Na+-H+ exchange inhibition at reperfusion is cardioprotective during myocardial ischemia-reperfusion; 31P NMR studies

To help resolve the controversy as to whether or not Na⁺-H⁺ exchange is functioning during reperfusion of the ischemic myocardium we assessed the effects of dimethylamiloride (DMA, an amiloride analogue possessing selectivity for inhibition of the Na⁺-H⁺ exchanger) on cardiac function and intracellular pH during ischemia-reperfusion. Studies were performed in the presence of bicarbonate (modified Krebs-Henseleit buffer) or in the nominal absence of bicarbonate (HEPES buffer) in order to determine if similar cardioprotection and effects on intracellular pH were observed in the presence and absence of bicarbonate dependent transport processes. Isovolumic rat hearts were perfused in the Langendorff mode at a constant pressure of 80 mm Hg and subjected to 28 min total global ischemia at 37°C. Intracellular pH was determined from the pH dependent shift of the inorganic phosphate peak in ³¹P nuclear magnetic resonance spectra. DMA (20 µM) was infused for either 2.5 min before ischemia, for the initial 5 min of reperfusion, or at both time intervals. DMA had no effect on the intracellular pH during ischemia. Intracellular pH returned to pre-ischemic levels within 2.5 min of reperfusion in bicarbonate buffer. This normalization of pH was slower in HEPES perfusate. In both bicarbonate and HEPES perfused hearts all drug dosing regimens caused a significant increase in the recovery of mechanical function after reperfusion and slowed the recovery of intracellular pH during reperfusion. These results suggest that the Na⁺-H⁺ exchanger is activated during reperfusion of the ischemic myocardium, that this activation of the exchanger contributes to ischemia-reperfusion induced cardiac dysfunction and that administration of an inhibitor of Na⁺-H⁺ exchange at reperfusion significantly attenuates the deleterious effects of exchanger activation.     

Intrinsic Quantum Beats of Atomic Populations and Their Nanoscale Realization Through Resonant Plasmonic Antenna

In the coherently trapped populations of a four-level atom, we demonstrated the quantum beats with different mechanism, which originate from the interference between transition channels with different dipole moments. The beat frequency is determined by the intrinsic atomic parameters, i.e., the spacing of upper levels and ratio of dipole moments. The resonant plasmonic nanoantenna, as a candidate for the creation of anisotropic vacuum, was proposed to achieve the nanoscale realization of the quantum beats, spontaneous emission cancellation, and Rabi oscillation in two-photon correlations through the enhanced near-field and modified decay rates.     

A new technique of coronary artery ligation: Experimental myocardial infarction in rats in vivo with reduced mortality

In vivo models of myocardial infarction following coronary artery ligation in the rat still suffer from high early mortality and a low rate of success of myocardial infarction. This study investigated the possibility of reducing early mortality and increasing the rate of myocardial infarction by modifications of surgical techniques. Eighteen rats were divided into two groups: normal control (3 rats) and ligation (15 rats). The major modifications of surgical techniques used in this study include: (1) no exteriorization of the heart, (2) ligation of the origins of the branches rather than the main trunk of the left coronary artery, (3) removal of air from the chest after closure, (4) supplying oxygen immediately after extubation. Following surgery, the rats recovered uneventfully and 11 rats were alive after 16 weeks. One rat, with a large myocardial infarction, died 2 h after surgery. Early mortality (during surgery and 1 week after surgery) was 6.7% with a success rate of myocardial infarction of 85%. The left ventricle in the ligation group showed significant dilation relative to normal and shamoperated control hearts (317% of control hearts, p < 0.001). However, myocardial mass did not increase. The average infarct size was 33%. These results demonstrate that a reduction in early mortality and an increased success rate of myocardial infarction can be achieved by modifications of surgical techniques.     

Protective effects of autophagy against blue light-induced retinal degeneration in aged mice

The aim of this study was to explore the role of autophagy in response to blue light damage in aged mice and in human retinal pigmented epithelium(hRPE) cells. Blue light damage to the retina was induced in 10-month-old(10 mo) C57 mice and hRPE cells. Flash electroretinography was used to assess retinal function. Retinal structure changes were observed by electron microscopy. Western blot was conducted to determine the expression levels of the following proteins: cleaved caspase-3, p38 mitogen-activated protein kinases, protein kinase R-like endoplasmic reticulum kinase(PERK), autophagy marker light chain 3(LC3), P62, and Beclin-1. On day 1 after light damage to the 10 mo mice, retinal function was changed. The latent periods of awave and b-wave were delayed, and amplitude was reduced. The electron microscopy results revealed mitochondria damage in the retinal pigmented epithelium and a disorganized photoreceptor outer segment(OS). PERK, LC3, and Beclin-1 were upregulated, whereas P62 was not. On day 5 after the blue light damage, restoration of electroretinography and OS was observed.PERK, LC3, and Beclin-1 were downregulated, whereas P62 was not. Protein changes in vitro were consistent with in vivo. The present study provided structural and functional evidence that autophagy plays an important role in the response to blue lightinduced retinal damage.     

SMetABF: A rapid algorithm for Bayesian GWAS meta-analysis with a large number of studies included

Bayesian methods are widely used in the GWAS meta-analysis. But the considerable consumption in both computing time and memory space poses great challenges for large-scale meta-analyses. In this research, we propose an algorithm named SMetABF to rapidly obtain the optimal ABF in the GWAS meta-analysis, where shotgun stochastic search (SSS) is introduced to improve the Bayesian GWAS meta-analysis framework, MetABF. Simulation studies confirm that SMetABF performs well in both speed and accuracy, compared to exhaustive methods and MCMC. SMetABF is applied to real GWAS datasets to find several essential loci related to Parkinson’s disease (PD) and the results support the underlying relationship between PD and other autoimmune disorders. Developed as an R package and a web tool, SMetABF will become a useful tool to integrate different studies and identify more variants associated with complex traits.     

Effects of Dielectric Anisotropy on Surface Plasmon Polaritons in Three-Layer Plasmonic Nanostructures

The effects of highly anisotropic dielectric on surface plasmon polaritons (SPPs) are investigated in several three-layer plasmonic nanostructures. Dispersion relations of SPPs in anisotropic-dielectric-metal (ADM), dielectric-anisotropic-metal (DAM), and metal-anisotropic-metal (MAM) structures are analytically derived. The numerical results in the visible indicate that, in ADM, the propagation length of a conductor-gap-dielectric mode is changed from 5.9 to 91 μm and its cutoff thickness from 83 to 7 nm with varying the optical axis, while in DAM, the influences of anisotropic dielectric are reversed on propagation length and cutoff thickness. In MAM, by tuning the optical axis, the light confinement of symmetry SPPs mode varies about 10 %. Further numerical calculations show that the above results induced by the anisotropy of dielectric can be extended to the telecommunication frequency. The improved mode properties may be used in plasmonic-based nanodevices and tunable single surface plasmon sources.