病原微生物黑胸败血芽孢杆菌（Bacillus bombyseptieus）等诱导家蚕（Bombyx mori）全基因组寄主应答研究
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摘要
在漫长的进化历程中,病原微生物与寄主之间形成了复杂的相互关系。黑胸败血芽孢杆菌(Bacillus bombyseptieus, Bb)是家蚕细菌性败血病的主要病原之一,1931年被分离鉴定。但迄今为止,Bb感染家蚕的分子病理、分子免疫等科学问题从未阐明。与之相似,典型的真菌病原球孢白僵菌(Beauveria bassiana)与家蚕相互作用的分子机制也尚不清楚；虽然BmNPV感染家蚕细胞的研究报道较多,但从个体水平系统分析BmNPV为代表的病毒感染家蚕引起的寄主应答机制也未阐明。
本研究在家蚕基因组信息的基础上,利用Bb感染家蚕的生物模型,主要采用基因芯片技术,探索了Bb感染家蚕后引起的分子病理、免疫应答模式和致病机理。在此基础上,采用同样的方法,比较分析了白僵菌、BmNPV、Bb和E.coli感染家蚕引起的基因表达调控关系。获得的主要结果如下：
(1)家蚕黑胸败血病病原-黑胸败血芽孢杆菌(Bacillus bombyseptieus, Bb),菌体大小为1-1.5μm×2.5-3gm,以单个、多个、短链或长链存在,能产生芽孢和伴孢晶体,添食感染能诱导家蚕死亡。克隆它的16S rRNA基因与NCBI己报道的同源序列比对和进化分析表明,Bb16S rRNA基因进化枝较长,这可能是由于它长期的独立进化所致。在进化关系上,它与蜡状芽孢杆菌(Bacillus cereus)和苏云金芽孢杆菌(Bacillus thuringiensis)的亲缘关系较近,而与炭疽芽孢杆菌(Bacillus anthracis)等种属的亲缘关系较远。
(2)Bb添食感染家蚕能诱导家蚕强烈的寄主应答。在添食后的各个时间点(3h、6h、12h和24 h)，Bb都诱导了大量有功能活性的酶类等编码基因表达,全基因组应答在感染后24 h达到高峰。在Bb诱导家蚕的过程中,大约占基因组17%的基因(2,436个)被诱导表达。KEGG分析发现,Bb诱导了大量基本代谢通路相关基因,包含遗传物质的加工和转录(包括RNA聚合酶和基本转录因子)、核苷酸代谢(包括嘌呤和嘧啶代谢)、外来物质的生物降解(包括2,4-D降解、苯甲酸通过羟基化降解、苯乙烯降解)、氨基酸和氮代谢(包括色氨酸代谢、组氨酸代谢、缬氨酸、亮氨酸和异亮氨酸降解、尿素循环代谢和氨基酸代谢、氨基磷酸酯代谢、氮代谢),以及糖类代谢(包括戊糖和糖醛酸转换、三羧酸循环、丙酮酸代谢、磷酸戊糖途径、丁酸代谢)等多种基本代谢通路相关基因。参与这些基本代谢通路的基因,大部分上调表达,表明在Bb诱导家蚕后,寄主家蚕的物质和能量代谢加速进行,推测这是为了满足家蚕自身生存以及被迫为Bb提供物质和能量的结果。
(3)无论是病毒病原BmNPV,还是真菌病原B.bassiana,都与革兰氏阳性细菌Bb一样,添食感染能引起家蚕强烈的寄主应答。比较这三种病原与非病原菌E.coli的诱导,病原菌的诱导强度更大,在4个时间点的感染过程中,分别有1804、2436和1743个基因被BmNPV、Bb及B.bassiana诱导表达,非病原菌E.coli诱导了912个基因表达,与病原比较相对较少。
基因的表达总是由一系列的转录调控激活,调查在家蚕中鉴定的665个转录因子,Bb诱导的转录因子数量相对最多(68个),B.bassiana和BmNPV次之(分别为60个和56个),E.coli最少(27个),都包含了基本转录因子和其它转录因子。
基因的诱导表达模式分析表明,从转录因子到其它基因表达,病毒BmNPV呈现了与众不同的诱导表达模式,主要表现在诱导的较早期(6h)强烈的寄主应答反应。而其它三种微生物的诱导表达模式比较相似,它们在诱导前中期(3 h-12h)的诱导反应较小,而在诱导后期24 h达到最高峰。
比较四种微生物诱导的基因,它们之间有共通性,也有差异性。在发育相关的信号传导方面,JH、Wnt、MAPK、P53和cell cycle通路相关的生长因子、受体和必须复合物相关基因都在感染过程中不同程度被诱导表达。在基本代谢通路方面,包括-炭库叶酸、组氨酸代谢和色氨酸代谢相关基因被四种微生物都显著诱导,显示对微生物袭击较敏感。病原微生物具有诱导寄主致病的共性,共有7个基本代谢通路相关基因被病原特异诱导,它们是：异源物质的生物降解及代谢(羟基苯甲酸通过羟基化降解)、碳水化合物代谢(丙酮酸代谢)、核苷酸代谢(嘌呤代谢),能量代谢(氮代谢)、氨基酸代谢(尿素循环和氨基酸代谢)及辅因子和维生素代谢(泛酸和辅酶A合成、卟啉和叶绿素代谢),提示这些基本代谢通路对病原感染较敏感。在病理发生相关方面,包括细胞骨架、角质层相关蛋白、呼吸链、金属蛋白酶、蛋白水解酶家族等相关基因被诱导表达。在分子免疫方面,四种微生物不同程度的诱导了家蚕免疫信号识别、信号调节和效应因子等免疫相关基因上调表达,显示能激活家蚕的免疫应答。
(4)对Bb引起的家蚕免疫相关基因分析表明,它可引起家蚕的细胞免疫、多酚氧化酶黑化级联,以及系统性免疫应答。在这些过程中,溶菌酶、凝集素、清道夫受体、铜／锌超氧化物歧化酶、免疫球蛋白超家族、肽聚糖识别蛋白、β-glucan识别蛋白、硫酯蛋白、CLIP丝氨酸蛋白酶、丝氨酸蛋白酶抑制剂(SPNs)、PPO、Toll信号通路JAK/STAT通路、抗菌肽Attacin、Enbocin、Gloverin、Lebocin和Moricin家族的部分基因都被诱导上调表达,提示Bb能引起家蚕较强烈的免疫应答反应。
(5)对Bb感染家蚕的致病机制初步分析表明，Bb感染家蚕的致病性与Bb较相似。推测该模型如下：首先,Bb及其携带的毒素进入家蚕中肠,毒素释放,被寄主中肠的蛋白酶如丝氨酸蛋白酶等所消化激活,破坏家蚕的中肠围食膜,与寄主中肠上皮细胞微绒毛上的APN受体结合,由此进入细胞膜,在细胞上形成孔洞,破坏细胞。最后导致寄主家蚕的渗透平衡和细胞内外物质交换平衡受到破坏；细菌及毒素通过中肠上皮细胞的孔洞进入血淋巴,引起中毒性败血病,最终导致家蚕死亡。
During the long evolutionary history, the relationships between pathogenic microorganisms and their hosts are very complex. Bacillus bombyseptieus (Bb) is one of the major pathogens of the silkworm, which can cause the silkworm bacterial septicemia by natural infection. Although Bb was identified in 1931, the scientific issues about Bb infection the silkworm such as the molecular pathology and molecular immunology of the silkworm host to Bb infection had never been investigated from now on. Similar conditions can be found about typical fungal pathogen Beauveria bassiana and typical virus pathogen BmNPV infection the silkworm. In order to explore the interaction relationships between pathogens and the silkworm, this study used the biological model of Bb oral infection the host silkworm to investigate the silkworm molecular pathology, its immune response patterns and its pathogenesis. Further, the biological models of silkworm pathogens Beauveria bassiana and BmNPV infection the host silkworm were also used to investigate the host-pathogen interactions at the host genome mRNA level. The main results obtained are showed as follows:
(1) Silkworm black-breasted septicemia pathogen Bb is a typical Bacillus, which can produce parasporal crystal and kill the silkworm by oral infection. We cloned a 1.5-kb sequence of its 16S rRNA gene using universal primers. After comparison of the Bb 16S rRNA gene sequence with others in the NCBI database, the resulting phylogenetic tree clearly indicated that Bb belongs to Bacillus with a relatively long branch which might caused by a long-term of independent evolution. The phylogenetic analysis showed that Bb is with closest relationship to Bacillus cereus, close relationship to Bacillus thuringiensis, yet relatively far relationship to Bacillus anthracis and other microbes.
(2) Bb oral infection the silkworm can cause the host strong responses which was involved in almost all silkworm tissues. During the infection (3 h,6 h,12 h and 24 h), totally 2,436 genes showed modulation, which is about 17% of all the silkworm genome genes. At the 24 h time point, the host silkworm showed the strongest response. Genome-wide survey of the host genes demonstrated many genes and pathways modulated after the infection. GO analysis of the induced genes indicated that their functions could be divided into 14 categories. KEGG pathway analysis identified that six types of basal metabolic pathway were regulated, including genetic information processing and transcription, carbohydrate metabolism, amino acid and nitrogen metabolism, nucleotide metabolism, metabolism of cofactors and vitamins, and xenobiotic biodegradation and metabolism.
(3) Regardless of virus pathogen BmNPV or fungal pathogen B.bassiana are like Gram-positive bacteria Bb and they all can cause strong host responses. Totally 1804,2436 and 1743 genes showed regulation after BmNPV, Bb and B.bassiana infection respectively during the course of infection. For the silkworm non-pathogen E.coli infection, totally 912 genes showed regulation, which is relatively a smaller number. Searching the identified 665 transcription factors (TFs) of the silkworm genome, there are 68,60,56 and 27 genes were induced by Bb, B.bassiana, BmNPV and E.coli, respectively. Among the genes induced by four microbes, from TFs to total induced genes, BmNPV showed a distinctive induced expression pattern, which showed strong response at the "earlier" time of infection (6 h). However, for the other three microbes'infection, they showed strong responses at the "later" time point of infection (24 h).
Notably, a lot of genes encode growth factors, receptors and essential components involved in development signaling pathways such as JH, Wnt, MAPK, P53 and cell cycle were modulated after microbes'infection. Major basic metabolic pathways, including genetic information processing and transcription, nucleic acid metabolism, metabolism of cofactors and vitamins, xenobiotics biodegradation and metabolism, amino acid metabolism and nitrogen metabolism, and carbohydrate metabolism illustrated their modulation. Among them three kinds of pathways that related to metabolism of cofactors and vitamins and amino acid metabolism were common induced after four microbes'infection, including one carbon pool by folate, histidine metabolism and tryptophan metabolism, indicating these pathways are very sensitive after microbes'infection. Totally seven pathways can be identified modulation by pathogens BmNPV, B.bombyseptieus and B.bassiana, including xenobiotics biodegradation and metabolism (benzoate degradation via hydroxylation), carbohydrate metabolism (pyruvate metabolism), nucleotide metabolism (purine metabolism), energy metabolism (nitrogen metabolism), amino acid metabolism (urea cycle and metabolism of amino groups), metabolism of Cofactors and vitamins (pantothenate and CoA biosynthesis and porphyrin and chlorophyll metabolism) indicating these pathways are very sensitive for pathogenic microbes'infection. Among the four induced microbes, BmNPV showed 14 specific pathways, which is much more than B.bombyseptieus (3 pathways), B.bassiana (5 pathways) and E.coli (2 pathways), indicating virus pathogen BmNPV leading to a broader level of host metabolic modulation. Gene expression associated with disease pathogenesis such as cytoskeleton, cuticle proteins, respiratory chain, metalloproteases, proteolytic enzymes coding genes were also modulated at different level. In the molecular immune response field, four kinds of microorganisms induced varying degrees of silkworm innate immune related genes up-regulation, such as signal recognition, signal modulation and effectors.
(4) Bb can trigger the host immune responses, including cellular immune response and serine protease cascade melanization response. Real time PCR analysis showed that Bb can induce the silkworm systemic immune response, mainly by the Toll pathway. Anti-microorganism peptides (AMPs), including of Attacin, Lebocin, Enbocin, Gloverin and Moricin families, were upregulated at 24 hours post the infection.
(5) Similar to Bacillus thuringiensis (Bt), Bb can also induce a silkworm poisoning-related response. This model has been speculated as follows:after oral infection, Bb interred the ingestion of silkworm. The parasporal crystal produced by Bb could be digested by silkworm midgut proteases. The digested toxins could pass through the peritrophic membrane to bind the aminopeptidase N receptors (APNs) of the midgut epithelial cells to damage them. Bb can go to the silkworm hemolymph from the damaged midgut and finally caused the silkworm toxic septicemia.
本研究在家蚕基因组信息的基础上,利用Bb感染家蚕的生物模型,主要采用基因芯片技术,探索了Bb感染家蚕后引起的分子病理、免疫应答模式和致病机理。在此基础上,采用同样的方法,比较分析了白僵菌、BmNPV、Bb和E.coli感染家蚕引起的基因表达调控关系。获得的主要结果如下：
(1)家蚕黑胸败血病病原-黑胸败血芽孢杆菌(Bacillus bombyseptieus, Bb),菌体大小为1-1.5μm×2.5-3gm,以单个、多个、短链或长链存在,能产生芽孢和伴孢晶体,添食感染能诱导家蚕死亡。克隆它的16S rRNA基因与NCBI己报道的同源序列比对和进化分析表明,Bb16S rRNA基因进化枝较长,这可能是由于它长期的独立进化所致。在进化关系上,它与蜡状芽孢杆菌(Bacillus cereus)和苏云金芽孢杆菌(Bacillus thuringiensis)的亲缘关系较近,而与炭疽芽孢杆菌(Bacillus anthracis)等种属的亲缘关系较远。
(2)Bb添食感染家蚕能诱导家蚕强烈的寄主应答。在添食后的各个时间点(3h、6h、12h和24 h)，Bb都诱导了大量有功能活性的酶类等编码基因表达,全基因组应答在感染后24 h达到高峰。在Bb诱导家蚕的过程中,大约占基因组17%的基因(2,436个)被诱导表达。KEGG分析发现,Bb诱导了大量基本代谢通路相关基因,包含遗传物质的加工和转录(包括RNA聚合酶和基本转录因子)、核苷酸代谢(包括嘌呤和嘧啶代谢)、外来物质的生物降解(包括2,4-D降解、苯甲酸通过羟基化降解、苯乙烯降解)、氨基酸和氮代谢(包括色氨酸代谢、组氨酸代谢、缬氨酸、亮氨酸和异亮氨酸降解、尿素循环代谢和氨基酸代谢、氨基磷酸酯代谢、氮代谢),以及糖类代谢(包括戊糖和糖醛酸转换、三羧酸循环、丙酮酸代谢、磷酸戊糖途径、丁酸代谢)等多种基本代谢通路相关基因。参与这些基本代谢通路的基因,大部分上调表达,表明在Bb诱导家蚕后,寄主家蚕的物质和能量代谢加速进行,推测这是为了满足家蚕自身生存以及被迫为Bb提供物质和能量的结果。
(3)无论是病毒病原BmNPV,还是真菌病原B.bassiana,都与革兰氏阳性细菌Bb一样,添食感染能引起家蚕强烈的寄主应答。比较这三种病原与非病原菌E.coli的诱导,病原菌的诱导强度更大,在4个时间点的感染过程中,分别有1804、2436和1743个基因被BmNPV、Bb及B.bassiana诱导表达,非病原菌E.coli诱导了912个基因表达,与病原比较相对较少。
基因的表达总是由一系列的转录调控激活,调查在家蚕中鉴定的665个转录因子,Bb诱导的转录因子数量相对最多(68个),B.bassiana和BmNPV次之(分别为60个和56个),E.coli最少(27个),都包含了基本转录因子和其它转录因子。
基因的诱导表达模式分析表明,从转录因子到其它基因表达,病毒BmNPV呈现了与众不同的诱导表达模式,主要表现在诱导的较早期(6h)强烈的寄主应答反应。而其它三种微生物的诱导表达模式比较相似,它们在诱导前中期(3 h-12h)的诱导反应较小,而在诱导后期24 h达到最高峰。
比较四种微生物诱导的基因,它们之间有共通性,也有差异性。在发育相关的信号传导方面,JH、Wnt、MAPK、P53和cell cycle通路相关的生长因子、受体和必须复合物相关基因都在感染过程中不同程度被诱导表达。在基本代谢通路方面,包括-炭库叶酸、组氨酸代谢和色氨酸代谢相关基因被四种微生物都显著诱导,显示对微生物袭击较敏感。病原微生物具有诱导寄主致病的共性,共有7个基本代谢通路相关基因被病原特异诱导,它们是：异源物质的生物降解及代谢(羟基苯甲酸通过羟基化降解)、碳水化合物代谢(丙酮酸代谢)、核苷酸代谢(嘌呤代谢),能量代谢(氮代谢)、氨基酸代谢(尿素循环和氨基酸代谢)及辅因子和维生素代谢(泛酸和辅酶A合成、卟啉和叶绿素代谢),提示这些基本代谢通路对病原感染较敏感。在病理发生相关方面,包括细胞骨架、角质层相关蛋白、呼吸链、金属蛋白酶、蛋白水解酶家族等相关基因被诱导表达。在分子免疫方面,四种微生物不同程度的诱导了家蚕免疫信号识别、信号调节和效应因子等免疫相关基因上调表达,显示能激活家蚕的免疫应答。
(4)对Bb引起的家蚕免疫相关基因分析表明,它可引起家蚕的细胞免疫、多酚氧化酶黑化级联,以及系统性免疫应答。在这些过程中,溶菌酶、凝集素、清道夫受体、铜／锌超氧化物歧化酶、免疫球蛋白超家族、肽聚糖识别蛋白、β-glucan识别蛋白、硫酯蛋白、CLIP丝氨酸蛋白酶、丝氨酸蛋白酶抑制剂(SPNs)、PPO、Toll信号通路JAK/STAT通路、抗菌肽Attacin、Enbocin、Gloverin、Lebocin和Moricin家族的部分基因都被诱导上调表达,提示Bb能引起家蚕较强烈的免疫应答反应。
(5)对Bb感染家蚕的致病机制初步分析表明，Bb感染家蚕的致病性与Bb较相似。推测该模型如下：首先,Bb及其携带的毒素进入家蚕中肠,毒素释放,被寄主中肠的蛋白酶如丝氨酸蛋白酶等所消化激活,破坏家蚕的中肠围食膜,与寄主中肠上皮细胞微绒毛上的APN受体结合,由此进入细胞膜,在细胞上形成孔洞,破坏细胞。最后导致寄主家蚕的渗透平衡和细胞内外物质交换平衡受到破坏；细菌及毒素通过中肠上皮细胞的孔洞进入血淋巴,引起中毒性败血病,最终导致家蚕死亡。
During the long evolutionary history, the relationships between pathogenic microorganisms and their hosts are very complex. Bacillus bombyseptieus (Bb) is one of the major pathogens of the silkworm, which can cause the silkworm bacterial septicemia by natural infection. Although Bb was identified in 1931, the scientific issues about Bb infection the silkworm such as the molecular pathology and molecular immunology of the silkworm host to Bb infection had never been investigated from now on. Similar conditions can be found about typical fungal pathogen Beauveria bassiana and typical virus pathogen BmNPV infection the silkworm. In order to explore the interaction relationships between pathogens and the silkworm, this study used the biological model of Bb oral infection the host silkworm to investigate the silkworm molecular pathology, its immune response patterns and its pathogenesis. Further, the biological models of silkworm pathogens Beauveria bassiana and BmNPV infection the host silkworm were also used to investigate the host-pathogen interactions at the host genome mRNA level. The main results obtained are showed as follows:
(1) Silkworm black-breasted septicemia pathogen Bb is a typical Bacillus, which can produce parasporal crystal and kill the silkworm by oral infection. We cloned a 1.5-kb sequence of its 16S rRNA gene using universal primers. After comparison of the Bb 16S rRNA gene sequence with others in the NCBI database, the resulting phylogenetic tree clearly indicated that Bb belongs to Bacillus with a relatively long branch which might caused by a long-term of independent evolution. The phylogenetic analysis showed that Bb is with closest relationship to Bacillus cereus, close relationship to Bacillus thuringiensis, yet relatively far relationship to Bacillus anthracis and other microbes.
