RESUMO
Students work through this Problem-Based Learning Case in order to discover how Nora ended up blue lipped and non-responsive. By exploring fundamental mechanisms of neuronal communication, students examine facts, research concepts, and propose hypotheses about how Nora's physiology was disrupted to cause her respiratory distress. The dramatic context supports student learning at many levels - from systems neurophysiology to synaptic pharmacology. The case as written is used in an undergraduate course for non-science majors, but because the case focuses on basic fundamental neuroscience concepts, the case could be easily used in high school or other undergraduate courses that cover basic neuroscience.
RESUMO
For the past six years, we have been teaching a neuroscience for non-science majors course titled "From Botox to Behavior: Neuroscience for non-scientists." The primary objectives for this course are to create science literate students using neuroscience concepts as the foundation. The evidence from our course assessments suggest that the students are learning fundamental concepts and developing skills of source evalution, using evidence in an argument and appreciating the role of neuroscience in society. While the course has been very successful as measured by student performance on assessments of content learning and student satisfaction, we have noticed a pervasive weakness in quantitative literacy. Our future directions include assessing what kinds of interventions and approaches work best to increase quanitative literacy among non-science majors.
RESUMO
BACKGROUND: The RING domain-containing protein RING finger protein 11 (RNF11) is a member of the A20 ubiquitin-editing protein complex and modulates peripheral NF-κB signaling. RNF11 is robustly expressed in neurons and colocalizes with a population of α-synuclein-positive Lewy bodies and neurites in Parkinson disease patients. The NF-κB pathway has an important role in the vertebrate nervous system, where the absence of NF-κB activity during development can result in learning and memory deficits, whereas chronic NF-κB activation is associated with persistent neuroinflammation. We examined the functional role of RNF11 with respect to canonical NF-κB signaling in neurons to gain understanding of the tight association of inflammatory pathways, including NF-κB, with the pathogenesis of neurodegenerative diseases. METHODS AND RESULTS: Luciferase assays were employed to assess NF-κB activity under targeted short hairpin RNA (shRNA) knockdown of RNF11 in human neuroblastoma cells and murine primary neurons, which suggested that RNF11 acts as a negative regulator of canonical neuronal NF-κB signaling. These results were further supported by analyses of p65 translocation to the nucleus following depletion of RNF11. Coimmunoprecipitation experiments indicated that RNF11 associates with members of the A20 ubiquitin-editing protein complex in neurons. Site-directed mutagenesis of the myristoylation domain, which is necessary for endosomal targeting of RNF11, altered the impact of RNF11 on NF-κB signaling and abrogated RNF11's association with the A20 ubiquitin-editing protein complex. A partial effect on canonical NF-κB signaling and an association with the A20 ubiquitin-editing protein complex was observed with mutagenesis of the PPxY motif, a proline-rich region involved in Nedd4-like protein interactions. Last, shRNA-mediated reduction of RNF11 in neurons and neuronal cell lines elevated levels of monocyte chemoattractant protein 1 and TNF-α mRNA and proteins, suggesting that NF-κB signaling and associated inflammatory responses are aberrantly regulated in the absence of RNF11. CONCLUSIONS: Our findings support the hypothesis that, in the nervous system, RNF11 negatively regulates canonical NF-κB signaling. Reduced or functionally compromised RNF11 could influence NF-κB-associated neuronal functions, including exaggerated inflammatory responses that may have implications for neurodegenerative disease pathogenesis and progression.