BackgroundInositol 1,4,5-trisphosphate receptors (IP3R1, 2, and 3) are intracellular Ca2+ release channels that regulate various vital processes. Although the ryanodine receptor type 2, another type of intracellular Ca2+ release channel, has been shown to play a role in embryonic cardiomyocytes, the functions of the IP3Rs in cardiogenesis remain unclear.Methodology/Principal FindingsWe found that IP3R1−/−-IP3R2−/− double-mutant mice died in utero with developmental defects of the ventricular myocardium and atrioventricular (AV) canal of the heart by embryonic day (E) 11.5, even though no cardiac defect was detectable in IP3R1−/− or IP3R2−/− single-mutant mice at this developmental stage. The double-mutant phenotype resembled that of mice deficient for calcineurin/NFATc signaling, and NFATc was inactive in embryonic hearts from the double knockout-mutant mice. The double mutation of IP3R1/R2 and pharmacologic inhibition of IP3Rs mimicked the phenotype of the AV valve defect that result from the inhibition of calcineurin, and it could be rescued by constitutively active calcineurin.Conclusions/SignificanceOur results suggest an essential role for IP3Rs in cardiogenesis in part through the regulation of calcineurin-NFAT signaling.

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Congenital heart diseases (CHD) result from abnormal morphogenesis of the embryonic cardiovascular system and usually involve defects in specific structural components of the developing heart and vessels. Therefore, an understanding of "Molecular Embryology", with specific focus on the individual modular steps involved in cardiovascular morphogenesis, is particularly relevant to those wishing to have a better insight into the origin of CHD. Recent advances in molecular embryology suggest that the cardiovascular system arises from multiple distinct embryonic origins, and a population of myocardial precursor cells in the pharyngeal mesoderm anterior to the early heart tube, denoted the "second heart field", has been identified. Discovery of the second heart field has important implications for the interpretation of cardiac outflow tract development and provides new insights into the morphogenesis of CHD.

Mycoplasma pneumoniae infection is conventionally diagnosed using serum antibody testing, microbial culture, and genetic testing. Recently, immunochromatography-based rapid mycoplasma antigen test kits have been developed and commercialised for rapid diagnosis of M. pneumoniae infection. However, as these kits do not provide sufficient sensitivity and specificity, a rapid test kit with improved accuracy is desired. The present prospective study evaluated a rapid M. pneumoniae diagnostic system utilizing a newly developed silver amplification immunochromatography (SAI) system. We performed dilution sensitivity test and the prospective clinical study evaluating the SAI system. The subjects of the clinical study included both children and adults. All patients suspected to have mycoplasma pneumonia (169 patients) were sequentially enrolled. Twelve patients did not agree to participate and 157 patients were enrolled in the study. The results demonstrate excellent performance of this system with 90.4% sensitivity and 100.0% specificity compared with real-time polymerase chain reaction. When compared with loop-mediated isothermal amplification (LAMP) methods, the results also demonstrate a high performance of this system with 93.0% sensitivity and 100.0% specificity. The SAI system uses a dedicated device for automatic analysis and reading, making it highly objective, and requires less human power, supporting its usefulness in clinical settings.

Excited-state proton transfer (ESPT) of 5,8-dicyano-2-naphthol (DCN2) in methanol at 30 MPa isobar between 294 and 543 K was studied using time-resolved fluorescence spectroscopy. From room temperature up to 513 K, a fluorescence band from an anionic form (RO − *, a proton dissociated form of DCN2) was observed, which indicates that the ESPT occurred under these thermal conditions. The time profiles of fluorescence intensity of the normal form of DCN2 (ROH*) (protonassociated form of DCN2) and RO − * were analyzed, considering the diffusion process of the contact ion pair RO − *•••H in the Coulomb field based on the Debye−Smoluchowski theory. Proton dissociation rate was slower than the solvent reorganization rate estimated from the dynamic Stokes shift, indicating that the proton transfer (PT) is not influenced by the solvent dynamic factor but by the solvation free energy. The proton dissociation rate constants were discussed from the change of the activation free energy of PT controlled by the solvent characteristics. It was found that the PT dissociation rate constants for various alcohols under different thermal conditions could be explained by the competing effects of hydrogen bonding and dipolarity/ polarizability that controlled the energy state of ROH* and RO − *•••H, respectively.