Assessment of the association between NUS1 variants and essential tremor.

BACKGROUND: A recent study on early onset Parkinson's disease (PD) revealed that NUS1 is a risk gene for PD. Clinically, essential tremor (ET) is closely related to PD. In this study, we aimed to detect NUS1 variants and assess the effect of those variants on patients with ET. METHODS: The 5 coding regions and the exon-intron boundaries of NUS1 were directly sequenced in 395 patients with ET and an equal number of healthy controls, matched for age and sex. The function of variants was assessed by pathogenic predictive software programs. Genetic analysis of variants was used to evaluate susceptibility to ET. RESULTS: A total of 6 exonic variants were identified, including 3 synonymous and 3 missense variants. The non-synonymous variants were predicted to be tolerable. No variants had significant association with ET (none of the p-values were less than 0.05, using Fisher's exact test). CONCLUSION: Our study suggested that NUS1 variants may not contribute to the risk of ET.

Impaired iPLA2ß activity affects iron uptake and storage without iron accumulation: An in vitro study excluding decreased iPLA2ß activity as the cause of iron deposition in PLAN.

PLA2G6-associated neurodegeneration (PLAN, NBIA2) is the second most common type of neurodegeneration with brain iron accumulation (NBIA), caused by recessive mutations of PLA2G6 gene, which encodes Ca2+-independent phospholipase A2ß (iPLA2ß). In most PLAN cases, decreased iPLA2ß activity and iron deposition was observed meanwhile, and researchers also identified a PLA2G6 mutation family without iron deposition shown by MRI images. This brought us the question of whether decreased iPLA2ß activity was the cause of iron deposition in PLAN. In this study, we used S-BEL as the antagonist of iPLA2ß to block its activity and used SH-SY5Y cells as the expression system. We incubated SH-SY5Y cells with different concentrations of S-BEL. The results showed that decreased iPLA2ß activity led no obvious iron accumulation, while changes of cells state and activation of apoptosis were observed. To further investigate the cause of unchanged iron level, we examined the cellular iron regulatory proteins involved in iron uptake, storage and export. The results were as follows: TfR1 (iron uptake protein) expression was decreased, the expression of ferritin heavy chain and light chain (iron storage protein) was increased. There was no alteration of the expression of DMT1 (iron uptake protein) and FPN1 (iron export protein). Under the condition of decreased iPLA2ß activity, there was no obvious iron accumulation but iron uptake activity decreased and iron storage activity increased. Therefore, we speculate that the decreased iPLA2ß activity may not be the main reason for iron deposition in PLAN.

Characterization of the enterovirus 71 P1 polyprotein expressed in Pichia pastor as a candidate vaccine.

Human enterovirus 71 (EV71) plays an important role in hand, foot, and mouth disease (HFMD), which recently caused the death of hundreds of children in the Asia-Pacific region. However, there are no specific treatments available for EV71 infections; thus, a safe and effective vaccine is needed urgently. In this study, we developed an effective and economical method for producing EV71 polyprotein (P1 protein) in Pichia pastoris. Furthermore, we evaluated the potential of P1 protein as a candidate vaccine against EV71 virus. The data revealed that P1 protein induced persistent high cross-neutralization antibodies for different EV71 subtypes, and elicited significant splenocyte proliferation. The high levels of interleukin-10(IL-10) and interferon-gamma (IFN-γ) showed that P1 protein induced Th1 and Th2 immune responses. Interestingly, vaccinating female mice with the P1 protein conferred cross-protection against different EV71 subtypes to their neonatal offspring.Compared with heat-inactivated EV71, the P1 protein elicited improved humoral and cellular immune responses and showed good cross-protection with different EV71 subtypes. Therefore, the EV71-P1 protein produced by P. pastoris is a promising candidate vaccine against EV71.

Association analysis of STK39, MCCC1/LAMP3 and sporadic PD in the Chinese Han population.

With the completion of the Human Genome Project, GWAS have been widely used in exploring the genetic studies of complex diseases. A meta-analysis of datasets from five Parkinson's disease GWAS from the USA and Europe found 11 loci that surpassed the threshold for genome-wide significance (p<5×10(-8)), and five were newly identified loci (ACMSD, STK39, MCCC1/LAMP3, SYT11 and CCDC62/HIP1R). Another GWAS of the Ashkenazi Jewish population also identified loci in STK39 and LAMP3. Because the association between the STK39 and MCCC1/LAMP3 genes and PD was confirmed in different populations, we conducted a case-control cohort to clarify the association between the four single nucleotide polymorphism (SNP) loci (rs2102808 and rs3754775 in the STK39; rs11711441 and rs12493050 in the MCCC1/LAMP3) and PD in the Chinese Han population. Polymerase chain reaction and direct DNA sequencing analyses were used to detect the four variations in a case-control cohort comprised of 993 ethnic Chinese subjects. We found that in the detection of the rs11711441, there was a significant difference between ungrouped populations, early-onset PD, late-onset PD, male PD, female PD and the corresponding control group in allele and genotype frequency (p<0.001, OR<1). In the detection of the rs2102808, rs3754775 and rs12493050, ungrouped populations, early-onset PD, late-onset PD, male PD or female PD with the corresponding control group showed no significant difference in allele and genotype frequency (p>0.0125). Our findings suggested that the allele G of rs11711441 of the MCCC1/LAMP3 gene can decrease the risk of PD in Chinese population. No statistically significant difference in genotype frequency between cases and controls was observed for the other three SNPs.