Fasciculation and elongation zeta/zygin(FEZ) proteins are a family of hub proteins and share many characteristics like high connectivity in interaction networks, they are involved in several cellular processes, evolve...Fasciculation and elongation zeta/zygin(FEZ) proteins are a family of hub proteins and share many characteristics like high connectivity in interaction networks, they are involved in several cellular processes, evolve slowly and in general have intrinsically disordered regions. In 1985, unc-76 gene was firstly described and involved in axonal growth in C. elegans, and in 1997 Bloom and Horvitz enrolled also the human homologues genes, FEZ1 and FEZ2, in this process. While nematodes possess one gene(unc-76), mammalians have one more copy(FEZ1 and FEZ2). Several animal models have been used to study FEZ family functions like: C. elegans, D. melanogaster, R. novergicus and human cells.Complementation assays were performed and demonstrated the function conservation between paralogues. Human FEZ1 protein is more studied followed by UNC-76 and FEZ2 proteins, respectively. While FEZ1 and UNC-76 shared interaction partners, FEZ2 evolved and increased the number of protein-protein interactions(PPI) with cytoplasmatic partners. FEZ proteins are implicated in intracellular transport, acting as bivalent cargo transport adaptors in kinesinmediated movement. Especially in light of this cellular function, this family of proteins has been involved in several processes like neuronal development,neurological disorders, viral infection and autophagy. However, nuclear functions of FEZ proteins have been explored as well, due to high content of PPI with nuclear proteins, correlating FEZ1 expression to Sox2 and Hoxb4 gene regulation and retinoic acid signaling. These recent findings open new avenue to study FEZ proteins functions and its involvement in already described processes.This review intends to reunite aspects of evolution, structure, interaction partners and function of FEZ proteins and correlate them to physiological and pathological processes.展开更多
目的利用生物信息学技术分析参与糖尿病肾病(DN)的关键基因及其有关的信号通路。方法从GEO数据库下载有关DN肾小球组织与正常人肾小球组织的所有基因,利用limma软件包筛选出两者的差异表达基因(DEG),并对DEG进行GO功能和KEGG通路富集分...目的利用生物信息学技术分析参与糖尿病肾病(DN)的关键基因及其有关的信号通路。方法从GEO数据库下载有关DN肾小球组织与正常人肾小球组织的所有基因,利用limma软件包筛选出两者的差异表达基因(DEG),并对DEG进行GO功能和KEGG通路富集分析,通过构建蛋白质-蛋白质相互作用(PPI)网络筛选出与DN相关的候选基因,通过候选基因与临床指标的相关性分析获得与DN密切相关的关键基因。结果通过GEO数据库筛选出52个DN肾小球组织与正常人肾小球组织的DEG。GO功能和KEGG通路富集分析显示,DEG主要参与细胞外结构组织、细胞外基质、细胞外基质结构组成成分以及补体和凝血级联反应等过程。经PPI网络分析筛选出14个与DN紧密相关的候选基因,经Pearson相关性分析确定了与DN患者临床指标具有显著相关性的11个关键基因(C 3、CCL 19、COL 1 A 2、COL 6 A 3、COL 15 A 1、LOX、LUM、SERPINF 1、TGFB I、THBS 2、VCAN)。结论通过生物信息学分析筛选出了与DN患者临床指标密切相关的11个关键基因,为阐明DN的分子机制以及潜在治疗靶点提供了新的思路。展开更多
Toxoplasma gondii (T. gondii) an intracellular protozoan parasite, infects mammals including human population world-wide. Upon primary infection, the parasite contributes to mild flu like symptoms in immune competent ...Toxoplasma gondii (T. gondii) an intracellular protozoan parasite, infects mammals including human population world-wide. Upon primary infection, the parasite contributes to mild flu like symptoms in immune competent host, but life threatening complication is seen in immune compromised patients and in pregnant women. Understanding the host-parasite interaction is critical for understanding the pathogenesis and biology parasite reactivation in the host. In this study, we used proteotrasncriptomics analyses by integrating the transcriptomics and proteomics data of T. gondii infected mouse liver to uncover the effector molecules responsible for disease pathogenesis that can be used as candidate markers for diagnosis and drug target. With this aim, we systematically integrated transcriptomicand proteomic data, representing the parasite infected mouse liver. Out of 2758 differentially expressed genes (DEGs) and 301 differentially expressed proteins (DEPs), 159 overlapping genes were identified. Among them, 86 genes were upregulated and 72 were downregulated in their respective mRNA and protein levels in the infected condition. Gene Ontology (GO) analysis revealed that the upregulated genes were mostly associated with immune system processes whereas the downregulated genes were involved in oxidation-reduction process and metabolism of lipid, and fatty acids. Protein-protein interaction (PPI) network analysis uncovered an interaction-hub including, Psmb8, Psmb9 and Tap1 for upregulated proteins and Cyp1A2, Cyp4A10 and Cyp3A11 for down-regulated proteins. Further studies are needed to validating these effector molecules. These molecules are likely to play a vital role in disease pathogenesis, as well as can be used as potential diagnostic marker and drug target candidates.展开更多