(2) Bb oral infection the silkworm can cause the host strong responses which was involved in almost all silkworm tissues. During the infection (3 h,6 h,12 h and 24 h), totally 2,436 genes showed modulation, which is about 17% of all the silkworm genome genes. At the 24 h time point, the host silkworm showed the strongest response. Genome-wide survey of the host genes demonstrated many genes and pathways modulated after the infection. GO analysis of the induced genes indicated that their functions could be divided into 14 categories. KEGG pathway analysis identified that six types of basal metabolic pathway were regulated, including genetic information processing and transcription, carbohydrate metabolism, amino acid and nitrogen metabolism, nucleotide metabolism, metabolism of cofactors and vitamins, and xenobiotic biodegradation and metabolism.
(3) Regardless of virus pathogen BmNPV or fungal pathogen B.bassiana are like Gram-positive bacteria Bb and they all can cause strong host responses. Totally 1804,2436 and 1743 genes showed regulation after BmNPV, Bb and B.bassiana infection respectively during the course of infection. For the silkworm non-pathogen E.coli infection, totally 912 genes showed regulation, which is relatively a smaller number. Searching the identified 665 transcription factors (TFs) of the silkworm genome, there are 68,60,56 and 27 genes were induced by Bb, B.bassiana, BmNPV and E.coli, respectively. Among the genes induced by four microbes, from TFs to total induced genes, BmNPV showed a distinctive induced expression pattern, which showed strong response at the "earlier" time of infection (6 h). However, for the other three microbes'infection, they showed strong responses at the "later" time point of infection (24 h).
Notably, a lot of genes encode growth factors, receptors and essential components involved in development signaling pathways such as JH, Wnt, MAPK, P53 and cell cycle were modulated after microbes'infection. Major basic metabolic pathways, including genetic information processing and transcription, nucleic acid metabolism, metabolism of cofactors and vitamins, xenobiotics biodegradation and metabolism, amino acid metabolism and nitrogen metabolism, and carbohydrate metabolism illustrated their modulation. Among them three kinds of pathways that related to metabolism of cofactors and vitamins and amino acid metabolism were common induced after four microbes'infection, including one carbon pool by folate, histidine metabolism and tryptophan metabolism, indicating these pathways are very sensitive after microbes'infection. Totally seven pathways can be identified modulation by pathogens BmNPV, B.bombyseptieus and B.bassiana, including xenobiotics biodegradation and metabolism (benzoate degradation via hydroxylation), carbohydrate metabolism (pyruvate metabolism), nucleotide metabolism (purine metabolism), energy metabolism (nitrogen metabolism), amino acid metabolism (urea cycle and metabolism of amino groups), metabolism of Cofactors and vitamins (pantothenate and CoA biosynthesis and porphyrin and chlorophyll metabolism) indicating these pathways are very sensitive for pathogenic microbes'infection. Among the four induced microbes, BmNPV showed 14 specific pathways, which is much more than B.bombyseptieus (3 pathways), B.bassiana (5 pathways) and E.coli (2 pathways), indicating virus pathogen BmNPV leading to a broader level of host metabolic modulation. Gene expression associated with disease pathogenesis such as cytoskeleton, cuticle proteins, respiratory chain, metalloproteases, proteolytic enzymes coding genes were also modulated at different level. In the molecular immune response field, four kinds of microorganisms induced varying degrees of silkworm innate immune related genes up-regulation, such as signal recognition, signal modulation and effectors.
(4) Bb can trigger the host immune responses, including cellular immune response and serine protease cascade melanization response. Real time PCR analysis showed that Bb can induce the silkworm systemic immune response, mainly by the Toll pathway. Anti-microorganism peptides (AMPs), including of Attacin, Lebocin, Enbocin, Gloverin and Moricin families, were upregulated at 24 hours post the infection.
(5) Similar to Bacillus thuringiensis (Bt), Bb can also induce a silkworm poisoning-related response. This model has been speculated as follows:after oral infection, Bb interred the ingestion of silkworm. The parasporal crystal produced by Bb could be digested by silkworm midgut proteases. The digested toxins could pass through the peritrophic membrane to bind the aminopeptidase N receptors (APNs) of the midgut epithelial cells to damage them. Bb can go to the silkworm hemolymph from the damaged midgut and finally caused the silkworm toxic septicemia.
引文
1. Isabelle Vallet-Gely BLaFB:Bacterial strategies to overcome insect defences.2008.
2. Acosta Muniz C, Jaillard D, Lemaitre B, Boccard F:Erwinia carotovora Evf antagonizes the elimination of bacteria in the gut of Drosophila larvae. Cell Microbiol 2007,9(l):106-119.
3. Grkovic S, Glare, T. R., Jackson, T. A.& Corbett, G. E.:Genes essential for amber disease in grass grubs are located on the large plasmid found in Serratia entomophila and Serratia proteamaculans ApplEnviron Microbiol 1995.
4. Hinnebusch BJea:Role of Yersinia murine toxin in survival of Yersinia pestis in the midgut of the flea vector. Science 2002.
5. Hinnebusch BJ, Perry, R. D.& Schwan, T. G.:Role of the Yersinia pestis hemin storage (hms) locus in the transmission of plague by fleas. Science 1996.
6. Liehl P, Blight M, Vodovar N, Boccard F, Lemaitre B:Prevalence of local immune response against oral infection in a Drosophila/Pseudomonas infection model. PLoS Pathog 2006, 2(6):e56.
7. 罗海波,鲍行豪主编：细菌毒素研究进展.1983：1-28.
8. Bravo A, Gill SS, Soberon M:Mode of action of Bacillus thuringiensis Cry and Cyt toxins and their potential for insect control. Toxicon 2007,49(4):423-435.
9. de Maagd RA, Bravo, A., Berry, C., Crickmore, N.& Schnepf, H. E.:Structure, diversity, and evolution of protein toxins from spore-forming entomopathogenic bacteria. Annu Rev Genet 2003.
10. Schnepf E, Crickmore N, Van Rie J, Lereclus D, Baum J, Feitelson J, Zeigler DR, Dean DH: Bacillus thuringiensis and its pesticidal crystal proteins. Microbiol Mol Biol Rev 1998, 62(3):775-806.
11. Aronson AI, Shai Y:Why Bacillus thuringiensis insecticidal toxins are so effective:unique features of their mode of action. FEMS Microbiol Lett 2001,195(1):1-8.
12. Charles JF, Silva-Filha, M.-H.& Nielsen-LeRoux, C.:in Entomopathogenic Bacteria:From Laboratory to Field Application 2000:237-252.
13. Bowen Dea:nsecticidal toxins from the bacterium Photorhabdus luminescens. Science 1998.
14. Morgan JA, Sergeant, M., Ellis, D., Ousley, M.&Jarrett, P.:Sequence analysis of insecticidal genes from Xenorhabdus nematophilus PMFI296. Appl Environ Microbiol Mol Biol Rev 2001.
15. Daborn PJea:A single Photorhabdus gene,makes caterpillars floppy (mcf), allows Escherichia coli to persist within and kill insects. Proc Natl Acad Sci USA 99 2002.
16. Duchaud Eea:The genome sequence of the entomopathogenic bacterium Photorhabdus luminescens. Nature Biotechnol 2003.
17. Matsumoto K:Role of bacterial proteases in pseudomonal and serratial keratitis. Biol Chem 2004.
18. Lee DH, Cha IH, Woo DS, Ohba M:Microbial ecology of Bacillus thuringiensis:fecal populations recovered from wildlife in Korea. Can J Microbiol 2003,49(7):465-471.
19. Travis J, Potempa, J.& Maeda, H.:Are bacterial proteinases pathogenic factors?. Trends Microbiol 1995.
20. ffrench-Constant Rea:Photorhabdus:towards a functional genomic analysis of a symbiont and pathogen. FEMS Microbiol Rev 2003.
21. Vodovar Nea:Complete genome sequence of the entomopathogenic and metabolically versatile soil bacterium Pseudomonas entomophila. Nature Biotechnol 2006.
22. Derzelle Sea:The PhoP/PhoQ two-component regulatory system of Photorhabdus luminescens is essential for virulence in insects. J Bacteriol 2004.
23. Cowles KN, Cowles, C. E., Richards, G. R., Martens,, E. C.& Goodrich-Blair H:The global regulator Lrp contributes to mutualism, pathogenesis and phenotypic variation in the bacterium Xenorhabdus nematophila Cell Microbiol 2007.
24. Salamitou Sea:The plcR regulon is involved in the opportunistic properties of Bacillus thuringiensis and Bacillus cereus in mice and insects. Microbiology 2000.
25. Basset A, Tzou P, Lemaitre B, Boccard F:A single gene that promotes interaction of a phytopathogenic bacterium with its insect vector, Drosophila melanogaster. EMBO Rep 2003,4(2):205-209.
26. Hoffmann BLaJ:The Host Defense of Drosophila melanogaster. Annu Rev Immunol 2007 2007.
27. Vallet-Gely I, Lemaitre B, Boccard F:Bacterial strategies to overcome insect defences. Nat Rev Microbiol 2008,6(4):302-313.
28. Ha EM OC, Bae YS, LeeWJ.:A direct role for dual oxidase in Drosophila gut immunity. Science 2005.
29. Ha EM OC, Ryu JH, Bae YS, Kang SW, et al.:An antioxidant systemrequired for host protection against gut infection in Drosophila. Dev Cell 2005.
30. Vodovar Nea:Drosophila host defense after oral infection by an entomopathogenic Pseudomonas species. Proc Natl Acad Sci USA 2005.
31. Nehme NT, Liegeois S, Kele B, Giammarinaro P, Pradel E, Hoffmann JA, Ewbank JJ, Ferrandon D:A model of bacterial intestinal infections in Drosophila melanogaster. PLoS Pathog 2007, 3(11):e173.
32. Ryu JHea:An essential complementary role of NF-κB pathway to microbicidal oxidants in Drosophila gut immunity.. EMBO J 2006.
33. Brennan CAA, K. V.:Drosophila:the genetics of innate immune recognition and response. Annu Rev Immunol 2004.
34. Mellroth P KJ, Steiner H.:A scavenger function for a Drosophila peptido-glycan recognition protein. J Biol Chem 2003.
35. Mellroth P S:PGRP-SB1:an N-acetylmuramoyl 1-alanine amidase with antibacterial activity. Biochem Biophys Res Commun 2006.
36. Michel T RJ, Hoffmann JA, Royet J.:Drosophila Toll is activated by Gram-positive bacteria through a circulating peptidoglycan recognition protein. Nature 2001.
37. GobertV G, Matskevich AA,Rutschmann S,Royet J, et al.:Dual activation of theDrosophilaToll pathway by two pattern recognition receptors. Science 2003.
38. Pili-Floury S LF, Takahashi K, Saigo K, Samain E, et al.:In vivo RNAi analysis reveals an unexpected role for GNBP1 in the defense against Gram-positive bacterial infection in Drosophila adults. J Biol Chem 2004.
39. Bischoff V VC, Boneca IG, Michel T, Hoffmann JA, Royet J.:Function of theDrosophila pattern-recognition receptor PGRP-SDin the detection ofGram-positive bacteria. Nat Immunol 2004.
40. Gottar M, Gobert V, Michel T, Belvin M, Duyk G, Hoffmann JA, Ferrandon D, Royet J:The Drosophila immune response against Gram-negative bacteria is mediated by a peptidoglycan recognition protein. Nature 2002,416(6881):640-644.
41. KanekoT Y, AggarwalK, LimJH,UedaK, et al.:PGRP-LCand PGRP-LE have essential yet distinct functions in the Drosophila immune response to monomeric DAP-type peptidoglycan. Nat Immunol 2006.
42. Leulier F PC, Pili-Floury S, Ryu JH, Caroff M, et al.:The Drosophila immune systemdetects bacteria through specific peptidoglycan recognition. Nat Immunol 2003.
43. Rizki T RR, Grell E.:A mutant affecting the crystal cells in Drosophila melanogaster. Roux's Arch Dev Biol 1980.
44. Ramet M PA, Manfruelli P, Li X, Koziel H, et al.:Drosophila scavenger receptor CI is a pattern recognition receptor for bacteria. Immunity 2001.
45. Kocks C CJ, NehmeN, Ulvila J, Pearson AM, et al.:Eater, a transmembrane protein mediating phagocytosis of bacterial pathogens in Drosophila. Cell 2005.
46. Watson FL P-HR, Thomas F, Lamar DL, Hughes M, et al.:Extensive diversity of Ig-superfamily proteins in the immune system of insects. Science 2005.
47. M. M:Blood cells of Drosophila:cell lineages and role in host defense. CurrOpin Immunol 2004.
48. Nappi AJ VE:Melanogenesis and the generation of cytotoxic molecules during insect cellular immune reactions. Pigment Cell Res 1993.
49. M. A:The prophenoloxidase cascade in insect immunity. Res Immunol 1990.
50. S(?) oderh(?)all K CL:Role of prophenoloxidase-activating system in invertebrate immunity. Curr Opin Immunol 1998.
51. Ochiai M AM:A pattern recognition protein for peptidoglycan. Cloning the cDNA and the gene of the silkworm, Bombyx mori. J Biol Chem 1999.
52. Ochiai M AM:A pattern-recognition protein for β-1,3-glucan. The binding domain and the cDNA cloning of β-1,3-glucan recognition protein from the silkworm,Bombyx mori. J Biol Chem 2000.
53. Ma C KM:A β1,3-glucan recognition protein from an insect, Manduca sexta, agglutinates microorganisms and activates the phenoloxidase cascade. JBiol Chem 2000.
54. Lee MH OT, Lee JY, Baek MJ, Zhang R, et al.:Peptidoglycan recognition proteins involved in 1,3-β-D-glucan-dependent prophenoloxidase activation system of insect. J Biol Chem 2003.
55. Kinoshita T, Inoue K:Bactericidal activity of the normal, cell-free hemolymph of silkworms (Bombyx mori). Infect Immun 1977,16(1):32-36.
56. Suzuki T, Natori S:Identification of a protein having hemagglutinating activity in the hemolymph of the silkworm, Bombyx mori. J Biochem 1983,93(2):583-590.
57. Ochiai M, Ashida M:Purification of a beta-1,3-glucan recognition protein in the prophenoloxidase activating system from hemolymph of the silkworm, Bombyx mori. J Biol Chem 1988,263(24):12056-12062.
58. Morishima I, Suginaka S, Ueno T, Hirano H:Isolation and structure of cecropins, inducible antibacterial peptides, from the silkworm, Bombyx mori. Comp Biochem Physiol B 1990, 95(3):551-554.
59. Ochiai M, Niki T, Ashida M:Immunocytochemical localization of beta-1,3-glucan recognition protein in the silkworm, Bombyx mori. Cell Tissue Res 1992,268(3):431-437.
60. Ochiai M, Ashida M:A pattern recognition protein for peptidoglycan. Cloning the cDNA and the gene of the silkworm, Bombyx mori. J Biol Chem 1999,274(17):11854-11858.
61. Yoshida H, Kinoshita K, Ashida M:Purification of a peptidoglycan recognition protein from hemolymph of the silkworm, Bombyx mori. J Biol Chem 1996,271(23):13854-13860.
62. Iketani M, Nishimura H, Akayama K, Yamano Y, Morishima I:Minimum structure of peptidoglycan required for induction of antibacterial protein synthesis in the silkworm, Bombyx mori. Insect Biochem Mol Biol 1999,29(1):19-24.
63. Lee WJ, Lee JD, Kravchenko VV, Ulevitch RJ, Brey PT:Purification and molecular cloning of an inducible gram-negative bacteria-binding protein from the silkworm, Bombyx mori. Proc Natl Acad Sci U S A 1996,93(15):7888-7893.
64. Sumida M, Ichimori H, Johchi S, Takaoka A, Yuhki T, Mori H, Matsubara F:Antibacterial activity inducible in the haemolymph of the silkworm, Bombyx mori, by injection of formalin-treated Escherichia coli K-12 during the fifth larval instar and pharate adult development. Comp Biochem Physiol B 1992,101(1-2):165-171.
65. Sumida M, Ichimori H, Yuhki T, Mori H, Matsubara F:Induction of antibacterial activity in the haemolymph of the silkworm, Bombyx mori, by injection of formalin-treated Escherichia coli K-12 in the anterior and posterior body part of the ligated larvae. Comp Biochem Physiol B 1992,101(1-2):173-178.
