybridization we show here that the diaphragm of FgfrL1 knockout animals lacks any slow muscle fibers at E18.5 as indicated by the absence of slow fiber markers Myh7, Myl2 and Myl3. Similar lesions are also found in other skeletal muscles that contain a high proportion of slow fibers at birth, such as the extraocular muscles. In contrast to the slow fibers, fast fibers do not appear to be affected as shown by expression of fast fiber markers Myh3, Myh8, Myl1 and MylPF. At early developmental stages (E10.5, E15.5), FgfrL1-deficient animals express slow fiber genes at normal levels. The loss of slow fibers cannot be attributed to the lack of kidneys, since Wnt4 knockout mice, which also lack metanephric kidneys, show normal expression of Myh7, Myl2 and Myl3. Thus, FgfrL1 is specifically required for embryonic development of slow muscle fibers.

Quick divergence but slow convergence during ecotype formation in lake and stream stickleback pairs of variable age

When genetic constraints restrict phenotypic evolution, diversification can be predicted to evolve along so-called lines of least resistance. To address the importance of such constraints and their resolution, studies of parallel phenotypic divergence that differ in their age are valuable. Here, we investigate the parapatric evolution of six lake and stream threespine stickleback systems from Iceland and Switzerland, ranging in age from a few decades to several millennia. Using phenotypic data, we test for parallelism in ecotypic divergence between parapatric lake and stream populations and compare the observed patterns to an ancestral-like marine population. We find strong and consistent phenotypic divergence, both among lake and stream populations and between our freshwater populations and the marine population. Interestingly, ecotypic divergence in low-dimensional phenotype space (i.e. single traits) is rapid and seems to be often completed within 100 years. Yet, the dimensionality of ecotypic divergence was highest in our oldest systems and only there parallel evolution of unrelated ecotypes was strong enough to overwrite phylogenetic contingency. Moreover, the dimensionality of divergence in different systems varies between trait complexes, suggesting different constraints and evolutionary pathways to their resolution among freshwater systems.

Slow Cities: Sustainable Places in a Fast World

This article examines the Slow Food and Slow City movement as an alternative approach to urban development that focuses on local resources, economic and cultural strengths, and the unique historical context of a town. Following recent discussions about the politics of alternative economic development, the study examines the Slow City movement as a strategy to address the interdependencies between goals for economic, environmental, and equitable urban development. In particular, we draw on the examples of two Slow Cities in Germany—Waldkirch and Hersbruck, and show how these towns are retooling their urban policies. The study is placed in the context of alternative urban development agendas as opposed to corporate-centered development. We conclude the article by offering some remarks about the institutional and political attributes of successful Slow Cities and the transferability of the concept.

Slow conduction in mixed cultured strands of primary ventricular cells and stem cell-derived cardiomyocytes

Modern concepts for the treatment of myocardial diseases focus on novel cell therapeutic strategies involving stem cell-derived cardiomyocytes (SCMs). However, functional integration of SCMs requires similar electrophysiological properties as primary cardiomyocytes (PCMs) and the ability to establish intercellular connections with host myocytes in order to contribute to the electrical and mechanical activity of the heart. The aim of this project was to investigate the properties of cardiac conduction in a co-culture approach using SCMs and PCMs in cultured cell strands. Murine embryonic SCMs were pooled with fetal ventricular cells and seeded in predefined proportions on microelectrode arrays to form patterned strands of mixed cells. Conduction velocity (CV) was measured during steady state pacing. SCM excitability was estimated from action potentials measured in single cells using the patch clamp technique. Experiments were complemented with computer simulations of conduction using a detailed model of cellular architecture in mixed cell strands. CV was significantly lower in strands composed purely of SCMs (5.5 ± 1.5 cm/s, n = 11) as compared to PCMs (34.9 ± 2.9 cm/s, n = 21) at similar refractoriness (100% SCMs: 122 ± 25 ms, n = 9; 100% PCMs: 139 ± 67 ms, n = 14). In mixed strands combining both cell types, CV was higher than in pure SCMs strands, but always lower than in 100% PCM strands. Computer simulations demonstrated that both intercellular coupling and electrical excitability limit CV. These data provide evidence that in cultures of murine ventricular cardiomyocytes, SCMs cannot restore CV to control levels resulting in slow conduction, which may lead to reentry circuits and arrhythmias.

Reactive, Slow and...Innovative? Decision-making Structures and Policy Outputs

Consensus democracies like Switzerland are generally known to have a low innovation capacity (Lijphart 1999). This is due to the high number of veto points such as perfect bicameralism or the popular referendum. These institutions provide actors opposing a policy with several opportunities to block potential policy change (Immergut 1990; Tsebelis 2002). In order to avoid a failure of a process because opposing actors activate veto points, decision-making processes in Switzerland tend to integrate a large number of actors with different - and often diverging - preferences (Kriesi and Trechsel 2008). Including a variety of actors in a decision-making process and taking into account their preferences implies important trade-offs. Integrating a large number of actors and accommodating their preferences takes time and carries the risk of resulting in lowest common denominator solutions. On the contrary, major innovative reforms usually fail or come only as a result of strong external pressures from either the international environment, economic turmoil or the public (Kriesi 1980: 635f.; Kriesi and Trechsel 2008; Sciarini 1994). Standard decision-making processes are therefore characterized as reactive, slow and capable of only marginal adjustments (Kriesi 1980; Kriesi and Trechsel 2008; Linder 2009; Sciarini 2006). This, in turn, may be at odds with the rapid developments of international politics, the flexibility of the private sector, or the speed of technological development.