It is generally believed that consolidation of long-term memory requires activation of protein kinases, transcription of genes, and new protein synthesis. However, little is known about the signal cascades involved in the extinction of memory, which occurs when the conditioned stimulus is no longer followed by the unconditioned stimulus. Here, we show for the first time that an intra-amygdala injection of transcription inhibitor actinomycin D at the dose that blocked acquisition failed to affect extinction of a learned response. Conversely, protein synthesis inhibitor anisomycin blocked both acquisition and extinction. Extinction training-induced expression of calcineurin was blocked by anisomycin but not by actinomycin D. NMDA receptor antagonist, phosphatidylinositol 3-kinase (PI-3 kinase), and MAP kinase inhibitors that blocked the acquisition also blocked the extinction of conditioned fear. Likewise, PI-3 kinase inhibitor blocked fear training-induced cAMP response element-binding protein (CREB) phosphorylation as well as extinction training-induced decrease in CREB phosphorylation, the latter of which was associated with calcineurin expression and could be reversed by a specific calcineurin inhibitor. Thus, molecular processes that underlie long-term behavioral changes after acquisition and extinction share some common mechanisms and also display different characteristics.

No abstract

In the present study, the apoptotic effect of cordycepin on MA-10 cells, a mouse Leydig tumor cell line, was investigated. Results demonstrated that the number of rounding-up cell increased by cordycepin (10 μM to 5 mM for 24 h), and cells with plasma membrane blebbing could be observed by 100 μM cordycepin. In viability test, MA-10 cell surviving rate significantly decreased as the dosage (10 μM to 5 mM) and duration (3–24 h) of cordycepin treatment increased (P < 0.05). Cordycepin at 100 μM and 1 mM for 24 h treatment induced significant DNA fragmentation (P < 0.05). In addition, the percentage of G1 and G2/M phase cell significantly declined by cordycepin (100 μM and 1 mM) for 24 h treatment, while the percentages of subG1 phase cell increased by 100 μM and/or 1 mM cordycepin in 6, 12 and 24 h treatments (P < 0.05), respectively, which highly suggested that cordycepin induced MA-10 cell apoptosis. In mechanism study with the treatments of caspases, c-Jun NH2 terminal kinase (JNK) or reactive oxygen species (ROS) inhibitors plus cordycepin for 24 h, only caspases inhibitor suppressed subG1 phase in MA-10 cells. Moreover, western blotting results showed that cordycepin induced caspase-9, -3 and -7 protein expressions, but not caspase-8, in time- and dose-dependent manners. In conclusion, cordycepin induced apoptosis in MA-10 mouse Leydig tumor cells through a caspase-9 and -3 and -7 dependent pathway.

InGaN-based light-emitting diodes (LEDs) grown on triangle-shaped patterned sapphire substrates were separated through a chemical lift-off process by laterally etching an AlN sacrificial layer at the GaN/sapphire substrate interface. After the epitaxial growth, an air-void structure was observed at the patterned region on the sapphire substrate that provided an empty space to increase the lateral etching rate of the AlN buffer layer. The lateral etching rate of the AlN buffer layer was calculated at 10 mu m/min for the 100-mu m-width LED chip that was lifted off from the sapphire substrate. A triangular-shaped hole structure and a hexagonal-shaped air-void structure were observed on the lift-off GaN surface that was transferred from the patterned sapphire substrate. Comparing to the LED/sapphire structure, a peak wavelength blueshift phenomenon of the micro-photoluminescence spectra was observed on the lifted off LED chip caused by the release of a compressive strain at the GaN/sapphire substrate interface. The chemical lift-off process was achieved by using an AlN buffer layer as a sacrificial layer in a hot potassium hydroxide solution. (C) 2010 The Japan Society of Applied Physic

Vascular disorders, resulting from endothelial cell dysfunction, may be caused by various stimuli, including infectious pathogens, cytotoxic reagents, and pathophysiological mechanisms mediated by immune responses. Endothelial cell dysfunction characterized by apoptosis and abnormal immune activation is, at least in part, induced by anti-endothelial cell antibody (AECA) in some cases of autoimmune disease. However, the molecular mechanisms of AECA-mediated pathogenetic damage to host vascular system remain unclear. The dual role of nitric oxide (NO) both in endothelial cell apoptosis and survival has been described. In this paper, endothelial cell apoptosis caused by the presence of cross-reactive AECA via a NO-mediated mechanism is demonstrated in dengue virus infection. Endothelial cells undergo apoptosis via the mitochondria-dependent pathway that is regulated by NO production. NO-regulated endothelial cell injury thus may play a role in the disruption of vessel endothelium and contribute to the AECA-induced pathogenesis of vasculopathy. The modulation of NO may provide the therapeutic strategies for autoimmune diseases by preventing the AECA-mediated endothelial cell damage.