66. Brey PT, Lee WJ, Yamakawa M, Koizumi Y, Perrot S, Francois M, Ashida M:Role of the integument in insect immunity:epicuticular abrasion and induction of cecropin synthesis- in cuticular epithelial cells. Proc Natl Acad Sci U S A 1993,90(13):6275-6279.
67. Chowdhury S, Taniai K, Hara S, Kadono-Okuda K, Kato Y, Yamamoto M, Xu J, Choi SK, Debnath NC, Choi HK et al:cDNA cloning and gene expression of lebocin, a novel member of antibacterial peptides from the silkworm, Bombyx mori. Biochem Biophys Res Commun 1995,214(1):271-278.
68. Hara S, Yamakawa M:Moricin, a novel type of antibacterial peptide isolated from the silkworm, Bombyx mori. J Biol Chem 1995,270(50):29923-29927.
69. Hara S, Yamakawa M:A novel antibacterial peptide family isolated from the silkworm, Bombyx mori. Biochem J 1995,310 (Pt 2):651-656.
70. Hara S, Yamakawa M:Production in Escherichia of moricin, a novel type antibacterial peptide from the silkworm, Bombyx mori. Biochem Biophys Res Commun 1996, 220(3):664-669.
71. Morishima I, Horiba T, Iketani M, Nishioka E, Yamano Y:Parallel induction of cecropin and lysozyme in larvae of the silkworm, Bombyx mori. Dev Comp Immunol 1995,19(5):357-363.
72. Morishima I, Yamano Y, Inoue K, Matsuo N:Eicosanoids mediate induction of immune genes in the fat body of the silkworm, Bombyx mori. FEBS Lett 1997,419(1):83-86.
73. Furukawa S, Taniai K, Ishibashi J, Hara S, Shono T, Yamakawa M:A novel member of lebocin gene family from the silkworm, Bombyx mori. Biochem Biophys Res Commun 1997, 238(3):769-774.
74. Taniai K, Wago H, Yamakawa M:In vitro phagocytosis of Escherichia coli and release of lipopolysaccharide by adhering hemocytes of the silkworm, Bombyx mori. Biochem Biophys Res Commun 1997,231(3):623-627.
75. Yamano Y, Matsumoto M, Sasahara K, Sakamoto E, Morishima I:Structure of genes for cecropin A and an inducible nuclear protein that binds to the promoter region of the genes from the silkworm, Bombyx mori. Biosci Biotechnol Biochem 1998,62(2):237-241.
76. Furukawa S, Tanaka H, Nakazawa H, Ishibashi J, Shono T, Yamakawa M:Inducible gene expression of moricin, a unique antibacterial peptide from the silkworm (Bombyx mori). Biochem J 1999,340 (Pt 1):265-271.
77. Furukawa S, Taniai K, Yang J, Shono T, Yamakawa M:Induction of gene expression of antibacterial proteins by chitin oligomers in the silkworm, Bombyx mori. Insect Mol Biol 1999,8(1):145-148.
78. Yang J, Furukawa S, Sagisaka A, Ishibashi J, Taniai K, Shono T, Yamakawa M:cDNA cloning and gene expression of cecropin D, an antibacterial protein in the silkworm, Bombyx mori. Comp Biochem Physiol B Biochem Mol Biol 1999,122(4):409-414.
79. Kotani E, Yamakawa M, Iwamoto S, Tashiro M, Mori H, Sumida M, Matsubara F, Taniai K, Kadono-Okuda K, Kato Y et al: Cloning and expression of the gene of hemocytin, an insect humoral lectin which is homologous with the mammalian von Willebrand factor. Biochim Biophys Acta 1995,1260(3):245-258.
80. Lee WJ, Brey PT:Isolation and characterization of the lysozyme-encoding gene from the silkworm Bombyx mori. Gene 1995,161(2):199-203.
81. Koizumi N, Morozumi A, Imamura M, Tanaka E, Iwahana H, Sato R: Lipopolysaccharide-binding proteins and their involvement in the bacterial clearance from the hemolymph of the silkworm Bombyx mori. Eur J Biochem 1997,248(1):217-224.
82. Koizumi N, Imamura M, Kadotani T, Yaoi K, Iwahana H, Sato R:The lipopolysaccharide-binding protein participating in hemocyte nodule formation in the silkworm Bombyx mori is a novel member of the C-type lectin superfamily with two different tandem carbohydrate-recognition domains. FEBS Lett 1999,443(2):139-143.
83. Cheng T, Zhao P, Liu C, Xu P, Gao Z, Xia Q, Xiang Z:Structures, regulatory regions, and inductive expression patterns of antimicrobial peptide genes in the silkworm Bombyx mori. Genomics 2006,87(3):356-365.
84. Hong SM, Kusakabe T, Lee JM, Tatsuke T, Kawaguchi Y, Kang MW, Kang SW, Kim KA, Nho SK:Structure and expression analysis of the cecropin-E gene from the silkworm, Bombyx mori. Biosci Biotechnol Biochem 2008,72(8):1992-1998.
85. Kaneko Y, Tanaka H, Ishibashi J, Iwasaki T, Yamakawa M:Gene expression of a novel defensin antimicrobial peptide in the silkworm, Bombyx mori. Biosci Biotechnol Biochem 2008,72(9):2353-2361.
86. Kawaoka S, Katsuma S, Daimon T, Isono R, Omuro N, Mita K, Shimada T:Functional analysis of four Gloverin-like genes in the silkworm, Bombyx mori. Arch Insect Biochem Physiol 2008,67(2):87-96.
87. Hemmi H, Ishibashi J, Hara S, Yamakawa M:Solution structure of moricin, an antibacterial peptide, isolated from the silkworm Bombyx mori. FEBS Lett 2002,518(1-3):33-38.
88. Wen H, Lan X, Cheng T, He N, Shiomi K, Kajiura Z, Zhou Z, Xia Q, Xiang Z, Nakagaki M: Sequence structure and expression pattern of a novel anionic defensin-like gene from silkworm (Bombyx mori). Mol Biol Rep 2009,36(4):711-716.
89. 刘忠渊金,郑树涛,徐涛,张富春：新疆家蚕抗菌肽抗菌作用的超微结构观察及抗菌机理初探.动物学杂志2008,43(2)：14-20.
90. 孙伟沈,向仲怀,张泽：家蚕抗菌肽基因研究进展.蚕业科学2009，35(1)：196-203.
91. Ochiai M, Ashida M:A pattern-recognition protein for beta-1,3-glucan. The binding domain and the cDNA cloning of beta-1,3-glucan recognition protein from the silkworm, Bombyx mori. JBiol Chem 2000,275(7):4995-5002.
92. Prasad MD, Han SJ, Nagaraju J, Lee WJ, Brey PT:Cloning and characterization of an eukaryotic initiation factor-2alpha kinase from the silkworm, Bombyx mori. Biochim Biophys Acta 2003,1628(1):56-63.
93. Hyrsl P, Ciz M, Kubala L, Lojek A:Silkworm (Bombyx mori) hemocytes do not produce reactive oxygen metabolites as a part of defense mechanisms. Folia Microbiol (Praha) 2004, 49(3):315-319.
94. Kim I, Kim SH, Lee YS, Yun EK, Lee HS, Kim JW, Ryu KS, Kang PD, Lee IH:Immune stimulation in the silkworm, Bombyx mori L., by CpG oligodeoxynucleotides. Arch Insect Biochem Physiol 2004,55(1):43-48.
95. Tanaka H, Sagisaka A, Fujita K, Kaneko Y, Imanishi S, Yamakawa M:Lipopolysaccharide elicits expression of immune-related genes in the silkworm, Bombyx mori. Insect Mol Biol 2009,18(1):71-75.
96. Tanaka H, Suzuki N, Nakajima Y, Sato M, Sagisaka A, Fujita K, Ishibashi J, Imanishi S, Mita K, Yamakawa M:Expression profiling of novel bacteria-induced genes from the silkworm, Bombyx mori. Arch Insect Biochem Physiol,73(3):148-162.
97. Imamura M, Yang J, Yamakawa M:cDNA cloning, characterization and gene expression of nitric oxide synthase from the silkworm, Bombyx mori. Insect Mol Biol 2002, 11(3):257-265.
98. Hu ZG, Chen KP, Yao Q, Gao GT, Xu JP, Chen HQ:Cloning and characterization of Bombyx mori PP-BP a gene induced by viral infection. Yi ChuanXue Bao 2006,33(11):975-983.
99. Wang Y, Cheng T, Rayaprolu S, Zou Z, Xia Q, Xiang Z, Jiang H:Proteolytic activation of pro-spatzle is required for the induced transcription of antimicrobial peptide genes in lepidopteran insects. Dev Comp Immunol 2007,31(10):1002-1012.
100. Cheng TC, Zhang YL, Liu C, Xu PZ, Gao ZH, Xia QY, Xiang ZH:Identification and analysis of Toll-related genes in the domesticated silkworm, Bombyx mori. Dev Comp Immunol 2008, 32(5):464-475.
101. Imamura M, Yamakawa M:Molecular cloning and expression of a Toll receptor gene homologue from the silkworm, Bombyx mori. Biochim Biophys Acta 2002,1576(3):246-254.
102. Wu S, Zhang X, Chen X, Cao P, Beerntsen BT, Ling E:BmToll9, an Arthropod conservative Toll, is likely involved in the local gut immune response in the silkworm, Bombyx mori. Dev Comp Immunol,34(2):93-96.
103. Tanaka H, Yamamoto M, Moriyama Y, Yamao M, Furukawa S, Sagisaka A, Nakazawa H, Mori H, Yamakawa M:A novel Rel protein and shortened isoform that differentially regulate antibacterial peptide genes in the silkworm Bombyx mori. Biochim Biophys Acta 2005, 1730(1):10-21.
104. Tanaka H, Sagisaka A, Nakajima Y, Fujita K, Imanishi S, Yamakawa M:Correlation of differential expression of silkworm antimicrobial Peptide genes with different amounts of rel family proteins and their gene transcriptional activity. Biosci Biotechnol Biochem 2009, 73(3):599-606.
105. Tanaka H, Matsuki H, Furukawa S, Sagisaka A, Kotani E, Mori H, Yamakawa M:Identification and functional analysis of Relish homologs in the silkworm, Bombyx mori. Biochim Biophys Acta 2007,1769(9-10):559-568.
106. Kaneko Y, Furukawa S, Tanaka H, Yamakawa M:Expression of antimicrobial peptide genes encoding Enbocin and Gloverin isoforms in the silkworm, Bombyx mori. Biosci Biotechnol Biochem 2007,71(9):2233-2241.
107. Xia Q, Zhou Z, Lu C, Cheng D, Dai F, Li B, Zhao P, Zha X, Cheng T, Chai C et al: A draft sequence for the genome of the domesticated silkworm (Bombyx mori). Science 2004, 306(5703):1937-1940.
108.程廷才：家蚕免疫系统相关基因的鉴定及其诱导表达模式研究.博士学位论文2008.
109. Tanaka H, Ishibashi J, Fujita K, Nakajima Y, Sagisaka A, Tomimoto K, Suzuki N, Yoshiyama M, Kaneko Y, Iwasaki T et al: A genome-wide analysis of genes and gene families involved in innate immunity of Bombyx mori. Insect Biochem Mol Biol 2008,38(12):1087-1110.
110. Nakahara Y, Kanamori Y, Kiuchi M, Kamimura M:Effects of silkworm paralytic peptide on in vitro hematopoiesis and plasmatocyte spreading. Arch Insect Biochem Physiol 2003, 52(4):163-174.
111. Nakahara Y, Shimura S, Ueno C, Kanamori Y, Mita K, Kiuchi M, Kamimura M:Purification and characterization of silkworm hemocytes by flow cytometry. Dev Comp Immunol 2009, 33(4):439-448.
112. Kaito C, Akimitsu N, Watanabe H, Sekimizu K:Silkworm larvae as an animal model of bacterial infection pathogenic to humans. Microb Pathog 2002,32(4):183-190.
113. Liu F, Ling E, Wu S:Gene expression profiling during early response to injury and microbial challenges in the silkworm, Bombyx mori. Arch Insect Biochem Physiol 2009, 72(1):16-33.
114. Sagisaka A, Fujita K, Nakamura Y, Ishibashi J, Noda H, Imanishi S, Mita K, Yamakawa M, Tanaka H:Genome-wide analysis of host gene expression in the silkworm cells infected with Bombyx mori nucleopolyhedrovirus. Virus Res 2009,147(2):166-175.
115. Wang Y, Zhang P, Fujii H, Banno Y, Yamamoto K, Aso Y:Proteomic studies of lipopolysaccharide-induced polypeptides in the silkworm, Bombyx mori. Biosci Biotechnol Biochem 2004,68(8):1821-1823.
116. 吕鸿声编著：昆虫免疫学原理.上海科学技术出版社2008.
117. 向仲怀主编：蚕丝生物学.中国林业出版社2005：254.
118. 吕鸿声,钱纪放编译：昆虫病理学.浙江科学技术出版社1982.
119. 宋爽 刘朱杨：家蚕传染病的检查与诊断.云南农业科技2008：65.
120. 陈亚梅,黄俊荣：家蚕细菌性败血病的发生与防治.云南农业科技2008：83-84.
121. 林国杂 陈,黄志君,李文楚：败血病菌感染家蚕马氏管组织碱性磷酸酶的病理学研究.广东蚕业，39(4)：28-31.
122. 李文楚：软化病感染家蚕的碱性磷酸酶活力测定及病理学究.华南农业大学学报2004,25(4)：120-122.
123. 王明霞,王连芳,丁礼全：对家蚕真菌病危害加重原因的调查及防治措施.江苏蚕业2007(1)：2.
124. 朱方容：广西部分地区桑蚕僵病流行的原因及防控对策.广西蚕业2008，45(3)：29-32.
125. K.马拉莫斯奇主编,刘岱岳、谭业平译：昆虫病毒图谱.农业出版社1982.
126. 黄知源：我国蚕型多角体病发生近况及其防疫.中国农学通报2001,17(3)：77-78.
127. 吴强：对陕西汉台家蚕血液型脓病为害加重原因的调查与防治对策.蚕学通讯2006,26(2)：32-35.
128. Shigematsu H, Noguchi A:Biochemical studies on the multiplication of a nuclear-polyhedrosis virus in the silkworm, Bombyx mori. I. Nucleic-acid synthesis in larval tissues after infection. J Invertebr Pathol 1969,14(2):143-149.
129. Shigematsu H, Noguchi A:Biochemical studies on the multiplication of a nuclear-polyhedrosis virus in the silkworm, Bombyx mori. II. Protein synthesis in larval tissues after infection. J Invertebr Pathol 1969,14(3):301-307.
130. Shigematsu H, Noguchi A:Biochemical studies on the multiplication of a nuclear-polyhedrosis virus in the silkworm, Bombyx mori. 3. Functional changes in infected cells, with reference to the synthesis of nucleic acids and proteins. J Invertebr Pathol 1969,14(3):308-315.
131. Rahman MM, Gopinathan KP:Systemic and in vitro infection process of Bombyx mori nucleopolyhedrovirus. Virus Res 2004,101(2):109-118.
132. 杨大帧、夏如山主编：实用蚕病学.四川科学技术出版社1992.
133. 闻玉梅主编：现代医学微生物学.上海医科学出版社1999.
134. Xia Q, Cheng D, Duan J, Wang G, Cheng T, Zha X, Liu C, Zhao P, Dai F, Zhang Z et al: Microarray-based gene expression profiles in multiple tissues of the domesticated silkworm, Bombyx mori. Genome Biol 2007,8(8):R162.
135. Yang YH, Dudoit S, Luu P, Lin DM, Peng V, Ngai J, Speed TP:Normalization for cDNA microarray data:a robust composite method addressing single and multiple slide systematic variation. Nucleic Acids Res 2002,30(4):e15.
136. Aoki KF, Kanehisa M:Using the KEGG database resource. Curr Protoc Bioinformatics 2005, Chapter 1:Unit 1 12.
137. Zhang R, Li X, Jiang Y, Liu G, Li C, Zhang F, Xiao Y, Gong B:Novel strategies to mine alcoholism-related haplotypes and genes by combining existing knowledge framework.Sci China C Life Sci 2009,52(2):163-172.
138. Masoudi-Nejad A, Goto S, Endo TR, Kanehisa M: KEGG bioinformatics resource for plant genomics research. Methods Mol Biol 2007,406:437-458.
139. Hashimoto K, Goto S, Kawano S, Aoki-Kinoshita KF, Ueda N, Hamajima M, Kawasaki T, Kanehisa M:KEGG as a glycome informatics resource. Glycobiology 2006,16(5):63R-70R.
140. Neill JD, Ridpath JF:Gene expression changes in BVDV2-infected MDBK cells. Biologicals 2003,31(2):97-102.
141. Kamatani N:Abnormalities in nucleic acid metabolism and gout. Nippon Naika Gakkai Zasshi 1997,86(3):374-379.
142. The genome of a lepidopteran model insect, the silkworm Bombyx mori. Insect Biochem Mol Biol 2008,38(12):1036-1045.
143. Vermunt AM, Kamimura M, Hirai M, Kiuchi M, Shiotsuki T:The juvenile hormone binding protein of silkworm haemolymph:gene and functional analysis. Insect Mol Biol 2001, 10(2):147-154.
144. 程道军：家蚕变态发育相关基因的基因组研究.博士学位论文2008.
145. Brasier AR:The NF-kappaB regulatory network. Cardiovasc Toxicol 2006,6(2):111-130.
146. Buttice G, Duterque-Coquillaud M, Basuyaux JP, Carrere S, Kurkinen M, Stehelin D:Erg, an Ets-family member, differentially regulates human collagenase1 (MMP1) and stromelysinl (MMP3)gene expression by physically interacting with the Fos/Jun complex. Oncogene 1996,13(11):2297-2306.
147. Sekimoto T, Iwami M, Sakurai S:20-Hydroxyecdysone regulation of two isoforms of the Ets transcription factor E74 gene in programmed cell death in the silkworm anterior silk gland. Insect Mol Biol 2007,16(5):581-590.
148. Song H, Sun Y, Zhang Y, Li M:Molecular cloning and characterization of Bombyx mori CREB gene. Arch Insect Biochem Physiol 2009,71(1):31-44.
