Detection of structural and conformational changes in ALS-causing mutant profilin-1 with hydrogen/deuterium exchange mass spectrometry and bioinformatics techniques.

The hydrogen/deuterium exchange (HDX) is a reliable method to survey the dynamic behavior of proteins and epitope mapping. Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry (MALDI-TOF MS) is a quantifying tool to assay for HDX in the protein of interest. We combined HDX-MALDI-TOF MS and molecular docking/MD simulation to identify accessible amino acids and analyze their contribution into the structural changes of profilin-1 (PFN-1). The molecular docking/MD simulations are computational tools for enabling the analysis of the type of amino acids that may be involved via HDX identified under the lowest binding energy condition. Glycine to valine amino acid (G117V) substitution mutation is linked to amyotrophic lateral sclerosis (ALS). This mutation is found to be in the actin-binding site of PFN-1 and prevents the dimerization/polymerization of actin and invokes a pathologic toxicity that leads to ALS. In this study, we sought to understand the PFN-1 protein dynamic behavior using purified wild type and mutant PFN-1 proteins. The data obtained from HDX-MALDI-TOF MS for PFN-1WT and PFN-1G117V at various time intervals, from seconds to hours, revealed multiple peaks corresponding to molecular weights from monomers to multimers. PFN-1/Benzaldehyde complexes identified 20 accessible amino acids to HDX that participate in the docking simulation in the surface of WT and mutant PFN-1. Consistent results from HDX-MALDI-TOF MS and docking simulation predict candidate amino acid(s) involved in the dimerization/polymerization of PFNG117V. This information may shed critical light on the structural and conformational changes with details of amino acid epitopes for mutant PFN-1s' dimerization, oligomerization, and aggregation.

Self-reported teaching effectiveness and job satisfaction among teachers: the role of subject matter and other demographic variables.

The pivotal responsibility of educating and nurturing students in any society is on the shoulders of teachers, whose knowledge, affection, and commitment exert a great influence over students' lives. Therefore, attending to teachers' emotional state and satisfaction with their profession is crucial. This study was therefore undertaken to investigate the relationship between Iranian English and nonEnglish teachers' job satisfaction and their teaching effectiveness. The relationship between these teachers' job satisfaction and their demographic background (e.g. teaching experience and gender) was also scrutinized. Using convenient sampling, 173 English and nonEnglish teachers were selected to participate in this research. In order to collect data, Kulsum (2000) Teacher Effectiveness Scale and Lester's (1987) Teacher Job Satisfaction questionnaire were used. The results revealed a positive correlation between teachers' job satisfaction and teaching effectiveness and this held true for both English and nonEnglish teachers. For policy makers and stakeholders in education, this study underlines the significance of addressing teachers' needs and their challenges to promote their job satisfaction.