利用秀丽隐杆线虫表达捻转血矛线虫H11蛋白的转基因研究
|
摘要
捻转血矛线虫(Haemonchus contortus)是牛、羊等反刍动物的主要寄生性线虫,寄生于动物皱胃粘膜的表面,引起捻转血矛线虫病,导致动物出现贫血、消瘦,甚至引起死亡。使用抗蠕虫药物是目前防治该病的主要措施,但线虫耐药性的日益严重迫切需要发展新的防治策略,疫苗作为一种新的有效的防治策略,具有广阔的应用前景。由于线虫具有复杂的生活史,抗原成分繁多,到现在为止,还没有一种线虫疫苗应用于生产。氨肽酶H11是捻转血矛线虫L4幼虫和成虫阶段表达的一种整合膜蛋白,被认为是目前为止免疫效果最好的一种候选抗原(减卵率>90%,减虫率>75%),而利用大肠杆菌和昆虫杆状病毒系统表达的重组形式均不能引起有效的免疫保护。秀丽隐杆线虫因其与寄生性线虫在进化上的近缘性,被认为是研究寄生性线虫基因功能和表达寄生性线虫疫苗候选抗原的理想系统。本研究的主要目的是：探明捻转血矛线虫疫苗候选抗原基因H11的基因组结构特征；同时以秀丽隐杆线虫为模式,建立研究寄生性线虫基因功能和表达寄生性线虫疫苗候选抗原的转基因技术体系；在此基础上分析H11基因5’侧翼区序列的启动子转录活性,研究利用建立的转基因技术体系,表达H11基因的可行性,为寄生性线虫的疫苗研制提供新方法。
1.捻转血矛线虫疫苗候选抗原基因H11的基因组结构分析
参照已发表的捻转血矛线虫疫苗候选抗原H11的基因序列,以捻转血矛线虫ZJ株的总RNA为模板,进行RT-PCR扩增,成功扩增出H11基因。对H11及其同源类似物进行比对分析,发现H11含有一个锌指结合基序HEXXHXW,具有典型的微粒体氨肽酶结构域特征。通过在功能域保守区域设计特异性引物,利用长距离PCR技术和基因步移技术,成功获得了H11的基因组序列。结果表明,H11的ORF大小为2919 bp,编码972个氨基酸；获得的H11基因组大小为14959 bp,拥有25个外显子和24个内含子,内含子和外显子之间具有典型的GT……AG结构。捻转血矛线虫H11基因组序列的获得为我们进一步开展H11的相关研究提供了重要素材。
2.以秀丽隐杆线虫为模式,建立研究寄生性线虫基因功能和表达寄生性线虫疫苗候选抗原的转基因技术体系
为建立秀丽隐杆线虫的转基因技术体系,利用PCR技术从秀丽隐杆线虫基因组DNA中扩增获得Act-1基因的核心启动子序列、T07F10.lA基因的核心启动子序列与3’UTR的Poly (A)信号序列,以及从表达载体pEGFP-N1上扩增获得SV40早期mRNA的Poly (A)信号序列与EGFP基因。以pBluescript SK+或pEGFP-4.1为基本载体骨架,分别构建由Act-1基因的核心启动子序列、T07F1O.lA基因的核心启动子序列调控,EGFP作为报告基因的重组表达载体。通过显微注射将重组载体与Marker质粒pRF4共注射到秀丽隐杆线虫性腺,结果发现重组载体Pact-EGFP中Act-1基因的核心启动子能够指导EGFP在秀丽隐杆线虫的皮层、副皮层以及咽部表达。利用脂质体介导转染Vero细胞,发现重组载体Pact-EGFP和pB-Pact-EGFP-SV40T中的核心启动子能够指导EGFP在Vero细胞中表达,但表达强度具有较大的差异,表明秀丽隐杆线虫Act-1基因的核心启动子区域上游以及基因下游的转录终止信号区域可能存在与转录水平密切相关的独特的转录调节元件。该研究为进一步实现寄生性线虫基因在秀丽隐杆线虫体内的表达奠定了基础。
3.利用建立的转基因技术体系,分析H11基因5’侧翼区序列的启动子转录活性
为进一步分析H11基因的5’侧翼区的转录活性,在获得的H11基因组序列的基础上,再次利用基因步移技术扩增5’上游的部分基因组序列,确认H11基因5’侧翼区大小为1517 bp；同时获得了H11亚型H11-4最后一个外显子和3’UTR序列,发现H11-4基因与H11基因在染色体上不仅是连锁的,而且具有相同的基因延伸方向。将获得的5’侧翼区序列单独或联合H11基因的前两个外显子、第一内含子以及第二内含子的部分序列克隆到表达载体ppd95.77 GFP基因的上游,显微注射到线虫的性腺。结果表明H11基因5’侧翼区序列能够指导GFP在秀丽隐杆线虫L4幼虫和成虫肠管的前端和末端特异性表达,且显示出与H11在捻转血矛线虫体内不完全相同的表达模式；H11的部分外显子和内含子序列在秀丽隐杆线虫体内不能实现正确的剪接,这可能与H11是捻转血矛线虫寄生阶段特异性表达的蛋白有关。
4.利用建立的转基因技术体系,筛选用于指导H11疫苗候选抗原表达的启动子序列,并在该启动子的指导下实现H11基因在秀丽隐杆线虫体内的表达
选择秀丽隐杆线虫体内H11的同系物T07F1O.1a基因以及肠道特异性表达的cpr-1和elt-2基因的5’侧翼区序列作为筛选对象,用以在秀丽隐杆线虫体内表达H11疫苗候选抗原。T07F10.1α、cpr-1和elt-2基因的1885 bp、1985 bp和1998 bp的5’侧翼区序列克隆到表达载体ppd95.77 GFP基因的上游,显微注射到线虫的性腺。结果显示,在T07F10.1a基因的5’侧翼区的转录下, GFP能够在秀丽隐杆线虫除去胚胎期的整个生命周期中都有表达,表达部位主要集中在秀丽隐杆线虫的尾部神经元、咽部、分泌细胞、肠道细胞以及神经系统；在cpr-1基因的5’侧翼区的转录下,GFP能够特异性的在线虫的整个肠道表达,尤其在L4幼虫和成虫阶段,GFP呈现较高强度的表达；在elt-2基因的5’侧翼区的转录下GFP能够在L3幼虫到成虫阶段的肠道表达,且呈现明显的区段性,即肠道最前端的肠环1(int1,前肠)、中肠(肠道最中间的部分)以及肠道末端,尤其int1位置的GFP呈现较高强度的表达,但表达强度与部位因虫体个体不同有较大差异。根据GFP表达的组织定位、L4幼虫和成虫阶段GFP的表达强度以及虫体表达GFP的稳定性等差异,最后采用cpr-1的5’侧翼区序列作为在秀丽隐杆线虫表达H11的启动子。
