RESUMEN
Ribonuclease (RNase) He1 is a small ribonuclease belonging to the RNase T1 family. Most of the RNase T1 family members are active at neutral pH, except for RNase Ms, U2, and He1, which function at an acidic pH. We crystallized and analyzed the structure of RNase He1 and elucidated how the acidic amino residues of the α1ß3- (He1:26-33) and ß67-loops (He1:87-95) affect their optimal pH. In He1, Ms, and U2, the hydrogen bonding network formed by the acidic amino acids in the ß67-loop suggested that the differences in the acidification mechanism of the optimum pH specified the function of these RNases. We found that the amino acid sequence of the ß67-loop was not conserved and contributed to acidification of the optimum pH in different ways. Mutations in the acidic residues in He1 promoted anti-tumor growth activity, which clarified the role of these acidic amino residues in the binding pocket. These findings will enable the identification of additional targets for modifying pH-mediated enzymatic activities.
Asunto(s)
Ribonucleasa T1 , Ribonucleasas , Ribonucleasas/química , Ribonucleasa T1/química , Endorribonucleasas , Secuencia de Aminoácidos , Concentración de Iones de HidrógenoRESUMEN
Renal cell carcinoma, which has clear cells in 70% of cases, has a high frequency of hematogenous distant metastases to lung, bone, liver, and other areas. Metastatic cancer accounts for 1 to 3% of malignant tumors in the stomatognathic region, and the metastasis of renal cell carcinoma to the oral mucosal tissue, though extremely rare, does occur. In addition, clear cells have been observed in some salivary gland cancers in the oral cavity. Therefore, the differential diagnosis of metastatic renal cell carcinoma and salivary gland cancer is important. This review discusses the differential diagnosis between metastatic renal cell carcinoma and malignant tumors of the salivary gland.
RESUMEN
The aim of this study was to build an in silico computer-aided design and computer-aided manufacturing (CAD/CAM) resin-composite-block (RCB) model with different silane coupling ratios and to evaluate the physical and mechanical properties of the models, including the elastic modulus, Poisson's ratio, compressive strength, and maximum principal strain. Nanoscale CAD/CAM RCB models were designed by using CAD software that consisted of twelve spherical silica nanofiller particles and a resin matrix. Seven nanoscale models with different silane coupling ratios were prepared with the same filler volume contents. Homogenization analysis was conducted by using voxel-base finite-element analysis software to predict the elastic moduli and Poisson's ratio of the macro CAD/CAM RCB. Localization analysis was used to analyze the maximum principal strain distribution in the hydrolysis layer. In silico multi-scale analysis demonstrated that the compressive strength of the CAD/CAM RCB was reduced with a decrease in the silane coupling ratios of the fillers.