149. Lefort S, Soucy-Faulkner A, Grandvaux N, Flamand L:Binding of Kaposi's sarcoma-associated herpesvirus K-bZIP to interferon-responsive factor 3 elements modulates antiviral gene expression. J Virol 2007,81(20):10950-10960.
150. Furlong MJ, Groden E:Starvation induced stress and the susceptibility of the Colorado potato beetle, Leptinotarsa decemlineata, to infection by Beauveria bassiana. J Invertebr Pathol 2003,83(2):127-138.
151. Tian CH, Tang XD, Xu HJ, Ge JQ, Miao YG, Zhang CX:Bombyx mori nucleopolyhedrovirus ORF51 encodes a budded virus envelope associated protein. Virus Genes 2009, 38(1):171-177.
152. 步宏主编：分子病理学进展.四川大学出版社2006：164-166.
153. Muramatsu D, Kinjoh T, Shinoda T, Hiruma K:The role of 20-hydroxyecdysone and juvenile hormone in pupal commitment of the epidermis of the silkworm, Bombyx mori. Mech Dev 2008,125(5-6):411-420.
154. Otaki T, Takeuchi S, Mori K:Juvenile hormone and synthetic analogues:effects on larval moult of silkworm, Bombyx mori. Jpn J Med Sci Biol 1971,24(4):251-255.
155. Bhattacharyya R, Noch EK, Khalili K:A novel role of Racl GTPase in JCV T-antigen-mediated beta-catenin stabilization. Oncogene 2007,26(55):7628-7636.
156. Nusse R:Wnt signaling in disease and in development. Cell Res 2005,15(1):28-32.
157. Logan CY, Nusse R:The Wnt signaling pathway in development and disease. Annu Rev Cell Dev Biol 2004,20:781-810.
158. Liu C, Wang Y, Smallwood PM, Nathans J:An essential role for Frizzled5 in neuronal survival in the parafascicular nucleus of the thalamus. J Neurosci 2008,28(22):5641-5653.
159. Croce J, Duloquin L, Lhomond G, McClay DR, Gache C:Frizzled5/8 is required in secondary mesenchyme cells to initiate archenteron invagination during sea urchin development. Development 2006,133(3):547-557.
160. Kemp CR, Willems E, Wawrzak D, Hendrickx M, Agbor Agbor T, Leyns L:Expression of Frizzled5, Frizzled7, and Frizzled10 during early mouse development and interactions with canonical Wnt signaling. Dev Dyn 2007,236(7):2011-2019.
161. Raman M, Chen W, Cobb MH:Differential regulation and properties of MAPKs. Oncogene 2007,26(22):3100-3112.
162. Muslin AJ:MAPK signalling in cardiovascular health and disease:molecular mechanisms and therapeutic targets. Clin Sci (Lond) 2008,115(7):203-218.
163. Sangha N, Wu R, Kuick R, Powers S, Mu D, Fiander D, Yuen K, Katabuchi H, Tashiro H, Fearon ER et al: Neurofibromin 1 (NF1) defects are common in human ovarian serous carcinomas and co-occur with TP53 mutations. Neoplasia 2008,10(12):1362-1372, following 1372.
164. MacDonald TJ, Brown KM, LaFleur B, Peterson K, Lawlor C, Chen Y, Packer RJ, Cogen P, Stephan DA:Expression profiling of medulloblastoma:PDGFRA and the RAS/MAPK pathway as therapeutic targets for metastatic disease. Nat Genet 2001,29(2):143-152.
165. Martinho O, Gouveia A, Viana-Pereira M, Silva P, Pimenta A, Reis RM, Lopes JM:Low frequency of MAP kinase pathway alterations in KIT and PDGFRA wild-type GISTs. Histopathology 2009,55(1):53-62.
166. Peippo M, Koivisto AM, Sarkamo T, Sipponen M, von Koskull H, Ylisaukko-oja T, Rehnstrom K, Froyen G, Ignatius J, Jarvela I:PAK3 related mental disability:further characterization of the phenotype. Am J Med Genet A 2007,143A(20):2406-2416.
167. Asano Y, Jimenez-Dalmaroni A, Liverpool TB, Marchetti MC, Giomi L, Kiger A, Duke T, Baum B:Pak3 inhibits local actin filament formation to regulate global cell polarity. Hfsp J 2009, 3(3):194-203.
168. Kim BJ, Ryu SW, Song BJ:JNK- and p38 kinase-mediated phosphorylation of Bax leads to its activation and mitochondrial translocation and to apoptosis of human hepatoma HepG2 cells. J Biol Chem 2006,281(30):21256-21265.
169. Levine AJ, Hu W, Feng Z:The P53 pathway:what questions remain to be explored? Cell Death Differ 2006,13(6):1027-1036.
170. Bell HS, Ryan KM:Targeting the p53 family for cancer therapy:'big brother'joins the fight. Cell Cycle 2007,6(16):1995-2000.
171. Piatti S, Bohm T, Cocker JH, Diffley JF, Nasmyth K:Activation of S-phase-promoting CDKs in late G1 defines a "point of no return" after which Cdc6 synthesis cannot promote DNA replication in yeast. Genes Dev 1996,10(12):1516-1531.
172. Dasika GK, Lin SC, Zhao S, Sung P, Tomkinson A, Lee EY:DNA damage-induced cell cycle checkpoints and DNA strand break repair in development and tumorigenesis. Oncogene 1999,18(55):7883-7899.
173. Laiho M, Latonen L:Cell cycle control, DNA damage checkpoints and cancer. Ann Med 2003, 35(6):391-397.
174. John PC, Mews M, Moore R:Cyclin/Cdk complexes:their involvement in cell cycle progression and mitotic division. Protoplasma 2001,216(3-4):119-142.
175. Mudryj M, Devoto SH, Hiebert SW, Hunter T, Pines J, Nevins JR:Cell cycle regulation of the E2F transcription factor involves an interaction with cyclin A. Cell 1991,65(7):1243-1253.
176. Draetta G, Beach D:The mammalian cdc2 protein kinase:mechanisms of regulation during the cell cycle. J Cell Sci Suppl 1989,12:21-27.
177. Draetta G:Cell cycle control in eukaryotes:molecular mechanisms of cdc2 activation. Trends Biochem Sci 1990,15(10):378-383.
178. Lee KS, Asano S, Park JE, Sakchaisri K, Erikson RL:Monitoring the cell cycle by multi-kinase-dependent regulation of Swe1/Weel in budding yeast. Cell Cycle 2005, 4(10):1346-1349.
179. Eijpe M, Heyting C, Gross B, Jessberger R:Association of mammalian SMC1 and SMC3 proteins with meiotic chromosomes and synaptonemal complexes. J Cell Sci 2000,113 (Pt 4):673-682.
180. Upadhyay AK, Ajay AK, Singh S, Bhat MK:Cell cycle regulatory protein 5 (Cdk5) is a novel downstream target of ERK in carboplatin induced death of breast cancer cells. Curr Cancer Drug Targets 2008,8(8):741-752.
181. Lopes JP, Oliveira CR, Agostinho P:Cdk5 acts as a mediator of neuronal cell cycle re-entry triggered by amyloid-beta and prion peptides. Cell Cycle 2009,8(1):97-104.
182. Philips A, Huet X, Plet A, Rech J, Vignais ML, Vie A, Blanchard JM:[Cyclin A:a good markers for the study of cell cycle control and tumor progression?]. C R Seances Soc Biol Fil 1998,192(2):223-230.
183. Sun A, Bagella L, Tutton S, Romano G, Giordano A:From G0 to S phase:a view of the roles played by the retinoblastoma (Rb) family members in the Rb-E2F pathway. J Cell Biochem 2007,102(6):1400-1404.
184. Yamamuro T, Kano K, Naito K:Functions of FZR1 and CDC20, activators of the anaphase-promoting complex, during meiotic maturation of swine oocytes. Biol Reprod 2008,79(6):1202-1209.
185. Pflumm MF, Botchan MR:Orc mutants arrest in metaphase with abnormally condensed chromosomes. Development 2001,128(9):1697-1707.
186. Dhar SK, Delmolino L, Dutta A:Architecture of the human origin recognition complex. J Biol Chem 2001,276(31):29067-29071.
187. Crosby ME, Jacobberger J, Gupta D, Macklis RM, Almasan A:E2F4 regulates a stable G2 arrest response to genotoxic stress in prostate carcinoma. Oncogene 2007,26(13):1897-1909.
188. Plesca D, Crosby ME, Gupta D, Almasan A:E2F4 function in G2:maintaining G2-arrest to prevent mitotic entry with damaged DNA. Cell Cycle 2007,6(10):1147-1152.
189. Kruidering M, Evan GI:Caspase-8 in apoptosis:the beginning of "the end"? IUBMB Life 2000,50(2):85-90.
190. Cha YJ, Kim HS, Rhim H, Kim BE, Jeong SW, Kim IK:Activation of caspase-8 in 3-deazaadenosine-induced apoptosis of U-937 cells occurs downstream of caspase-3 and caspase-9 without Fas receptor-ligand interaction. Exp Mol Med 2001,33(4):284-292.
191. Bhattacharyya A, Lahiry L, Mandal D, Sa G, Das T:Black tea induces tumor cell apoptosis by Bax translocation, loss in mitochondrial transmembrane potential, cytochrome c release and caspase activation. Int J Cancer 2005,117(2):308-315.
192. Denef VJ, Park J, Tsoi TV, Rouillard JM, Zhang H, Wibbenmeyer JA, Verstraete W, Gulari E, Hashsham SA, Tiedje JM:Biphenyl and benzoate metabolism in a genomic context: outlining genome-wide metabolic networks in Burkholderia xenovorans LB400. Appl Environ Microbiol 2004,70(8):4961-4970.
193. Spizizen J:The effect of virus infection of pyruvate metabolism. Biochim Biophys Acta 1957, 23(2):333-341.
194. Yesilkaya H, Spissu F, Carvalho SM, Terra VS, Homer KA, Benisty R, Porat N, Neves AR, Andrew PW:Pyruvate formate lyase is required for pneumococcal fermentative metabolism and virulence. Infect Immun 2009.
195. Webster HK, Whaun JM:Purine metabolism during continuous erythrocyte culture of human malaria parasites (P. falciparum). Prog Clin Biol Res 1981,55:557-573.
196. Becker W:Purine metabolism in Biomphalaria glabrata under starvation and infection with Schistosoma mansoni. Comp Biochem Physiol B 1983,76(2):215-219.
197. Gandra YR, Scrimsha WN:Infection and nutritional status. II. Effect of mild virus infection induced by 17-D yellow fever vaccine on nitrogen metabolism in children. Am J Clin Nutr 1961,9:159-163.
198. Bucovaz ET, Macleod RM, Morrison JC, Whybrew WD:The coenzyme A-synthesizing protein complex and its proposed role in CoA biosynthesis in bakers' yeast. Biochimie 1997, 79(12):787-798.
199. Bron PA, Grangette C, Mercenier A, de Vos WM, Kleerebezem M:Identification of Lactobacillus plantarum genes that are induced in the gastrointestinal tract of mice. J Bacteriol 2004,186(17):5721-5729.
200. Wei BL, Denton PW, O'Neill E, Luo T, Foster JL, Garcia JV:Inhibition of lysosome and proteasome function enhances human immunodeficiency virus type 1 infection. J Virol 2005, 79(9):5705-5712.
201. Shalitin D, Wolf S:Cucumber mosaic virus infection affects sugar transport in melon plants. Plant Physiol 2000,123(2):597-604.
202. Murti KG, Goorha R:Interaction of frog virus-3 with the cytoskeleton. I. Altered organization of microtubules, intermediate filaments, and microfilaments. J Cell Biol 1983, 96(5):1248-1257.
203. Tilney LG, DeRosier DJ, Tilney MS:How Listeria exploits host cell actin to form its own cytoskeleton. I. Formation of a tail and how that tail might be involved in movement. J Cell Biol 1992,118(1):71-81.
204. Tsarfaty I, Sandovsky-Losica H, Mittelman L, Berdicevsky I, Segal E:Cellular actin is affected by interaction with Candida albicans. FEMS Microbiol Lett 2000,189(2):225-232.
205. Root-Bernstein R, Vonck J, Podufaly A:Antigenic complementarity between coxsackie virus and streptococcus in the induction of rheumatic heart disease and autoimmune myocarditis. Autoimmunity 2009,42(1):1-16.
206. Wei T, Shimizu T, Omura T:Endomembranes and myosin mediate assembly into tubules of Pns10 of Rice dwarf virus and intercellular spreading of the virus in cultured insect vector cells. Virology 2008,372(2):349-356.
207. Lehmann MJ, Sherer NM, Marks CB, Pypaert M, Mothes W:Actin-and myosin-driven movement of viruses along filopodia precedes their entry into cells. J Cell Biol 2005, 170(2):317-325.
208. Ridgway ID, Small HJ, Atkinson RJ, Birkbeck HT, Taylor AC, Neil DM:Extracellular proteases and possible disease related virulence mechanisms of two marine bacteria implicated in an opportunistic bacterial infection of Nephrops norvegicus. J Invertebr Pathol 2008,99(1):14-19.
209. Fan Y, Zhang Y, Yang X, Pei X, Guo S, Pei Y:Expression of a Beauveria bassiana chitinase (Bbchitl) in Escherichia coli and Pichia pastoris. Protein Expr Pur if 2007,56(1):93-99.
210. Qiuhong N, Xiaowei H, Baoyu T, Jinkui Y, Jiang L, Lin Z, Keqin Z:Bacillus sp. B16 kills nematodes with a serine protease identified as a pathogenic factor. Appl Microbiol Biotechnol 2006,69(6):722-730.
211. Niu Q, Huang X, Zhang L, Li Y, Li J, Yang J, Zhang K:A neutral protease from Bacillus nematocida, another potential virulence factor in the infection against nematodes. Arch Microbiol 2006,185(6):439-448.
212. Tellam RL, Wijffels G, Willadsen P:Peritrophic matrix proteins. Insect Biochem Mol Biol 1999,29(2):87-101.
213. Nagase H:Metalloproteases. Curr Protoc Protein Sci 2001, Chapter 21:Unit 21 24.
214. Prakobwong S, Pinlaor S, Yongvanit P, Sithithaworn P, Pairojkul C, Hiraku Y:Time profiles of the expression of metalloproteinases, tissue inhibitors of metalloproteases, cytokines and collagens in hamsters infected with Opisthorchis viverrini with special reference to peribiliary fibrosis and liver injury. Int J Parasitol 2009,39(7):825-835.
215. Pigott CR, Ellar DJ:Role of receptors in Bacillus thuringiensis crystal toxin activity. Microbiol Mol Biol Rev 2007,71(2):255-281.
216. Fernandez LE, Gomez I, Pacheco S, Arenas I, Gilla SS, Bravo A, Soberon M:Employing phage display to study the mode of action of Bacillus thuringiensis Cry toxins. Peptides 2008, 29(2):324-329.
217. Miguel B, Pharr GT, Wang C:The role of feline aminopeptidase N as a receptor for infectious bronchitis virus. Brief review. Arch Virol 2002,147(11):2047-2056.
218. Lassnig C, Kolb A, Strobl B, Enjuanes L, Muller M:Studying human pathogens in animal models:fine tuning the humanized mouse. Transgenic Res 2005,14(6):803-806.
219. Ohara-Nemoto Y, Sasaki M, Kaneko M, Nemoto T, Ota M:Cysteine protease activity of streptococcal pyrogenic exotoxin B. Can JMicrobiol 1994,40(11):930-936.
220. Ohta M, Hayashi K:Inactivation of toxin B from the Indian cobra by cleavage of a specific bond during limited hydrolysis with trypsin. Biochem Int 1984,9(2):243-250.
221. Pinkney M, Kapur V, Smith J, Weller U, Palmer M, Glanville M, Messner M, Musser JM, Bhakdi S, Kehoe MA:Different forms of streptolysin O produced by Streptococcus pyogenes and by Escherichia coli expressing recombinant toxin:cleavage by streptococcal cysteine protease. Infect Immun 1995,63(7):2776-2779.
222. Ferreira-DaSilva CT, Gombarovits ME, Masuda H, Oliveira CM, Carlini CR:Proteolytic activation of canatoxin, a plant toxic protein, by insect cathepsin-like enzymes. Arch Insect Biochem Physiol 2000,44(4):162-171.
223. Lemaitre B, Hoffmann J:The host defense of Drosophila melanogaster. Annu Rev Immunol 2007,25:697-743.
224. Kan H, Kim CH, Kwon HM, Park JW, Roh KB, Lee H, Park BJ, Zhang R, Zhang J, Soderhall K et al:Molecular control of phenoloxidase-induced melanin synthesis in an insect. J Biol Chem 2008,283(37):25316-25323.
225. An C, Ishibashi J, Ragan EJ, Jiang H, Kanost MR:Functions of Manduca sexta hemolymph proteinases HP6 and HP8 in two innate immune pathways. J Biol Chem 2009, 284(29):19716-19726.
226. Mangan MS, Kaiserman D, Bird PI:The role of serpins in vertebrate immunity. Tissue Antigens 2008,72(1):1-10.
227. Wang WX, Wang YP, Deng XJ, Dang XL, Tian JH, Yi HY, Li YF, He XF, Cao Y, Xia QY et al: Molecular and functional characterization of a c-type lysozyme from the Asian corn borer, Ostrinia furnacalis. J Insect Sci 2009,9:17.
228. Gandhe AS, Janardhan G, Nagaraju J:Immune upregulation of novel antibacterial proteins from silkmoths (Lepidoptera) that resemble lysozymes but lack muramidase activity. Insect Biochem Mol Biol 2007,37(7):655-666.
229. De Gregorio E, Han SJ, Lee WJ, Baek MJ, Osaki T, Kawabata S, Lee BL, Iwanaga S, Lemaitre B, Brey PT:An immune-responsive Serpin regulates the melanization cascade in Drosophila. Dev Cell 2002,3(4):581-592.
230. Rinaldo CR, Jr., Torpey DJ,3rd:Cell-mediated immunity and immunosuppression in herpes simplex virus infection. Immunodeficiency 1993,5(1):33-90.
