Adeno-associated virus (AAV) has been used extensively as a vector for gene therapy. Despite its widespread use, the mechanisms by which AAV enters the cell and is trafficked to the nucleus are poorly understood. In this study, we performed two pooled, genome-wide screens to identify positive and negative factors modulating AAV2 transduction. Genome-wide libraries directed against all human genes with four designs per gene or eight designs per gene were transduced into U-2 OS cells. These pools were transduced with AAV2 encoding EGFP and sorted based on the intensity of EGFP expression. Analysis of enriched and depleted barcodes in the sorted samples identified several genes that putatively decreased AAV2 transduction. A subset of screen hits was validated in flow cytometry and imaging studies. In addition to KIAA0319L (AAVR), we confirmed the role of two genes, GPR108 and TM9SF2, in mediating viral transduction in eight different AAV serotypes. Interestingly, GPR108 displayed serotype selectivity and was not required for AAV5 transduction. Follow-up studies suggested that GPR108 localized primarily to the Golgi, where it may interact with AAV and play a critical role in mediating virus escape or trafficking. Cumulatively, these results expand our understanding of the process of AAV transduction in different cell types and serotypes.
Received: March 2016, Accepted: June 2016 Background: Determining quality requirements and quality dimensions is one of the most reliable ways of providing high quality services. The objective of the present study was to investigate the association between quality requirements and quality dimensions according to the points of view of physicians, nurses, and patients. Materials and Methods: This descriptive study was carried out in hospitals under supervision of Medical Sciences Universities, in 4 provinces of Tehran, Fars, Lorestan, and Yazd (Iran). A group of 432 physicians and nurses answered the Quality Requirements Questionnaire which includes the 4 components of competitive, ethical, professional, and accountability requirements. Furthermore, 500 patients answered the Quality Dimensions Questionnaire, including the 11 dimensions of security (safety), professionalism, empathy (friendship), politeness, reliability, accountability, working speed, competency, accessibility, flexibility, and tangibles. The Pearson correlation coefficient and multiple regression method were used to analyze the data in SPSS software. Results: The mean quality requirements and quality dimensions scores in the studied hospitals were, respectively, 3.75 and 3.61, both of which were at a higher than medium level. Moreover, the results of Pearson correlation coefficient suggested that the competitive, professional, and ethical components of quality requirement had a significant and direct association with quality dimensions. However, there was no significant association between the accountability component and quality dimensions variables. Furthermore, based on the results of multiple regression and the determination coefficient, it is possible to claim that approximately 13% of variance in quality dimensions depend upon the mean of components of quality requirements. Conclusions: It can be concluded that work commitment, attention to work, respect for ethical principles, and fair competition at the work place between physicians and nurses lead to the provision of safe and high quality services in hospitals.
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