信号转导通路与异常黑胆质证NEI网络功能紊乱的关系

 为探讨信号转导通路与异常黑胆质证神经-内分泌-免疫(NEI)网络功能紊乱的关系,采用基因芯片技术检测异常黑胆质证与非异常黑胆质(异常血液质、异常黏液质、异常胆液质)证白细胞结构基因表达水平,筛选差异表达基因,利用生物信息学技术分析差异表达基因参与的相关信号转导通路。芯片结果提示,与非异常黑胆质证相比,异常黑胆质证白细胞中有75个结构基因表达上调,生物信息学分析显示差异表达基因中富集到信号转导生物学过程的基因有12个,这些基因主要涉及MAPK、Toll样受体和Wnt信号转导通路等。由此可见,MAPK、Toll样受体、Wnt信号转导通路在异常黑胆质证患者体内存在异常激活现象,这可能与异常黑胆质证神经-内分泌-免疫网络功能紊乱密切相关。     

月季插穗不定根起始的转录组分析和关键基因筛选

为研究月季插穗在不定根发生过程中的关键基因调控机理,利用Illumina平台测序技术对切花月季品种‘卡罗拉’插穗的3个发育阶段(不定根未启动期、愈伤组织形成期和不定根伸长期)插穗基部1 cm皮层进行转录组测序分析,结果表明:月季插穗不定根发生的3个阶段中,在不定根未启动期与愈伤组织形成期之间共筛选出差异表达基因5 033个,其中2 313个基因上调,2 720个基因下调;在愈伤组织形成期与不定根伸长期之间共筛选出差异表达基因1 865个,其中1 332个基因上调,533个基因下调;GO功能分析表明,差异表达基因主要参与生物过程、分子功能和细胞组分3大功能;KEGG富集分析结果表明,差异表达基因主要参与植物激素信号转导、次生代谢产物的合成以及碳水化合物的合成等代谢通路;将月季插穗生根过程中差异性最为显著的8个基因通过实时荧光定量PCR检测其转录水平变化,结果表明: 实时荧光定量PCR的验证结果与转录组测序结果基本一致.     

盐胁迫下棉花根系的转录组分析及耐盐基因筛选

为揭示棉花耐盐分子机制，筛选出棉花盐胁迫应答相关基因.文章从4个新疆主栽棉花品种中筛选得到一个对盐胁迫具有强耐受性的‘新陆中69号’，并在盐胁迫下对棉花根系进行了转录组分析.结果表明:有891个基因表达量上调，666个基因表达量下调；GO富集分析结果表明:差异表达基因数量较多的主要集中在分子功能、细胞组分、生物学过程中；KEGG分析结果表明:差异表达基因主要参与木质素生物合成和植物MAPK信号通路.     

低能离子束辐照诱导的水稻差异表达基因的调控网络研究

用基因芯片检测鉴定离子束辐照下水稻中的差异表达基因（DEGs）.结果共检测到26个上调和6个下调的差异表达基因.共表达网络分析（RiceNET）表明,这些基因都存在着直接或间接的互作网络,暗示水稻存在着以前没有充分认识的基因网络.为进一步研究植物应答离子束辐照候选基因提供了基础.     

乳腺癌-冠心病共享生物标志物筛选

运用生物信息学方法筛选乳腺癌-冠心病标志物,为乳腺癌诱发的冠心病治疗提供潜在的作用靶点.从基因表达数据库(gene expression omnibus,GEO)中下载乳腺癌和冠心病相关表达谱芯片数据,使用GEO2R筛选差异表达基因,依据Venn图交集获取差异共表达基因,通过DAVID网站进行基因功能注释(gene ontology,GO)及京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)生物功能富集分析,STRING网站和Cytoscape 3.7.2软件进行蛋白互作分析.GE-PIA和Kaplan-Meier Plotter进行对乳腺癌患者hub基因mRNA表达水平和预后分析.结果表明:2个数据集筛选得到差异表达基因286个,基于在乳腺癌中mRNA显著性表达水平筛选出45个基因.GO功能富集分析发现差异表达基因主要在泛素蛋白转移酶活性、糖蛋白结合、泛素蛋白连接酶结合等生物学过程发挥作用.KEGG分析显示差异基因主要参与缝隙连接、肾素分泌、5-羟色胺能突触、谷氨酸能突触、血管平滑肌收缩、血小板活化、癌细胞蛋白多糖等多条信号通路.基因mRNA表达水平和预后分析显示NLN、POSTN、MAPT、MYO6、MAP1B、FBXO31、KIT、PIK3R1等8个与冠心病相关的hub基因参与乳腺癌的发生、发展过程.NLN、POSTN、MAPT、MYO6、MAP1B、FBXO31、KIT、PIK3R1可作为检测乳腺癌诱导冠心病的潜在标志物.     

