Last data update: May 13, 2024. (Total: 46773 publications since 2009)
Records 1-6 (of 6 Records) |
Query Trace: Nawaz S[original query] |
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Serine 970 of RNA helicase MOV10 is phosphorylated and controls unfolding activity and fate of mRNAs targeted for AGO2-mediated silencing.
Nawaz A , Kenny PJ , Shilikbay T , Reed M , Stuchlik O , Pohl J , Ceman S . J Biol Chem 2023 299 (4) 104577 MOV10 is an RNA helicase that is required for organismal development and is highly expressed in postnatal brain. MOV10 was identified as an AGO2 associated protein that is also necessary for AGO2-mediated silencing. AGO2 is the primary effector of the miRNA pathway. MOV10 has been shown to be ubiquitinated, leading to its degradation and release from bound mRNAs but no other post-translational modifications with functional implications have been described. Using mass spectrometry, we show that MOV10 is phosphorylated in cells at the C-terminus, specifically at serine 970 (S970). Substitution of S970 to phospho-mimic aspartic acid (S970D) blocked unfolding of an RNA G-quadruplex, similar to when the helicase domain was mutated (K531A). In contrast, the alanine substitution (S970A) of MOV10 unfolded the model RNA G-quadruplex. To examine its role in cells, our RNA-seq analysis showed that the expression of S970D causes decreased expression of MOV10 enhanced Cross-Linking Immunoprecipitation (eCLIP) targets compared to WT. Introduction of S970A had an intermediate effect, suggesting that S970 was protective of mRNAs. In whole cell extracts, MOV10 and its substitutions bound AGO2 comparably; however, knockdown of AGO2 abrogated the S970D-induced mRNA degradation. Thus, MOV10 activity protects mRNA from AGO2; phosphorylation of S970 restricts this activity resulting in AGO2-mediated mRNA degradation. S970 is positioned C-terminal to the defined MOV10-AGO2 interaction site and is proximal to a disordered region that likely modulates AGO2 interaction with target mRNAs upon phosphorylation. In summary, we provide evidence for a model whereby MOV10 phosphorylation facilitates AGO2 association with the 3'UTR of translating mRNAs that leads to their degradation. |
Developing the evidence base to inform best practice: a scoping study of breast and cervical cancer reviews in low- and middle-income countries
Demment MM , Peters K , Dykens JA , Dozier A , Nawaz H , McIntosh S , Smith JS , Sy A , Irwin T , Fogg TT , Khaliq M , Blumenfeld R , Massoudi M , De Ver Dye T . PLoS One 2015 10 (9) e0134618 BACKGROUND: Breast and cervical cancers have emerged as major global health challenges and disproportionately lead to excess morbidity and mortality in low- and middle-income countries (LMICs) when compared to high-income countries. The objective of this paper was to highlight key findings, recommendations, and gaps in research and practice identified through a scoping study of recent reviews in breast and cervical cancer in LMICs. METHODS: We conducted a scoping study based on the six-stage framework of Arskey and O'Malley. We searched PubMed, Cochrane Reviews, and CINAHL with the following inclusion criteria: 1) published between 2005-February 2015, 2) focused on breast or cervical cancer 3) focused on LMIC, 4) review article, and 5) published in English. RESULTS: Through our systematic search, 63 out of the 94 identified cervical cancer reviews met our selection criteria and 36 of the 54 in breast cancer. Cervical cancer reviews were more likely to focus upon prevention and screening, while breast cancer reviews were more likely to focus upon treatment and survivorship. Few of the breast cancer reviews referenced research and data from LMICs themselves; cervical cancer reviews were more likely to do so. Most reviews did not include elements of the PRISMA checklist. CONCLUSION: Overall, a limited evidence base supports breast and cervical cancer control in LMICs. Further breast and cervical cancer prevention and control studies are necessary in LMICs. |
Defining and assessing quality improvement outcomes: a framework for public health
McLees AW , Nawaz S , Thomas C , Young A . Am J Public Health 2015 105 Suppl 2 e1-e7 We describe an evidence-based framework to define and assess the impact of quality improvement (QI) in public health. Developed to address programmatic and research-identified needs for articulating the value of public health QI in aggregate, this framework proposes a standardized set of measures to monitor and improve the efficiency and effectiveness of public health programs and operations. We reviewed the scientific literature and analyzed QI initiatives implemented through the Centers for Disease Control and Prevention's National Public Health Improvement Initiative to inform the selection of 5 efficiency and 8 effectiveness measures. This framework provides a model for identifying the types of improvement outcomes targeted by public health QI efforts and a means to understand QI's impact on the practice of public health. |
Federal public health workforce development: an evidence-based approach for defining competencies
