ABSTRACT
Objective This study aimed to verify the association between osteoprotegerin gene () and its variants with osteoporosis (OP) by performing integrative analysis.Methods We used the KGG software to perform gene-based association analysis, which integrated all publicly available single-nucleotide polymorphism (SNP)-based values and obtained an overall value for the . The significant SNPs were screened for expression quantitative trait loci (eQTLs). Meta-analysis was used to combine the associations between the variants of and bone mineral density (BMD) reported in the literatures. Then we performed dual-luciferase reporter gene systems for the functional verification of the variants of .Results In the gene-based association analysis, the over all value of was 6.24×10 for BMD at femoral neck (FN) and 7.37×10 for BMD at lumbar spine (LS), indicating the importance of for OP. The publicly available eQTL database identified 5 eQTLs which exert cis-regulation effects on at FN and LS. Literature searching found that rs2073617 (known as T950C) was the hot spot SNP. There were 13 relevant studies on rs2073617 besides the GEFOS-2 study identified from the PubMed. Significant differences among TT, TC and CC genotypes at FN (= 0.047) and LS (= 0.025) were shown by meta-analysis, demonstrating the associations between T950C polymorphism and BMD. Luciferase gene expression was significantly higher at the presence of allele C than allele T in the 293T cells (=-9.47, <0.01). Conclusion The integrative analysis further confirmed the importance of in OP and the correlation of T950C polymorphism with BMD of OP. The strategy can be used as a reference for functional interpretation of other disease-related genes.
ABSTRACT
We investigated whether hepatitis B spliced protein affect the NF-kappa B activities by interacting with ubiquitously expressed transcript splice variant 1 (UXT-V1).The HBSP-UXT-V1 protein interactions were screened by yeast two hybrid assay,and confirmed by immunoprecipitation,confocal microscopy,mammalian two hybrid assay,and GST-Pulldown assay.The reporter plasmids driven by NF-kappa B promoter were transfected into UXT-knockdown HBSP stably expressed cell lines,and the reporter genes were detected after transfection.Results showed that the interaction between UXT-V1 and HBSP in yeast was demonstrated.Furtherly,HBSP could interact with UXT-V1 in mammalian cells.HBSP could enhance NF-kappa B activities,and this effect was partly achieved by the interaction with UXT-V1.In conclusion,the effect of HBSPUXT-V1 interaction on the NF-kappa B pathway in hepatocytes may have an impact on HBV related liver diseases.
ABSTRACT
<p><b>OBJECTIVE</b>To analyze the impact of depletion of the twin arginine translocation (TAT) system on virulence and physiology of Yersinia enterocolitica for a better understanding of its pathogenicity.</p><p><b>METHODS</b>We constructed a DeltatatC::SpR mutant of Yersinia enterocolitica by P1 phage mediated transduction using Escherichia coli K-12 DeltatatC::SpR strain as a donor.</p><p><b>RESULTS</b>A P1-mediated genetic material transfer was found between the two species of enterobacteria, indicating a great potential of acquisition of antibiotic resistance in emergency of a new threatening pathogen by genetic material exchanges. Periplasmic trimethylamine N-oxidase reductase activity was detected in the wild type Y. enterocolitica strain and translocation of this enzyme was completely abolished by the DeltatatC::SpR mutation. In addition, the DeltatatC::SpR mutation showed a pleiotropic effect on the metabolism of Y. enterocolitica. However, the tat mutation did not seem to affect the mobility and virulence of Y. enterocolitica under the conditions used.</p><p><b>CONCLUSION</b>Unlike other pathogenic bacteria studied, the TAT system of Y. enterocolitica might play an important role in the pathogenic process, which is distinct from other pathogens, such as Pseudomonas aeruginosa and enterohemorrhagic E. coli O157:H7.</p>