SNX14 deficiency-induced defective axonal mitochondrial transport in Purkinje cells underlies cerebellar ataxia and can be reversed by valproate

共济失调是一类以运动协调性紊乱为主要特征的神经系统症状，临床表现包括步态不稳、丧失平衡、吞咽困难、眼球运动异常、肌张力受损等。厦门大学医学院神经科学研究所王鑫教授团队首次从轴突线粒体运输这一全新视角揭示了一类遗传性共济失调的发病机制，并发现抗癫痫药--丙戊酸大幅度减缓模型小鼠的疾病进程，具有较强的转化应用价值，有望为共济失调提供新的治疗手段。 该研究工作由王鑫教授指导完成，厦门大学医学院助理教授张洪峰和博士生洪育娟共同完成主要实验工作。Loss-of-function mutations in SNX14 cause autosomal recessive spinocerebellar ataxia 20, which is a form of early-onset cerebellar ataxia that lacks molecular mechanisms and mouse models. We generated Snx14-deficient mouse models and observed severe motor deficits and cell-autonomous Purkinje cell degeneration. SNX14 deficiency disrupted microtubule organization and mitochondrial transport in axons by destabilizing the microtubule-severing enzyme spastin, which is implicated in dominant hereditary spastic paraplegia with cerebellar ataxia, and compromised axonal integrity and mitochondrial function. Axonal transport disruption and mitochondrial dysfunction further led to degeneration of high-energy-demanding Purkinje cells, which resulted in the pathogenesis of cerebellar ataxia. The antiepileptic drug valproate ameliorated motor deficits and cerebellar degeneration in Snx14-deficient mice via the restoration of mitochondrial transport and function in Purkinje cells. Our study revealed an unprecedented role for SNX14-dependent axonal transport in cerebellar ataxia, demonstrated the convergence of SNX14 and spastin in mitochondrial dysfunction, and suggests valproate as a potential therapeutic agent.We thank Tim Huang for helpful discussion, Wei Mo for sharing mouse lines, Li Zhong for sharing reagents, Aidong Han, Luming Yao, Caiming Wu, Mingxia Zhu, Qingfeng Liu, Lin Zhu, Shuo Zhang, Haiping Zheng, and Changchuan Xie for technical assistance, and Cui Li for providing bioinformatics software. We also thank Novogene Co., Ltd. and PTM Biolab Co., Ltd. for technical assistance in the transcriptomic and proteomic analyses, respectively. 厦门大学医学院许华曦、赵颖俊、张云武、杜丹教授在研究过程中给予大力帮助和支持。本研究工作得到国家重点研发计划项目、国家自然科学基金、福建省自然科学基金、厦门大学校长基金的资助和支持

A Study of Global Financial Imbalance and Precautionary Saving

[[abstract]]The purpose of this paper is to explore the global financial imbalances from a perspective on a precautionary savings motive. This study will be divided into theoretical analysis and empirical investigation. The theoretical derivation mainly follows the framework of Carroll and Jeanne (2008), which emphasizes the size of the individual precautionary motive (that is, the size of the net foreign assets held by individuals) will be related to their survival probability, unemployment probability and social insurance multiplier. Furthermore, to discuss the global financial imbalances, the precautionary motive framework is extended to a two-country general equilibrium model. As for the empirical analysis, this study calibrates the movements of the net foreign assets, using the parameter values in China and the United States. We expect that, when the degree of the insurance covering the uncertainty is relatively high, the precautionary saving will diminish, leading to a decrease in the country's net foreign asset positions and thereby a reduction of global financial imbalances. The policy implication of moderating global financial imbalances is that China can improve the social welfare policy to reduce world unemployment rate, ameliorating the U.S. current account deficits

全球金融失衡與預防儲蓄之探討

[[abstract]]本文目的係就預防儲蓄動機之觀點，探討全球金融失衡之現象。本研究將 分為理論推導與實證分析兩大部分。在理論推導部分主要遵循 Carroll and Jeanne (2008) 之架構，強調個人預防動機的大小 (即個人持有淨國資產部位的 大小) 會與其存活率、失業率以及社會保險乘數有關，故將此等預防動機的概 念擴展至兩國一般均衡模型，對全球金融失衡的議題加以討論。就實證分析的 部分，本研究係以刻畫模擬的方式，模擬中國與美國的相關參數值，如何影響 其淨國外資產的移動方向；我們預期當不確定性被保險的程度越高時，那麼預 防動機將會減少，導致國家的淨國外資產部位也將減少，降低全球金融失衡的 現象。在政策建議上，中國可採行提高社會福利之政策，與降低世界失業率， 使美國經常帳赤字有所改善，以緩和全球金融失衡的問題

The Work plan of Shourthern Environmental Education Regional Center.

[[abstract]]本計畫以「環境教育增能計畫」(EECapacity)的運作架構，計畫執行區域範圍，包括：嘉義縣、嘉義市、台南市、高雄市、屏東縣、澎湖縣等六縣市，並依照美國環境教育增能計畫的五個主要方案規劃工作項目，包括：專業領導、增能學習、科技支援、研究評估與夥伴傳播。本年度計畫工作以整合南部地區產、官、學及民間組織等各方的環境教育資源及人力，形成夥伴網絡並建置專業學習社群，彙整併歸納南部地區的環境資源特色，以有效推廣環境教育工作，針對目前環境教育實施現況，進行機構、場域及人員之現況分析，提出可行方案。並以產業化導向作為主軸發展，提出試運行方案評估後續發展之可能。[[abstract]]"Environmental education (EE) capacity" is used as the operational framework in this project. Six cities and counties are covered in this project: Chiayi, Tainan, Kaohsiung, Pingtung, and Penghu. The tasks including leadership academy, capacity building, technological support, research and evaluation, and dissemination partnership are planned according to the five programs of a US EE capacity project.This year, we integrated the environmental education resources and manpower of industries, governments, academic institutes, and NGOs in southern region to form partner networks, developed professional learning communities, summarized the features of local environmental resources to effectively promote environmental education, analyzed the current status of environmental education in terms of agencies, venues,and personnel to propose feasible measures. We also adopted industrialization as a theme for development and devised a tentative program to assess subsequent developmental possibilities.[[note]]EPA-103-EA04-03-A14