The non-classical HLA class Ⅰ antigen HLA-G is an immune modulator which inhibits the functions of T cells, NK cells, and the Dendritic cells (DC). As a result, HLA-G expression in malignant cells may provide them ...The non-classical HLA class Ⅰ antigen HLA-G is an immune modulator which inhibits the functions of T cells, NK cells, and the Dendritic cells (DC). As a result, HLA-G expression in malignant cells may provide them with a mechanism to escape the immune surveillance. In melanoma, HLA-G antigen expression has been found in 30% of surgically removed lesions but in less than 1% of established cell lines. One possible mechanism underlying the differential HLA-G expression in vivo and in vitro is that the HLA-G gene is epigenetically repressed in melanoma cells in vitro. To test this hypothesis, we treated the HLA-G negative melanoma cell line OCM-1A with the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine (5-AC) and analyzed whether HLA-G expression can be restored. Our data strongly suggest that HLA-G is silenced as a result of CpG hypermethylation within a 5' regulatory region encompassing 220 bp upstream of the start codon. After treatment, HLA-G mRNA expression was dramatically increased. Western blot and flow cytometry showed that HLA-G protein was induced. Interestingly, HLA-G cell surface expression on the 5-AC treated OCM-1A cells is much less than that on the HLA-G positive JEG-3 cells while a similar amount of total HLA-G was observed. Possible mechanisms for the difference were analyzed in the study such as cell cold-treatment, peptide loading and antigen processing machinery components (APM) as well as β2 microglobulin (β2-m) expression. Data revealed that the APM component calreticulin might be involved in the lower HLA-G surface expression on OCM-1A cells. Taken together, our results indicated that DNA methylation is an important epigenetic mechanism by which HLA-G antigen expression is modulated in melanoma cells in vitro. Furthermore, to the first time, we hypothesized that the deficiency of calreticulin might be involved in the low HLA-G surface expression on the 5-AC treated OCM-1A cells.展开更多
A model of vibrating device coupling two pendulums (VDP) which is highly nonlinear was put forward to conduct vibration analysis. Based on energy analysis, dynamic equations with cubic nonlinearities were established ...A model of vibrating device coupling two pendulums (VDP) which is highly nonlinear was put forward to conduct vibration analysis. Based on energy analysis, dynamic equations with cubic nonlinearities were established using Lagrange's equation. In order to obtain approximate solution, multiple time scales method, one of perturbation technique, was applied. Cases of non-resonant and 1:1:2:2 internal resonant were discussed. In the non-resonant case, the validity of multiple time scales method is confirmed, comparing numerical results derived from fourth order Runge-Kutta method with analytical results derived from first order approximate expression. In the 1:1:2:2 internal resonant case, modal amplitudes of Aa1 and Ab2 increase, respectively, from 0.38 to 0.63 and from 0.19 to 0.32, while the corresponding frequencies have an increase of almost 1.6 times with changes of initial conditions, indicating the existence of typical nonlinear phenomenon. In addition, the chaotic motion is found under this condition.展开更多
文摘The non-classical HLA class Ⅰ antigen HLA-G is an immune modulator which inhibits the functions of T cells, NK cells, and the Dendritic cells (DC). As a result, HLA-G expression in malignant cells may provide them with a mechanism to escape the immune surveillance. In melanoma, HLA-G antigen expression has been found in 30% of surgically removed lesions but in less than 1% of established cell lines. One possible mechanism underlying the differential HLA-G expression in vivo and in vitro is that the HLA-G gene is epigenetically repressed in melanoma cells in vitro. To test this hypothesis, we treated the HLA-G negative melanoma cell line OCM-1A with the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine (5-AC) and analyzed whether HLA-G expression can be restored. Our data strongly suggest that HLA-G is silenced as a result of CpG hypermethylation within a 5' regulatory region encompassing 220 bp upstream of the start codon. After treatment, HLA-G mRNA expression was dramatically increased. Western blot and flow cytometry showed that HLA-G protein was induced. Interestingly, HLA-G cell surface expression on the 5-AC treated OCM-1A cells is much less than that on the HLA-G positive JEG-3 cells while a similar amount of total HLA-G was observed. Possible mechanisms for the difference were analyzed in the study such as cell cold-treatment, peptide loading and antigen processing machinery components (APM) as well as β2 microglobulin (β2-m) expression. Data revealed that the APM component calreticulin might be involved in the lower HLA-G surface expression on OCM-1A cells. Taken together, our results indicated that DNA methylation is an important epigenetic mechanism by which HLA-G antigen expression is modulated in melanoma cells in vitro. Furthermore, to the first time, we hypothesized that the deficiency of calreticulin might be involved in the low HLA-G surface expression on the 5-AC treated OCM-1A cells.
基金Projects(50574091, 50774084) supported by the National Natural Science Foundation of ChinaProject supported by the Priority Academic Program Development of Jiangsu Higher Education Institutions+1 种基金Project(CXLX12_0949) supported by Research and Innovation Project for College Graduates of Jiangsu Province, ChinaProject(2013DXS03) supported by the Fundamental Research Funds for the Central Universities, China
文摘A model of vibrating device coupling two pendulums (VDP) which is highly nonlinear was put forward to conduct vibration analysis. Based on energy analysis, dynamic equations with cubic nonlinearities were established using Lagrange's equation. In order to obtain approximate solution, multiple time scales method, one of perturbation technique, was applied. Cases of non-resonant and 1:1:2:2 internal resonant were discussed. In the non-resonant case, the validity of multiple time scales method is confirmed, comparing numerical results derived from fourth order Runge-Kutta method with analytical results derived from first order approximate expression. In the 1:1:2:2 internal resonant case, modal amplitudes of Aa1 and Ab2 increase, respectively, from 0.38 to 0.63 and from 0.19 to 0.32, while the corresponding frequencies have an increase of almost 1.6 times with changes of initial conditions, indicating the existence of typical nonlinear phenomenon. In addition, the chaotic motion is found under this condition.