利用基因芯片检测大鼠衰老相关的记忆障碍的调控基因

许多证据表明,正常衰老过程伴随着记忆力的衰退.但有些动物却不表现出这种年龄相关的记忆障碍.为了检测其中的分子机制,将24个月的老年大鼠按在水迷宫中的行为表现分成记忆损伤组和记忆未损伤组,分别取海马和内嗅皮层进行基因芯片检测.结果显示,在海马和内嗅皮层中分别有47和37个基因的表达发生了显著变化.但两个脑区的基因表达变化...     

Comparative proteomic analysis of the response in resistant and susceptible maize inbred lines to infection by Curvularia lunata

Proteins differentially expressed from maize leaves in response to the infection by Curvularia lunata strain CX-3 were identified through a high-resolution two-dimensional gel electrophoresis (2-DE) method. Two inbred lines, 78599-1 and E28, were used, respectively, as resistant and susceptible lines to CX-3 infection. Proteins were extracted from the fourth leaves of six- or seven-leaf stage plants sampled at 24, 36, 48, 60, and 72 h after inoculation with CX-3. Twenty-seven differentially expressed protein spots resolved on the 2-DE gels were identified by MALDI-TOF MS/MS. The results showed that these proteins are associated with photosynthesis, respiration,oxidative and drought stress tolerance as well as signal transduction in maize. Among stress-related proteins, the 22 kDa drought-inducible protein, putative glutathione peroxidase (GPX), and translation initiation factor (eIF-5A) were up-regulated in the resistant inbred line and were implicated in host defense response to C. lunata infection. It suggests that drought-inducible and oxidation stress-related proteins might directly contribute to maize resistance to C. lunata.     

基于表达谱分析筛选肾母细胞瘤关键基因

为探究肾母细胞瘤(Nephroblastoma)发生的关键基因,并筛选出潜在的治疗靶点及生物标志,采用由GEO数据库获取的基因芯片GSE11151和GSE53224,经归一化处理后,通过GO和KEGG分析筛选出差异基因,并通过构建蛋白互作网络获得其中的关键基因.总计获得差异基因404个,其中上调基因385个,下调基因19个.PMCH、CCR5、CCR7、RGS1和KNG1作为关键基因,涉及趋化因子信号通路、G蛋白偶联信号通路,参与肿瘤微环境的形成.这5个关键基因在肾母细胞瘤的发生中有着重要作用,并可能作为潜在治疗靶点及生物标志.     

甲基乙二醛诱导牙周膜成纤维细胞基因表达与分析

运用基因芯片研究甲基乙二醛诱导人牙周膜成纤维细胞基因表达谱的变化。原代培养人牙周膜成纤维细胞,诱导组以终质量浓度为0.1 g/L的甲基乙二醛刺激培养细胞,对照组不含甲基乙二醛。24 h后收获细胞,提取mRNA,逆转录cDNA时用Cy3和Cy5荧光染料标记,制备成cDNA探针,与表达谱芯片进行杂交、扫描和分析。芯片检测结果用实时定量聚合酶链反应验证和生物信息学分析。结果共有18条基因显著差异表达,其中上调基因有11条,下调基因有7条,差异性表达的基因按功能可分为程序性细胞死亡、信号转导、细胞因子、代谢酶类、载体蛋白和未知基因等。与程序性细胞死亡、信号转导和细胞因子相关基因的差异表达可能是甲基乙二醛通过线粒体信号通路,诱导人牙周膜成纤维程序性细胞死亡,破坏牙周组织增生,从而导致牙周病发生的机制。     

