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Cardiac looping and trabeculation are key processes during cardiac chamber maturation. However, the underlying mechanisms remain incompletely understood. Here, we report the isolation, cloning and characterization of the proprotein convertase furina from the cardiovascular mutant loft in zebrafish. loft is an ethylnitrosourea-induced mutant and has evident defects in the cardiac outflow tract, heart looping and trabeculation, the craniofacial region and pharyngeal arch arteries. Positional cloning revealed that furina mRNA was barely detectable in loft mutants, and loft failed to complement the TALEN-induced furina mutant pku338, confirming that furina is responsible for the loft mutant phenotypes. Mechanistic studies demonstrated that Notch reporter Tg(tp1:mCherry) signals were largely eliminated in mutant hearts, and overexpression of the Notch intracellular domain partially rescued the mutant phenotypes, probably due to the lack of Furina-mediated cleavage processing of Notch1b proteins, the only Notch receptor expressed in the heart. Together, our data suggest a potential post-translational modification of Notch1b proteins via the proprotein convertase Furina in the heart, and unveil the function of the Furina-Notch1b axis in cardiac looping and trabeculation in zebrafish, and possibly in other organisms.

This work proposes a simple automatic supervisory control system (ASCS) that is based on an energy-saving decoupling indoor comfort control (ESDICC) for regulating the indoor comforts of an office building. Three energy-saving indoor comfort control algorithms are modified to yield the ESDICC algorithms. The ESDICC-based ASCS is modeled using a Petri net (PN), whose graph is presented in detail and whose dynamics are thoroughly described. Results of two test cases demonstrate the simplicity of the operations of ESDICC-based ASCS and the energy-saving effect of the ESDICC algorithms.