231. Glinski Z, Jarosz J:Molluscan immune defenses. Arch Immunol Ther Exp (Warsz) 1997, 45(2-3):149-155.
232. Waterhouse RM, Kriventseva EV, Meister S, Xi Z, Alvarez KS, Bartholomay LC, Barillas-Mury C, Bian G, Blandin S, Christensen BM et al:Evolutionary dynamics of immune-related genes and pathways in disease-vector mosquitoes. Science 2007,316(5832):1738-1743.
233. Takase H, Watanabe A, Yoshizawa Y, Kitami M, Sato R:Identification and comparative analysis of three novel C-type lectins from the silkworm with functional implications in pathogen recognition. Dev Comp Immunol 2009,33(6):789-800.
234. Watanabe A, Miyazawa S, Kitami M, Tabunoki H, Ueda K, Sato R:Characterization of a novel C-type lectin, Bombyx mori multibinding protein, from the B. mori hemolymph: mechanism of wide-range microorganism recognition and role in immunity. J Immunol 2006,177(7):4594-4604.
235. Bettencourt R, Assefaw-Redda Y, Faye I:The insect immune protein hemolin is expressed during oogenesis and embryogenesis. Mech Dev 2000,95(1-2):301-304.
236. Garver LS, Xi Z, Dimopoulos G:Immunoglobulin superfamily members play an important role in the mosquito immune system. Dev Comp Immunol 2008,32(5):519-531.
237. Huang L, Cheng T, Xu P, Duan J, Fang T, Xia Q:Immunoglobulin superfamily is conserved but evolved rapidly and is active in the silkworm, Bombyx mori. Insect Mol Biol 2009, 18(4):517-530.
238. Pancer Z, Amemiya CT, Ehrhardt GR, Ceitlin J, Gartland GL, Cooper MD:Somatic diversification of variable lymphocyte receptors in the agnathan sea lamprey. Nature 2004, 430(6996):174-180.
239. Agarwala KL, Nakamura S, Tsutsumi Y, Yamakawa K:Down syndrome cell adhesion molecule DSCAM mediates homophilic intercellular adhesion. Brain Res Mol Brain Res 2000,79(1-2):118-126.
240. Zou Z, Shin SW, Alvarez KS, Bian G, Kokoza V, Raikhel AS:Mosquito RUNX4 in the immune regulation of PPO gene expression and its effect on avian malaria parasite infection. Proc Natl Acad Sci USA 2008,105(47):18454-18459.
241. Hartzer KL, Zhu KY, Baker JE:Phenoloxidase in larvae of Plodia interpunctella (Lepidoptera:Pyralidae):molecular cloning of the proenzyme cDNA and enzyme activity in larvae paralyzed and parasitized by Habrobracon hebetor (Hymenoptera:Braconidae). Arch Insect Biochem Physiol 2005,59(2):67-79.
242. Schmidt RL, Trejo TR, Plummer TB, Platt JL, Tang AH:Infection-induced proteolysis of PGRP-LC controls the IMD activation and melanization cascades in Drosophila. Faseb J 2008,22(3):918-929.
243. Ashida M, Ochiai M, Niki T:Immunolocalization of prophenoloxidase among hemocytes of the silkworm, Bombyx mori. Tissue Cell 1988,20(4):599-610.
244. Satoh D, Horii A, Ochiai M, Ashida M:Prophenoloxidase-activating enzyme of the silkworm, Bombyx mori. Purification, characterization, and cDNA cloning. J Biol Chem 1999, 274(11):7441-7453.
245. Naitza S, Ligoxygakis P:Antimicrobial defences in Drosophila:the story so far. Mol Immunol 2004,40(12):887-896.
246. Tanji T, Hu X, Weber AN, Ip YT:Toll and IMD pathways synergistically activate an innate immune response in Drosophila melanogaster. Mol Cell Biol 2007,27(12):4578-4588.
247. Hayashi F, Smith KD, Ozinsky A, Hawn TR, Yi EC, Goodlett DR, Eng JK, Akira S, Underhill DM, Aderem A:The innate immune response to bacterial flagellin is mediated by Toll-like receptor 5. Nature 2001,410(6832):1099-1103.
248. Massari P, Henneke P, Ho Y, Latz E, Golenbock DT, Wetzler LM:Cutting edge:Immune stimulation by neisserial porins is toll-like receptor 2 and MyD88 dependent. J Immunol 2002,168(4):1533-1537.
249. Towb P, Galindo RL, Wasserman SA:Recruitment of Tube and Pelle to signaling sites at the surface of the Drosophila embryo. Development 1998,125(13):2443-2450.
250. Ferrandon D, Imler JL, Hetru C, Hoffmann JA:The Drosophila systemic immune response: sensing and signalling during bacterial and fungal infections. Nat Rev Immunol 2007, 7(11):862-874.
251. Matova N, Anderson KV:Rel/NF-kappaB double mutants reveal that cellular immunity is central to Drosophila host defense. Proc Natl Acad Sci U S A 2006,103(44):16424-16429.
252. O'Shea JJ, Gadina M, Schreiber RD:Cytokine signaling in 2002:new surprises in the Jak/Stat pathway. Cell 2002,109 Suppl:S121-131.
253. Luo H, Dearolf CR:The JAK/STAT pathway and Drosophila development. Bioessays 2001, 23(12):1138-1147.
254. Pourquie O:The segmentation clock:converting embryonic time into spatial pattern. Science 2003,301(5631):328-330.
255. Grace MJ, Cutler D:Pegylating IFNs at his-34 improves the in vitro antiviral activity through the JAK/STAT pathway. Antivir Chem Chemother 2004,15(6):287-297.
256. Chaudhuri A, Yang B, Gendelman HE, Persidsky Y, Kanmogne GD:STAT1 signaling modulates HIV-1-induced inflammatory responses and leukocyte transmigration across the blood-brain barrier. Blood 2008, 111(4):2062-2072.
257. 余子全：苏云金芽胞杆菌杀线虫蛋白基因cry6Aa的表达负调控及杀线虫晶体蛋白进入根结线虫体内的模式.博士学位论文2007.
258. 李赛男：昆虫中肠Bt毒素受体氨肽酶N的研究进展.安徽农业科学2007，35(9)：2523-2525.
259. Takesue S, Yokota K, Miyajima S, Taguchi R, Ikezawa H, Takesue Y:Partial release of aminopeptidase N from larval midgut cell membranes of the silkworm, Bombyx mori, by phosphatidylinositol-specific phospholipase C. Comp Biochem Physiol B 1992,102(1):7-11.
260. Yaoi K, Kadotani T, Kuwana H, Shinkawa A, Takahashi T, Iwahana H, Sato R:Aminopeptidase N from Bombyx mori as a candidate for the receptor of Bacillus thuringiensis CrylAa toxin. Eur J Biochem 1997,246(3):652-657.
261. Hua G, Tsukamoto K, Taguchi R, Tomita M, Miyajima S, Ikezawa H:Characterization of aminopeptidase N from the brush border membrane of the larvae midgut of silkworm, Bombyx mori as a zinc enzyme. Biochim Biophys Acta 1998,1383(2):301-310.
262. Shinkawa A, Yaoi K, Kadotani T, Imamura M, Koizumi N, Iwahana H, Sato R:Binding of phylogenetically distant Bacillus thuringiensis cry toxins to a Bombyx mori aminopeptidase N suggests importance of Cry toxin's conserved structure in receptor binding. Curr Microbiol 1999,39(1):14-20.
263. Jenkins JL, Dean DH:Binding specificity of Bacillus thuringiensis CrylAa for purified, native Bombyx mori aminopeptidase N and cadherin-like receptors. BMC Biochem 2001, 2:12.
264. 余洁,林锦庄,黄勤清,等：苏云金芽孢杆菌对新秀丽小杆线虫的作用.农业生物技术学报2007,15(2)：306-311.
265. 张红：Bt基因重组工程菌毒蛋白的表达及其对昆虫的毒性研究.硕士学位论文2004.
266. Ihara H, Himeno M:Study of the irreversible binding of Bacillus thuringiensis CrylAa to brush border membrane vesicles from Bombyx mori midgut. J Invertebr Pathol 2008, 98(2):177-183.
267. Nakanishi K, Yaoi K, Nagino Y, Hara H, Kitami M, Atsumi S, Miura N, Sato R: Aminopeptidase N isoforms from the midgut of Bombyx mori and Plutella xylostella -their classification and the factors that determine their binding specificity to Bacillus thuringiensis CrylA toxin. FEBS Lett 2002,519(1-3):215-220.
268. Li H, Oppert B, Higgins RA, Huang F, Zhu KY, Buschman LL:Comparative analysis of proteinase activities of Bacillus thuringiensis-resistant and-susceptible Ostrinia nubilalis (Lepidoptera:Crambidae). Insect Biochem Mol Biol 2004,34(8):753-762.
269. Alvarez-Alfageme F, Ferry N, Castanera P, Ortego F, Gatehouse AM:Prey mediated effects of Bt maize on fitness and digestive physiology of the red spider mite predator Stethorus punctillum Weise (Coleoptera:Coccinellidae). Transgenic Res 2008,17(5):943-954.
270. Karumbaiah L, Oppert B, Jurat-Fuentes JL, Adang MJ:Analysis of midgut proteinases from Bacillus thuringiensis-susceptible and-resistant Heliothis virescens (Lepidoptera: Noctuidae). Comp Biochem Physiol B Biochem Mol Biol 2007,146(1):139-146.
271. Lavazec C, Bonnet S, Thiery I, Boisson B, Bourgouin C:cpbAgl encodes an active carboxypeptidase B expressed in the midgut of Anopheles gambiae. Insect Mol Biol 2005, 14(2):163-174.
272. Lechner AJ, Ryerse JS, Matuschak GM:Acute lung injury during bacterial or fungal sepsis. Microsc Res Tech 1993,26(5):444-456.
273. Walters LL, Irons KP, Guzman H, Tesh RB:-Formation and composition of the peritrophic membrane in the sand fly, Phlebotomus perniciosus (Diptera:Psychodidae). J Med Entomol 1993,30(1):179-198.
274. Rees JS, Jarrett P, Ellar DJ:Peritrophic membrane contribution to Bt Cry delta-endotoxin susceptibility in Lepidoptera and the effect of Calcofluor. J Invertebr Pathol 2009, 100(3):139-146.
275. Lee MK, Milne RE, Ge AZ, Dean DH:Location of a Bombyx mori receptor binding region on a Bacillus thuringiensis delta-endotoxin. J Biol Chem 1992,267(5):3115-3121.
276. Ingle SS, Trivedi N, Prasad R, Kuruvilla J, Rao KK, Chhatpar HS:Aminopeptidase-N from the Helicoverpa armigera (Hubner) brush border membrane vesicles as a receptor of Bacillus thuringiensis crylac delta-endotoxin. Curr Microbiol 2001,43(4):255-259.
277. Angelucci C, Barrett-Wilt GA, Hunt DF, Akhurst RJ, East PD, Gordon KH, Campbell PM: Diversity of aminopeptidases, derived from four lepidopteran gene duplications, and polycalins expressed in the midgut of Helicoverpa armigera:identification of proteins binding the delta-endotoxin, Cryl Ac of Bacillus thuringiensis. Insect Biochem Mol Biol 2008, 38(7):685-696.
278. Lesieur C, Vecsey-Semjen B, Abrami L, Fivaz M, Gisou van der Goot F:Membrane insertion: The strategies of toxins (review). Mol Membr Biol 1997,14(2):45-64.
279. Dean DH, Rajamohan F, Lee MK, Wu SJ, Chen XJ, Alcantara E, Hussain SR:Probing the mechanism of action of Bacillus thuringiensis insecticidal proteins by site-directed mutagenesis-a minireview. Gene 1996,179(1):111-117.
280. Sanders HR, Foy BD, Evans AM, Ross LS, Beaty BJ, Olson KE, Gill SS:Sindbis virus induces transport processes and alters expression of innate immunity pathway genes in the midgut of the disease vector, Aedes aegypti. Insect Biochem Mol Biol 2005,35(11):1293-1307.
281. Roth CW, Holm I, Graille M, Dehoux P, Rzhetsky A, Wincker P, Weissenbach J, Brey PT: Identification of the Anopheles gambiae ATP-binding cassette transporter superfamily genes. Mol Cells 2003,15(2):150-158.
282. Meidanis J, Braga MD, Verjovski-Almeida S:Whole-genome analysis of transporters in the plant pathogen Xylella fastidiosa. Microbiol Mol Biol Rev 2002,66(2):272-299.
2. Acosta Muniz C, Jaillard D, Lemaitre B, Boccard F:Erwinia carotovora Evf antagonizes the elimination of bacteria in the gut of Drosophila larvae. Cell Microbiol 2007,9(l):106-119.
3. Grkovic S, Glare, T. R., Jackson, T. A.& Corbett, G. E.:Genes essential for amber disease in grass grubs are located on the large plasmid found in Serratia entomophila and Serratia proteamaculans ApplEnviron Microbiol 1995.
4. Hinnebusch BJea:Role of Yersinia murine toxin in survival of Yersinia pestis in the midgut of the flea vector. Science 2002.
5. Hinnebusch BJ, Perry, R. D.& Schwan, T. G.:Role of the Yersinia pestis hemin storage (hms) locus in the transmission of plague by fleas. Science 1996.
6. Liehl P, Blight M, Vodovar N, Boccard F, Lemaitre B:Prevalence of local immune response against oral infection in a Drosophila/Pseudomonas infection model. PLoS Pathog 2006, 2(6):e56.
7. 罗海波,鲍行豪主编：细菌毒素研究进展.1983：1-28.
8. Bravo A, Gill SS, Soberon M:Mode of action of Bacillus thuringiensis Cry and Cyt toxins and their potential for insect control. Toxicon 2007,49(4):423-435.
9. de Maagd RA, Bravo, A., Berry, C., Crickmore, N.& Schnepf, H. E.:Structure, diversity, and evolution of protein toxins from spore-forming entomopathogenic bacteria. Annu Rev Genet 2003.
10. Schnepf E, Crickmore N, Van Rie J, Lereclus D, Baum J, Feitelson J, Zeigler DR, Dean DH: Bacillus thuringiensis and its pesticidal crystal proteins. Microbiol Mol Biol Rev 1998, 62(3):775-806.
11. Aronson AI, Shai Y:Why Bacillus thuringiensis insecticidal toxins are so effective:unique features of their mode of action. FEMS Microbiol Lett 2001,195(1):1-8.
12. Charles JF, Silva-Filha, M.-H.& Nielsen-LeRoux, C.:in Entomopathogenic Bacteria:From Laboratory to Field Application 2000:237-252.
13. Bowen Dea:nsecticidal toxins from the bacterium Photorhabdus luminescens. Science 1998.
14. Morgan JA, Sergeant, M., Ellis, D., Ousley, M.&Jarrett, P.:Sequence analysis of insecticidal genes from Xenorhabdus nematophilus PMFI296. Appl Environ Microbiol Mol Biol Rev 2001.
15. Daborn PJea:A single Photorhabdus gene,makes caterpillars floppy (mcf), allows Escherichia coli to persist within and kill insects. Proc Natl Acad Sci USA 99 2002.
16. Duchaud Eea:The genome sequence of the entomopathogenic bacterium Photorhabdus luminescens. Nature Biotechnol 2003.
17. Matsumoto K:Role of bacterial proteases in pseudomonal and serratial keratitis. Biol Chem 2004.
18. Lee DH, Cha IH, Woo DS, Ohba M:Microbial ecology of Bacillus thuringiensis:fecal populations recovered from wildlife in Korea. Can J Microbiol 2003,49(7):465-471.
19. Travis J, Potempa, J.& Maeda, H.:Are bacterial proteinases pathogenic factors?. Trends Microbiol 1995.
20. ffrench-Constant Rea:Photorhabdus:towards a functional genomic analysis of a symbiont and pathogen. FEMS Microbiol Rev 2003.
21. Vodovar Nea:Complete genome sequence of the entomopathogenic and metabolically versatile soil bacterium Pseudomonas entomophila. Nature Biotechnol 2006.
22. Derzelle Sea:The PhoP/PhoQ two-component regulatory system of Photorhabdus luminescens is essential for virulence in insects. J Bacteriol 2004.
23. Cowles KN, Cowles, C. E., Richards, G. R., Martens,, E. C.& Goodrich-Blair H:The global regulator Lrp contributes to mutualism, pathogenesis and phenotypic variation in the bacterium Xenorhabdus nematophila Cell Microbiol 2007.
24. Salamitou Sea:The plcR regulon is involved in the opportunistic properties of Bacillus thuringiensis and Bacillus cereus in mice and insects. Microbiology 2000.
25. Basset A, Tzou P, Lemaitre B, Boccard F:A single gene that promotes interaction of a phytopathogenic bacterium with its insect vector, Drosophila melanogaster. EMBO Rep 2003,4(2):205-209.
26. Hoffmann BLaJ:The Host Defense of Drosophila melanogaster. Annu Rev Immunol 2007 2007.
27. Vallet-Gely I, Lemaitre B, Boccard F:Bacterial strategies to overcome insect defences. Nat Rev Microbiol 2008,6(4):302-313.
28. Ha EM OC, Bae YS, LeeWJ.:A direct role for dual oxidase in Drosophila gut immunity. Science 2005.
29. Ha EM OC, Ryu JH, Bae YS, Kang SW, et al.:An antioxidant systemrequired for host protection against gut infection in Drosophila. Dev Cell 2005.
30. Vodovar Nea:Drosophila host defense after oral infection by an entomopathogenic Pseudomonas species. Proc Natl Acad Sci USA 2005.
31. Nehme NT, Liegeois S, Kele B, Giammarinaro P, Pradel E, Hoffmann JA, Ewbank JJ, Ferrandon D:A model of bacterial intestinal infections in Drosophila melanogaster. PLoS Pathog 2007, 3(11):e173.
32. Ryu JHea:An essential complementary role of NF-κB pathway to microbicidal oxidants in Drosophila gut immunity.. EMBO J 2006.
33. Brennan CAA, K. V.:Drosophila:the genetics of innate immune recognition and response. Annu Rev Immunol 2004.
34. Mellroth P KJ, Steiner H.:A scavenger function for a Drosophila peptido-glycan recognition protein. J Biol Chem 2003.
35. Mellroth P S:PGRP-SB1:an N-acetylmuramoyl 1-alanine amidase with antibacterial activity. Biochem Biophys Res Commun 2006.