在已获得的重组载体cpr-1 5’侧翼区∷GFP基础上,利用特异性引物ppdF/ppdR,在高保真酶作用下,通过长距离PCR扩增切除GFP基因,进行载体自连、环化,同时在载体上引入SacⅠ.SaccⅡ等4个酶切位点构建重组表达载体cpr-pPD95.77(G-)；通过引入EGFP基因对重组载体验证后,利用SacⅠ和SacⅡ限制性内切酶将基因两端加有6×His标签的H11及其部分基因片段Trans-HSP分别引入重组表达载体。cpr-pPD95.77(G-)中crp-1 5'则翼区能够指导EGFP在秀丽隐杆线虫的肠道特异性表达表明改造后的重组载体在秀丽隐杆线虫体内具有表达外源基因的功能。Western-blot分析结果显示,在cpr-1 5’侧翼区的启动下,H11基因在秀丽隐杆线虫体内没有明显表达,而Trans-HPS能够在秀丽隐杆线虫体内表达；尽管His单克隆抗体与多克隆抗体能够检测到大小一致的特异性目的条带,利用镍琼脂糖凝胶的方法却未能实现对Trans-HPS的纯化,因此,我们选择Trans-HPS转基因线虫的全虫抗原作为免疫原进行动物免疫保护性试验。
5.利用获得的转基因蛋白免疫山羊,比较分析免疫保护效果
采用液体培养的方法大量获取转基因表达Trans-HPS蛋白的秀丽隐杆线虫成虫,制备全虫抗原,以250μg/只的剂量免疫山羊,加强免疫一次,用捻转血矛线虫L3幼虫5000条/只的感染强度感染山羊,结合各种指标检测含有Trans-HPS蛋白的全虫抗原的免疫保护效果。ELISA检测结果表明首免后两周既可检测到较高的IgG抗体水平,二免后两周达到高峰,二免后7周抗体水平仍可维持较高水平；外周血淋巴增殖试验结果显示,Trans-HSP蛋白能够显著增强Trans-HPS蛋白免疫组(p<0.01)和HPS蛋白免疫组(p<0.05)淋巴细胞的增殖活性；对不同免疫组山羊排出虫卵数、幼虫孵化率和成虫数进行统计分析,发现Trans-HPS蛋白免疫组减卵率为41.4%,且能明显延缓排卵高峰期的到来；Trans-HPS蛋白免疫组成虫减少率为17.79%,与感染阳性组比较差异不显著。
综上,本研究首次获得了H11的基因组序列,发现了亚型H11-4与H11之间的基因连锁现象；建立了以秀丽隐杆线虫为模式的转基因技术体系,利用该体系成功实现了H11部分基因片段Trans-HPS的转基因表达,并对该转基因表达蛋白的免疫保护性进行了评估。本研究为开发寄生性线虫疫苗提供了新技术,为进一步研究寄生性线虫的基因功能奠定了理论基础。
The gastrointestinal nematode Haemonchus contortus is a major blood feeding pathogen of sheep and goats, which inhabits the mucosal surface of the abomasum in these ruminants and causes haemonchosis. Its infections may be manifested as anemia, weight loss or even death in some cases. Current control of Haemonchosis mainly depends on the use of anthelmintic drugs. But the increasing problem of resistance to all classes of anthelmintics highlights the need for novel control strategy, such as vaccination. No vaceine has yet been commercialized, due to the complicated life-cycle and incomprehensible components of antigens. Aminopeptidase H11 is an integral membrane glycoprotein which is present only in the intestinal microvilli of L4 and adults worms, and considered to be one of the best characterized hidden antigens from H. contortus (on average a greater than 90% reduction in faecal egg counts and a greater than 75% reduction in worm burdens). But no effective protection was provided by vaccination with the recombinant forms expressed in E. coli or baculovirus. The free-living nematode Caenorhabditis elegans has been validated as an alternative expression system to attempt to express proteins similar to their native forms, as it is closely related to H. contortus in evolutionary terms. Here, the study was aimed to characterizing genomic structure of Hll gene from H. contoruts, and to establish a transgenic platform for functional exploitation of genes and expression of antigen candidates from parasitic nematodes, taking C. elegans as a heterologous system, then to estimate the transcriptional activity of H11 5' flanking region and make sure the feasibility in expression of Hll using C. elegans, which could provide a novel strategy for vaccination against parasitic namatodes.
