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P-Rex1 Overexpression Results in Aberrant Neuronal Polarity and Psychosis-Related Behaviors 被引量:2
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作者 Qiongwei Li Lifang Wang +3 位作者 Yuanlin Ma Weihua Yue Dai Zhang Jun Li 《Neuroscience Bulletin》 SCIE CAS CSCD 2019年第6期1011-1023,共13页
Neuronal polarity is involved in multiple developmental stages, including cortical neuron migration,multipolar-to-bipolar transition, axon initiation, apical/basal dendrite differentiation, and spine formation. All of... Neuronal polarity is involved in multiple developmental stages, including cortical neuron migration,multipolar-to-bipolar transition, axon initiation, apical/basal dendrite differentiation, and spine formation. All of these processes are associated with the cytoskeleton and are regulated by precise timing and by controlling gene expression. The P-Rex1(phosphatidylinositol-3,4,5-trisphosphate dependent Rac exchange factor 1) gene for example, is known to be important for cytoskeletal reorganization, cell motility, and migration. Deficiency of P-Rex1 protein leads to abnormal neuronal migration and synaptic plasticity, as well as autism-related behaviors.Nonetheless, the effects of P-Rex1 overexpression on neuronal development and higher brain functions remain unclear. In the present study, we explored the effect of P-Rex1 overexpression on cerebral development and psychosis-related behaviors in mice. In utero electroporation at embryonic day 14.5 was used to assess the influence of P-Rex1 overexpression on cell polarity and migration.Primary neuron culture was used to explore the effects of P-Rex1 overexpression on neuritogenesis and spine morphology. In addition, P-Rex1 overexpression in the medial prefrontal cortex(m PFC) of mice was used to assess psychosis-related behaviors. We found that P-Rex1 overexpression led to aberrant polarity and inhibited the multipolar-to-bipolar transition, leading to abnormal neuronal migration. In addition, P-Rex1 overexpression affected the early development of neurons, manifested as abnormal neurite initiation with cytoskeleton change,reduced the axon length and dendritic complexity, and caused excessive lamellipodia in primary neuronal culture.Moreover, P-Rex1 overexpression decreased the density of spines with increased height, width, and head area in vitro and in vivo. Behavioral tests showed that P-Rex1 overexpression in the mouse m PFC caused anxiety-like behaviors and a sensorimotor gating deficit. The appropriate P-Rex1 level plays a critical role in the developing cerebral cortex and excessive P-Rex1 might be related to psychosis-related behaviors. 展开更多
关键词 P-rex1 NEURODEVELOPMENT Polarity LAMELLIPODIA Psychosis-related behavior
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基于生物信息学分析P-Rex1在胃癌组织中的表达及临床意义 被引量:1
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作者 张刚 杜娟(指导) +2 位作者 刘敏 余琼 夏伶俐 《中国免疫学杂志》 CAS CSCD 北大核心 2020年第8期987-991,共5页
目的:分析P-Rex1在胃癌肿瘤组织中的表达,探讨其在胃癌发展过程中的临床意义及其可能的调控网络。方法:利用TCGA胃癌数据库分析P-Rex1在胃癌肿瘤组织和癌旁组织中的表达差异,并分析其在不同肿瘤进展阶段的表达差异以及其与幽门螺旋杆菌... 目的:分析P-Rex1在胃癌肿瘤组织中的表达,探讨其在胃癌发展过程中的临床意义及其可能的调控网络。方法:利用TCGA胃癌数据库分析P-Rex1在胃癌肿瘤组织和癌旁组织中的表达差异,并分析其在不同肿瘤进展阶段的表达差异以及其与幽门螺旋杆菌感染的相关性;利用Oncomine和Kaplan-Meier Plotter工具分析P-Rex1表达与胃癌患者预后的关系,并阐述其与胃癌临床病理学参数的相关性;基于cBioPortal工具分析TCGA胃癌患者肿瘤组织P-Rex1基因的共表达网络,进行GO聚类分析以及蛋白-蛋白相互作用网络分析。结果:胃癌肿瘤组织中的P-Rex1基因表达显著增加;P-Rex1基因表达水平与肿瘤分期存在正相关的联系,但与幽门螺旋杆菌感染与否无显著相关性;高表达P-Rex1的胃癌患者总生存期和进展后生存期都显著下降;HER2阴性胃癌患者中P-Rex1高表达组总生存期显著低于P-Rex1低表达组患者;伴有淋巴结转移的胃癌患者P-Rex1高表达组总生存期显著低于P-Rex1低表达组;P-Rex1蛋白质相互作用共表达网络发现P-Rex1与CDC42、Rac分子和系列Rho信号分子存在紧密联系,通过聚类分析发现P-Rex1可能参与淋巴细胞的激活、细胞因子释放、炎症免疫信号通路等过程。结论:P-Rex1在胃癌组织中高表达,其表达水平与胃癌发展过程存在紧密联系,生存期分析发现在HER2阴性或淋巴结转移胃癌患者中,P-Rex1表达与患者预后存在紧密的联系,并且可能参与胃癌的炎症免疫信号网络调节。 展开更多
关键词 3 4 5-三磷酸肌醇依赖的Rac交换因子1 高表达 免疫炎症
