In the present study, I first performed DNA microarray analysis of the replicon-bearing cells to identify cellular factors associated with NV replication. The analysis demonstrated that genes in lipid (cholesterol) or carbohydrate metabolic pathways were significantly (P < 0.001) changed by the
gene ontology analysis. Among genes in the cholesterol pathways, I found that mRNA levels of hydroxymethylglutaryl-coenzyme A (HMG-CoA) synthase, squalene epoxidase, and acyl-CoA: cholesterol acyltransferase (ACAT), ACAT2, small heterodimer partner, and low-density lipoprotein receptor check details (LDLR)-related proteins were significantly changed in the cells. I also found that the inhibition of cholesterol biosynthesis using statins (an HMG-CoA reductase inhibitor) significantly increased the levels of NV proteins and RNA, whereas inhibitors of ACAT significantly reduced the replication of NV in replicon-bearing cells. Up-or downregulation of virus replication with these agents significantly correlated with the mRNA level
of LDLR in replicon-bearing cells. Finally, I found that the expression of LDLR promoted NV replication in trans by transfection study with pNV-GFP. I conclude that the selleck kinase inhibitor cholesterol pathways such as LDLR expression and ACAT activity may be crucial in the replication of noroviruses in cells, which may provide potential therapeutic targets for viral infection.”
“The contribution of different sensory modalities to balance control is modified by age. Postural responses to Achilles tendon vibration were investigated see more in order to understand the influence of age on proprioceptive input from lower legs in human stance. Postural responses to bilateral vibrations of Achilles tendon with 10s duration were recorded at three frequencies (40, 60 and 80Hz) in 9 healthy young (range, 24-27 years) and in 9 healthy older adults (59-70 years). Subjects were instructed to keep standing on firm surface with eyes closed. They performed three trials in each of three vibration frequencies. Postural responses were characterized by displacement of the centre of foot pressure (CoP) and by kinematics
of body segments in the anterior-posterior direction. Bilateral vibrations of Achilles tendon induced backward body lean increasing with frequency of vibration and with age. The leg angle response to vibration was found similar in both groups of subjects. Slight trunk tilts from vertical position were induced by vibration in young subjects while in older subjects the trunk tilted backward together with the whole body. This observation was supported also by the minimal change of hip angle in older subjects contrary to increased hip activity in young subjects. The findings showed that the trunk and hip angle responses to proprioceptive stimulation might be a good indicator of age-related destabilization in balance control. (C) 2009 Elsevier Ireland Ltd. All rights reserved.