36. Michel T RJ, Hoffmann JA, Royet J.:Drosophila Toll is activated by Gram-positive bacteria through a circulating peptidoglycan recognition protein. Nature 2001.
37. GobertV G, Matskevich AA,Rutschmann S,Royet J, et al.:Dual activation of theDrosophilaToll pathway by two pattern recognition receptors. Science 2003.
38. Pili-Floury S LF, Takahashi K, Saigo K, Samain E, et al.:In vivo RNAi analysis reveals an unexpected role for GNBP1 in the defense against Gram-positive bacterial infection in Drosophila adults. J Biol Chem 2004.
39. Bischoff V VC, Boneca IG, Michel T, Hoffmann JA, Royet J.:Function of theDrosophila pattern-recognition receptor PGRP-SDin the detection ofGram-positive bacteria. Nat Immunol 2004.
40. Gottar M, Gobert V, Michel T, Belvin M, Duyk G, Hoffmann JA, Ferrandon D, Royet J:The Drosophila immune response against Gram-negative bacteria is mediated by a peptidoglycan recognition protein. Nature 2002,416(6881):640-644.
41. KanekoT Y, AggarwalK, LimJH,UedaK, et al.:PGRP-LCand PGRP-LE have essential yet distinct functions in the Drosophila immune response to monomeric DAP-type peptidoglycan. Nat Immunol 2006.
42. Leulier F PC, Pili-Floury S, Ryu JH, Caroff M, et al.:The Drosophila immune systemdetects bacteria through specific peptidoglycan recognition. Nat Immunol 2003.
43. Rizki T RR, Grell E.:A mutant affecting the crystal cells in Drosophila melanogaster. Roux's Arch Dev Biol 1980.
44. Ramet M PA, Manfruelli P, Li X, Koziel H, et al.:Drosophila scavenger receptor CI is a pattern recognition receptor for bacteria. Immunity 2001.
45. Kocks C CJ, NehmeN, Ulvila J, Pearson AM, et al.:Eater, a transmembrane protein mediating phagocytosis of bacterial pathogens in Drosophila. Cell 2005.
46. Watson FL P-HR, Thomas F, Lamar DL, Hughes M, et al.:Extensive diversity of Ig-superfamily proteins in the immune system of insects. Science 2005.
47. M. M:Blood cells of Drosophila:cell lineages and role in host defense. CurrOpin Immunol 2004.
48. Nappi AJ VE:Melanogenesis and the generation of cytotoxic molecules during insect cellular immune reactions. Pigment Cell Res 1993.
49. M. A:The prophenoloxidase cascade in insect immunity. Res Immunol 1990.
50. S(?) oderh(?)all K CL:Role of prophenoloxidase-activating system in invertebrate immunity. Curr Opin Immunol 1998.
51. Ochiai M AM:A pattern recognition protein for peptidoglycan. Cloning the cDNA and the gene of the silkworm, Bombyx mori. J Biol Chem 1999.
52. Ochiai M AM:A pattern-recognition protein for β-1,3-glucan. The binding domain and the cDNA cloning of β-1,3-glucan recognition protein from the silkworm,Bombyx mori. J Biol Chem 2000.
53. Ma C KM:A β1,3-glucan recognition protein from an insect, Manduca sexta, agglutinates microorganisms and activates the phenoloxidase cascade. JBiol Chem 2000.
54. Lee MH OT, Lee JY, Baek MJ, Zhang R, et al.:Peptidoglycan recognition proteins involved in 1,3-β-D-glucan-dependent prophenoloxidase activation system of insect. J Biol Chem 2003.
55. Kinoshita T, Inoue K:Bactericidal activity of the normal, cell-free hemolymph of silkworms (Bombyx mori). Infect Immun 1977,16(1):32-36.
56. Suzuki T, Natori S:Identification of a protein having hemagglutinating activity in the hemolymph of the silkworm, Bombyx mori. J Biochem 1983,93(2):583-590.
57. Ochiai M, Ashida M:Purification of a beta-1,3-glucan recognition protein in the prophenoloxidase activating system from hemolymph of the silkworm, Bombyx mori. J Biol Chem 1988,263(24):12056-12062.
58. Morishima I, Suginaka S, Ueno T, Hirano H:Isolation and structure of cecropins, inducible antibacterial peptides, from the silkworm, Bombyx mori. Comp Biochem Physiol B 1990, 95(3):551-554.
59. Ochiai M, Niki T, Ashida M:Immunocytochemical localization of beta-1,3-glucan recognition protein in the silkworm, Bombyx mori. Cell Tissue Res 1992,268(3):431-437.
60. Ochiai M, Ashida M:A pattern recognition protein for peptidoglycan. Cloning the cDNA and the gene of the silkworm, Bombyx mori. J Biol Chem 1999,274(17):11854-11858.
61. Yoshida H, Kinoshita K, Ashida M:Purification of a peptidoglycan recognition protein from hemolymph of the silkworm, Bombyx mori. J Biol Chem 1996,271(23):13854-13860.
62. Iketani M, Nishimura H, Akayama K, Yamano Y, Morishima I:Minimum structure of peptidoglycan required for induction of antibacterial protein synthesis in the silkworm, Bombyx mori. Insect Biochem Mol Biol 1999,29(1):19-24.
63. Lee WJ, Lee JD, Kravchenko VV, Ulevitch RJ, Brey PT:Purification and molecular cloning of an inducible gram-negative bacteria-binding protein from the silkworm, Bombyx mori. Proc Natl Acad Sci U S A 1996,93(15):7888-7893.
64. Sumida M, Ichimori H, Johchi S, Takaoka A, Yuhki T, Mori H, Matsubara F:Antibacterial activity inducible in the haemolymph of the silkworm, Bombyx mori, by injection of formalin-treated Escherichia coli K-12 during the fifth larval instar and pharate adult development. Comp Biochem Physiol B 1992,101(1-2):165-171.
65. Sumida M, Ichimori H, Yuhki T, Mori H, Matsubara F:Induction of antibacterial activity in the haemolymph of the silkworm, Bombyx mori, by injection of formalin-treated Escherichia coli K-12 in the anterior and posterior body part of the ligated larvae. Comp Biochem Physiol B 1992,101(1-2):173-178.
66. Brey PT, Lee WJ, Yamakawa M, Koizumi Y, Perrot S, Francois M, Ashida M:Role of the integument in insect immunity:epicuticular abrasion and induction of cecropin synthesis- in cuticular epithelial cells. Proc Natl Acad Sci U S A 1993,90(13):6275-6279.
67. Chowdhury S, Taniai K, Hara S, Kadono-Okuda K, Kato Y, Yamamoto M, Xu J, Choi SK, Debnath NC, Choi HK et al:cDNA cloning and gene expression of lebocin, a novel member of antibacterial peptides from the silkworm, Bombyx mori. Biochem Biophys Res Commun 1995,214(1):271-278.
68. Hara S, Yamakawa M:Moricin, a novel type of antibacterial peptide isolated from the silkworm, Bombyx mori. J Biol Chem 1995,270(50):29923-29927.
69. Hara S, Yamakawa M:A novel antibacterial peptide family isolated from the silkworm, Bombyx mori. Biochem J 1995,310 (Pt 2):651-656.
70. Hara S, Yamakawa M:Production in Escherichia of moricin, a novel type antibacterial peptide from the silkworm, Bombyx mori. Biochem Biophys Res Commun 1996, 220(3):664-669.
71. Morishima I, Horiba T, Iketani M, Nishioka E, Yamano Y:Parallel induction of cecropin and lysozyme in larvae of the silkworm, Bombyx mori. Dev Comp Immunol 1995,19(5):357-363.
72. Morishima I, Yamano Y, Inoue K, Matsuo N:Eicosanoids mediate induction of immune genes in the fat body of the silkworm, Bombyx mori. FEBS Lett 1997,419(1):83-86.
73. Furukawa S, Taniai K, Ishibashi J, Hara S, Shono T, Yamakawa M:A novel member of lebocin gene family from the silkworm, Bombyx mori. Biochem Biophys Res Commun 1997, 238(3):769-774.
74. Taniai K, Wago H, Yamakawa M:In vitro phagocytosis of Escherichia coli and release of lipopolysaccharide by adhering hemocytes of the silkworm, Bombyx mori. Biochem Biophys Res Commun 1997,231(3):623-627.
75. Yamano Y, Matsumoto M, Sasahara K, Sakamoto E, Morishima I:Structure of genes for cecropin A and an inducible nuclear protein that binds to the promoter region of the genes from the silkworm, Bombyx mori. Biosci Biotechnol Biochem 1998,62(2):237-241.
76. Furukawa S, Tanaka H, Nakazawa H, Ishibashi J, Shono T, Yamakawa M:Inducible gene expression of moricin, a unique antibacterial peptide from the silkworm (Bombyx mori). Biochem J 1999,340 (Pt 1):265-271.
77. Furukawa S, Taniai K, Yang J, Shono T, Yamakawa M:Induction of gene expression of antibacterial proteins by chitin oligomers in the silkworm, Bombyx mori. Insect Mol Biol 1999,8(1):145-148.
78. Yang J, Furukawa S, Sagisaka A, Ishibashi J, Taniai K, Shono T, Yamakawa M:cDNA cloning and gene expression of cecropin D, an antibacterial protein in the silkworm, Bombyx mori. Comp Biochem Physiol B Biochem Mol Biol 1999,122(4):409-414.
79. Kotani E, Yamakawa M, Iwamoto S, Tashiro M, Mori H, Sumida M, Matsubara F, Taniai K, Kadono-Okuda K, Kato Y et al: Cloning and expression of the gene of hemocytin, an insect humoral lectin which is homologous with the mammalian von Willebrand factor. Biochim Biophys Acta 1995,1260(3):245-258.
80. Lee WJ, Brey PT:Isolation and characterization of the lysozyme-encoding gene from the silkworm Bombyx mori. Gene 1995,161(2):199-203.
81. Koizumi N, Morozumi A, Imamura M, Tanaka E, Iwahana H, Sato R: Lipopolysaccharide-binding proteins and their involvement in the bacterial clearance from the hemolymph of the silkworm Bombyx mori. Eur J Biochem 1997,248(1):217-224.
82. Koizumi N, Imamura M, Kadotani T, Yaoi K, Iwahana H, Sato R:The lipopolysaccharide-binding protein participating in hemocyte nodule formation in the silkworm Bombyx mori is a novel member of the C-type lectin superfamily with two different tandem carbohydrate-recognition domains. FEBS Lett 1999,443(2):139-143.
83. Cheng T, Zhao P, Liu C, Xu P, Gao Z, Xia Q, Xiang Z:Structures, regulatory regions, and inductive expression patterns of antimicrobial peptide genes in the silkworm Bombyx mori. Genomics 2006,87(3):356-365.
84. Hong SM, Kusakabe T, Lee JM, Tatsuke T, Kawaguchi Y, Kang MW, Kang SW, Kim KA, Nho SK:Structure and expression analysis of the cecropin-E gene from the silkworm, Bombyx mori. Biosci Biotechnol Biochem 2008,72(8):1992-1998.
85. Kaneko Y, Tanaka H, Ishibashi J, Iwasaki T, Yamakawa M:Gene expression of a novel defensin antimicrobial peptide in the silkworm, Bombyx mori. Biosci Biotechnol Biochem 2008,72(9):2353-2361.
86. Kawaoka S, Katsuma S, Daimon T, Isono R, Omuro N, Mita K, Shimada T:Functional analysis of four Gloverin-like genes in the silkworm, Bombyx mori. Arch Insect Biochem Physiol 2008,67(2):87-96.
87. Hemmi H, Ishibashi J, Hara S, Yamakawa M:Solution structure of moricin, an antibacterial peptide, isolated from the silkworm Bombyx mori. FEBS Lett 2002,518(1-3):33-38.
88. Wen H, Lan X, Cheng T, He N, Shiomi K, Kajiura Z, Zhou Z, Xia Q, Xiang Z, Nakagaki M: Sequence structure and expression pattern of a novel anionic defensin-like gene from silkworm (Bombyx mori). Mol Biol Rep 2009,36(4):711-716.
89. 刘忠渊金,郑树涛,徐涛,张富春：新疆家蚕抗菌肽抗菌作用的超微结构观察及抗菌机理初探.动物学杂志2008,43(2)：14-20.
90. 孙伟沈,向仲怀,张泽：家蚕抗菌肽基因研究进展.蚕业科学2009，35(1)：196-203.
91. Ochiai M, Ashida M:A pattern-recognition protein for beta-1,3-glucan. The binding domain and the cDNA cloning of beta-1,3-glucan recognition protein from the silkworm, Bombyx mori. JBiol Chem 2000,275(7):4995-5002.
92. Prasad MD, Han SJ, Nagaraju J, Lee WJ, Brey PT:Cloning and characterization of an eukaryotic initiation factor-2alpha kinase from the silkworm, Bombyx mori. Biochim Biophys Acta 2003,1628(1):56-63.
93. Hyrsl P, Ciz M, Kubala L, Lojek A:Silkworm (Bombyx mori) hemocytes do not produce reactive oxygen metabolites as a part of defense mechanisms. Folia Microbiol (Praha) 2004, 49(3):315-319.
94. Kim I, Kim SH, Lee YS, Yun EK, Lee HS, Kim JW, Ryu KS, Kang PD, Lee IH:Immune stimulation in the silkworm, Bombyx mori L., by CpG oligodeoxynucleotides. Arch Insect Biochem Physiol 2004,55(1):43-48.
95. Tanaka H, Sagisaka A, Fujita K, Kaneko Y, Imanishi S, Yamakawa M:Lipopolysaccharide elicits expression of immune-related genes in the silkworm, Bombyx mori. Insect Mol Biol 2009,18(1):71-75.
96. Tanaka H, Suzuki N, Nakajima Y, Sato M, Sagisaka A, Fujita K, Ishibashi J, Imanishi S, Mita K, Yamakawa M:Expression profiling of novel bacteria-induced genes from the silkworm, Bombyx mori. Arch Insect Biochem Physiol,73(3):148-162.
97. Imamura M, Yang J, Yamakawa M:cDNA cloning, characterization and gene expression of nitric oxide synthase from the silkworm, Bombyx mori. Insect Mol Biol 2002, 11(3):257-265.
98. Hu ZG, Chen KP, Yao Q, Gao GT, Xu JP, Chen HQ:Cloning and characterization of Bombyx mori PP-BP a gene induced by viral infection. Yi ChuanXue Bao 2006,33(11):975-983.
99. Wang Y, Cheng T, Rayaprolu S, Zou Z, Xia Q, Xiang Z, Jiang H:Proteolytic activation of pro-spatzle is required for the induced transcription of antimicrobial peptide genes in lepidopteran insects. Dev Comp Immunol 2007,31(10):1002-1012.
100. Cheng TC, Zhang YL, Liu C, Xu PZ, Gao ZH, Xia QY, Xiang ZH:Identification and analysis of Toll-related genes in the domesticated silkworm, Bombyx mori. Dev Comp Immunol 2008, 32(5):464-475.
101. Imamura M, Yamakawa M:Molecular cloning and expression of a Toll receptor gene homologue from the silkworm, Bombyx mori. Biochim Biophys Acta 2002,1576(3):246-254.
102. Wu S, Zhang X, Chen X, Cao P, Beerntsen BT, Ling E:BmToll9, an Arthropod conservative Toll, is likely involved in the local gut immune response in the silkworm, Bombyx mori. Dev Comp Immunol,34(2):93-96.
103. Tanaka H, Yamamoto M, Moriyama Y, Yamao M, Furukawa S, Sagisaka A, Nakazawa H, Mori H, Yamakawa M:A novel Rel protein and shortened isoform that differentially regulate antibacterial peptide genes in the silkworm Bombyx mori. Biochim Biophys Acta 2005, 1730(1):10-21.
104. Tanaka H, Sagisaka A, Nakajima Y, Fujita K, Imanishi S, Yamakawa M:Correlation of differential expression of silkworm antimicrobial Peptide genes with different amounts of rel family proteins and their gene transcriptional activity. Biosci Biotechnol Biochem 2009, 73(3):599-606.
105. Tanaka H, Matsuki H, Furukawa S, Sagisaka A, Kotani E, Mori H, Yamakawa M:Identification and functional analysis of Relish homologs in the silkworm, Bombyx mori. Biochim Biophys Acta 2007,1769(9-10):559-568.
106. Kaneko Y, Furukawa S, Tanaka H, Yamakawa M:Expression of antimicrobial peptide genes encoding Enbocin and Gloverin isoforms in the silkworm, Bombyx mori. Biosci Biotechnol Biochem 2007,71(9):2233-2241.
107. Xia Q, Zhou Z, Lu C, Cheng D, Dai F, Li B, Zhao P, Zha X, Cheng T, Chai C et al: A draft sequence for the genome of the domesticated silkworm (Bombyx mori). Science 2004, 306(5703):1937-1940.
108.程廷才：家蚕免疫系统相关基因的鉴定及其诱导表达模式研究.博士学位论文2008.
109. Tanaka H, Ishibashi J, Fujita K, Nakajima Y, Sagisaka A, Tomimoto K, Suzuki N, Yoshiyama M, Kaneko Y, Iwasaki T et al: A genome-wide analysis of genes and gene families involved in innate immunity of Bombyx mori. Insect Biochem Mol Biol 2008,38(12):1087-1110.
110. Nakahara Y, Kanamori Y, Kiuchi M, Kamimura M:Effects of silkworm paralytic peptide on in vitro hematopoiesis and plasmatocyte spreading. Arch Insect Biochem Physiol 2003, 52(4):163-174.
111. Nakahara Y, Shimura S, Ueno C, Kanamori Y, Mita K, Kiuchi M, Kamimura M:Purification and characterization of silkworm hemocytes by flow cytometry. Dev Comp Immunol 2009, 33(4):439-448.
112. Kaito C, Akimitsu N, Watanabe H, Sekimizu K:Silkworm larvae as an animal model of bacterial infection pathogenic to humans. Microb Pathog 2002,32(4):183-190.
113. Liu F, Ling E, Wu S:Gene expression profiling during early response to injury and microbial challenges in the silkworm, Bombyx mori. Arch Insect Biochem Physiol 2009, 72(1):16-33.