1. Characterization of genomic structure of Hll gene from H. contoruts
Referred to the sequence of Hll from H. contortus reported by Smith (1997), RT-PCR was carried out to amplify the cDNA of Hll, taking total RNA of H. contortus as a template. Alignment with its similarities from other organisms revealed a typical characterization of microsomal aminopeptidase with a zinc-binding motif HEXXHXW. Specific primers were designed, according to the conserved domains among these similarities, to amplify the genomic DNA of H11, employing the long-distance PCR and genome walking technique. The results revealed the open reading frame of H11 was 2919 bp in size, while the genomic DNA was 14,959 bp in size which contained 25 exons separated by 24 introns, and canonical GT-AG consensus sequences were at each intron-exon splice junction. These findings provided interesting materials to our further research.
2. Establishment of a transgenic platform to exploitation of gene function and vaccine development of parasitic nematodes, taking C. elegans as a heterologous system
To establish the transgenic platform, the core promoter regions of Act-1 gene and T07F10 gene, and the Poly (A) signal region of T07F10 gene were amplified from the genomic DNA of C. elegans using PCR, and SV40 early mRNA poly(A) signal sequence and EGFP gene were amplified from eukaryotic vector pEGFP-N1, respectively. Taking the vector pBluescript SK+ or pEGFP-4.1 as backbone, several varied recombinants were constructed, three of which, that is recombinant Pact-EGFP, pB-Pact-EGFP-T07F10T and pB-Pact-EGFP-SV40T, contained the core promoter region of Act-1 gene, and the others, named as recombinant pB-PT07F10-EGFP-T07F10T and pB-PT07F10-EGFP-SV40T, contained the core promoter region of T07F10 gene. After microinjection into the gonad of C. elegans together with pRF4 as a gene marker, only the core promoter region of Act-1 gene in vector Pact-EGFP could direct the expression of EGFP and green fluorescence was detected in the cortex, vice cortex and the pharyngeal of C. elegans. In contrast, the core promoter region of Pact-EGFP and pB-Pact-EGFP-SV40T could direct the expression of EGFP in Vero cell with different intensity, when transfected into Vero cell by liposome, which indicated that unique regulatory elements to transcription may exist in the 5'upstream of the core promoter or the 3'UTR of the gene. These results prompted greatly the further research on gene function of parasitic nematodes using C. elegans.
3. Characterization of transcriptional activity of Hll 5'-flanking region, taking advantage of C. elegans
To proceed characterizing the transcriptional activity of Hll 5'-flanking region, genome walking was employed again to obtain more information of Hll 5'upstream. Alignment revealed the 1517-bp 5'-flanking region of Hll, and the last exon and its 3' UTR of an isoform H11-4. The result indicated that H11-4 had a tandem link to Hll gene, with the same orientation in gene extension in the chromosome. The 1517-bp 5'-flanking region of Hll was cloned upstream of GFP gene in ppd95.77 vector only or fused with the first two exons, the first intron and part of the second intron. After microinjected recombinant plasmid with 5'-flanking region of H11 into the gonads of C. elegans, the transformed animals exhibited fluorescence in the most anterior intestine and distal intestine in the L4 larvae and adult worms, which demonstrated different transcriptional patterns compared with that in H. contortus. The correct splice did not occur in C. elegans, when the first two exons, the first intron and part of the second intron of Hll gene was clone behind 5'-flanking region of H11, which was probably correlated with its unique function to the parasitism of H. contortus.
4. Screening of promoters used to direct expression of heterologous gene and transgenic expression of Hll gene regulated by cpr-1 5'-flanking region in C. elegans
The 5'-flanking regions of three genes from C. elegans, that is T07F10.1a gene which codes the similarity of H11, cpr-1 and elt-2 gene which are only expressed in intestine, were screened to direct the expression of H11 in C. elegans. The 1885-bp, 1985-bp,1998 bp 5'-flanking region of these three genes were amplified and cloned upstream of GFP gene in pPD95.77 vector. After microinjection into the gonad of C. elegans, the progenies of trangenic worms were picked out and investigated. The results showed that the fluorescence directed by T07F10.1a 5'-flanking region is distinctively expressed in the intestine, excretory cells, nervous system and tail neurons in C. elegans of all stages but embryonic development, while directed by cpr-1 and elt-2 5'-flanking region were only detected in intestine, particularly in the L4 and adult C. elegans. cpr-1 5'-flanking region can direct intensive expression of GFP in the whole intestine. elt-2 5' flanking region direct the expression of GFP in the most-anterior intestine (int 1), mid-intestine and the distal intestine, and various differences in fluorescence intensity were shown among different individuals. cpr-1 5'-flanking region was determined to direct the expression of H11 gene, referred to tissue location of GFP, expression intensity in L4 and adult C. elegans and stability among different individuals.
To obtain expression vector cpr-pPD95.77(G-), a specific pair of primers were designed. Taking advantage of PrimeStarTM SH DNA polymerase, GFP gene in recombinant vector cpr-1 5'-flanking region::GFP was removed employing long-distance PCR. The vector cpr-pPD95.77(G-) was formulated after self-ligation and cyclization of the amplification product with addition of four restriction enzymes. EGFP gene was subcloned downstream of cpr-1 5'-flanking region to verify the validation in expression of heterologous genes. Then, H11 gene and its partial sequence were cloned downstream of cpr-1 5'-flanking region into cpr-pPD95.77(G-), respectively, with 6 fold His tag added at both sides of the genes. SDS-PAGE and Western-blot were introduced to analyze the expression of both genes. Green fluorescence could be detected in the intestine at a high level, which indicated that recombinant vector cpr-pPD95.77(G-) also had the ability to express heterologous genes. The results suggested that it was not H11 but Trans-HPS could expressed in C. elegans, at the direction of cpr-1 5'-flanking region and specific bands termed Trans-HPS could be detected using both anti-His monoclonal antibody and polyclonal antibody, although Trans-HPS could not be purified using Nickel agarose gel affinity chromatography.
