Roles of the Skp2/p27 axis in the progression of chronic nephropathy

S-phase kinase-associated protein 2 (Skp2) is an F-box protein component of the Skp/Cullin/F-box-type E3 ubiquitin ligase that targets several cell cycle regulatory proteins for degradation through the ubiquitin-dependent pathway. Skp2-mediated degradation of p27, a cyclin-dependent kinase inhibitor, is involved in cell cycle regulation. Tubular epithelial cell proliferation is a characteristic feature of renal damage that is apparent in the early stages of nephropathy. The p27 level is associated with the progression of renal injury, and increased Skp2 expression in progressive nephropathy is implicated in decreases of p27 expression. In Skp2^?/? mice, renal damage caused by unilateral ureteral obstruction (UUO) was ameliorated by p27 accumulation, mainly in tubular epithelial cells. However, the amelioration of UUO-induced renal injury in Skp2^?/? mice was prevented by p27 deficiency in Skp2^?/?/p27^?/? mice. These results suggest that the Skp2-mediated reduction in p27 is a pathogenic activity that occurs during the progression of nephropathy. Here, we discuss the roles of the Skp2/p27 axis and/or related signaling pathways/components in the progression of chronic nephropathy.     

车辆起-停巡航控制系统的加速度跟踪控制

针对低速行驶工况下的车辆StopandGo(起停)巡航控制系统,在研究其加速度动态响应非线性特性的基础上,设计了一种基于滑模变结构控制(SMC)的模型匹配控制器,该控制器综合了SMC的鲁棒性及模型匹配控制(MMC)快速响应的优点。通过仿真计算,结果表明该控制器不但能有效提高车辆在低速工况下加速度的快速跟踪性,而且还改善了系统对外界干扰的鲁棒性能。