Nanjing Automation Research Institute (NARI) is a specialized institute that engages in the researches of automation of electric mper system and its application. The paper introduces the architecture of NARI Intranet ...Nanjing Automation Research Institute (NARI) is a specialized institute that engages in the researches of automation of electric mper system and its application. The paper introduces the architecture of NARI Intranet as well as the techniques and application development on the Intranet. The first stage network of NARI and the building and the second stage network are both introduced. We lay emphasis on the system softWare used in NAm intranet, network management software developed by ourselves according to the characteristic of NARI network users, technique characteristics of application system on this platform and its running status. The paper also discusses the further development of NARI network application.展开更多
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...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.展开更多
文摘Nanjing Automation Research Institute (NARI) is a specialized institute that engages in the researches of automation of electric mper system and its application. The paper introduces the architecture of NARI Intranet as well as the techniques and application development on the Intranet. The first stage network of NARI and the building and the second stage network are both introduced. We lay emphasis on the system softWare used in NAm intranet, network management software developed by ourselves according to the characteristic of NARI network users, technique characteristics of application system on this platform and its running status. The paper also discusses the further development of NARI network application.
基金This work was supported by the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB13000000 to B.M.)the National Natural Science Foundation of China(32170965 to P.M.and 82060292 to S.Z.)+1 种基金Yunnan Basic Research Program(202001AS070036 to B.M.)the open project of State Key Laboratory of Genetic Resources and Evolution(GREKF20-07 to S.Z.and GREKF18-12 to Yan Li).P.M.was supported by the Youth Innovation Promotion Association of Chinese Academy of Sciences.
文摘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.