5. Assessment of the immuno-protection of Trans-HPS against H. contortus in goats
Liquid culture was employed to bulk preparation of crude extraction from transgenic worms with Trans-HPS.250μg per goat of crude extraction was administered at primary immunization and booster two weeks later with the same dose. Assessment of the immuno-protection proceeded after orally challenged with 5000 infective H. contortus L3 2 weeks after the second immunization. High titre level of serum IgG was mounted just two-week post-primary immunization. Serum IgG levels reached peak values at two-week post-second immunization and remained significant titre until the end of this trial. Significant elevation in T cell proliferative responses stimulated by Trans-HPS was observed in both Trans-HPS immunized group and HPS immunized group. Faecal egg counts was reduced by 41.4% and the advent of the peak in FEC was markedly delayed in Trans-HPS immunized group. And worm burdens were reduced by 17.79%, which showed no statistical significance as positive control.
In summary, the genomic DNA of H11 was first sequenced and characterized, and the tandem relationship between Hll gene and its isoform H11-4 was first revealed in our study; transgenic platform for exploitation of gene function and vaccine development of parasitic nematodes was developed and expression characterization and immuno-protection assessment of Trans-H11 proceeded, taking advantage of C. elegans. This system will be particularly important for expression of complex glycan epitopes and examination of their influence on the immune response to parasitic nematodes.
1.捻转血矛线虫疫苗候选抗原基因H11的基因组结构分析
参照已发表的捻转血矛线虫疫苗候选抗原H11的基因序列,以捻转血矛线虫ZJ株的总RNA为模板,进行RT-PCR扩增,成功扩增出H11基因。对H11及其同源类似物进行比对分析,发现H11含有一个锌指结合基序HEXXHXW,具有典型的微粒体氨肽酶结构域特征。通过在功能域保守区域设计特异性引物,利用长距离PCR技术和基因步移技术,成功获得了H11的基因组序列。结果表明,H11的ORF大小为2919 bp,编码972个氨基酸；获得的H11基因组大小为14959 bp,拥有25个外显子和24个内含子,内含子和外显子之间具有典型的GT……AG结构。捻转血矛线虫H11基因组序列的获得为我们进一步开展H11的相关研究提供了重要素材。
2.以秀丽隐杆线虫为模式,建立研究寄生性线虫基因功能和表达寄生性线虫疫苗候选抗原的转基因技术体系
为建立秀丽隐杆线虫的转基因技术体系,利用PCR技术从秀丽隐杆线虫基因组DNA中扩增获得Act-1基因的核心启动子序列、T07F10.lA基因的核心启动子序列与3’UTR的Poly (A)信号序列,以及从表达载体pEGFP-N1上扩增获得SV40早期mRNA的Poly (A)信号序列与EGFP基因。以pBluescript SK+或pEGFP-4.1为基本载体骨架,分别构建由Act-1基因的核心启动子序列、T07F1O.lA基因的核心启动子序列调控,EGFP作为报告基因的重组表达载体。通过显微注射将重组载体与Marker质粒pRF4共注射到秀丽隐杆线虫性腺,结果发现重组载体Pact-EGFP中Act-1基因的核心启动子能够指导EGFP在秀丽隐杆线虫的皮层、副皮层以及咽部表达。利用脂质体介导转染Vero细胞,发现重组载体Pact-EGFP和pB-Pact-EGFP-SV40T中的核心启动子能够指导EGFP在Vero细胞中表达,但表达强度具有较大的差异,表明秀丽隐杆线虫Act-1基因的核心启动子区域上游以及基因下游的转录终止信号区域可能存在与转录水平密切相关的独特的转录调节元件。该研究为进一步实现寄生性线虫基因在秀丽隐杆线虫体内的表达奠定了基础。
3.利用建立的转基因技术体系,分析H11基因5’侧翼区序列的启动子转录活性
为进一步分析H11基因的5’侧翼区的转录活性,在获得的H11基因组序列的基础上,再次利用基因步移技术扩增5’上游的部分基因组序列,确认H11基因5’侧翼区大小为1517 bp；同时获得了H11亚型H11-4最后一个外显子和3’UTR序列,发现H11-4基因与H11基因在染色体上不仅是连锁的,而且具有相同的基因延伸方向。将获得的5’侧翼区序列单独或联合H11基因的前两个外显子、第一内含子以及第二内含子的部分序列克隆到表达载体ppd95.77 GFP基因的上游,显微注射到线虫的性腺。结果表明H11基因5’侧翼区序列能够指导GFP在秀丽隐杆线虫L4幼虫和成虫肠管的前端和末端特异性表达,且显示出与H11在捻转血矛线虫体内不完全相同的表达模式；H11的部分外显子和内含子序列在秀丽隐杆线虫体内不能实现正确的剪接,这可能与H11是捻转血矛线虫寄生阶段特异性表达的蛋白有关。
4.利用建立的转基因技术体系,筛选用于指导H11疫苗候选抗原表达的启动子序列,并在该启动子的指导下实现H11基因在秀丽隐杆线虫体内的表达
