Spinocerebellar ataxia type 3 (SCA3) also known as Machado-Joseph Disease (MJD), is one of nine polyglutamine (polyQ) diseases caused by a CAG-trinucelotide repeat expansion within the coding sequence of the ATXN3 gene. There are no disease-modifying treatments for polyQ diseases. Recent studies suggest that an imbalance in histone acetylation may be a key process leading to transcriptional dysregulation in polyQ diseases. Because of this possible imbalance, the application of histone deacetylase (HDAC) inhibitors may be feasible for the treatment of polyQ diseases. To further explore the therapeutic potential of HDAC inhibitors, we constructed two independent preclinical trials with valproic acid (VPA), a promising therapeutic HDAC inhibitor, in both Drosophila and cell SCA3 models. We demonstrated that prolonged use of VPA at specific dose partly prevented eye depigmentation, alleviated climbing disability, and extended the average lifespan of SCA3/MJD transgenic Drosophila. We found that VPA could both increase the acetylation levels of histone H3 and histone H4 and reduce the early apoptotic rate of cells without inhibiting the aggregation of mutant ataxin-3 proteins in MJDtr-Q68- expressing cells. These results collectively support the premise that VPA is a promising therapeutic agent for the treatment of SCA3 and other polyQ diseases.

Mutants of a highly pathogenic, porcine reproductive, and respiratory syndrome virus (PRRSV), JXA1 strain, were prepared by continuous in vitro passage. Genomic sequence comparisons were made between mutants obtained at different passages and the parental strain JXA1. The mutant strain obtained at passage 80 contained a 12 nucleotide insertion and 108 nucleotide mutations that resulted in 45 amino acid changes. Most of these changes (89%) occurred between passage 10 and 45 and were genetically stable for the next 35-70 passages. A comparison of the mutants, their parental strain, and several American PRRSV strains, identified 13 characteristic amino acid changes. These sites, as well as the distinct 12 nucleotide insertion, represent possible genetic markers for the evaluation of live vaccine applications, particularly for additional studies of the safety and potency of live PRRSV vaccines.

Voltage-gated L-type calcium channels (VLCC) are distributed widely throughout the brain. Among the genes involved in schizophrenia (SCZ), genes encoding VLCC subunits have attracted widespread attention. Among the four subunits comprising the VLCC (α − 1, α −2/δ, β, and γ), the γ subunit that comprises an eight-member protein family is the least well understood. In our study, to further investigate the risk susceptibility by the γ subunit gene family to SCZ, we conducted a large-scale association study in Han Chinese individuals. The SNP rs17645023 located in the intergenic region of CACNG4 and CACNG5 was identified to be significantly associated with SCZ (OR = 0.856, P = 5.43 × 10−5). Similar results were obtained in the meta-analysis with the current SCZ PGC data (OR = 0.8853). We also identified a two-SNP haplotype (rs10420331-rs11084307, P = 1.4 × 10−6) covering the intronic region of CACNG8 to be significantly associated with SCZ. Epistasis analyses were conducted, and significant statistical interaction (OR = 0.622, P = 2.93 × 10−6, Pperm < 0.001) was observed between rs192808 (CACNG6) and rs2048137 (CACNG5). Our results indicate that CACNG4, CACNG5, CACNG6 and CACNG8 may contribute to the risk of SCZ. The statistical epistasis identified between CACNG5 and CACNG6 suggests that there may be an underlying biological interaction between the two genes.

Our study confirms the association between SPINK5 and AD.

It has been reported that single nucleotide polymorphisms (SNPs) of Alpha-synuclein (SNCA) are associated with Parkinson's disease (PD). Some researchers have attempted to validate this finding in various ethnic populations. The results of studies concerning SNCA polymorphisms and PD susceptibility remain conflicting. To evaluate the association between these SNPs and PD, the authors conducted a series of meta-analyses using a predefined protocol. Databases including PubMed, MEDLINE and PD gene were searched to identify relevant studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the association. All analyses were calculated using STATA11.0. A total of 19 studies on the SNPS rs181489, rs356186, rs356219, rs894278, rs2583988, rs2619363, rs2619364, rs2737029, rs10005233 and rs11931074 were included. This meta-analysis showed that eight out of these 10 candidate SNPs may be associated with PD risk. Significant association was found between PD and the following SNPs: rs181489, rs356186, rs356219, rs894278 rs2583988, rs2619364, rs10005233 and rs11931074. Among these SNPs, rs356186 was found to be the only SNP that may play a protective role in Parkinson's disease. These results suggest that the SNCA gene may be associated with PD.