Ceramide accumulation mediates inflammation, cell death and infection susceptibility in cystic fibrosis

Microbial lung infections are the major cause of morbidity and mortality in the hereditary metabolic disorder cystic fibrosis, yet the molecular mechanisms leading from the mutation of cystic fibrosis transmembrane conductance regulator (CFTR) to lung infection are still unclear. Here, we show that ceramide age-dependently accumulates in the respiratory tract of uninfected Cftr-deficient mice owing to an alkalinization of intracellular vesicles in Cftr-deficient cells. This change in pH results in an imbalance between acid sphingomyelinase (Asm) cleavage of sphingomyelin to ceramide and acid ceramidase consumption of ceramide, resulting in the higher levels of ceramide. The accumulation of ceramide causes Cftr-deficient mice to suffer from constitutive age-dependent pulmonary inflammation, death of respiratory epithelial cells, deposits of DNA in bronchi and high susceptibility to severe Pseudomonas aeruginosa infections. Partial genetic deficiency of Asm in Cftr(-/-)Smpd1(+/-) mice or pharmacological treatment of Cftr-deficient mice with the Asm blocker amitriptyline normalizes pulmonary ceramide and prevents all pathological findings, including susceptibility to infection. These data suggest inhibition of Asm as a new treatment strategy for cystic fibrosis

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

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