Mumford K , Young AC , Nawaz S . J Public Health Manag Pract 2015 22 (3) 290-7 OBJECTIVE: This study reports the use of exploratory factor analysis to describe essential skills and knowledge for an important segment of the domestic public health workforce-Centers for Disease Control and Prevention (CDC) project officers-using an evidence-based approach to competency development and validation. DESIGN:: A multicomponent survey was conducted. Exploratory factor analysis was used to examine the underlying domains and relationships between competency domains and key behaviors. The Cronbach alpha coefficient determined the reliability of the overall scale and identified factors. SETTING AND PARTICIPANTS: All domestic (US state, tribe, local, and territorial) grantees who received funding from the CDC during fiscal year 2011 to implement nonresearch prevention or intervention programs were invited to participate in a Web-based questionnaire. MAIN OUTCOME MEASURE(S): A total of 34 key behaviors representing knowledge, skills, and abilities, grouped in 7 domains-communication, grant administration and management, public health applied science and knowledge, program planning and development, program management, program monitoring and improvement, and organizational consultation-were examined. RESULTS: There were 795 responses (58% response rate). A total of 6 factors were identified with loadings of 0.40 or more for all 34 behavioral items. The Cronbach alpha coefficient was 0.95 overall and ranged between 0.73 and 0.91 for the factors. CONCLUSIONS: This study provides empirical evidence for the construct validity of 6 competencies and 34 key behaviors important for CDC project officers and serves as an important first step to evidence-driven workforce development efforts in public health. |
Targeting alphabeta integrin reduces mucosal transmission of simian immunodeficiency virus and protects gut-associated lymphoid tissue from infection
Byrareddy SN , Kallam B , Arthos J , Cicala C , Nawaz F , Hiatt J , Kersh EN , McNicholl JM , Hanson D , Reimann KA , Brameier M , Walter L , Rogers K , Mayne AE , Dunbar P , Villinger T , Little D , Parslow TG , Santangelo PJ , Villinger F , Fauci AS , Ansari AA . Nat Med 2014 20 (12) 1397-400 alpha4beta7 integrin-expressing CD4+ T cells preferentially traffic to gut-associated lymphoid tissue (GALT) and have a key role in HIV and simian immunodeficiency virus (SIV) pathogenesis. We show here that the administration of an anti-alpha4beta7 monoclonal antibody just prior to and during acute infection protects rhesus macaques from transmission following repeated low-dose intravaginal challenges with SIVmac251. In treated animals that became infected, the GALT was significantly protected from infection and CD4+ T cell numbers were maintained in both the blood and the GALT. Thus, targeting alpha4beta7 reduces mucosal transmission of SIV in macaques. |
Advances in public health accreditation readiness and quality improvement: evaluation findings from the National Public Health Improvement Initiative
McLees AW , Thomas CW , Nawaz S , Young AC , Rider N , Davis M . J Public Health Manag Pract 2014 20 (1) 29-35 INTRODUCTION: Continuous quality improvement is a central tenet of the Public Health Accreditation Board's (PHAB) national voluntary public health accreditation program. Similarly, the Centers for Disease Control and Prevention launched the National Public Health Improvement Initiative (NPHII) in 2010 with the goal of advancing accreditation readiness, performance management, and quality improvement (QI). OBJECTIVE: Evaluate the extent to which NPHII awardees have achieved program goals. DESIGN: NPHII awardees responded to an annual assessment and program monitoring data requests. Analysis included simple descriptive statistics. SETTING: Seventy-four state, tribal, local, and territorial public health agencies receiving NPHII funds. PARTICIPANTS: NPHII performance improvement managers or principal investigators. MAIN OUTCOME MEASURE(S): Development of accreditation prerequisites, completion of an organizational self-assessment against the PHAB Standards and Measures, Version 1.0, establishment of a performance management system, and implementation of QI initiatives to increase efficiency and effectiveness. RESULTS: Of the 73 responding NPHII awardees, 42.5% had a current health assessment, 26% had a current health improvement plan, and 48% had a current strategic plan in place at the end of the second program year. Approximately 26% of awardees had completed an organizational PHAB self-assessment, 72% had established at least 1 of the 4 components of a performance management system, and 90% had conducted QI activities focused on increasing efficiencies and/or effectiveness. CONCLUSIONS: NPHII appears to be supporting awardees' initial achievement of program outcomes. As NPHII enters its third year, there will be additional opportunities to advance the work of NPHII, compile and disseminate results, and inform a vision of high-quality public health necessary to improve the health of the population. |
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