IntroductionDesmocollin 3 (DSC3) is a member of the cadherin superfamily of calcium-dependent cell adhesion molecules and a principle component of desmosomes. Desmosomal proteins such as DSC3 are integral to the maintenance of tissue architecture and the loss of these components leads to a lack of adhesion and a gain of cellular mobility. DSC3 expression is down-regulated in breast cancer cell lines and primary breast tumors; however, the loss of DSC3 is not due to gene deletion or gross rearrangement of the gene. In this study, we examined the prevalence of epigenetic silencing of DSC3 gene expression in primary breast tumor specimens.MethodsWe used bisulfite genomic sequencing to analyze the methylation state of the DSC3 promoter region from 32 primary breast tumor specimens. We also used a quantitative real-time RT-PCR approach, and analyzed all breast tumor specimens for DSC3 expression. Finally, in addition to bisulfite sequencing and RT-PCR, we used an in vivo nuclease accessibility assay to determine the chromatin architecture of the CpG island region from DSC3-negative breast cancer cells lines.ResultsDSC3 expression was downregulated in 23 of 32 (72%) breast cancer specimens comprising: 22 invasive ductal carcinomas, 7 invasive lobular breast carcinomas, 2 invasive ductal carcinomas that metastasized to the lymph node, and a mucoid ductal carcinoma. Of the 23 specimens showing a loss of DSC3 expression, 13 (56%) were associated with cytosine hypermethylation of the promoter region. Furthermore, DSC3 expression is limited to cells of epithelial origin and its expression of mRNA and protein is lost in a high proportion of breast tumor cell lines (79%). Lastly, DNA hypermethylation of the DSC3 promoter is highly correlated with a closed chromatin structure.ConclusionThese results indicate that the loss of DSC3 expression is a common event in primary breast tumor specimens, and that DSC3 gene silencing in breast tumors is frequently linked to aberrant cytosine methylation and concomitant changes in chromatin structure.
miRNAs are important regulators of gene expression that are frequently deregulated in cancer, with aberrant DNA methylation being an epigenetic mechanism involved in this process. We previously identified miRNA promoter regions active in normal mammary cell types and here we analyzed which of these promoters are targets of aberrant DNA methylation in human breast cancer cell lines and breast tumor specimens. Using 5-methylcytosine immunoprecipitation coupled to miRNA tiling microarray hybridization, we performed comprehensive evaluation of DNA methylation of miRNA gene promoters in breast cancer. We found almost one third (55/167) of miRNA promoters were targets for aberrant methylation in breast cancer cell lines. Breast tumor specimens displayed DNA methylation of majority of these miRNA promoters, indicating that these changes in DNA methylation might be clinically relevant. Aberrantly methylated miRNA promoters were, similar to protein coding genes, enriched for promoters targeted by polycomb in normal cells. Detailed analysis of selected miRNA promoters revealed decreased expression of miRNA linked to increased promoter methylation for mir-31, mir-130a, let-7a-3/let-7b, mir-155, mir-137 and mir-34b/mir-34c genes. The proportion of miRNA promoters we found aberrantly methylated in breast cancer is several fold larger than that observed for protein coding genes, indicating an important role of DNA methylation in miRNA deregulation in cancer.
This paper analyzes the extent to which sustainability is present in the curricula of the sixteen Education Degree programs belonging to the EDINSOST project: Six Early Childhood Education Degrees, seven Primary Education Degrees, two Pedagogy Degrees and one Social Education Degree. The results obtained suggest that sustainability is present in all Degrees, but not uniformly so. A great disparity is observed in the number of subjects that develop sustainability, with an average of 22.63 subjects per Degree. The competency most present is the 'Application of ethical principles related to the values of sustainability in personal and professional behaviors', while the least present is 'Sustainable use of resources and prevention of negative impacts on the natural and social environment'. Sustainability is not developed uniformly in the different universities either. Three universities (UAM, UCA and UIC) develop sustainability competencies at 100%, while others such as the USAL do so at only 50%.
The presence of the 4G allele of the 4G/5G polymorphism of the PAI-1 gene may be an additional risk factor for the development of arterial thrombosis in APS.
Nearby lightning strikes are prone to induce overvoltage transients in photovoltaic (PV) modules and in their power conditioning circuitry, which can permanently damage the PV system. Therefore, it becomes important to establish a method for accurate assessment of such transients. To this aim, the authors propose a three-dimensional (3D) semi-analytical numerical method to study the electromagnetic transients caused in PV modules by nearby lightning strikes. The approach bases on a semi-analytical expression of the magnetic vector potential generated by a geometrically complex lightning channel. The proposed method is able to calculate the transient overvoltage in a PV module, both in common and differential-mode, taking also into account capacitive and inductive couplings between the internal circuit and the PV metallic frame. Both modes are required to design the surge protective devices (SPDs) in PV power systems. Comparing to the models in literature, the proposed approach explicitly considers the complex geometry of the lightning channel. Statistical analysis allows assessing the impact of channel geometry by randomly generating a number of likely lightning paths. Results show that the lightning-induced overvoltage in a PV module is highly dependent on factors such as distance to the lightning channel and lightning channel geometry.
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