SECIS-binding protein 2 (SBP2) is an essential component of the selenocysteine insertion machinery. SBP2 is also the only factor known to differentiate among selenoprotein mRNAs, thereby modulating the relative expression of the individual selenoproteins. Here, we show that expression of SBP2 protein varies widely across tissues and cell types examined, despite previous observations of only modest variation in SBP2 mRNA levels. This discrepancy between IPI-145 molecular weight SBP2 mRNA and protein levels implies translational regulation, which is often mediated via untranslated regions (UTRs) in regulated transcripts. We have identified multiple sequences in
the SBP2 3′ UTR that are highly conserved. The proximal short conserved region is GU rich and was subsequently shown to be a binding site for CUG-BP1. The distal half of the 3′ UTR is largely conserved, and multiple proteins interact with this region. One of these proteins was identified as HuR. Both CUG-BP1 and HuR are members of the Turnover and Translation Regulatory RNA-Binding Protein family (TTR-RBP). Members of this protein family are
linked by the common ability to rapidly effect gene expression through alterations www.selleckchem.com/products/MGCD0103(Mocetinostat).html in the stability and translatability of target mRNAs. The identification of CUG-BP1 and HuR as factors that bind to the SBP2 3′ UTR suggests that TTR-RBPs play a role in the regulation of SBP2, which then dictates the expression of the selenoproteome.”
“QUESTIONS UNDER STUDY: Drug-drug interactions (DDI) are considered a risk factor in medication selleck safety and computerised alerting tools are increasingly promoted and implemented in order to detect and minimise DDI. As only little is known about the frequency and nature of DDI in hospitalised patients in Switzerland as well as about the usefulness of current alerting systems, this analysis based on a computerised medication record in a typical regional hospital setting was performed.
METHODS: All inpatients with
at least one drug prescription between 2006 and 2010 were included. A total of 1,654,987 prescriptions were analysed with regard to the maximal seriousness level of DDI between each added prescription versus the existing prescription and with regard to all underlying DDI.
RESULTS: On average, each inpatient received 16 different drugs including on-demand prescriptions and encountered 5 DDI. A total of 27% of all prescriptions caused DDI. Within the last 12 months, 5% of all DDI were classified in category 1 (contraindicated), 3% in category 2, 53% in category 3, 8% in category 4 and 31% in category 5. The vast majority of DDI were caused by a very limited number of drugs.
DISCUSSION: Drug-drug interactions were very frequent and were very stable over the years studied, involving on average 27% of all prescriptions and 44% in internal medicine.