114. Sagisaka A, Fujita K, Nakamura Y, Ishibashi J, Noda H, Imanishi S, Mita K, Yamakawa M, Tanaka H:Genome-wide analysis of host gene expression in the silkworm cells infected with Bombyx mori nucleopolyhedrovirus. Virus Res 2009,147(2):166-175.
115. Wang Y, Zhang P, Fujii H, Banno Y, Yamamoto K, Aso Y:Proteomic studies of lipopolysaccharide-induced polypeptides in the silkworm, Bombyx mori. Biosci Biotechnol Biochem 2004,68(8):1821-1823.
116. 吕鸿声编著：昆虫免疫学原理.上海科学技术出版社2008.
117. 向仲怀主编：蚕丝生物学.中国林业出版社2005：254.
118. 吕鸿声,钱纪放编译：昆虫病理学.浙江科学技术出版社1982.
119. 宋爽 刘朱杨：家蚕传染病的检查与诊断.云南农业科技2008：65.
120. 陈亚梅,黄俊荣：家蚕细菌性败血病的发生与防治.云南农业科技2008：83-84.
121. 林国杂 陈,黄志君,李文楚：败血病菌感染家蚕马氏管组织碱性磷酸酶的病理学研究.广东蚕业，39(4)：28-31.
122. 李文楚：软化病感染家蚕的碱性磷酸酶活力测定及病理学究.华南农业大学学报2004,25(4)：120-122.
123. 王明霞,王连芳,丁礼全：对家蚕真菌病危害加重原因的调查及防治措施.江苏蚕业2007(1)：2.
124. 朱方容：广西部分地区桑蚕僵病流行的原因及防控对策.广西蚕业2008，45(3)：29-32.
125. K.马拉莫斯奇主编,刘岱岳、谭业平译：昆虫病毒图谱.农业出版社1982.
126. 黄知源：我国蚕型多角体病发生近况及其防疫.中国农学通报2001,17(3)：77-78.
127. 吴强：对陕西汉台家蚕血液型脓病为害加重原因的调查与防治对策.蚕学通讯2006,26(2)：32-35.
128. Shigematsu H, Noguchi A:Biochemical studies on the multiplication of a nuclear-polyhedrosis virus in the silkworm, Bombyx mori. I. Nucleic-acid synthesis in larval tissues after infection. J Invertebr Pathol 1969,14(2):143-149.
129. Shigematsu H, Noguchi A:Biochemical studies on the multiplication of a nuclear-polyhedrosis virus in the silkworm, Bombyx mori. II. Protein synthesis in larval tissues after infection. J Invertebr Pathol 1969,14(3):301-307.
130. Shigematsu H, Noguchi A:Biochemical studies on the multiplication of a nuclear-polyhedrosis virus in the silkworm, Bombyx mori. 3. Functional changes in infected cells, with reference to the synthesis of nucleic acids and proteins. J Invertebr Pathol 1969,14(3):308-315.
131. Rahman MM, Gopinathan KP:Systemic and in vitro infection process of Bombyx mori nucleopolyhedrovirus. Virus Res 2004,101(2):109-118.
132. 杨大帧、夏如山主编：实用蚕病学.四川科学技术出版社1992.
133. 闻玉梅主编：现代医学微生物学.上海医科学出版社1999.
134. Xia Q, Cheng D, Duan J, Wang G, Cheng T, Zha X, Liu C, Zhao P, Dai F, Zhang Z et al: Microarray-based gene expression profiles in multiple tissues of the domesticated silkworm, Bombyx mori. Genome Biol 2007,8(8):R162.
135. Yang YH, Dudoit S, Luu P, Lin DM, Peng V, Ngai J, Speed TP:Normalization for cDNA microarray data:a robust composite method addressing single and multiple slide systematic variation. Nucleic Acids Res 2002,30(4):e15.
136. Aoki KF, Kanehisa M:Using the KEGG database resource. Curr Protoc Bioinformatics 2005, Chapter 1:Unit 1 12.
137. Zhang R, Li X, Jiang Y, Liu G, Li C, Zhang F, Xiao Y, Gong B:Novel strategies to mine alcoholism-related haplotypes and genes by combining existing knowledge framework.Sci China C Life Sci 2009,52(2):163-172.
138. Masoudi-Nejad A, Goto S, Endo TR, Kanehisa M: KEGG bioinformatics resource for plant genomics research. Methods Mol Biol 2007,406:437-458.
139. Hashimoto K, Goto S, Kawano S, Aoki-Kinoshita KF, Ueda N, Hamajima M, Kawasaki T, Kanehisa M:KEGG as a glycome informatics resource. Glycobiology 2006,16(5):63R-70R.
140. Neill JD, Ridpath JF:Gene expression changes in BVDV2-infected MDBK cells. Biologicals 2003,31(2):97-102.
141. Kamatani N:Abnormalities in nucleic acid metabolism and gout. Nippon Naika Gakkai Zasshi 1997,86(3):374-379.
142. The genome of a lepidopteran model insect, the silkworm Bombyx mori. Insect Biochem Mol Biol 2008,38(12):1036-1045.
143. Vermunt AM, Kamimura M, Hirai M, Kiuchi M, Shiotsuki T:The juvenile hormone binding protein of silkworm haemolymph:gene and functional analysis. Insect Mol Biol 2001, 10(2):147-154.
144. 程道军：家蚕变态发育相关基因的基因组研究.博士学位论文2008.
145. Brasier AR:The NF-kappaB regulatory network. Cardiovasc Toxicol 2006,6(2):111-130.
146. Buttice G, Duterque-Coquillaud M, Basuyaux JP, Carrere S, Kurkinen M, Stehelin D:Erg, an Ets-family member, differentially regulates human collagenase1 (MMP1) and stromelysinl (MMP3)gene expression by physically interacting with the Fos/Jun complex. Oncogene 1996,13(11):2297-2306.
147. Sekimoto T, Iwami M, Sakurai S:20-Hydroxyecdysone regulation of two isoforms of the Ets transcription factor E74 gene in programmed cell death in the silkworm anterior silk gland. Insect Mol Biol 2007,16(5):581-590.
148. Song H, Sun Y, Zhang Y, Li M:Molecular cloning and characterization of Bombyx mori CREB gene. Arch Insect Biochem Physiol 2009,71(1):31-44.
149. Lefort S, Soucy-Faulkner A, Grandvaux N, Flamand L:Binding of Kaposi's sarcoma-associated herpesvirus K-bZIP to interferon-responsive factor 3 elements modulates antiviral gene expression. J Virol 2007,81(20):10950-10960.
150. Furlong MJ, Groden E:Starvation induced stress and the susceptibility of the Colorado potato beetle, Leptinotarsa decemlineata, to infection by Beauveria bassiana. J Invertebr Pathol 2003,83(2):127-138.
151. Tian CH, Tang XD, Xu HJ, Ge JQ, Miao YG, Zhang CX:Bombyx mori nucleopolyhedrovirus ORF51 encodes a budded virus envelope associated protein. Virus Genes 2009, 38(1):171-177.
152. 步宏主编：分子病理学进展.四川大学出版社2006：164-166.
153. Muramatsu D, Kinjoh T, Shinoda T, Hiruma K:The role of 20-hydroxyecdysone and juvenile hormone in pupal commitment of the epidermis of the silkworm, Bombyx mori. Mech Dev 2008,125(5-6):411-420.
154. Otaki T, Takeuchi S, Mori K:Juvenile hormone and synthetic analogues:effects on larval moult of silkworm, Bombyx mori. Jpn J Med Sci Biol 1971,24(4):251-255.
155. Bhattacharyya R, Noch EK, Khalili K:A novel role of Racl GTPase in JCV T-antigen-mediated beta-catenin stabilization. Oncogene 2007,26(55):7628-7636.
156. Nusse R:Wnt signaling in disease and in development. Cell Res 2005,15(1):28-32.
157. Logan CY, Nusse R:The Wnt signaling pathway in development and disease. Annu Rev Cell Dev Biol 2004,20:781-810.
158. Liu C, Wang Y, Smallwood PM, Nathans J:An essential role for Frizzled5 in neuronal survival in the parafascicular nucleus of the thalamus. J Neurosci 2008,28(22):5641-5653.
159. Croce J, Duloquin L, Lhomond G, McClay DR, Gache C:Frizzled5/8 is required in secondary mesenchyme cells to initiate archenteron invagination during sea urchin development. Development 2006,133(3):547-557.
160. Kemp CR, Willems E, Wawrzak D, Hendrickx M, Agbor Agbor T, Leyns L:Expression of Frizzled5, Frizzled7, and Frizzled10 during early mouse development and interactions with canonical Wnt signaling. Dev Dyn 2007,236(7):2011-2019.
161. Raman M, Chen W, Cobb MH:Differential regulation and properties of MAPKs. Oncogene 2007,26(22):3100-3112.
162. Muslin AJ:MAPK signalling in cardiovascular health and disease:molecular mechanisms and therapeutic targets. Clin Sci (Lond) 2008,115(7):203-218.
163. Sangha N, Wu R, Kuick R, Powers S, Mu D, Fiander D, Yuen K, Katabuchi H, Tashiro H, Fearon ER et al: Neurofibromin 1 (NF1) defects are common in human ovarian serous carcinomas and co-occur with TP53 mutations. Neoplasia 2008,10(12):1362-1372, following 1372.
164. MacDonald TJ, Brown KM, LaFleur B, Peterson K, Lawlor C, Chen Y, Packer RJ, Cogen P, Stephan DA:Expression profiling of medulloblastoma:PDGFRA and the RAS/MAPK pathway as therapeutic targets for metastatic disease. Nat Genet 2001,29(2):143-152.
165. Martinho O, Gouveia A, Viana-Pereira M, Silva P, Pimenta A, Reis RM, Lopes JM:Low frequency of MAP kinase pathway alterations in KIT and PDGFRA wild-type GISTs. Histopathology 2009,55(1):53-62.
166. Peippo M, Koivisto AM, Sarkamo T, Sipponen M, von Koskull H, Ylisaukko-oja T, Rehnstrom K, Froyen G, Ignatius J, Jarvela I:PAK3 related mental disability:further characterization of the phenotype. Am J Med Genet A 2007,143A(20):2406-2416.
167. Asano Y, Jimenez-Dalmaroni A, Liverpool TB, Marchetti MC, Giomi L, Kiger A, Duke T, Baum B:Pak3 inhibits local actin filament formation to regulate global cell polarity. Hfsp J 2009, 3(3):194-203.
168. Kim BJ, Ryu SW, Song BJ:JNK- and p38 kinase-mediated phosphorylation of Bax leads to its activation and mitochondrial translocation and to apoptosis of human hepatoma HepG2 cells. J Biol Chem 2006,281(30):21256-21265.
169. Levine AJ, Hu W, Feng Z:The P53 pathway:what questions remain to be explored? Cell Death Differ 2006,13(6):1027-1036.
170. Bell HS, Ryan KM:Targeting the p53 family for cancer therapy:'big brother'joins the fight. Cell Cycle 2007,6(16):1995-2000.
171. Piatti S, Bohm T, Cocker JH, Diffley JF, Nasmyth K:Activation of S-phase-promoting CDKs in late G1 defines a "point of no return" after which Cdc6 synthesis cannot promote DNA replication in yeast. Genes Dev 1996,10(12):1516-1531.
172. Dasika GK, Lin SC, Zhao S, Sung P, Tomkinson A, Lee EY:DNA damage-induced cell cycle checkpoints and DNA strand break repair in development and tumorigenesis. Oncogene 1999,18(55):7883-7899.
173. Laiho M, Latonen L:Cell cycle control, DNA damage checkpoints and cancer. Ann Med 2003, 35(6):391-397.
174. John PC, Mews M, Moore R:Cyclin/Cdk complexes:their involvement in cell cycle progression and mitotic division. Protoplasma 2001,216(3-4):119-142.
175. Mudryj M, Devoto SH, Hiebert SW, Hunter T, Pines J, Nevins JR:Cell cycle regulation of the E2F transcription factor involves an interaction with cyclin A. Cell 1991,65(7):1243-1253.
176. Draetta G, Beach D:The mammalian cdc2 protein kinase:mechanisms of regulation during the cell cycle. J Cell Sci Suppl 1989,12:21-27.
177. Draetta G:Cell cycle control in eukaryotes:molecular mechanisms of cdc2 activation. Trends Biochem Sci 1990,15(10):378-383.
178. Lee KS, Asano S, Park JE, Sakchaisri K, Erikson RL:Monitoring the cell cycle by multi-kinase-dependent regulation of Swe1/Weel in budding yeast. Cell Cycle 2005, 4(10):1346-1349.
179. Eijpe M, Heyting C, Gross B, Jessberger R:Association of mammalian SMC1 and SMC3 proteins with meiotic chromosomes and synaptonemal complexes. J Cell Sci 2000,113 (Pt 4):673-682.
180. Upadhyay AK, Ajay AK, Singh S, Bhat MK:Cell cycle regulatory protein 5 (Cdk5) is a novel downstream target of ERK in carboplatin induced death of breast cancer cells. Curr Cancer Drug Targets 2008,8(8):741-752.
181. Lopes JP, Oliveira CR, Agostinho P:Cdk5 acts as a mediator of neuronal cell cycle re-entry triggered by amyloid-beta and prion peptides. Cell Cycle 2009,8(1):97-104.
182. Philips A, Huet X, Plet A, Rech J, Vignais ML, Vie A, Blanchard JM:[Cyclin A:a good markers for the study of cell cycle control and tumor progression?]. C R Seances Soc Biol Fil 1998,192(2):223-230.
183. Sun A, Bagella L, Tutton S, Romano G, Giordano A:From G0 to S phase:a view of the roles played by the retinoblastoma (Rb) family members in the Rb-E2F pathway. J Cell Biochem 2007,102(6):1400-1404.
184. Yamamuro T, Kano K, Naito K:Functions of FZR1 and CDC20, activators of the anaphase-promoting complex, during meiotic maturation of swine oocytes. Biol Reprod 2008,79(6):1202-1209.
185. Pflumm MF, Botchan MR:Orc mutants arrest in metaphase with abnormally condensed chromosomes. Development 2001,128(9):1697-1707.
186. Dhar SK, Delmolino L, Dutta A:Architecture of the human origin recognition complex. J Biol Chem 2001,276(31):29067-29071.
187. Crosby ME, Jacobberger J, Gupta D, Macklis RM, Almasan A:E2F4 regulates a stable G2 arrest response to genotoxic stress in prostate carcinoma. Oncogene 2007,26(13):1897-1909.
188. Plesca D, Crosby ME, Gupta D, Almasan A:E2F4 function in G2:maintaining G2-arrest to prevent mitotic entry with damaged DNA. Cell Cycle 2007,6(10):1147-1152.
189. Kruidering M, Evan GI:Caspase-8 in apoptosis:the beginning of "the end"? IUBMB Life 2000,50(2):85-90.
190. Cha YJ, Kim HS, Rhim H, Kim BE, Jeong SW, Kim IK:Activation of caspase-8 in 3-deazaadenosine-induced apoptosis of U-937 cells occurs downstream of caspase-3 and caspase-9 without Fas receptor-ligand interaction. Exp Mol Med 2001,33(4):284-292.
191. Bhattacharyya A, Lahiry L, Mandal D, Sa G, Das T:Black tea induces tumor cell apoptosis by Bax translocation, loss in mitochondrial transmembrane potential, cytochrome c release and caspase activation. Int J Cancer 2005,117(2):308-315.
192. Denef VJ, Park J, Tsoi TV, Rouillard JM, Zhang H, Wibbenmeyer JA, Verstraete W, Gulari E, Hashsham SA, Tiedje JM:Biphenyl and benzoate metabolism in a genomic context: outlining genome-wide metabolic networks in Burkholderia xenovorans LB400. Appl Environ Microbiol 2004,70(8):4961-4970.
193. Spizizen J:The effect of virus infection of pyruvate metabolism. Biochim Biophys Acta 1957, 23(2):333-341.
194. Yesilkaya H, Spissu F, Carvalho SM, Terra VS, Homer KA, Benisty R, Porat N, Neves AR, Andrew PW:Pyruvate formate lyase is required for pneumococcal fermentative metabolism and virulence. Infect Immun 2009.
195. Webster HK, Whaun JM:Purine metabolism during continuous erythrocyte culture of human malaria parasites (P. falciparum). Prog Clin Biol Res 1981,55:557-573.
196. Becker W:Purine metabolism in Biomphalaria glabrata under starvation and infection with Schistosoma mansoni. Comp Biochem Physiol B 1983,76(2):215-219.
197. Gandra YR, Scrimsha WN:Infection and nutritional status. II. Effect of mild virus infection induced by 17-D yellow fever vaccine on nitrogen metabolism in children. Am J Clin Nutr 1961,9:159-163.
198. Bucovaz ET, Macleod RM, Morrison JC, Whybrew WD:The coenzyme A-synthesizing protein complex and its proposed role in CoA biosynthesis in bakers' yeast. Biochimie 1997, 79(12):787-798.
199. Bron PA, Grangette C, Mercenier A, de Vos WM, Kleerebezem M:Identification of Lactobacillus plantarum genes that are induced in the gastrointestinal tract of mice. J Bacteriol 2004,186(17):5721-5729.
200. Wei BL, Denton PW, O'Neill E, Luo T, Foster JL, Garcia JV:Inhibition of lysosome and proteasome function enhances human immunodeficiency virus type 1 infection. J Virol 2005, 79(9):5705-5712.
201. Shalitin D, Wolf S:Cucumber mosaic virus infection affects sugar transport in melon plants. Plant Physiol 2000,123(2):597-604.
202. Murti KG, Goorha R:Interaction of frog virus-3 with the cytoskeleton. I. Altered organization of microtubules, intermediate filaments, and microfilaments. J Cell Biol 1983, 96(5):1248-1257.
203. Tilney LG, DeRosier DJ, Tilney MS:How Listeria exploits host cell actin to form its own cytoskeleton. I. Formation of a tail and how that tail might be involved in movement. J Cell Biol 1992,118(1):71-81.
204. Tsarfaty I, Sandovsky-Losica H, Mittelman L, Berdicevsky I, Segal E:Cellular actin is affected by interaction with Candida albicans. FEMS Microbiol Lett 2000,189(2):225-232.
205. Root-Bernstein R, Vonck J, Podufaly A:Antigenic complementarity between coxsackie virus and streptococcus in the induction of rheumatic heart disease and autoimmune myocarditis. Autoimmunity 2009,42(1):1-16.