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Methylation patterns in 5' terminal regions of pluripotency-related genes in bovine in vitro fertilized and cloned embryos 被引量:1
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作者 Jie Lan Song Hua Hailin Zhang Yongli Song Jun Liu Yong Zhang 《Journal of Genetics and Genomics》 SCIE CAS CSCD 2010年第5期297-304,共8页
In order to investigate DNA methylation profiles of five pluripotency-related genes (Oct4, Sox2, Nanog, Rexl and Fgf4) during bovine maternal to zygotic transition (MZT) in both in vitro fertilized (IVF) and nuc... In order to investigate DNA methylation profiles of five pluripotency-related genes (Oct4, Sox2, Nanog, Rexl and Fgf4) during bovine maternal to zygotic transition (MZT) in both in vitro fertilized (IVF) and nuclear transfer (NT) embryos, sodium bisulfite sequencing method was used to detect DNA methylation levels, accompanied by the statistical analysis of embryo developmental rates. The results showed that Oct4, Nanog, Rexl and Fgf4 were respectively demethylated by 25.22% (P 〈 0.01), 3.84% (P 〉 0.05), 31.82% (P 〈 0.01) and 10% (P 〉 0.05) while Sox2 retained unmethylafion during MZT in IVF embryos. By contrast, Oct4 and Rexl respectively underwent demethylation by 23.04% (P 〈 0.01) and 6.02% (P 〉 0.05), and, reversely, Sox2, Nanog and Fgf4 respectively experienced remethylation by 0.84% (P 〉 0.05), 5.39% (P 〉 0.05) and 5.46% (P 〉 0.05) during MZT in NT embryos. Interestingly, the CpG 14 site of Sox2 was specifically methylated in both 8-cell and morula NT embryos. In addition, the development of blastocysts between IVF and NT embryos showed no significant difference. DNA methylation analysis showed that only Oct4 and Sox2 underwent the correct methylation reprogramming process, which may be responsible for the development of blastocysts of NT embryos to a certain extent. In conclusion, the five genes respectively experienced demethylation to different extents and incomplete DNA methylation reprogramming during bovine MZT in both IVF and NT embryos, suggesting that they may be used as indicators for bovine embryo developmental competence. 展开更多
关键词 BOVINE DNA methylation Fgf4 NANOG OCT4 rex1 SOX2
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Magnetic properties and magnetic exchange interactions in Gd_(1–x)RE_x(RE=Pr,Nd) alloys 被引量:1
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作者 肖素芬 陈云贵 《Journal of Rare Earths》 SCIE EI CAS CSCD 2016年第5期489-494,共6页
The effect of Pr,Nd addition on the magnetic properties and magnetic exchange interaction of gadolinium alloys was systematically studied.Curie temperature TC and magnetic moment of Gd(1–x)REx(RE=Pr,Nd)systems wi... The effect of Pr,Nd addition on the magnetic properties and magnetic exchange interaction of gadolinium alloys was systematically studied.Curie temperature TC and magnetic moment of Gd(1–x)REx(RE=Pr,Nd)systems with x〈0.05 were investigated.When x〈0.05,Pr and Nd formed respectively with Gd continuous solid solution which has the crystalline structure HCP.Study on the magnetic behavior indicated that at near room temperature,the simple ferromagnetism prevailed in these two systems of alloy.The Curie temperature and magnetic moment of Gd(1–x)REx alloy decreased with RE(RE= Pr,Nd)content x increasing.The de Gennes factor of Gd(1–x)REx alloy which was associated with the exchange interaction between magnetic spin components also decreased with RE content increasing.The above results showed that the magnetic exchange interaction between magnetic atoms in gadolinium could be effectively changed by the Pr,Nd addition. 展开更多
关键词 Gd(1–x)REx(RE=Pr Nd)alloys Curie temperature magnetic moment de Gennes factor G rare earths
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