Lipidomic Analysis Reveals Altered Fatty Acid Metabolism in the Liver of the Symptomatic Niemann–Pick,Type C1 Mouse Model

Niemann–Pick disease, type C1 (NPC1) is a fatal, autosomal recessive, neurodegenerative disorder caused by mutations in the NPC1 gene. As a result of the genetic defect, there is accumulation of unesterified cholesterol and sphingolipids in the late endosomal/lysosomal system causing both visceral and neurological defects. These manifest clinically as hepatosplenomegaly, liver dysfunction, and neurodegeneration. While significant progress has been made to better understand NPC1, the downstream effects of cholesterol storage and the major mechanisms that drive these pathologies remains less understood. In this study, it is sought to investigate free fatty acid levels in Npc1^?/? mice with focus on the polyunsaturated ω‐3 and ω‐6 fatty acids. Since fatty acids are the main constituents of numerous lipids species, a discovery based lipidomic study of liver tissue in Npc1^?/? mice is also performed. To this end, alterations in fatty acid synthesis, including the ω‐3 and 6 fatty acids, are reported. Further, alterations in enzymes that regulate the synthesis of ω‐3 and 6 fatty acids are reported. Analysis of the liver lipidome reveals alterations in both storage and membrane lipids including ceramides, fatty acids, phosphatidylcholamines, phosphatidylglycerols, phosphatidylethanolamines, sphingomyelins, and triacylglycerols in Npc1^?/? mice at a late stage of disease.     

Exploring continuity equation via a modeling activity: in the context of crowd science

Abstract

Using problems from real life contexts which is related to learners’ environment or their culture plays an important role in their learning that concept. In this regard, science educators especially physics educators search for real-life domain of theoretical concepts for effective science teaching and they consider analogical and physical models as an opportunity in their instruction. In the presented activity, we worked with 66 senior pre-service science teachers from our science teaching methods course. We used crowd movements as a real-life domain of our analogical models to scientifically explain a stampede case, then utilized physical model to explore continuity equation. Real life problem based scenarios could be used while taking advantage of the 3?D modeling in teaching of scientific principle. As a result, we found that pre-service teachers were able to make scientific explanation for causes of stampedes by using modeling activity. High school teachers and upper-level instructors could benefit from including the modeling activity introduced in this study to help their students understand the concepts related to continuity equation by designing a physical model based on an analogical model. Via the physical model, students are able to make predictions, observations, interpretations and explanations of a complex and abstract scientific phenomenon.