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Rui M Costa Nikolai B Federov Jeff H Kogan Geoffrey G Murphy Joel Stern Masuo Ohno Raju Kucherlapati Tyler Jacks Alcino J Silva 《Nature》2002,415(6871):526-530
Neurofibromatosis type I (NF1) is one of the most common single-gene disorders that causes learning deficits in humans. Mice carrying a heterozygous null mutation of the Nfl gene (Nfl(+/-) show important features of the learning deficits associated with NF1 (ref. 2). Although neurofibromin has several known properties and functions, including Ras GTPase-activating protein activity, adenylyl cyclase modulation and microtubule binding, it is unclear which of these are essential for learning in mice and humans. Here we show that the learning deficits of Nf1(+/-) mice can be rescued by genetic and pharmacological manipulations that decrease Ras function. We also show that the Nf1(+/-) mice have increased GABA (gamma-amino butyric acid)-mediated inhibition and specific deficits in long-term potentiation, both of which can be reversed by decreasing Ras function. Our results indicate that the learning deficits associated with NF1 may be caused by excessive Ras activity, which leads to impairments in long-term potentiation caused by increased GABA-mediated inhibition. Our findings have implications for the development of treatments for learning deficits associated with NF1. 相似文献
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The INDSCAL individual differences scaling model is extended by assuming dimensions specific to each stimulus or other object, as well as dimensions common to all stimuli or objects. An alternating maximum likelihood procedure is used to seek maximum likelihood estimates of all parameters of this EXSCAL (Extended INDSCAL) model, including parameters of monotone splines assumed in a quasi-nonmetric approach. The rationale for and numerical details of this approach are described and discussed, and the resulting EXSCAL method is illustrated on some data on perception of musical timbres. 相似文献
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Douglas A. Wilson Victoria Raish Alison Carr-Chellman 《Systemic Practice and Action Research》2017,30(3):277-293
The paper explores cinematic films as a pedagogical tool to promote critical thinking and student discussions in a doctoral-level learning, design, and technology seminar course at a major U.S. research university. These discussions focused on systemic change and systemic thinking concepts. The authors offer evidence from the literature that supports films’ power as a visual metaphor and neurocognitive stimulator to promote development of new perspectives in graduate students on case studies through articulation, reflection, and explanation of their thought processes on change and diffusion of innovation. There are theoretical, political, social, and technological issues that create tensions during any systemic change effort. The goal of using film in this seminar is to equip students with the requisite skills, theoretical frameworks, and interpersonal experiences needed to address these issues within organizations and communities. The change expected from systemic thinking is for students to think more deeply about the interconnectedness of systems and the importance of bottom-up change efforts that consider the perspective of all stakeholders. 相似文献
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Tollefson J 《Nature》2007,450(7171):767
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