Tristetraprolin expression and microRNA-mediated regulation during simian immunodeficiency virus infection of the central nervous system

BACKGROUND: The RNA-binding protein tristetraprolin (TTP) participates in normal post-transcriptional control of cytokine and chemokine gene expression, dysregulation of which contributes to the HIV-associated neurocognitive disorders. Transcriptional and post-transcriptional regulation of TTP has been described, including regulation by microRNA-29a. In the simian immunodeficiency virus (SIV) model of HIV CNS disease, control of cytokine/chemokine expression coincides with the end of acute phase infection. This control is lost during progression to disease. In this study, we assessed TTP regulation and association with cytokine regulation in the brain during SIV infection. RESULTS: Quantitation of TTP expression over the course of SIV infection revealed downregulation of TTP during acute infection, maintenance of relatively low levels during asymptomatic phase, and increased expression only during late-stage CNS disease, particularly in association with severe disease. The ability of miR-29a to regulate TTP was confirmed, and evidence for additional miRNA targeters of TTP was found. However, increased miR-29a expression in brain was not found to be significantly negatively correlated with TTP. Similarly, increased TTP during late-stage disease was not associated with lower cytokine expression. CONCLUSIONS: TTP expression is regulated during SIV infection of the CNS. The lack of significant negative correlation of miR-29a and TTP expression levels suggests that while miR-29a may contribute to TTP regulation, additional factors are involved. Reduced TTP expression during acute infection is consistent with increased cytokine production during this phase of infection, but the increases in TTP observed during late-stage infection were insufficient to halt runaway cytokine levels. While antisense inhibitors of the post-transcriptional targeters of TTP identified here could conceivably be used further to augment TTP regulation of cytokines, it is possible that high levels of TTP are undesirable. Additional research is needed to characterize members of the miRNA/TTP/cytokine regulatory network and identify nodes that may be best targeted therapeutically to ameliorate the effects of chronic inflammation in retrovirus-associated CNS disease

Determination of the potential bioavailability of plant microRNAs using a simulated human digestion process

The “dietary xenomiR hypothesis” proposes that microRNAs (miRNAs) in foodstuffs survive transit through the mammalian gastrointestinal tract and pass into cells intact to affect gene regulation. However, debate continues as to whether dietary intake poses a feasible route for such exogenous gene regulators. Understanding on miRNA levels during pre-treatments of human diet is essential to test their bioavailability during digestion. This study makes the novel first use of an in vitro method to eliminate the inherent complexities and variability of in vivo approaches used to test this hypothesis. Plant miRNA levels in soybean and rice were measured during storage, processing, cooking, and early digestion using real-time PCR. We have demonstrated for the first time that storage, processing, and cooking does not abolish the plant miRNAs present in the foodstuffs. In addition, utilizing a simulated human digestion system revealed significant plant miRNA bioavailability after early stage digestion for 75 min. Attenuation of plant messenger RNA and synthetic miRNA was observed under these conditions. Even after an extensive pretreatment, plant-derived miRNA, delivered by typical dietary ingestion, has a robustness that could make them bioavailable for uptake during early digestion. The potential benefit of these regulatory molecules in pharma-nutrition could be explored further

A benchmark for microRNA quantification algorithms using the OpenArray platform

miRcompData R package source. The source code for the miRcompData R package, also available at: http://bioconductor.org/packages/miRcompData/ . (GZ 8765 kb

Constructing the Yellow Peril: East Asia as the Enemy in American Discourse and Political Rhetoric

The notion of the Yellow Peril, the perceived racial threat of Asians or Asian nations overtaking Western Nations and Western culture, is not a new phenomenon, but instead an idea that has existed for many centuries, becoming popular in the nineteenth century. The Yellow Peril has been a potent belief which has influenced not only personal opinions, but has also affected Western foreign policy. The United States, whose ideological foundations were built upon Western ideology, was not immune to concerns of the Yellow Peril. Drawing on the theories of critical constructivism, poststructuralism, and postcolonialism, this study analyzes the manifestation of the Yellow Peril in American discourse and political rhetoric from the mid-nineteenth century to the present

In-depth exploration of successful weight loss management

The purpose of this study was to advance knowledge in the area of health behavior change maintenance, specifically weight loss maintenance, and develop a substantive theory of successful weight loss maintenance in adults. Using classical grounded theory methodology, the researcher conducted in-depth interviews with 12 adult men and women who lost at least 10% of their body weight and had maintained the weight loss for at least one year. Analysis of the interviews revealed a basic social process called Transforming Self, wherein participants described a process through which they designed and made significant lifestyle changes that resulted in weight loss and maintenance. Three stages of change and significant factors associated with each stage emerged from the data. In addition, critical junctures and important contextual factors thaat supported or impeded successful weight loss and maintenance were described. Social processes were similar among study demographics of gender and age. This model has implications for nurses and other health care professionals seeking ways to support individuals in weight loss efforts