Cardiomyocytes contract against a mechanical load during each heartbeat, and excessive mechanical stress leads to heart diseases. Using a cell-in-gel system that imposes an afterload during cardiomyocyte contraction, we found that nitric oxide synthase (NOS) was involved in transducing mechanical load to alter Ca2+ dynamics. In mouse ventricular myocytes, afterload increased the systolic Ca2+ transient, which enhanced contractility to counter mechanical load, but also caused spontaneous Ca2+ sparks during diastole that could be arrhythmogenic. The increases in the Ca2+ transient and sparks were attributable to increased ryanodine receptor (RyR) sensitivity because the amount of Ca2+ in the sarcoplasmic reticulum load was unchanged. Either pharmacological inhibition or genetic deletion of nNOS (or NOS1), but not of eNOS (or NOS3), prevented afterload-induced Ca2+ sparks. This differential effect may arise from localized NO signaling, arising from the proximity of nNOS to RyR, as determined by super-resolution imaging. Ca2+-calmodulin–dependent protein kinase II (CaMKII) and nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) also contributed to afterload-induced Ca2+ sparks. Cardiomyocytes from a mouse model of familial hypertrophic cardiomyopathy exhibited enhanced mechanotransduction and frequent arrhythmogenic Ca2+ sparks. Inhibiting nNOS and CaMKII, but not NOX2, in cardiomyocytes from this model eliminated the Ca2+ sparks, suggesting mechanotransduction activated nNOS and CaMKII independently from NOX2. Thus, our data identify nNOS, CaMKII, and NOX2 as key mediators in mechanochemotransduction during cardiac contraction, which provides new therapeutic targets for treating mechanical stress–induced Ca2+ dysregulation, arrhythmias, and cardiomyopathy.
The development and processing of hybrid inorganic-organic thin film materials plays a critical role in advancing interdisciplinary sciences and device manufacturing. Here we present a novel approach to synthesize and deposit acrylate-containing organic/inorganic hybrid films. The material is based on a chemical solution and includes specifically desired metal dopants that are fully-integrated into the backbone of the polymer structure. The film can be deposited by simple spin coating, and we confer photosensitive properties to the material making it directly patterned by traditional UV photolithography techniques. Film thickness, chemical characterization and wet/dry etching capability of the film are also investigated. We believe this innovative material has the potential to be used in a broad range of applications for electronic, photonic, biology and other interdisciplinary fields.
We have developed a simple method to synthesize organic-inorganic films containing a Pb(II) acrylate precursor in a silicon-methacrylate solution in the presence of a photoactive compound. Film deposition is achieved by simple spin coating, and the presence of a photoactive compound enables rapid polymerization when the film is subjected to UV irradiation. This creates a patternable film that acts as both an imaging layer and also as a functional metal-containing layer for the final device. We also investigated the chemical composition of the film by energy dispersive x-ray spectroscopy.
A CdZnTe detector based on high-quality Cd0.9Zn0.1Te crystals was developed and tested as a monitor in high-intensity radiation fields. The current–voltage measurements were performed using thermally evaporated Au contacts deposited on the crystals, which revealed resistivity of 1010 Ω·cm. Typical leakage current for the planar devices was ∼3 nA for a field strength of 1000 V·cm–1. The test results show that the CdZnTe detector has a fast time response, with a rise time of approximately 2 ns, when exposed to transient and pulsed irradiation of X-rays or electron beams. The decay of current curves is observed and discussed according to charge carrier trapping effects and space-charge accumulation mechanisms. It is suggested that the current decreases quickly with strengthening of the electric field, possibly because of charge de-trapping
Carbon-based electronic materials have received much attention since the discovery and elucidation of the properties of the nanotube, fullerene allotropes, and conducting polymers. Amorphous carbon, graphite, graphene, and diamond have also been the topics of intensive research. In accordance with this interest, we herein provide the details of a novel and facile method for synthesis of poly(hydridocarbyne) (PHC), a preceramic carbon polymer reported to undergo a conversion to diamond-like carbon (DLC) upon pyrolysis and also provide electrical characterization after low-temperature processing and pyrolysis of this material. The results indicate that the strongly insulating polymer becomes notably conductive in bulk form upon heating and contains interspersed micro-and nanostructures, which are the subject of ongoing research.
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