The lack of models for sporadic ALS has hampered efforts to identify disease mechanisms and therapeutic targets that apply broadly to multiple sporadic forms of ALS (3, 7). To address this, we derived induced pluripotent stem cells (iPSCs) from a cohort of sporadic ALS patients and generated induced motor neurons (iMNs) from these iPSCs. We show that similarly to C9ORF72 ALS iMNs, the sporadic ALS iMNs from all 6 donors degenerate significantly faster than controls and show pronounced mislocalization of transactive response DNA-binding protein 43 kDa (TDP-43). Thus, these sporadic ALS iMNs display relevant disease processes.
All of the Taichang Emperor's sons died before reaching adulthood except for Zhu Youxiao and Zhu Youjian. Zhu Youjian grew up in a relatively lonely but quiet environment. After the Taichang Emperor died in 1620, Zhu Youjian's elder brother Zhu Youxiao succeeded their father and was enthroned as the Tianqi Emperor. He granted the title "Prince of Xin" (信王) to Zhu Youjian and posthumously honoured Zhu Youjian's mother, Lady Liu, as "Consort Xian" (賢妃). Fearing the court eunuch Wei Zhongxian, who controlled the Tianqi Emperor, Zhu Youjian avoided attending imperial court sessions under the pretext of illness until he was summoned to court by his brother in 1627. At the time, the Tianqi Emperor was gravely ill and wanted Zhu Youjian to rely on Wei Zhongxian in the future.
3K3A-APC also rescued the survival of iMNs from all 6 sporadic ALS lines (Figure 5H and Supplemental Figure 6, A–F; 6 sporadic ALS patients). When we tested iMNs from separate iPSC clones of the sporadic patient lines, 3K3A-APC also significantly improved their survival, indicating that the rescue effects were not specific to iMNs derived from certain iPSC clones (Supplemental Figure 6, G–J; 3 sporadic ALS patients). Reinforcing the notion that activating autophagosome formation in ALS iMNs could increase survival, rapamycin treatment significantly improved the survival of iMNs from 4 of 5 sporadic ALS lines tested (Supplemental Figure 7, A–J; 6 sporadic ALS patients). In contrast, rapamycin slightly decreased the survival of control iMNs (Supplemental Figure 7, K and L). These results suggest that rescuing autophagosome formation in sporadic ALS iMNs can increase their survival.
To determine significant pathways, differentially expressed genes for inactive 3K3A-APC versus 3K3A-APC treatment at 3 days were uploaded and analyzed by using the IPA tool (Qiagen). We focused on “Top Canonical Pathways.” Only canonical pathways with –log(P value) greater than 1.5 were retained. P values were calculated by using Fisher’s exact test.
Ho Khai Leong 何启良 (ed.). Kuangzheng yu liubian: Malaixiya huaren lishi yu renwu zhengzhipian 匡正与流变：马来西亚华人历史与人物政治篇 (Malaysian Chinese History and Personalities: The Political Elites). Kuala Lumpur: Centre for Malaysian Chinese Studies, 2003; Hou Kok Chung 何国忠(ed.), Jicheng yu jueze: Malaixiya huaren lishi yu renwu wenhuapian 继承与抉择：马来西亚华人历史与人物文化篇 (Malaysian Chinese History and Personalities: The Intellectual Elites). Kuala Lumpur: Centre for Malaysian Chinese Studies, 2003; Lim Chooi Kwa 林水豪 (ed.), Chuangye yu hugen: Malaixiya huaren lishi yu renwu rushangpian 创业与护根：马来西亚华人历史与人物儒商篇 (Malaysian Chinese History and Personalities: The Entrepreneurial Elites). Kuala Lumpur: Centre for Malaysian Chinese Studies, 2003. In Xin Jiyuan Xueyuan xuebao 新纪元学院学报 (New Era College Academic Journal) Vol. 2 (April 2005): 169-171.
* “Zhongguo xin yimin he Xinjiapo shehui” 中国新移民和新加坡社会 (New Chinese Migrants and Singapore Society), presented at the Fourth Migration Law Forum on “Law of Exit and Administration, China and the World, in Beijing,” organized The School of Law, Beijing Institute of Technology, Beijing Association of International Law, Centre for China and Globalization, and China Western Returned Scholars Association, 18 November 2012.
