Calcium (Ca(2+))-activated chloride channels are fundamental mediators in numerous physiological processes including transepithelial secretion, cardiac and neuronal excitation, sensory transduction, smooth muscle contraction and fertilization. Despite their physiological importance, their molecular identity has remained largely unknown. Here we show that transmembrane protein 16A (TMEM16A, which we also call anoctamin 1 (ANO1)) is a bona fide Ca(2+)-activated chloride channel that is activated by intracellular Ca(2+) and Ca(2+)-mobilizing stimuli. With eight putative transmembrane domains and no apparent similarity to previously characterized channels, ANO1 defines a new family of ionic channels. The biophysical properties as well as the pharmacological profile of ANO1 are in full agreement with native Ca(2+)-activated chloride currents. ANO1 is expressed in various secretory epithelia, the retina and sensory neurons. Furthermore, knockdown of mouse Ano1 markedly reduced native Ca(2+)-activated chloride currents as well as saliva production in mice. We conclude that ANO1 is a candidate Ca(2+)-activated chloride channel that mediates receptor-activated chloride currents in diverse physiological processes.
Highly versatile nanocomposite nanoparticles were synthesized by decorating the surface of mesoporous dye-doped silica nanoparticles with multiple magnetite nanocrystals. The superparamagnetic property of the magnetite nanocrystals enabled the nanoparticles to be used as a contrast agent in magnetic resonance (MR) imaging, and the dye molecule in the silica framework imparted optical imaging modality. Integrating a multitude of magnetite nanocrystals on the silica surface resulted in remarkable enhancement of MR signal due to the synergistic magnetism. An anticancer drug, doxorubicin (DOX), could be loaded in the pores and induced efficient cell death. In vivo passive targeting and accumulation of the nanoparticles at the tumor sites was confirmed by both T2 MR and fluorescence imaging. Furthermore, apoptotic morphology was clearly detected in tumor tissues of mice treated with DOX loaded nanocomposite nanoparticles, demonstrating that DOX was successfully delivered to the tumor sites and its anticancer activity was retained.
Uniform 3 nm-sized ceria nanoparticles can protect against ischemic stroke by scavenging reactive oxygen species (ROS) and reducing apoptosis. PEGylated ceria nanoparticles showed protective effects against ROS-induced cell death in vitro. Optimal doses of ceria nanoparticles reduced infarct volumes and the rate of ischemic cell death in vivo.
Core/shell upconverting nanoparticles (UCNPs) of NaGdF4:Er3+,Yb3+/NaGdF4 (see figure) are shown to serve as a multimodal imaging probe that works for both background‐free optical imaging and magnetic resonance imaging (MRI). The nonblinking and nonbleaching properties of UCNPs can contribute to minimization of possible artifacts in long‐term imaging experiments. Owing to Gd3+ ions in the host matrix, contrast is enhanced in T1‐weighted MRI.
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