Transcriptional Activity of the Islet β Cell Factor Pdx1 is Augmented by Lysine Methylation Catalyzed by the Methyltransferase Set7/9

The transcription factor Pdx1 is crucial to islet β cell function and regulates target genes in part through interaction with coregulatory factors. Set7/9 is a Lys methyltransferase that interacts with Pdx1. Here we tested the hypothesis that Lys methylation of Pdx1 by Set7/9 augments Pdx1 transcriptional activity. Using mass spectrometry and mutational analysis of purified proteins, we found that Set7/9 methylates the N-terminal residues Lys-123 and Lys-131 of Pdx1. Methylation of these residues occurred only in the context of intact, full-length Pdx1, suggesting a specific requirement of secondary and/or tertiary structural elements for catalysis by Set7/9. Immunoprecipitation assays and mass spectrometric analysis using β cells verified Lys methylation of endogenous Pdx1. Cell-based luciferase reporter assays using wild-type and mutant transgenes revealed a requirement of Pdx1 residue Lys-131, but not Lys-123, for transcriptional augmentation by Set7/9. Lys-131 was not required for high-affinity interactions with DNA in vitro, suggesting that its methylation likely enhances post-DNA binding events. To define the role of Set7/9 in β cell function, we generated mutant mice in which the gene encoding Set7/9 was conditionally deleted in β cells (SetΔβ). SetΔβ mice exhibited glucose intolerance similar to Pdx1-deficient mice, and their isolated islets showed impaired glucose-stimulated insulin secretion with reductions in expression of Pdx1 target genes. Our results suggest a previously unappreciated role for Set7/9-mediated methylation in the maintenance of Pdx1 activity and β cell function

FASD

Regardless of our current knowledge base on the consumption of alcohol during pregnancy, the mistake continues to be made with the result being children born with Fetal Alcohol Spectrum Disorder. As these children move through their public education, it is often the case that their challenges are not met and they do not receive adequate help to overcome their difficulties with academics and social skills. When these students begin to transition into their adult lives, secondary conditions often arise from our failure as a support network to intervene on their behalf earlier on. This meta-synthesis of the literature on individuals with FASD investigates the current realities of the difficulties surrounding prenatal alcohol consumption as it relates to children, their families and communities

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

The Loss of Spoken Word

The rapid emergence of social media has the potential to negatively affect young people moving into the job market. In this paper, I examine whether there has been a loss of communication and soft skills, interpersonal skills, and how this has an impact on workforce readiness. Numerous studies have explored the social interactions and the effects technology has had on human behavior. Based on the insights from sociologists, psychologists, educators, and researchers, it appears that interpersonal skills (soft skills) are critical to being successful in the workforce. Research indicates that social media can hamper verbal communication in young people. Additionally, in a technology-driven world, the need for interpersonal conversation is a necessary element in the development of self-reflection and personal relationships, and the success of the young people depends on the ability to communicate both nonverbally and verbally in a variety of environments. All of these are important interpersonal skills that employers desire, but which young people may fail to develop if they are preoccupied with social media at the expense of interpersonal conversation