Zhè zhong tísheng dào changhé de nénglì you yigè jingshén céngmiàn. Jiézòu, xiàng xilà zhéxué de lixiang, you yidìng de tiansheng de pinzhí. Zhishì dì xìngzhì kenéng, kenéng, bangzhù yourén shengchan ta de xuqiú. Zài yu dingjí yùndòngyuán de fangtán zhong, xinli xué jia yijing xuéhuì rèn shì nénggòu dài lái gaofeng biaoxiàn de mou xie jìshù. Lìrú, keshìhuà jìshù bangzhù yùndòngyuán jingshén shàng jízhong yú shoutóu de rènwù. Gao'erfu qiú shou jiékè·níkè láo si (Jack Nicklaus) shuo, ta zài chángshì shèmén zhiqián jingcháng huì zài ta tóunao zhong “kàn diànying”.
In 2006, the General Administration of Press and Publication of China began enforcing the first batch of the ‘China Digital Newspaper Laboratory Programs’, in which 18 national and local press groups were involved in officially unfolding the prelude of the ‘full-media convergence’, namely an intensive integration of new media into the system of traditional press. Since 2012, Chinese press industry has stepped into a ‘cold winter’. Throughout 2014 alone, the total revenue of newspaper circulation experienced a substantial decrease of 25%, with advertising revenue simultaneously decreasing by 15% (Cui and He, 2015). Several scholars suggested that vulnerable profit-making pattern, global economic recession and the decelerating growth rate of the domestic economy were the key factors for the predicament that Chinese press industry is experiencing (Zhao, 2015). However, the industry tends to ascribe the dramatic revenue decline to the prosperity of new media (cf. Cao, 2010; Zhou, 2015).
Wo duì nuxìng de tàidù tài bèidòngle. Wo bùshì jijí dì zhuiqiú wo suo ài de rén, ér shì qingxiàng yú ràng nurén jìnrù wo de shenghuó, kàn kàn fashengle shénme. Wo dangshí zhuyào guanzhù xiezuò hé wo de kuàijì gongzuò. Suízhe zhu dí zoule, an huíláile. Women xiàng yiqián yiyàng jìxù xiàqù. Women bù zài zài shuo hunyin, zhishì hua shíjian zài yiqi, baokuò shuìjiào shíjian.
“Locating Chinese New Migrants in National and Ethnic Contexts: The Singapore Case,” presented at the book launch of Lee Guan Kin (ed.), Demarcating Ethnicity in New Nations: Cases of the Chinese in Singapore, Malaysia, and Indonesia 新马印华人：族群关系与国家建构(Singapore: Singapore Society of Asian Studies, Konrad-Adenauer-Stiftung, 2006)and public talk on “Culture and Nation: Ethnic Chinese in Singapore, Malaysia, and Indonesia” 新马印华人：文化与国家 at the National Library, Singapore, organized by Singapore Society of Asian Studies, Kondrad-Adenauer-Stiftung, and Singapore’s National Library Board, 17 December 2006.
After 2008, ‘full-media’ became a keyword with which scholars discussed China’s press industry. Studies that focus on the effects of full-media are categorised into two approaches: media economics and media performance approaches. The media economics approach generalises the experience and lessons of convergence practices and evaluates the influence of media convergence on newspaper development mostly from a business operation perspective by adopting case studies combined with the personal observation of researchers (cf. Tang and Cao, 2015; Yang, 2013). By contrast, the media performance approach analyses the method of content delivery on the new media platforms of newspapers as well as predicts (through content analysis) the influence of convergence on the progress of society’s democratisation from the media ethics perspective (cf. Huang, 2013; Cai, 2011).
To determine if increased glutamate receptor levels might be a conserved mechanism that drives hyperexcitability in multiple forms of ALS, we examined levels of the NR1 NMDA receptor subunit in neurites of control, C9ORF72 ALS, and sporadic ALS iMNs by immunostaining. Similarly to our previous study, C9ORF72 iMNs possessed significantly more NR1+ punctae on neurites than control iMNs (Figure 4, A and B; 2 controls and 2 C9ORF72 ALS patients, and ref. 4). Colabeling with a MAP2-specific antibody verified that the NR1+ punctae that were increased in abundance were localized on dendrites (Supplemental Figure 4, A and B). Interestingly, sporadic ALS iMNs also displayed more NR1+ punctae on neurites than control iMNs (Figure 4, A and C, and Supplemental Figure 4, C–H; 2 controls and 6 sporadic ALS patients). Calcium imaging confirmed that C9ORF72 and sporadic ALS iMNs experienced more calcium transients than controls in response to glutamate, indicating that they may be more sensitive to excitotoxicity (Figure 4, D and E; 3 controls, 3 C9ORF72 ALS patients, 1 sporadic ALS patient). Thus, both C9ORF72 and sporadic ALS iMNs display increased NR1 levels, which could reflect a shared mechanism of increased susceptibility to excitotoxicity.