Crosstalk between SOX2 and cytokine signaling in endometrial carcinoma.

Endometrial carcinoma is a cancer derived from oncogenesis of the regenerating uterine cavity, in which cytokine stimulation shapes cell differentiation and tissue remodeling. Expression of the stem cell factors SOX2, OCT4, NANOG, and MYC has been linked to tumor malignancy in several cancers. However, how these stem cell factors crosstalk with cytokine signaling to promote malignancy in endometrial carcinoma is still elusive. Here we report that the expression of SOX2 and MYC, but not that of OCT4 and NANOG, correlate with poor histological differentiation and prognosis, while SOX2 expression is negatively associated with MYC level. We found that SOX2-high endometrial carcinoma cells possessed a higher colony-forming ability than their SOX2-low counterparts, and knockdown of SOX2 attenuated the colony-forming ability. We observed that SOX2 regulated EGFR expression in a SOX2-EGFR positive feedback loop. EGF stimulation induced SOX2 expression and promoted migration of endometrial carcinoma cells, whereas TGF-ß stimulation inhibited SOX2 expression and attenuated the colony-forming ability. Immunohistochemistry analysis revealed that SOX2 expression correlated with lymph node infiltration of endometrial carcinoma. Our findings support that cytokine-induced stem cell factor SOX2 possesses oncogenic properties, with the potential to serve as a prognostic biomarker in endometrial carcinoma.

Using a Mixed Model to Explore Evaluation Criteria for Bank Supervision: A Banking Supervision Law Perspective.

Financial supervision means that monetary authorities have the power to supervise and manage financial institutions according to laws. Monetary authorities have this power because of the requirements of improving financial services, protecting the rights of depositors, adapting to industrial development, ensuring financial fair trade, and maintaining stable financial order. To establish evaluation criteria for bank supervision in China, this study integrated fuzzy theory and the decision making trial and evaluation laboratory (DEMATEL) and proposes a fuzzy-DEMATEL model. First, fuzzy theory was applied to examine bank supervision criteria and analyze fuzzy semantics. Second, the fuzzy-DEMATEL model was used to calculate the degree to which financial supervision criteria mutually influenced one another and their causal relationship. Finally, an evaluation criteria model for evaluating bank and financial supervision was established.

Using a Mixed Model to Evaluate Job Satisfaction in High-Tech Industries.

R&D professionals are the impetus behind technological innovation, and their competitiveness and capability drive the growth of a company. However, high-tech industries have a chronic shortage of such indispensable professionals. Accordingly, reducing R&D personnel turnover has become a major human resource management challenge facing innovative companies. This study combined importance-performance analysis (IPA) with the decision-making trial and evaluation laboratory (DEMATEL) method to propose an IPA-DEMATEL model. Establishing this model involved three steps. First, an IPA was conducted to measure the importance of and satisfaction gained from job satisfaction criteria. Second, the DEMATEL method was used to determine the causal relationships of and interactive influence among the criteria. Third, a criteria model was constructed to evaluate job satisfaction of high-tech R&D personnel. On the basis of the findings, managerial suggestions are proposed.

Deactivation of TBP contributes to SCA17 pathogenesis.

Spinocerebellar ataxia type 17 (SCA17) is an autosomal dominant cerebellar ataxia caused by the expansion of polyglutamine (polyQ) within the TATA box-binding protein (TBP). Previous studies have shown that polyQ-expanded TBP forms neurotoxic aggregates and alters downstream genes. However, how expanded polyQ tracts affect the function of TBP and the link between dysfunctional TBP and SCA17 is not clearly understood. In this study, we generated novel Drosophila models for SCA17 that recapitulate pathological features such as aggregate formation, mobility defects and premature death. In addition to forming neurotoxic aggregates, we determined that polyQ-expanded TBP reduces its own intrinsic DNA-binding and transcription abilities. Dysfunctional TBP also disrupts normal TBP function. Furthermore, heterozygous dTbp amorph mutant flies exhibited SCA17-like phenotypes and flies expressing polyQ-expanded TBP exhibited enhanced retinal degeneration, suggesting that loss of TBP function may contribute to SCA17 pathogenesis. We further determined that the downregulation of TBP activity enhances retinal degeneration in SCA3 and Huntington's disease fly models, indicating that the deactivation of TBP is likely to play a common role in polyQ-induced neurodegeneration.

Genetic analysis of Parkin in early onset Parkinson's disease (PD): Novel intron 9 g > a single nucleotide polymorphism and risk of Taiwanese PD.

Early onset Parkinson's disease (PD) has been associated with mutations in Parkin. We screened Parkin mutations in a cohort of Taiwanese early onset PD using direct cDNA sequencing. Two deletions (Ex2-3del and Ex5del), one point mutation (R334C), one 86-bp IVS9 insertion (c.1084intron(+)), and two polymorphisms (S167N and V380L) were identified. The mutations identified are heterozygous and none of the mutation carriers possess two Parkin mutations. The c.1084intron(+) was due to a novel IVS9 g > a change. To assess the association of IVS9 g > a, S167N and V380L with the risk of PD, we conducted a case-control study in a cohort of PD and ethnically matched controls. Although the difference is not significant, the V380L C allele frequency was notably lower in PD patients than the controls and a trend toward decrease in risk of developing PD was evident (odds ratio: 0.71, 95% confidence interval: 0.53-0.97, P = 0.029). Contrarily the IVS9 g > a a allele frequency was notably higher in PD patients than the controls and a trend toward increase in risk of developing PD was also evident (odds ratio: 1.65, 95% confidence interval: 1.06-2.59, P = 0.028). Quantitative real-time PCR showed that the relative Parkin c.1084intron(+) mRNA expression was increased in PD patients with IVS9 ga genotype as compared to gg genotype. Pairwise genotype analysis revealed that IVS9 gg genotype strengthens the negative association of the V380L GC genotype with PD (odds ratio: 0.67, 95% confidence interval: 0.48-0.94, P = 0.021). The results of Parkin mutation/polymorphism screening may contribute to our understanding of PD.

Analysis of heat-shock protein 70 gene polymorphisms and the risk of Parkinson's disease.

Parkinson's disease (PD) involves several genetic and environmental components. Heat-shock protein 70, a chaperone that is up-regulated in stress responses and that refolds protein, may be involved in the pathogenesis of PD. We have investigated the association of polymorphisms -110 A/C, +190 G/C, +1267 A/G, +2074 G/C, and +2437 G/C in the 5' and coding regions of the HSP70-1, HSP70-2, and HSP70-hom genes with the risk of PD by screening DNA samples from 274 PD patients and 183 controls in assays based on the polymerase chain reaction. There was no statistically significant difference in genotype distribution between patients and controls for the three coding-region polymorphisms in HSP70-2 and HSP70-hom. However, for HSP70-1, the overall genotype distribution was significantly different at the -110 site (P=0.004) and tended to be different at the +190 site (P=0.012) between patients and controls. The frequencies of the -110 CC and +190 CC genotypes were significantly higher in PD patients than in controls (P=0.001 and 0.006, respectively). Both -110 CC (odds ratio: 2.91; 95% CI: 1.51-5.96; P=0.002) and +190 CC (odds ratio: 3.59; 95% CI: 1.53-9.88; P=0.006) genotypes were significantly associated with PD. Reporter constructs containing the -110 A allele cloned into a luciferase reporter plasmid drove marginally higher transcriptional activity of HSP70-1 compared with the -110 C allele in both control and heat-shocked IMR32 and 293 cells. Therefore, -110 A/C may be a functional polymorphism in the 5' promoter region of HSP70-1 and may affect susceptibility to PD.