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Recent studies have shown that histone acetylation is involved with the regulation of enzyme glutamate decarboxylases (GADs), including GAD67 and GAD65. Here, we investigated the histone acetylation modifications of GADs in the pathogenesis of epilepsy and explored the therapeutic effect of a novel second-generation histone deacetylase inhibitor (HDACi) JNJ-26481585 in epilepsy animals. We revealed the suppression of GADs protein and mRNA level, and histone hypoacetylation in patients with temporal lobe epilepsy and pilocarpine-induced epilepsy mice model. Double-immunofluorescence also indicated that the hypoacetyl-H3 was located in hippocampal GAD67/GAD65 positive neurons in epilepsy mice. JNJ-26481585 significantly reversed the decrease of the GAD67/GAD65 both protein and mRNA levels, and the histone hypoacetylation of GABAergic neurons in epilepsy mice. Meanwhile, single-cell real-time PCR performed in GFP-GAD67/GAD65 transgenic mice demonstrated that JNJ-26481585 induced increase of GAD67/GAD65 mRNA level in GABAergic neurons. Furthermore, JNJ-26481585 significantly alleviated the epileptic seizures in mice model. Together, our findings demonstrate inhibition of GADs gene via histone acetylation plays an important role in the pathgenesis of epilepsy, and suggest JNJ-26481585 as a promising therapeutic strategy for epilepsy. [ABSTRACT FROM AUTHOR]

In this paper a novel policy is proposed to solve the deadlock problem in a class of flexible manufacturing systems based on the notion that each shared buffer is partitioned into parts to store different types of products, respectively. A subclass of Petri nets called resource-shared net with buffers (RSNB) is defined. An RSNB is constructed by synthesizing some marked graphs, and each marked graph can model the process of manufacturing one type of product. RSNB cannot only model the concurrent execution of manufacturing processes, but also ensure that the modeled system is live. The process of constructing RSNB is described in detail, and a minimal siphon based necessary and sufficient condition is provided to characterize the liveness of RSNB. [ABSTRACT FROM AUTHOR]