选择秀丽隐杆线虫体内H11的同系物T07F1O.1a基因以及肠道特异性表达的cpr-1和elt-2基因的5’侧翼区序列作为筛选对象,用以在秀丽隐杆线虫体内表达H11疫苗候选抗原。T07F10.1α、cpr-1和elt-2基因的1885 bp、1985 bp和1998 bp的5’侧翼区序列克隆到表达载体ppd95.77 GFP基因的上游,显微注射到线虫的性腺。结果显示,在T07F10.1a基因的5’侧翼区的转录下, GFP能够在秀丽隐杆线虫除去胚胎期的整个生命周期中都有表达,表达部位主要集中在秀丽隐杆线虫的尾部神经元、咽部、分泌细胞、肠道细胞以及神经系统；在cpr-1基因的5’侧翼区的转录下,GFP能够特异性的在线虫的整个肠道表达,尤其在L4幼虫和成虫阶段,GFP呈现较高强度的表达；在elt-2基因的5’侧翼区的转录下GFP能够在L3幼虫到成虫阶段的肠道表达,且呈现明显的区段性,即肠道最前端的肠环1(int1,前肠)、中肠(肠道最中间的部分)以及肠道末端,尤其int1位置的GFP呈现较高强度的表达,但表达强度与部位因虫体个体不同有较大差异。根据GFP表达的组织定位、L4幼虫和成虫阶段GFP的表达强度以及虫体表达GFP的稳定性等差异,最后采用cpr-1的5’侧翼区序列作为在秀丽隐杆线虫表达H11的启动子。
在已获得的重组载体cpr-1 5’侧翼区∷GFP基础上,利用特异性引物ppdF/ppdR,在高保真酶作用下,通过长距离PCR扩增切除GFP基因,进行载体自连、环化,同时在载体上引入SacⅠ.SaccⅡ等4个酶切位点构建重组表达载体cpr-pPD95.77(G-)；通过引入EGFP基因对重组载体验证后,利用SacⅠ和SacⅡ限制性内切酶将基因两端加有6×His标签的H11及其部分基因片段Trans-HSP分别引入重组表达载体。cpr-pPD95.77(G-)中crp-1 5'则翼区能够指导EGFP在秀丽隐杆线虫的肠道特异性表达表明改造后的重组载体在秀丽隐杆线虫体内具有表达外源基因的功能。Western-blot分析结果显示,在cpr-1 5’侧翼区的启动下,H11基因在秀丽隐杆线虫体内没有明显表达,而Trans-HPS能够在秀丽隐杆线虫体内表达；尽管His单克隆抗体与多克隆抗体能够检测到大小一致的特异性目的条带,利用镍琼脂糖凝胶的方法却未能实现对Trans-HPS的纯化,因此,我们选择Trans-HPS转基因线虫的全虫抗原作为免疫原进行动物免疫保护性试验。
5.利用获得的转基因蛋白免疫山羊,比较分析免疫保护效果
采用液体培养的方法大量获取转基因表达Trans-HPS蛋白的秀丽隐杆线虫成虫,制备全虫抗原,以250μg/只的剂量免疫山羊,加强免疫一次,用捻转血矛线虫L3幼虫5000条/只的感染强度感染山羊,结合各种指标检测含有Trans-HPS蛋白的全虫抗原的免疫保护效果。ELISA检测结果表明首免后两周既可检测到较高的IgG抗体水平,二免后两周达到高峰,二免后7周抗体水平仍可维持较高水平；外周血淋巴增殖试验结果显示,Trans-HSP蛋白能够显著增强Trans-HPS蛋白免疫组(p<0.01)和HPS蛋白免疫组(p<0.05)淋巴细胞的增殖活性；对不同免疫组山羊排出虫卵数、幼虫孵化率和成虫数进行统计分析,发现Trans-HPS蛋白免疫组减卵率为41.4%,且能明显延缓排卵高峰期的到来；Trans-HPS蛋白免疫组成虫减少率为17.79%,与感染阳性组比较差异不显著。
综上,本研究首次获得了H11的基因组序列,发现了亚型H11-4与H11之间的基因连锁现象；建立了以秀丽隐杆线虫为模式的转基因技术体系,利用该体系成功实现了H11部分基因片段Trans-HPS的转基因表达,并对该转基因表达蛋白的免疫保护性进行了评估。本研究为开发寄生性线虫疫苗提供了新技术,为进一步研究寄生性线虫的基因功能奠定了理论基础。
The gastrointestinal nematode Haemonchus contortus is a major blood feeding pathogen of sheep and goats, which inhabits the mucosal surface of the abomasum in these ruminants and causes haemonchosis. Its infections may be manifested as anemia, weight loss or even death in some cases. Current control of Haemonchosis mainly depends on the use of anthelmintic drugs. But the increasing problem of resistance to all classes of anthelmintics highlights the need for novel control strategy, such as vaccination. No vaceine has yet been commercialized, due to the complicated life-cycle and incomprehensible components of antigens. Aminopeptidase H11 is an integral membrane glycoprotein which is present only in the intestinal microvilli of L4 and adults worms, and considered to be one of the best characterized hidden antigens from H. contortus (on average a greater than 90% reduction in faecal egg counts and a greater than 75% reduction in worm burdens). But no effective protection was provided by vaccination with the recombinant forms expressed in E. coli or baculovirus. The free-living nematode Caenorhabditis elegans has been validated as an alternative expression system to attempt to express proteins similar to their native forms, as it is closely related to H. contortus in evolutionary terms. Here, the study was aimed to characterizing genomic structure of Hll gene from H. contoruts, and to establish a transgenic platform for functional exploitation of genes and expression of antigen candidates from parasitic nematodes, taking C. elegans as a heterologous system, then to estimate the transcriptional activity of H11 5' flanking region and make sure the feasibility in expression of Hll using C. elegans, which could provide a novel strategy for vaccination against parasitic namatodes.