206. Wei T, Shimizu T, Omura T:Endomembranes and myosin mediate assembly into tubules of Pns10 of Rice dwarf virus and intercellular spreading of the virus in cultured insect vector cells. Virology 2008,372(2):349-356.
207. Lehmann MJ, Sherer NM, Marks CB, Pypaert M, Mothes W:Actin-and myosin-driven movement of viruses along filopodia precedes their entry into cells. J Cell Biol 2005, 170(2):317-325.
208. Ridgway ID, Small HJ, Atkinson RJ, Birkbeck HT, Taylor AC, Neil DM:Extracellular proteases and possible disease related virulence mechanisms of two marine bacteria implicated in an opportunistic bacterial infection of Nephrops norvegicus. J Invertebr Pathol 2008,99(1):14-19.
209. Fan Y, Zhang Y, Yang X, Pei X, Guo S, Pei Y:Expression of a Beauveria bassiana chitinase (Bbchitl) in Escherichia coli and Pichia pastoris. Protein Expr Pur if 2007,56(1):93-99.
210. Qiuhong N, Xiaowei H, Baoyu T, Jinkui Y, Jiang L, Lin Z, Keqin Z:Bacillus sp. B16 kills nematodes with a serine protease identified as a pathogenic factor. Appl Microbiol Biotechnol 2006,69(6):722-730.
211. Niu Q, Huang X, Zhang L, Li Y, Li J, Yang J, Zhang K:A neutral protease from Bacillus nematocida, another potential virulence factor in the infection against nematodes. Arch Microbiol 2006,185(6):439-448.
212. Tellam RL, Wijffels G, Willadsen P:Peritrophic matrix proteins. Insect Biochem Mol Biol 1999,29(2):87-101.
213. Nagase H:Metalloproteases. Curr Protoc Protein Sci 2001, Chapter 21:Unit 21 24.
214. Prakobwong S, Pinlaor S, Yongvanit P, Sithithaworn P, Pairojkul C, Hiraku Y:Time profiles of the expression of metalloproteinases, tissue inhibitors of metalloproteases, cytokines and collagens in hamsters infected with Opisthorchis viverrini with special reference to peribiliary fibrosis and liver injury. Int J Parasitol 2009,39(7):825-835.
215. Pigott CR, Ellar DJ:Role of receptors in Bacillus thuringiensis crystal toxin activity. Microbiol Mol Biol Rev 2007,71(2):255-281.
216. Fernandez LE, Gomez I, Pacheco S, Arenas I, Gilla SS, Bravo A, Soberon M:Employing phage display to study the mode of action of Bacillus thuringiensis Cry toxins. Peptides 2008, 29(2):324-329.
217. Miguel B, Pharr GT, Wang C:The role of feline aminopeptidase N as a receptor for infectious bronchitis virus. Brief review. Arch Virol 2002,147(11):2047-2056.
218. Lassnig C, Kolb A, Strobl B, Enjuanes L, Muller M:Studying human pathogens in animal models:fine tuning the humanized mouse. Transgenic Res 2005,14(6):803-806.
219. Ohara-Nemoto Y, Sasaki M, Kaneko M, Nemoto T, Ota M:Cysteine protease activity of streptococcal pyrogenic exotoxin B. Can JMicrobiol 1994,40(11):930-936.
220. Ohta M, Hayashi K:Inactivation of toxin B from the Indian cobra by cleavage of a specific bond during limited hydrolysis with trypsin. Biochem Int 1984,9(2):243-250.
221. Pinkney M, Kapur V, Smith J, Weller U, Palmer M, Glanville M, Messner M, Musser JM, Bhakdi S, Kehoe MA:Different forms of streptolysin O produced by Streptococcus pyogenes and by Escherichia coli expressing recombinant toxin:cleavage by streptococcal cysteine protease. Infect Immun 1995,63(7):2776-2779.
222. Ferreira-DaSilva CT, Gombarovits ME, Masuda H, Oliveira CM, Carlini CR:Proteolytic activation of canatoxin, a plant toxic protein, by insect cathepsin-like enzymes. Arch Insect Biochem Physiol 2000,44(4):162-171.
223. Lemaitre B, Hoffmann J:The host defense of Drosophila melanogaster. Annu Rev Immunol 2007,25:697-743.
224. Kan H, Kim CH, Kwon HM, Park JW, Roh KB, Lee H, Park BJ, Zhang R, Zhang J, Soderhall K et al:Molecular control of phenoloxidase-induced melanin synthesis in an insect. J Biol Chem 2008,283(37):25316-25323.
225. An C, Ishibashi J, Ragan EJ, Jiang H, Kanost MR:Functions of Manduca sexta hemolymph proteinases HP6 and HP8 in two innate immune pathways. J Biol Chem 2009, 284(29):19716-19726.
226. Mangan MS, Kaiserman D, Bird PI:The role of serpins in vertebrate immunity. Tissue Antigens 2008,72(1):1-10.
227. Wang WX, Wang YP, Deng XJ, Dang XL, Tian JH, Yi HY, Li YF, He XF, Cao Y, Xia QY et al: Molecular and functional characterization of a c-type lysozyme from the Asian corn borer, Ostrinia furnacalis. J Insect Sci 2009,9:17.
228. Gandhe AS, Janardhan G, Nagaraju J:Immune upregulation of novel antibacterial proteins from silkmoths (Lepidoptera) that resemble lysozymes but lack muramidase activity. Insect Biochem Mol Biol 2007,37(7):655-666.
229. De Gregorio E, Han SJ, Lee WJ, Baek MJ, Osaki T, Kawabata S, Lee BL, Iwanaga S, Lemaitre B, Brey PT:An immune-responsive Serpin regulates the melanization cascade in Drosophila. Dev Cell 2002,3(4):581-592.
230. Rinaldo CR, Jr., Torpey DJ,3rd:Cell-mediated immunity and immunosuppression in herpes simplex virus infection. Immunodeficiency 1993,5(1):33-90.
231. Glinski Z, Jarosz J:Molluscan immune defenses. Arch Immunol Ther Exp (Warsz) 1997, 45(2-3):149-155.
232. Waterhouse RM, Kriventseva EV, Meister S, Xi Z, Alvarez KS, Bartholomay LC, Barillas-Mury C, Bian G, Blandin S, Christensen BM et al:Evolutionary dynamics of immune-related genes and pathways in disease-vector mosquitoes. Science 2007,316(5832):1738-1743.
233. Takase H, Watanabe A, Yoshizawa Y, Kitami M, Sato R:Identification and comparative analysis of three novel C-type lectins from the silkworm with functional implications in pathogen recognition. Dev Comp Immunol 2009,33(6):789-800.
234. Watanabe A, Miyazawa S, Kitami M, Tabunoki H, Ueda K, Sato R:Characterization of a novel C-type lectin, Bombyx mori multibinding protein, from the B. mori hemolymph: mechanism of wide-range microorganism recognition and role in immunity. J Immunol 2006,177(7):4594-4604.
235. Bettencourt R, Assefaw-Redda Y, Faye I:The insect immune protein hemolin is expressed during oogenesis and embryogenesis. Mech Dev 2000,95(1-2):301-304.
236. Garver LS, Xi Z, Dimopoulos G:Immunoglobulin superfamily members play an important role in the mosquito immune system. Dev Comp Immunol 2008,32(5):519-531.
237. Huang L, Cheng T, Xu P, Duan J, Fang T, Xia Q:Immunoglobulin superfamily is conserved but evolved rapidly and is active in the silkworm, Bombyx mori. Insect Mol Biol 2009, 18(4):517-530.
238. Pancer Z, Amemiya CT, Ehrhardt GR, Ceitlin J, Gartland GL, Cooper MD:Somatic diversification of variable lymphocyte receptors in the agnathan sea lamprey. Nature 2004, 430(6996):174-180.
239. Agarwala KL, Nakamura S, Tsutsumi Y, Yamakawa K:Down syndrome cell adhesion molecule DSCAM mediates homophilic intercellular adhesion. Brain Res Mol Brain Res 2000,79(1-2):118-126.
240. Zou Z, Shin SW, Alvarez KS, Bian G, Kokoza V, Raikhel AS:Mosquito RUNX4 in the immune regulation of PPO gene expression and its effect on avian malaria parasite infection. Proc Natl Acad Sci USA 2008,105(47):18454-18459.
241. Hartzer KL, Zhu KY, Baker JE:Phenoloxidase in larvae of Plodia interpunctella (Lepidoptera:Pyralidae):molecular cloning of the proenzyme cDNA and enzyme activity in larvae paralyzed and parasitized by Habrobracon hebetor (Hymenoptera:Braconidae). Arch Insect Biochem Physiol 2005,59(2):67-79.
242. Schmidt RL, Trejo TR, Plummer TB, Platt JL, Tang AH:Infection-induced proteolysis of PGRP-LC controls the IMD activation and melanization cascades in Drosophila. Faseb J 2008,22(3):918-929.
243. Ashida M, Ochiai M, Niki T:Immunolocalization of prophenoloxidase among hemocytes of the silkworm, Bombyx mori. Tissue Cell 1988,20(4):599-610.
244. Satoh D, Horii A, Ochiai M, Ashida M:Prophenoloxidase-activating enzyme of the silkworm, Bombyx mori. Purification, characterization, and cDNA cloning. J Biol Chem 1999, 274(11):7441-7453.
245. Naitza S, Ligoxygakis P:Antimicrobial defences in Drosophila:the story so far. Mol Immunol 2004,40(12):887-896.
246. Tanji T, Hu X, Weber AN, Ip YT:Toll and IMD pathways synergistically activate an innate immune response in Drosophila melanogaster. Mol Cell Biol 2007,27(12):4578-4588.
247. Hayashi F, Smith KD, Ozinsky A, Hawn TR, Yi EC, Goodlett DR, Eng JK, Akira S, Underhill DM, Aderem A:The innate immune response to bacterial flagellin is mediated by Toll-like receptor 5. Nature 2001,410(6832):1099-1103.
248. Massari P, Henneke P, Ho Y, Latz E, Golenbock DT, Wetzler LM:Cutting edge:Immune stimulation by neisserial porins is toll-like receptor 2 and MyD88 dependent. J Immunol 2002,168(4):1533-1537.
249. Towb P, Galindo RL, Wasserman SA:Recruitment of Tube and Pelle to signaling sites at the surface of the Drosophila embryo. Development 1998,125(13):2443-2450.
250. Ferrandon D, Imler JL, Hetru C, Hoffmann JA:The Drosophila systemic immune response: sensing and signalling during bacterial and fungal infections. Nat Rev Immunol 2007, 7(11):862-874.
251. Matova N, Anderson KV:Rel/NF-kappaB double mutants reveal that cellular immunity is central to Drosophila host defense. Proc Natl Acad Sci U S A 2006,103(44):16424-16429.
252. O'Shea JJ, Gadina M, Schreiber RD:Cytokine signaling in 2002:new surprises in the Jak/Stat pathway. Cell 2002,109 Suppl:S121-131.
253. Luo H, Dearolf CR:The JAK/STAT pathway and Drosophila development. Bioessays 2001, 23(12):1138-1147.
254. Pourquie O:The segmentation clock:converting embryonic time into spatial pattern. Science 2003,301(5631):328-330.
255. Grace MJ, Cutler D:Pegylating IFNs at his-34 improves the in vitro antiviral activity through the JAK/STAT pathway. Antivir Chem Chemother 2004,15(6):287-297.
256. Chaudhuri A, Yang B, Gendelman HE, Persidsky Y, Kanmogne GD:STAT1 signaling modulates HIV-1-induced inflammatory responses and leukocyte transmigration across the blood-brain barrier. Blood 2008, 111(4):2062-2072.
257. 余子全：苏云金芽胞杆菌杀线虫蛋白基因cry6Aa的表达负调控及杀线虫晶体蛋白进入根结线虫体内的模式.博士学位论文2007.
258. 李赛男：昆虫中肠Bt毒素受体氨肽酶N的研究进展.安徽农业科学2007，35(9)：2523-2525.
259. Takesue S, Yokota K, Miyajima S, Taguchi R, Ikezawa H, Takesue Y:Partial release of aminopeptidase N from larval midgut cell membranes of the silkworm, Bombyx mori, by phosphatidylinositol-specific phospholipase C. Comp Biochem Physiol B 1992,102(1):7-11.
260. Yaoi K, Kadotani T, Kuwana H, Shinkawa A, Takahashi T, Iwahana H, Sato R:Aminopeptidase N from Bombyx mori as a candidate for the receptor of Bacillus thuringiensis CrylAa toxin. Eur J Biochem 1997,246(3):652-657.
261. Hua G, Tsukamoto K, Taguchi R, Tomita M, Miyajima S, Ikezawa H:Characterization of aminopeptidase N from the brush border membrane of the larvae midgut of silkworm, Bombyx mori as a zinc enzyme. Biochim Biophys Acta 1998,1383(2):301-310.
262. Shinkawa A, Yaoi K, Kadotani T, Imamura M, Koizumi N, Iwahana H, Sato R:Binding of phylogenetically distant Bacillus thuringiensis cry toxins to a Bombyx mori aminopeptidase N suggests importance of Cry toxin's conserved structure in receptor binding. Curr Microbiol 1999,39(1):14-20.
263. Jenkins JL, Dean DH:Binding specificity of Bacillus thuringiensis CrylAa for purified, native Bombyx mori aminopeptidase N and cadherin-like receptors. BMC Biochem 2001, 2:12.
264. 余洁,林锦庄,黄勤清,等：苏云金芽孢杆菌对新秀丽小杆线虫的作用.农业生物技术学报2007,15(2)：306-311.
265. 张红：Bt基因重组工程菌毒蛋白的表达及其对昆虫的毒性研究.硕士学位论文2004.
266. Ihara H, Himeno M:Study of the irreversible binding of Bacillus thuringiensis CrylAa to brush border membrane vesicles from Bombyx mori midgut. J Invertebr Pathol 2008, 98(2):177-183.
267. Nakanishi K, Yaoi K, Nagino Y, Hara H, Kitami M, Atsumi S, Miura N, Sato R: Aminopeptidase N isoforms from the midgut of Bombyx mori and Plutella xylostella -their classification and the factors that determine their binding specificity to Bacillus thuringiensis CrylA toxin. FEBS Lett 2002,519(1-3):215-220.
268. Li H, Oppert B, Higgins RA, Huang F, Zhu KY, Buschman LL:Comparative analysis of proteinase activities of Bacillus thuringiensis-resistant and-susceptible Ostrinia nubilalis (Lepidoptera:Crambidae). Insect Biochem Mol Biol 2004,34(8):753-762.
269. Alvarez-Alfageme F, Ferry N, Castanera P, Ortego F, Gatehouse AM:Prey mediated effects of Bt maize on fitness and digestive physiology of the red spider mite predator Stethorus punctillum Weise (Coleoptera:Coccinellidae). Transgenic Res 2008,17(5):943-954.
270. Karumbaiah L, Oppert B, Jurat-Fuentes JL, Adang MJ:Analysis of midgut proteinases from Bacillus thuringiensis-susceptible and-resistant Heliothis virescens (Lepidoptera: Noctuidae). Comp Biochem Physiol B Biochem Mol Biol 2007,146(1):139-146.
271. Lavazec C, Bonnet S, Thiery I, Boisson B, Bourgouin C:cpbAgl encodes an active carboxypeptidase B expressed in the midgut of Anopheles gambiae. Insect Mol Biol 2005, 14(2):163-174.
272. Lechner AJ, Ryerse JS, Matuschak GM:Acute lung injury during bacterial or fungal sepsis. Microsc Res Tech 1993,26(5):444-456.
273. Walters LL, Irons KP, Guzman H, Tesh RB:-Formation and composition of the peritrophic membrane in the sand fly, Phlebotomus perniciosus (Diptera:Psychodidae). J Med Entomol 1993,30(1):179-198.
274. Rees JS, Jarrett P, Ellar DJ:Peritrophic membrane contribution to Bt Cry delta-endotoxin susceptibility in Lepidoptera and the effect of Calcofluor. J Invertebr Pathol 2009, 100(3):139-146.
275. Lee MK, Milne RE, Ge AZ, Dean DH:Location of a Bombyx mori receptor binding region on a Bacillus thuringiensis delta-endotoxin. J Biol Chem 1992,267(5):3115-3121.
276. Ingle SS, Trivedi N, Prasad R, Kuruvilla J, Rao KK, Chhatpar HS:Aminopeptidase-N from the Helicoverpa armigera (Hubner) brush border membrane vesicles as a receptor of Bacillus thuringiensis crylac delta-endotoxin. Curr Microbiol 2001,43(4):255-259.
277. Angelucci C, Barrett-Wilt GA, Hunt DF, Akhurst RJ, East PD, Gordon KH, Campbell PM: Diversity of aminopeptidases, derived from four lepidopteran gene duplications, and polycalins expressed in the midgut of Helicoverpa armigera:identification of proteins binding the delta-endotoxin, Cryl Ac of Bacillus thuringiensis. Insect Biochem Mol Biol 2008, 38(7):685-696.
278. Lesieur C, Vecsey-Semjen B, Abrami L, Fivaz M, Gisou van der Goot F:Membrane insertion: The strategies of toxins (review). Mol Membr Biol 1997,14(2):45-64.
279. Dean DH, Rajamohan F, Lee MK, Wu SJ, Chen XJ, Alcantara E, Hussain SR:Probing the mechanism of action of Bacillus thuringiensis insecticidal proteins by site-directed mutagenesis-a minireview. Gene 1996,179(1):111-117.
280. Sanders HR, Foy BD, Evans AM, Ross LS, Beaty BJ, Olson KE, Gill SS:Sindbis virus induces transport processes and alters expression of innate immunity pathway genes in the midgut of the disease vector, Aedes aegypti. Insect Biochem Mol Biol 2005,35(11):1293-1307.
281. Roth CW, Holm I, Graille M, Dehoux P, Rzhetsky A, Wincker P, Weissenbach J, Brey PT: Identification of the Anopheles gambiae ATP-binding cassette transporter superfamily genes. Mol Cells 2003,15(2):150-158.
282. Meidanis J, Braga MD, Verjovski-Almeida S:Whole-genome analysis of transporters in the plant pathogen Xylella fastidiosa. Microbiol Mol Biol Rev 2002,66(2):272-299.
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