Gene expression profiles of the developing human retina

Retinaplaysimportantrolesintheperception,proc-essandtransmissionofvisualsignalsandthefunctionsoftheretinadepend,toalargeextent,onitshighlyorganizedstructure.During3—6weeksinhumanembryogenesis,theneuralectodermgrowsoutfromthediencephalonstoformtheopticvesicleandtheninvaginatestoformtheopticcup.Theouterlayeroftheopticcupbecomesthenon-neuralretinalpigmentepithelium(RPE)andtheinnerlayerbecomestheneuralretina.RPEcellsproliferateslowlyandappeardifferentiatedandpigmentedasearlyas6—8weeksandremain…     

Systemic defense signaling in tomato

The wound-inducible expression of proteinase inhibitors （PIs） genes in tomato provides a powerful model system to elucidate the signal transduction pathway of systemic defense response. An increasing body of evidence indicates that systemin and jasmonic acid （JA） work in the same signaling pathway to activate the expression of Pls and other defense-related genes. However, little is known about how systemin and JA interact to regulate cell to cell communication over long distances. Genetic analysis of the systemin/JA signaling pathway in tomato plants provides a unique opportunity to dissect the mechanism by which peptide and oxylipin signals interact to coordinate systemic expression of defense-related genes. Previously, it has been proposed that systemin is the long-distance mobile signal for systemic expression of defense related genes. However, recent genetic approach provided new evidence that jasmonic acid, rather than systemin, functions as the systemic wound signal, and that the peptide systemin works to regulate the biosynthesis of JA.     

植物盐胁迫的信号传导途径

植物耐盐性研究具有重要意义.近年来,植物盐胁迫信号传导途径一直是植物耐盐性研究的热点.目前已阐明的盐胁迫信号传导途径有酵母和植物中的MAPK(mitogen-actirated protein kinase)途径、拟南芥中缓解离子胁迫的SOS(salt overIy sensitive)途径以及其他蛋白激酶参与的信号传导途径,其中包括钙依赖而钙调素不依赖的蛋白激酶、受体蛋白激酶、糖原合成酶的激酶和组蛋白激酶.因此,植物的耐盐性是个非常复杂的问题,可能是由多种信号分子参与的网络体系.大量转基因实验证明,信号传导途径中的某些组分可改善植物的耐盐性.因此,深入研究植物的盐胁迫信号传导是提高植物耐盐性的前提和基础.     

基于距离相关性的乳腺癌通路串扰研究

乳腺癌(Breast Cancer, BC)作为女性最常见的恶性肿瘤迄今为止起因尚不明确,近年来针对单个基因或单条信号通路(pathway)的研究难以分析疾病的复杂发病机理。考虑到信号传导通路之间普遍存在相互关联和相互串扰的分子生物学特性,本文从基因之间的关联性出发,首先基于互信息(Mutual Information,MI)算法提取出了BC患病和健康对照样本中关联度具有明显变化的基因作为特征基因,在此基础上,基于KEGG通路分析获取特征基因所涉及的信号传导通路,并利用距离相关性(Distance Correlation,DC)算法度量它们之间的串扰关系,最终探寻到26条BC患病前后串扰关系变化较大的通路,通过生物学分析得到：胰岛素信号通路(Insulin signaling pathway)、I型糖尿病信号通路(Type I diabetes mellitus pathway)、核糖体(Ribosome pathway)信号通路等通路间的串扰及特征基因的显著变化对BC的发生和发展具有重要的推动作用,研究结果为探寻BC的致病机理提供了新的思路和有益的支撑。     

Identification of auxin responsive genes in Arabidopsis by cDNA array

The plant hormone auxin influences a variety of developmental and physiological processes. But the mechanism of its action is quite unclear. In order to identify and analyze the expression of auxin responsive genes, a cDNA array approach was used to screen for genes with altered expression from Arabidopsis suspension culture after IAA treatment and was identified 50 differentially expressed genes from 13824 cDNA clones. These genes were related to signal transduction, stress responses, senescence, photosynthesis, protein biosynthesis and transportation. The results provide the molecular evidence that auxin influences a variety of physiological processes and pave a way for further investigation of the mechanism of auxin action. Furthermore,we found that the expression of a ClpC (regulation subunit of Clp protease) was repressed by exogenous auxin, but increased in dark-induced senescing leaves. This suggests that ClpC may be a senescence-associated gene and can be regulated by auxin.     

