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Sequential stabilization of RNF220 by RLIM and ZC4H2 during cerebellum development and Shh-group medulloblastoma progression

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Journal of Molecular Cell Biology 2022年第1期14卷 32-46页

作者： Yuwei Li Chencheng Yang Huishan Wang Ling Zhao Qinghua Kong Yu Cang Shuhua Zhao longbao lv Yan Li Bingyu Mao Pengcheng Ma State Key Laboratory of Genetic Resources and Evolution Kunming Institute of ZoologyChinese Academy of SciencesKunming 650223China Kunming College of Life Science University of Chinese Academy of SciencesKunming 650203China Experimental Animal Center Kunming Institute of ZoologyChinese Academy of SciencesKunming 650223China Kunming Institute of Botany Chinese Academy of SciencesKunming 650223China Department of Urology the Affiliated Hospital of Yunnan UniversityKunming 650021China First Affiliated Hospital of Kunming Medical University Kunming 650032China Center for Excellence in Animal Evolution and Genetics Chinese Academy of SciencesKunming 650223China

Sonic hedgehog (Shh) signaling is essential for the proliferation of cerebellar granule neuron progenitors (CGNPs), and its misregulation is linked to various disorders, including cerebellar cancer medulloblastoma (MB). During vertebrate neural development, RNF220, a ubiquitin E3 ligase, is involved in spinal cord patterning by modulating the subcellular location of glioma-associated oncogene homologs (Glis) through ubiquitination. RNF220 is also required for full activation of Shh signaling during cerebellum development in an epigenetic manner through targeting embryonic ectoderm development. ZC4H2 was reported to be involved in spinal cord patterning by acting as an RNF220 stabilizer. Here, we provided evidence to show that ZC4H2 is also required for full activation of Shh signaling in CGNP and MB progression by stabilizing RNF220. In addition, we found that the ubiquitin E3 ligase RING finger LIM domain-binding protein (RLIM) is responsible for ZC4H2 stabilization via direct ubiquitination, through which RNF220 is also thus stabilized. RLIM is a direct target of Shh signaling and is also required for full activation of Shh signaling in CGNP and MB cell proliferation. We further provided clinical evidence to show that the RLIM‒ZC4H2‒RNF220 cascade is involved in Shh-group MB progression. Disease-causative human RLIM and ZC4H2 mutations affect their interaction and regulation. Therefore, our study sheds light on the regulation of Shh signaling during cerebellar development and MB progression and provides insights into neural disorders caused by RLIM or ZC4H2 mutations.

关键词： ZC4H2 RLIM RNF220 Shh signaling cerebellum medulloblastoma(MB)

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Co-editing PINK1 and DJ-1 Genes Via Adeno-Associated Virus-Delivered CRISPR/Cas9 System in Adult Monkey Brain Elicits Classical Parkinsonian Phenotype

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Neuroscience Bulletin 2021年第9期37卷 1271-1288页

作者： Hao Li Shihao Wu Xia Ma Xiao Li Tianlin Cheng Zhifang Chen Jing Wu longbao lv Ling Li Liqi Xu Wenchao Wang Yingzhou Hu Haisong Jiang Yong Yin Zilong Qiu Xintian Hu Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province Kunming Institute of ZoologyChinese Academy of Sciences650223 KunmingChina Institute of Neuroscience CAS Key Laboratory of Primate NeurobiologyState Key Laboratory of NeuroscienceChinese Academy of SciencesShanghai 200031China Institutes of Physical Science and Information Technology Anhui UniversityHefei 230601China Center for Excellence in Brain Science and Intelligence Technology Chinese Academy of SciencesShanghai 200031China National Resource Center for Non-human Primates Kunming Primate Research Centerand National Research Facility for Phenotypic and Genetic Analysis of Model Animals(Primate Facility)Kunming Institute of ZoologyChinese Academy of Sciences650107 KunmingChina Diagnostic Radiology Department 920 Hospital of the Joint Logistics Support Force of the PLAKunming 650032China Ultrasound diagnosis Department 920 Hospital of the Joint Logistics Support Force of the PLAKunming 650032China Sichuan Provincial People’s Hospital University of Electronic Science and Technology of ChinaChengdu 610072China Department of Rehabilitation Medicine The Second People’s Hospital of Yunnan ProvinceKunming 650021China National Clinical Research Center for Aging and Medicine Huashan HospitalFudan UniversityShanghai 200433China