1. Characterization of genomic structure of Hll gene from H. contoruts
Referred to the sequence of Hll from H. contortus reported by Smith (1997), RT-PCR was carried out to amplify the cDNA of Hll, taking total RNA of H. contortus as a template. Alignment with its similarities from other organisms revealed a typical characterization of microsomal aminopeptidase with a zinc-binding motif HEXXHXW. Specific primers were designed, according to the conserved domains among these similarities, to amplify the genomic DNA of H11, employing the long-distance PCR and genome walking technique. The results revealed the open reading frame of H11 was 2919 bp in size, while the genomic DNA was 14,959 bp in size which contained 25 exons separated by 24 introns, and canonical GT-AG consensus sequences were at each intron-exon splice junction. These findings provided interesting materials to our further research.
2. Establishment of a transgenic platform to exploitation of gene function and vaccine development of parasitic nematodes, taking C. elegans as a heterologous system
To establish the transgenic platform, the core promoter regions of Act-1 gene and T07F10 gene, and the Poly (A) signal region of T07F10 gene were amplified from the genomic DNA of C. elegans using PCR, and SV40 early mRNA poly(A) signal sequence and EGFP gene were amplified from eukaryotic vector pEGFP-N1, respectively. Taking the vector pBluescript SK+ or pEGFP-4.1 as backbone, several varied recombinants were constructed, three of which, that is recombinant Pact-EGFP, pB-Pact-EGFP-T07F10T and pB-Pact-EGFP-SV40T, contained the core promoter region of Act-1 gene, and the others, named as recombinant pB-PT07F10-EGFP-T07F10T and pB-PT07F10-EGFP-SV40T, contained the core promoter region of T07F10 gene. After microinjection into the gonad of C. elegans together with pRF4 as a gene marker, only the core promoter region of Act-1 gene in vector Pact-EGFP could direct the expression of EGFP and green fluorescence was detected in the cortex, vice cortex and the pharyngeal of C. elegans. In contrast, the core promoter region of Pact-EGFP and pB-Pact-EGFP-SV40T could direct the expression of EGFP in Vero cell with different intensity, when transfected into Vero cell by liposome, which indicated that unique regulatory elements to transcription may exist in the 5'upstream of the core promoter or the 3'UTR of the gene. These results prompted greatly the further research on gene function of parasitic nematodes using C. elegans.
3. Characterization of transcriptional activity of Hll 5'-flanking region, taking advantage of C. elegans
To proceed characterizing the transcriptional activity of Hll 5'-flanking region, genome walking was employed again to obtain more information of Hll 5'upstream. Alignment revealed the 1517-bp 5'-flanking region of Hll, and the last exon and its 3' UTR of an isoform H11-4. The result indicated that H11-4 had a tandem link to Hll gene, with the same orientation in gene extension in the chromosome. The 1517-bp 5'-flanking region of Hll was cloned upstream of GFP gene in ppd95.77 vector only or fused with the first two exons, the first intron and part of the second intron. After microinjected recombinant plasmid with 5'-flanking region of H11 into the gonads of C. elegans, the transformed animals exhibited fluorescence in the most anterior intestine and distal intestine in the L4 larvae and adult worms, which demonstrated different transcriptional patterns compared with that in H. contortus. The correct splice did not occur in C. elegans, when the first two exons, the first intron and part of the second intron of Hll gene was clone behind 5'-flanking region of H11, which was probably correlated with its unique function to the parasitism of H. contortus.
4. Screening of promoters used to direct expression of heterologous gene and transgenic expression of Hll gene regulated by cpr-1 5'-flanking region in C. elegans
The 5'-flanking regions of three genes from C. elegans, that is T07F10.1a gene which codes the similarity of H11, cpr-1 and elt-2 gene which are only expressed in intestine, were screened to direct the expression of H11 in C. elegans. The 1885-bp, 1985-bp,1998 bp 5'-flanking region of these three genes were amplified and cloned upstream of GFP gene in pPD95.77 vector. After microinjection into the gonad of C. elegans, the progenies of trangenic worms were picked out and investigated. The results showed that the fluorescence directed by T07F10.1a 5'-flanking region is distinctively expressed in the intestine, excretory cells, nervous system and tail neurons in C. elegans of all stages but embryonic development, while directed by cpr-1 and elt-2 5'-flanking region were only detected in intestine, particularly in the L4 and adult C. elegans. cpr-1 5'-flanking region can direct intensive expression of GFP in the whole intestine. elt-2 5' flanking region direct the expression of GFP in the most-anterior intestine (int 1), mid-intestine and the distal intestine, and various differences in fluorescence intensity were shown among different individuals. cpr-1 5'-flanking region was determined to direct the expression of H11 gene, referred to tissue location of GFP, expression intensity in L4 and adult C. elegans and stability among different individuals.
To obtain expression vector cpr-pPD95.77(G-), a specific pair of primers were designed. Taking advantage of PrimeStarTM SH DNA polymerase, GFP gene in recombinant vector cpr-1 5'-flanking region::GFP was removed employing long-distance PCR. The vector cpr-pPD95.77(G-) was formulated after self-ligation and cyclization of the amplification product with addition of four restriction enzymes. EGFP gene was subcloned downstream of cpr-1 5'-flanking region to verify the validation in expression of heterologous genes. Then, H11 gene and its partial sequence were cloned downstream of cpr-1 5'-flanking region into cpr-pPD95.77(G-), respectively, with 6 fold His tag added at both sides of the genes. SDS-PAGE and Western-blot were introduced to analyze the expression of both genes. Green fluorescence could be detected in the intestine at a high level, which indicated that recombinant vector cpr-pPD95.77(G-) also had the ability to express heterologous genes. The results suggested that it was not H11 but Trans-HPS could expressed in C. elegans, at the direction of cpr-1 5'-flanking region and specific bands termed Trans-HPS could be detected using both anti-His monoclonal antibody and polyclonal antibody, although Trans-HPS could not be purified using Nickel agarose gel affinity chromatography.