Expression pattern of GASA,downstream genes of DELLA,in Arabidopsis

Separation and functional research of related components involved in gibberellins （GAs） signaling are important to clarify the mechanism of GA functioning. Research on the downstream components of DELLA, the key factor of the GA signaling pathway, is limited at present. GASA （GA-Stimulated in Arabidopsis） family contains 15 genes usually regulated by GA in Arabidopsis thaliana. All GASA proteins have a cleavable signal peptide in N terminus and a conserved GASA domain including 12 cysteines in C terminus. RT-PCR analysis revealed that the expression of GASA4 and GASA6 were down-regulated, but GASA 1 and GASA9 were up-regulated in the DELLA mutants, gai-t6 and rga-24, as well as the double mutant, consisting with the results that GASA4 and GASA6 were induced, but GASA1 and GASA9 were inhibited by exogenous GA3. In addition, the expression patterns of other GASA genes were regulated by GA and ABA, separately or cooperatively. Most of GASA genes were expressed in roots, stems, leaves, flowers and developing siliques. GUS gene driven by the promoters of GASA6, GASA7, GASA8, GASA9, GASAIO, GASA11 and GASA12were used as reporters and it was found that all GASA genes expressed in the growing and differentiating organs and abscission zones, suggesting the role of these genes in cell growth and differentiation. This study provided an important basis for functional study of the GASA gene family in the GA and ABA signaling pathway.     

基于网络药理学的桑白皮治疗2型糖尿病的作用机制

通过网络药理学和分子对接方法探讨桑白皮治疗2型糖尿病的作用机制。运用中药系统药理学数据库与分析平台筛选桑白皮的活性成分及相应作用靶点,借助DrugBank、GeneCards和TTD数据库检索疾病靶点。活性成分靶点与疾病靶点取交集得到桑白皮作用于2型糖尿病的预测靶点,构建活性成分-潜在靶点网络图和关键靶点蛋白质-蛋白质相互作用(protein protein interaction, PPI)网络。将交集基因进行基因本体(gene ontology, GO)分析和京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes, KEGG)富集分析;最后应用AutoDock软件进行活性成分及关键靶点之间的分子对接验证。预测得到桑白皮活性成分25个,桑白皮与疾病的交集靶点126个。PPI网络发现AKT1、IL-6、TNF、VEGFA、TP53、CASP3等可能是桑白皮治疗2型糖尿病的关键靶点。GO富集分析涉及细胞因子信号转导通路、对脂质的反应和凋亡信号通路等生物过程。KEGG通路分析涉及糖尿病并发症中AGE-RAGE信号通路、IL-17信号通路、T...     

Regulation of mouse blastocyst adhesion,outgrowth and matrix metalloproteinase—2 by focal adhesion kinase

The interaction of extracellular matrix-integrin markedly influences the adhesion,outgrowth,differentiation and expression of serine proteinases by the blastocyst,so it is regarded as a vital factor in blastocyst implantation.Although the mechanism of extracellular interactions between extracellular matrix and integrins has been well elucidated,the roles of the signaling molecules in the extracellular matrix-integrin signal transduction pathway in blastocyst implantation are unknown.This limits the understanding of blastocyst implantation and ECM-integrin signal transduction pathway.In the present study,in vitro blastocyst culture and indirect immunocytochemistry,matrix metalloproteinases(MMPs) zymography and antisense oligodeoxynucleotide(ODN) were used to investigate the expression of a fundamental molecule of integrin-dependent signal transduction pathways,focal adhesion kinase(FAK),in mouse blastocysts and its influence on mouse blastocyst adhesion,outgrowth and MMP-2.The results showed that mouse blastocysts expressed FAK.FAK protein was clustered in the peripheral migrating trophoblast cells and dispersed in the central area of blastocyst outgrowth.Fibronectin triggered pro-MMP-2 and 64kD MMP-2 activities.The antisense ODN to FAK attnuated pro-MMP-2 and 64kD MMP-2 activites which decreased abruptly and tended to disappear with increasting concentrations of the antisense ODN.Both mouse blastocyst adhesion and outgrowth on fibronectin were also influenced by the antisense ODN.Up to 20μg/mL of the antisense ODN concentration,the adhesion and out-growth rates were decreased in a dose-dependent manner.The results indicated that FAK influenced mouse blastocyst adhesion,outgrowth and MMP-2 activity by intracellular signal transduction.In other words,FAK regulates mouse implantation in terms of blastocyst adhesive and invasive abilities.