Whether direct manipulation of Parkinson’s disease(PD)risk genes in the adult monkey brain can elicit a Parkinsonian phenotype remains an unsolved ***,we used an adeno-associated virus serotype 9(AAV9)-delivered CRISPR/Cas9 system to directly co-edit PINK1 and DJ-1 genes in the substantia nigras(SNs)of two monkey groups:an old group and a middle-aged *** the operation,the old group exhibited all the classic PD symptoms,including bradykinesia,tremor,and postural instability,accompanied by key pathological hallmarks of PD,such as severe nigral dopaminergic neuron loss(>64%)and evidentα-synuclein pathology in the gene-edited *** contrast,the phenotype of their middle-aged counterparts,which also showed clear PD symptoms and pathological hallmarks,were less *** addition to the higher final total PD scores and more severe pathological changes,the old group were also more susceptible to gene editing by showing a faster process of PD *** results suggested that both genetic and aging factors played important roles in the development of PD in the *** together,this system can effectively develop a large number of genetically-edited PD monkeys in a short time(6–10 months),and thus provides a practical transgenic monkey model for future PD studies.

关键词： Parkinson’s disease Monkey Adeno-associated virus-delivered CRISPR/Cas9 PINK1 DJ-1 Parkinsonian phenotype

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多重PCR技术在实验动物病原检测中的应用

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中国比较医学杂志 2018年第10期28卷 111-116页

作者：张飞燕赵玲金洁王芸吕龙宝中国科学院昆明动物研究所昆明650000 中国科学院昆明灵长类研究中心昆明650223

多重PCR作为一种新型的分子生物学检测技术,具有高效、快捷、特异性和灵敏度高等优点,能够同时扩增出多个核酸片段,克服了普通PCR缺点,实现了对多种病原微生物的同时检测,为临床病原鉴别诊断、基因分型、耐药基因等领域的研究提供了新思... 详细信息

多重PCR作为一种新型的分子生物学检测技术,具有高效、快捷、特异性和灵敏度高等优点,能够同时扩增出多个核酸片段,克服了普通PCR缺点,实现了对多种病原微生物的同时检测,为临床病原鉴别诊断、基因分型、耐药基因等领域的研究提供了新思路,具有较大的发展前景。笔者对多重PCR的原理及技术特点,多重PCR技术在实验动物病毒、细菌、寄生虫病原体和微生物耐药等方面进行综述,旨在为多重PCR技术应用在实验动物疫病病原体的检测提供参考依据。

关键词：多重PCR技术实验动物病原检测

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3例滇金丝猴传染性痢疾的诊断与治疗

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黑龙江畜牧兽医 2021年第8期 102-104,154页

作者：马玉华邬继文张飞燕张玉林胡正飞刘超王芸陈佳琦张庆宇吕龙宝中国科学院昆明动物研究所灵长类研究中心昆明650223 国家非人灵长类实验动物资源库昆明650223

2020年2月13日,中国科学院昆明动物研究所灵长类研究中心3只滇金丝猴相继出现精神沉郁、食欲废绝、频繁腹泻、排黏液脓性带血且腥臭粪便的临床症状。为了有效控制疾病的传播蔓延,提高笼养条件下滇金丝猴的饲养成活率,笔者根据一线生产... 详细信息

