33 research outputs found

    Mutations in KEOPS-Complex Genes Cause Nephrotic Syndrome with Primary Microcephaly

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    Galloway-Mowat syndrome (GAMOS) is an autosomal-recessive disease characterized by the combination of early-onset nephrotic syndrome (SRNS) and microcephaly with brain anomalies. Here we identified recessive mutations in OSGEP, TP53RK, TPRKB, and LAGE3, genes encoding the four subunits of the KEOPS complex, in 37 individuals from 32 families with GAMOS. CRISPR-Cas9 knockout in zebrafish and mice recapitulated the human phenotype of primary microcephaly and resulted in early lethality. Knockdown of OSGEP, TP53RK, or TPRKB inhibited cell proliferation, which human mutations did not rescue. Furthermore, knockdown of these genes impaired protein translation, caused endoplasmic reticulum stress, activated DNA-damage-response signaling, and ultimately induced apoptosis. Knockdown of OSGEP or TP53RK induced defects in the actin cytoskeleton and decreased the migration rate of human podocytes, an established intermediate phenotype of SRNS. We thus identified four new monogenic causes of GAMOS, describe a link between KEOPS function and human disease, and delineate potential pathogenic mechanisms

    Reflections on urban science teacher-student self-efficacy dynamics

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    This forum article consists of commentaries-authored by Sumi Hagiwara, Maria S. Rivera Maulucci and Lizette Ramos-on the feature article by Virginia Jennings Bolshakova, Carla C. Johnson, and Charlene M. Czerniak. We reflect on a series of questions that take retrospective, introspective, and prospective views of self-efficacy in science education. We review selected studies that explore some of the historical developments and methodological approaches in the literature and examine a teacher-student self-efficacy system model that shows the ways in which teachers\u27 and students\u27 self-efficacy judgments are based upon multiple individual and shared components, such as identity and social interaction within the classroom and school. We close with a call for the design of measures of teacher-student self-efficacy systems, so that we can begin to tailor professional development experiences to the goals and motivations of individual and collective groups of teachers and students in ways that accommodate the unique cultural features of their classrooms and foster student self-efficacy

    Examining the evolution education literature with a focus on teachers: major findings, goals for teacher preparation, and directions for future research

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    The theory of evolution is the fundamental backbone to the discipline of biology, yet many students possess misunderstandings. The teacher is the most important school-based factor in student learning, and therefore to improve students’ understandings of evolution, we must better prepare teachers. The purpose of this paper is three-fold. First, we reviewed empirical research studies focused on K-12 teachers regarding evolution education from 1993 to 2011 with the purpose of identifying major themes of research and corresponding findings. Second, we used our understandings of current findings to inform the development and articulation of five goals for teacher preparation. Third, we discuss implications of this work for teacher preparation initiatives and directions of future research. We found that current evolution education research specific to K-12 teachers falls within four major themes, which collectively inform the development of five goals for preparing teachers to teach evolution. We argue that teachers should: (1) develop content knowledge of evolution; (2) develop understandings of the nature of science related to evolution; (3) develop acceptance of evolution as valid within science; (4) develop knowledge of and strategies for handling the public controversy; and (5) develop pedagogical content knowledge for teaching evolution. Based on our review, evolution courses and professional development initiatives for K-12 teachers should integrate the five goals, with more attention to teaching evolution in the classroom. Investigating the nature of teachers’ acceptance of evolution and pedagogical content knowledge for teaching evolution are areas of research in need of continued pursuit
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