Sterol Response Element Binding Protein 2 (SREBP2) transcription factor is a master regulator of cholesterol homeostasis. Treatment with statins, inhibitors of cholesterol synthesis, activates intestinal SREBP2, which may hinder their cholesterol-lowering effects. Overactivation of SREBP2 in mouse liver was shown to have no effect on plasma cholesterol. However, the influence of activating intestinal SREBP2 on plasma cholesterol is not known. We have generated a novel transgenic mouse model with intestine specific overexpression of active SREBP2 (ISR2) driven by villin promoter. ISR2 mice showed overexpression of active SREBP2 specifically in the intestine. Microarray analysis of jejunal RNA from ISR2 mice showed a significant increase in genes involved in fatty acid and cholesterol synthesis. Cholesterol and triglyceride (TG) in jejunum and liver (mg/g protein) were significantly increased in ISR2 vs wild type mice. Serum Cholesterol was significantly increased in VLDL and LDL fractions whereas the level of serum triglycerides was decreased in ISR2 vs wild type mice. In conclusion, activation of intestinal SREBP2 alone seems to be sufficient to increase plasma cholesterol, highlighting the essential role of intestine in maintaining cholesterol homeostasis in the body.

Virtual machine (VM) live migration is a critical feature for managing virtualized environments, enabling dynamic load balancing, consolidation for power management, preparation for planned maintenance, and other management features. However, not all virtual machine live migration is created equal. Variants include memory migration, which relies on shared backend storage between the source and destination of the migration, and storage migration, which migrates storage state as well as memory state. We have developed an automated testing framework that measures important performance characteristics of live migration, including total migration time, the time a VM is unresponsive during migration, and the amount of data transferred over the network during migration. We apply this testing framework and present the results of studying live migration, both memory migration and storage migration, in various virtualization systems including KVM, XenServer, VMware, and Hyper-V. The results provide important data to guide the migration decisions of both system administrators and autonomic cloud management systems.

Background: Cholesterol transporter NPC1L1 is expressed in small intestine but not in colon. Results: DNA in the mouse NPC1L1 gene is hypermethylated in colon as compared with small intestine. DNA methylation decreases the promoter activity of NPC1L1. Conclusion: DNA hypermethylation may be responsible for silencing NPC1L1 expression in the colon. Significance: Altering DNA methylation may represent a novel mechanism to modulate NPC1L1 expression and cholesterol absorption.

The expression of intestinal Niemann-Pick C1-like 1 (NPC1L1) cholesterol transporter has been shown to be elevated in patients with diseases associated with hypercholesterolemia such as diabetes mellitus. High levels of glucose were shown to directly increase the expression of NPC1L1 in intestinal epithelial cells, but the underlying mechanisms are not fully defined. The present studies were, therefore, undertaken to examine the transcriptional regulation of NPC1L1 expression in human intestinal Caco2 cells in response to glucose. Removal of glucose from the culture medium of Caco2 cells for 24 h significantly decreased the NPC1L1 mRNA, protein expression, as well as the promoter activity. Glucose replenishment significantly increased the promoter activity of NPC1L1 in a dose-dependent manner compared with control cells. Exposure of Caco2 cells to nonmetabolizable form of glucose, 3-O-methyl-d-glucopyranose (OMG) had no effect on NPC1L1 promoter activity, indicating that the observed effects are dependent on glucose metabolism. Furthermore, glucose-mediated increase in promoter activity was abrogated in the presence of okadaic acid, suggesting the involvement of protein phosphatases. Glucose effects on several deletion constructs of NPC1L1 promoter demonstrated that cis elements mediating the effects of glucose are located in the region between -291 and +56 of NPC1L1 promoter. Consistent with the effects of glucose removal on NPC1L1 expression in Caco2 cells, 24-h fasting resulted in a significant decrease in the relative expression of NPC1L1 in mouse jejunum. In conclusion, glucose appears to directly modulate NPC1L1 expression via transcriptional mechanisms and the involvement of phosphatase-dependent pathways.