5. Assessment of the immuno-protection of Trans-HPS against H. contortus in goats
Liquid culture was employed to bulk preparation of crude extraction from transgenic worms with Trans-HPS.250μg per goat of crude extraction was administered at primary immunization and booster two weeks later with the same dose. Assessment of the immuno-protection proceeded after orally challenged with 5000 infective H. contortus L3 2 weeks after the second immunization. High titre level of serum IgG was mounted just two-week post-primary immunization. Serum IgG levels reached peak values at two-week post-second immunization and remained significant titre until the end of this trial. Significant elevation in T cell proliferative responses stimulated by Trans-HPS was observed in both Trans-HPS immunized group and HPS immunized group. Faecal egg counts was reduced by 41.4% and the advent of the peak in FEC was markedly delayed in Trans-HPS immunized group. And worm burdens were reduced by 17.79%, which showed no statistical significance as positive control.
In summary, the genomic DNA of H11 was first sequenced and characterized, and the tandem relationship between Hll gene and its isoform H11-4 was first revealed in our study; transgenic platform for exploitation of gene function and vaccine development of parasitic nematodes was developed and expression characterization and immuno-protection assessment of Trans-H11 proceeded, taking advantage of C. elegans. This system will be particularly important for expression of complex glycan epitopes and examination of their influence on the immune response to parasitic nematodes.
引文
王祥,姚宝安,夏雪山等.苏云金芽孢杆菌伴胞晶体蛋白对捻转血矛线虫第四期幼虫的毒杀作用[J].中国兽医科技,1999,29(6)：33-34.
郑润宽,郝文俊.冬季舍内捻转血矛线虫的生态学研究[J].内蒙古畜牧科学,1994,11(1)：1-4.
Abbas, A.K., Murphy, K.M., Sher, A.,1996. Functional diversity of helper T lymphocytes. Nature 383, 787-793.
Aboobaker, A.A., Blaxter, M.L.,2003. Use of RNA interference to investigate gene function in the human filarial nematode parasite Brugia malayi. Molecular and biochemical parasitology 129, 41-51.
Alexander, D.L., Mital. J., Ward, G.E., Bradley, P., Boothroyd, J.C.,2005. Identification of the moving junction complex of Toxoplasma gondii:a collaboration between distinct secretory organelles. PLoS pathogens 1,e17.
Alfonso, A., Grundahl, K., McManus, J.R., Asbury, J.M., Rand, J.B.,1994. Alternative splicing leads to two cholinergic proteins in Caenorhabditis elegans. Journal of molecular biology 241,627-630.
Aliberti, J., Jankovic, D., Sher, A.,2004. Turning it on and off:regulation of dendritic cell function in Toxoplasma gondii infection. Immunological reviews 201,26-34.
Anonymous,1998. Genome sequence of the nematode C. elegans:a platform for investigating biology. Science (New York, N.Y 282,2012-2018.
Ashton, F.T., Li, J., Schad, G.A.,1999. Chemo-and thermosensory neurons:structure and function in animal parasitic nematodes. Veterinary parasitology 84,297-316.
Babu, S., Blauvelt, C.P., Kumaraswami, V., Nutman, T.B.,2006. Regulatory networks induced by live parasites impair both Thl and Th2 pathways in patent lymphatic filariasis:implications for parasite persistence. J Immunol 176,3248-3256.
Bakker, N., Vervelde, L., Kanobana, K., Knox, D.P., Cornelissen, A.W., de Vries, E., Yatsuda, A.P., 2004. Vaccination against the nematode Haemonchus contortus with a thiol-binding fraction from the excretory/secretory products (ES). Vaccine 22,618-628.
Balic, A., Bowles, V.M., Meeusen, E.N.,2000. The immunobiology of gastrointestinal nematode infections in ruminants. Advances in parasitology 45,181-241.
Balic, A., Bowles, V.M., Meeusen, E.N.,2002. Mechanisms of immunity to Haemonchus contortus infection in sheep. Parasite immunology 24,39-46.
Banchereau, J., Steinman, R.M.,1998. Dendritic cells and the control of immunity. Nature 392,245-252.
Bancroft, A.J., Artis, D., Donaldson, D.D., Sypek, J.P., Grencis, R.K.,2000. Gastrointestinal nematode expulsion in IL-4 knockout mice is IL-13 dependent. European journal of immunology 30, 2083-2091.
Barnes, D.A., Bonnin, A., Huang, J.X., Gousset, L., Wu, J., Gut, J., Doyle, P., Dubremetz, J.F., Ward, H., Petersen, C.,1998. A novel multi-domain mucin-like glycoprotein of Cryptosporidium parvum mediates invasion. Molecular and biochemical parasitology 96,93-110.
Barta, J.R., Thompson, R.C.,2006. What is Cryptosporidium? Reappraising its biology and phylogenetic affinities. Trends in parasitology 22,463-468.
Belkaid, Y., Rouse, B.T.,2005. Natural regulatory T cells in infectious disease. Nature immunology 6, 353-360.
