Mechanism for the learning deficits in a mouse model of neurofibromatosis type 1.

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.     

'Rejuvenation' protects neurons in mouse models of Parkinson's disease

Why dopamine-containing neurons of the brain's substantia nigra pars compacta die in Parkinson's disease has been an enduring mystery. Our studies suggest that the unusual reliance of these neurons on L-type Ca(v)1.3 Ca2+ channels to drive their maintained, rhythmic pacemaking renders them vulnerable to stressors thought to contribute to disease progression. The reliance on these channels increases with age, as juvenile dopamine-containing neurons in the substantia nigra pars compacta use pacemaking mechanisms common to neurons not affected in Parkinson's disease. These mechanisms remain latent in adulthood, and blocking Ca(v)1.3 Ca2+ channels in adult neurons induces a reversion to the juvenile form of pacemaking. Such blocking ('rejuvenation') protects these neurons in both in vitro and in vivo models of Parkinson's disease, pointing to a new strategy that could slow or stop the progression of the disease.     

由建构与算理看戴震的《勾股割圜记》

戴震对中算的贡献,一向被认为只局限于算书的整理上,如校《九章算术》、恢复《算经十书》,等等。他的数学成就,常被批评为无足轻重。文章从学术建构的角度,来分析戴震的《勾股割圜记》,认为戴震著书的目的是希望由中算固有的性质中,创造出一个具文化传承且能与西方三角学匹敌的勾股割圆术。由此观点,戴书中许多被诟病之处,可得到合理的解释。另外,在研究戴震算学的文献中,很少谈到戴震对算理的强调。文章的另一目的是讨论算理在《勾股割圜记》中的重要性。戴震宣称割圜之法尽于勾股互权(相似直角三角形三边互求)。而在其书中勾股术的推导过程,除了图式,戴更明确地列出相似勾股形的对应边。无论是平面或是球面,戴的确是用该性质推导出所有的勾股术。