文摘Fasciculation and elongation zeta/zygin(FEZ) proteins are a family of hub proteins and share many characteristics like high connectivity in interaction networks, they are involved in several cellular processes, evolve slowly and in general have intrinsically disordered regions. In 1985, unc-76 gene was firstly described and involved in axonal growth in C. elegans, and in 1997 Bloom and Horvitz enrolled also the human homologues genes, FEZ1 and FEZ2, in this process. While nematodes possess one gene(unc-76), mammalians have one more copy(FEZ1 and FEZ2). Several animal models have been used to study FEZ family functions like: C. elegans, D. melanogaster, R. novergicus and human cells.Complementation assays were performed and demonstrated the function conservation between paralogues. Human FEZ1 protein is more studied followed by UNC-76 and FEZ2 proteins, respectively. While FEZ1 and UNC-76 shared interaction partners, FEZ2 evolved and increased the number of protein-protein interactions(PPI) with cytoplasmatic partners. FEZ proteins are implicated in intracellular transport, acting as bivalent cargo transport adaptors in kinesinmediated movement. Especially in light of this cellular function, this family of proteins has been involved in several processes like neuronal development,neurological disorders, viral infection and autophagy. However, nuclear functions of FEZ proteins have been explored as well, due to high content of PPI with nuclear proteins, correlating FEZ1 expression to Sox2 and Hoxb4 gene regulation and retinoic acid signaling. These recent findings open new avenue to study FEZ proteins functions and its involvement in already described processes.This review intends to reunite aspects of evolution, structure, interaction partners and function of FEZ proteins and correlate them to physiological and pathological processes.
文摘目的利用生物信息学技术分析参与糖尿病肾病(DN)的关键基因及其有关的信号通路。方法从GEO数据库下载有关DN肾小球组织与正常人肾小球组织的所有基因,利用limma软件包筛选出两者的差异表达基因(DEG),并对DEG进行GO功能和KEGG通路富集分析,通过构建蛋白质-蛋白质相互作用(PPI)网络筛选出与DN相关的候选基因,通过候选基因与临床指标的相关性分析获得与DN密切相关的关键基因。结果通过GEO数据库筛选出52个DN肾小球组织与正常人肾小球组织的DEG。GO功能和KEGG通路富集分析显示,DEG主要参与细胞外结构组织、细胞外基质、细胞外基质结构组成成分以及补体和凝血级联反应等过程。经PPI网络分析筛选出14个与DN紧密相关的候选基因,经Pearson相关性分析确定了与DN患者临床指标具有显著相关性的11个关键基因(C 3、CCL 19、COL 1 A 2、COL 6 A 3、COL 15 A 1、LOX、LUM、SERPINF 1、TGFB I、THBS 2、VCAN)。结论通过生物信息学分析筛选出了与DN患者临床指标密切相关的11个关键基因,为阐明DN的分子机制以及潜在治疗靶点提供了新的思路。
文摘Toxoplasma gondii (T. gondii) an intracellular protozoan parasite, infects mammals including human population world-wide. Upon primary infection, the parasite contributes to mild flu like symptoms in immune competent host, but life threatening complication is seen in immune compromised patients and in pregnant women. Understanding the host-parasite interaction is critical for understanding the pathogenesis and biology parasite reactivation in the host. In this study, we used proteotrasncriptomics analyses by integrating the transcriptomics and proteomics data of T. gondii infected mouse liver to uncover the effector molecules responsible for disease pathogenesis that can be used as candidate markers for diagnosis and drug target. With this aim, we systematically integrated transcriptomicand proteomic data, representing the parasite infected mouse liver. Out of 2758 differentially expressed genes (DEGs) and 301 differentially expressed proteins (DEPs), 159 overlapping genes were identified. Among them, 86 genes were upregulated and 72 were downregulated in their respective mRNA and protein levels in the infected condition. Gene Ontology (GO) analysis revealed that the upregulated genes were mostly associated with immune system processes whereas the downregulated genes were involved in oxidation-reduction process and metabolism of lipid, and fatty acids. Protein-protein interaction (PPI) network analysis uncovered an interaction-hub including, Psmb8, Psmb9 and Tap1 for upregulated proteins and Cyp1A2, Cyp4A10 and Cyp3A11 for down-regulated proteins. Further studies are needed to validating these effector molecules. These molecules are likely to play a vital role in disease pathogenesis, as well as can be used as potential diagnostic marker and drug target candidates.
