Microenvironment alters epigenetic and gene expression profiles in Swarm rat chondrosarcoma tumors

<p>Abstract</p> <p>Background</p> <p>Chondrosarcomas are malignant cartilage tumors that do not respond to traditional chemotherapy or radiation. The 5-year survival rate of histologic grade III chondrosarcoma is less than 30%. An animal model of chondrosarcoma has been established - namely, the Swarm Rat Chondrosarcoma (SRC) - and shown to resemble the human disease. Previous studies with this model revealed that tumor microenvironment could significantly influence chondrosarcoma malignancy.</p> <p>Methods</p> <p>To examine the effect of the microenvironment, SRC tumors were initiated at different transplantation sites. Pyrosequencing assays were utilized to assess the DNA methylation of the tumors, and SAGE libraries were constructed and sequenced to determine the gene expression profiles of the tumors. Based on the gene expression analysis, subsequent functional assays were designed to determine the relevancy of the specific genes in the development and progression of the SRC.</p> <p>Results</p> <p>The site of transplantation had a significant impact on the epigenetic and gene expression profiles of SRC tumors. Our analyses revealed that SRC tumors were hypomethylated compared to control tissue, and that tumors at each transplantation site had a unique expression profile. Subsequent functional analysis of differentially expressed genes, albeit preliminary, provided some insight into the role that thymosin-β4, c-fos, and CTGF may play in chondrosarcoma development and progression.</p> <p>Conclusion</p> <p>This report describes the first global molecular characterization of the SRC model, and it demonstrates that the tumor microenvironment can induce epigenetic alterations and changes in gene expression in the SRC tumors. We documented changes in gene expression that accompany changes in tumor phenotype, and these gene expression changes provide insight into the pathways that may play a role in the development and progression of chondrosarcoma. Furthermore, specific functional analysis indicates that thymosin-β4 may have a role in chondrosarcoma metastasis.</p

A Computational Model of the LGI1 Protein Suggests a Common Binding Site for ADAM Proteins

Mutations of human leucine-rich glioma inactivated (LGI1) gene encoding the epitempin protein cause autosomal dominant temporal lateral epilepsy (ADTLE), a rare familial partial epileptic syndrome. The LGI1 gene seems to have a role on the transmission of neuronal messages but the exact molecular mechanism remains unclear. In contrast to other genes involved in epileptic disorders, epitempin shows no homology with known ion channel genes but contains two domains, composed of repeated structural units, known to mediate protein-protein interactions

Microscopic characterization of xenon adsorption in wedge pores

© 2019, Springer Science+Business Media, LLC, part of Springer Nature. We explored the possibility of using xenon as a molecular probe to characterize graphitic non-uniform pores in activated carbon (AC), and studied its isotherms with a Grand Canonical Monte Carlo (GCMC) simulation. To model non-uniform pores, we used a wedge pore model, a better description of the pore space in AC, and studied the effects of the pore length, the wedge angle and the temperature on the behaviour of the adsorption and desorption isotherms. For temperatures below the triple point, the isotherm exhibits two distinct regions: in the region of low loadings it shows a step-wise behaviour as the adsorption progresses from the tip of the wedge, followed by the second region of gradual increase in the adsorbed density with pressure. A distinct feature is the possible existence of multiple hysteresis loop in the first region and the reversibility of the isotherm in the second region. The hysteresis is due to the commensurate packing of molecular layers across the pore to form domains along the axial direction of the pore and the number of layers is incremented by one as we move from one domain to the next. We have found that the hysteresis disappears when either the wedge angle is greater than a critical value or the temperature is greater than the so-called bifurcation temperature. The second region of reversibility is due to the formation of the condensate separated from the gas phase with a concave interface whose radius of curvature is found to satisfy the Kelvin equation