Structural characterization of respiratory syncytial virus fusion inhibitor escape mutants: homology model of the F protein and a syncytium formation assay

Respiratory syncytial virus (RSV) is a ubiquitous human pathogen and the leading cause of lower respiratory tract infections in infants. Infection of cells and subsequent formation of syncytia occur through membrane fusion mediated by the RSV fusion protein (RSV-F). A novel in vitro assay of recombinant RSV-F function has been devised and used to characterize a number of escape mutants for three known inhibitors of RSV-F that have been isolated. Homology modeling of the RSV-F structure has been carried out on the basis of a chimera derived from the crystal structures of the RSV-F core and a fragment from the orthologous fusion protein from Newcastle disease virus (NDV). The structure correlates well with the appearance of RSV-F in electron micrographs, and the residues identified as contributing to specific binding sites for several monoclonal antibodies are arranged in appropriate solvent-accessible clusters. The positions of the characterized resistance mutants in the model structure identify two promising regions for the design of fusion inhibitors. (C) 2003 Elsevier Science (USA). All rights reserved.

Evaluating a model of parental influence on youth physical activity

Objective: To test a conceptual model linking parental physical activity orientations, parental support for physical activity, and children's self-efficacy perceptions with physical activity participation. Participants and Setting: The sample consisted of 380 students in grades 7 through 12 (mean age, 14.0 +/- 1.6 years) and their parents. Data collection took place during the fall of 1996. Main Outcome Measures: Parents completed a questionnaire assessing their physical activity habits, enjoyment of physical activity, beliefs regarding the importance of physical activity, and supportive behaviors for their child's physical activity. Students completed a 46-item inventory assessing physical activity during the previous 7 days and a 5-item physical activity self-efficacy scale. The model was tested via observed variable path analysis using structural equation modeling techniques (AMOS 4.0). Results: An initial model, in which parent physical activity orientations predicted child physical activity via parental support and child self-efficacy, did not provide an acceptable fit to the data. Inclusion of a direct path from parental support to child physical activity and deletion of a nonsignificant path from parental physical activity to child physical activity significantly improved model fit. Standardized path coefficients for the revised model ranged from 0.17 to 0.24, and all were significant at the p < 0.0001 level. Conclusions: Parental support was an important correlate of youth physical activity, acting directly or indirectly through its influence on self-efficacy. Physical activity interventions targeted at youth should include and evaluate the efficacy of individual-level and community-level strategies to increase parents' capacity to provide instrumental and motivational support for their children's physical activity.