Identification of processing elements and interactors implicate SMN, coilin and the pseudogene-encoded coilp1 in telomerase and box C/D scaRNP biogenesis

<p>Many cellular functions, such as translation, require ribonucleoproteins (RNPs). The biogenesis of RNPs is a multi-step process that, depending on the RNP, can take place in many cellular compartments. Here we examine 2 different RNPs: telomerase and small Cajal body-specific RNPs (scaRNPs). Both of these RNPs are enriched in the Cajal body (CB), which is a subnuclear domain that also has high concentrations of another RNP, small nuclear RNPs (snRNPs). SnRNPs are essential components of the spliceosome, and scaRNPs modify the snRNA component of the snRNP. The CB contains many proteins, including WRAP53, SMN and coilin, the CB marker protein. We show here that coilin, SMN and coilp1, a newly identified protein encoded by a pseudogene in human, associate with telomerase RNA and a subset of scaRNAs. We also have identified a processing element within box C/D scaRNA. Our findings thus further strengthen the connection between the CB proteins coilin and SMN in the biogenesis of telomeras e and box C/D scaRNPs, and reveal a new player, coilp1, that likely participates in this process.</p

Persistent organic pollutants (POPs) increase rage signaling to promote downstream cardiovascular remodeling

© 2019 by the authors. Licensee MDPI, Basel, Switzerland. Background: Antimicrobial resistance (AMR) is a global threat and the antimicrobial stewardship program (ASP) is a globally used tool to combat AMR. There is little information on the views among Pakistani physicians regarding AMR and the benefits of hospital antimicrobial stewardship implementation. This study was designed to explore the physicians’ views about ASP. Methods: Qualitative face-to-face and telephonic interviews were conducted by using purposive sampling method with 22 physicians working in seven tertiary care public hospitals of Punjab, Pakistan. All interviews were audio recorded and transcribed verbatim. Qualitative software was used, and a thematic analysis was conducted. Results: Three broad themes were identified: (1) the growing concern of antimicrobial resistance in Pakistan, (2) the role(s) of healthcare professionals in antibiotic prescribing, and (3) managing antibiotic resistance in hospitals. Inadequate resources, poor healthcare facilities, and insufficiently trained medical staff were the major hurdles in ASP implementation in Pakistan. Conclusions: Our study found a poor familiarity of hospital ASP among physicians working in public sector tertiary care teaching hospitals, and a number of distinct themes emerged during this study that could be helpful in establishing the concept of hospital ASP in Pakistan. Overall, physicians showed a positive attitude towards the enforcement of ASP in all healthcare settings, including teaching hospitals