2020年2月13日,中国科学院昆明动物研究所灵长类研究中心3只滇金丝猴相继出现精神沉郁、食欲废绝、频繁腹泻、排黏液脓性带血且腥臭粪便的临床症状。为了有效控制疾病的传播蔓延,提高笼养条件下滇金丝猴的饲养成活率,笔者根据一线生产实践经验、临床症状与实验室检查结果对疾病进行诊断,并根据诊断结果进行治疗。结果表明:3只滇金丝猴为鞭虫、阿米巴原虫混合感染所致的传染性痢疾,经过药物治疗,3只滇金丝猴均恢复健康,并于隔离后第16天放回大笼饲养。说明通过早发现、早隔离、准确诊断、及时治疗与精心护理能有效提高该病治愈率。

关键词：滇金丝猴阿米巴原虫鞭虫菌痢诊断治疗

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Design and Application of Homework Digitization Resources Based on Knowledge Management

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International Journal of Technology Management 2013年第8期 145-147页

作者： Zeng Yi lv Hui Mei longbao Information Science and Technology College of Jiujiang University Jiangxi Province 332005 China

Analyzing the education resource construction and management from knowledge management perspective is the hot spot and focus of current education research. We make the knowledge management concept of knowledge acquisition, knowledge application and knowledge creation as the core throughuot the whole process of homework management activities to realize the optimization of homework management process. It mainly illustrates the sharing design and application of homework digitization resources. The sharing and application of homework digitization resources will promote the accumulation of teaching knowledge, which has a guiding research significance for promoting the use of educational resources, the application of education knowledge and the virtuous cycle of transformation and accumulation.

关键词： knowledge management homework digitization resources sharing

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猕猴结肠镜检查前的肠道准备

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实验动物科学 2021年第4期38卷 69-72页

作者：唐川君龚慧黄志寅冯哲高锦航谭庆华赵旭东吕龙宝刘超吕维敏王芸胡兵唐承薇张琼英四川大学华西护理学院/四川大学华西医院消化内镜中心成都610041 四川大学华西医院消化内科成都610041 中国科学院昆明动物研究所实验动物中心昆明650201

猕猴是非常重要且珍贵的实验动物。不处死猕猴为前提,以反复多次对猕猴进行全结肠肠道检查及研究为目的,建立猕猴全结肠内镜检查前的肠道准备方法尤为重要。本研究补充此方法目前尚无报道的空白。30只猕猴,结肠镜检查前3 h分多次予以芒... 详细信息

猕猴是非常重要且珍贵的实验动物。不处死猕猴为前提,以反复多次对猕猴进行全结肠肠道检查及研究为目的,建立猕猴全结肠内镜检查前的肠道准备方法尤为重要。本研究补充此方法目前尚无报道的空白。30只猕猴,结肠镜检查前3 h分多次予以芒硝溶液管喂。通过肠镜观察肠道清洁情况,其中3只猕猴肠道准备为Ⅲ级,其余猕猴肠道准备均为Ⅰ~Ⅱ级。所有猕猴在洗肠过程中,无严重脱水、休克、死亡等并发症发生,肠道准备为Ⅰ~Ⅱ级猕猴顺利完成全结肠内镜检查。

关键词：猕猴肠道准备结肠清洁度芒硝结肠内镜

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淮安区防汛防旱指挥系统设计与实现

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水利信息化 2016年第3期 66-72页

作者：王龙宝陶飞飞吕鑫余霖韦明伦河海大学计算机与信息学院江苏南京210098

针对淮安区防汛防旱信息系化建设中存在的问题,合理整合淮安市已建成的信息化资源,通过淮安市水利局私有云实现资源整合与数据共享,给出已建云平台的实施方案。采用Java EE相关技术,构建灵活的系统中间层,最终实现淮安区原始办公形式向... 详细信息

针对淮安区防汛防旱信息系化建设中存在的问题,合理整合淮安市已建成的信息化资源,通过淮安市水利局私有云实现资源整合与数据共享,给出已建云平台的实施方案。采用Java EE相关技术,构建灵活的系统中间层,最终实现淮安区原始办公形式向高效信息化办公形式的转变和GIS地图预警,提供防汛防旱参考解决方案,大大提高淮安区水利局日常办公效率,加速淮安区信息化建设的步伐。

关键词：防汛防旱信息化私有云中间层 Java EE 效率

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