Bhat, N., Joe, A., PereiraPerrin, M., Ward, H.D.,2007. Cryptosporidium p30, a galactose/N-acetylgalactosamine-specific lectin, mediates infection in vitro. The Journal of biological chemistry 282,34877-34887.
Blaxter, M.L., De Ley. P., Garey, J.R., Liu, L.X.. Scheldeman, P., Vierstraete, A., Vanfleteren, J.R., Mackey, L.Y., Dorris, M., Frisse, L.M.,Vida, J.T., Thomas, W.K.,1998. A molecular evolutionary framework for the phylum Nematoda. Nature 392,71-75.
Bliss, S.K., Gavrilescu, L.C., Alcaraz, A., Denkers, E.Y.,2001. Neutrophil depletion during Toxoplasma gondii infection leads to impaired immunity and lethal systemic pathology. Infection and immunity 69,4898-4905.
Bonnin, A., Lapillonne, A., Petrella, T., Lopez, J., Chaponnier, C., Gabbiani, G., Robine, S., Dubremetz, J.F.,1999. Immunodetection of the microvillous cytoskeleton molecules villin and ezrin in the parasitophorous vacuole wall of Cryptosporidium parvum (Protozoa: Apicomplexa). European journal of cell biology 78,794-801.
Borgsteede, F.H., Pekelder, J.J., Dercksen, D.P., Sol, J., Vellema, P., Gaasenbeek, C.P., van der Linden, J.N.,1997. A survey of anthelmintic resistance in nematodes of sheep in The Netherlands. The Veterinary quarterly 19,167-172.
Boutz, P.L., Stoilov, P., Li, Q., Lin, C.H., Chawla, G., Ostrow, K., Shiue, L., Ares, M., Jr., Black, D.L. 2007. A post-transcriptional regulatory switch in polypyrimidine tract-binding proteins reprograms alternative splicing in developing neurons. Genes& development 21,1636-1652.
Boxem, M., Tsai, C.W., Zhang, Y., Saito, R.M., Liu, J.O.,2004. The C. elegans methionine aminopeptidase 2 analog map-2 is required for germ cell proliferation. FEBS letters 576,245-250.
Brett, D., Pospisil, H., Valcarcel, J., Reich, J., Bork, P.,2002. Alternative splicing and genome complexity. Nature genetics 30,29-30.
Britton, C., Redmond, D.L., Knox, D.F., McKerrow, J.H., Barry, J.D.,1999. Identification of promoter elements of parasite nematode genes in transgenic Caenorhabditis elegans. Molecular and biochemical parasitology 103,171-181.
Britton, C., Murray, L.,2002. A cathepsin L protease essential for Caenorhabditis elegans embryogenesis is functionally conserved in parasitic nematodes. Molecular and biochemical parasitology 122,21-33.
Britton, C., Murray, L.,2004. Cathepsin L protease (CPL-1) is essential for yolk processing during embryogenesis in Caenorhabditis elegans. Journal of cell science 117,5133-5143.
Britton, C., Murray, L.,2006. Using Caenorhabditis elegans for functional analysis of genes of parasitic nematodes. International journal for parasitology 36,651-659.
Brooks, D.R., Isaac, R. E. (ed.),2004. Nematode Aminopeptidases. Kluwer Academic/Plenum Press, New York.
Burglin, T.R., Lobos, E., Blaxter, M.L.,1998. Caenorhabditis elegans as a model for parasitic nematodes. International journal for parasitology 28,395-411.
Butaeva, F., Paskerova, G., Entzeroth, R.,2006. Ditrypanocystis sp. (Apicomplexa, Gregarinia, Selenidiidae):the mode of survival in the gut of Enchytraeus albidus (Annelida, Oligochaeta, Enchytraeidae) is close to that of the coccidian genus Cryptosporidium. Tsitologiia 48,695-704.
Butcher, B.A., Greene, R.I., Henry, S.C., Annecharico, K.L., Weinberg, J.B.. Denkers, E.Y., Sher, A.. Taylor, G.A.,2005a. p47 GTPases regulate Toxoplasma gondii survival in activated macrophages. Infection and immunity 73,3278-3286.
Butcher, B.A., Kim, L., Panopoulos, A.D., Watowich, S.S., Murray, P.J., Denkers, E.Y.,2005b. IL-10-independent STAT3 activation by Toxoplasma gondii mediates suppression of IL-12 and TNF-alpha in host macrophages. J Immunol 174,3148-3152.
Buzoni-Gatel, D., Schulthess, J., Menard, L.C., Kasper, L.H.,2006. Mucosal defences against orally acquired protozoan parasites, emphasis on Toxoplasma gondii infections. Cellular microbiology 8,535-544.
Campbell, B.E., Nagaraj, S.H., Hu, M., Zhong, W., Sternberg, P.W., Ong, E.K., Loukas, A., Ranganathan, S., Beveridge, I., McInnes, R.L., Hutchinson, G.W., Gasser, R.B.,2008. Gender-enriched transcripts in Haemonchus contortus--predicted functions and genetic interactions based on comparative analyses with Caenorhabditis elegans. International journal for parasitology 38,65-83.
Carruthers, V.B., Sibley, L.D.,1997. Sequential protein secretion from three distinct organelles of Toxoplasma gondii accompanies invasion of human fibroblasts. European journal of cell biology 73,114-123.
Cevallos, A.M., Bhat, N., Verdon, R., Hamer, D.H., Stein, B., Tzipori, S., Pereira, M.E., Keusch, G.T., Ward, H.D.,2000. Mediation of Cryptosporidium parvum infection in vitro by mucin-like glycoproteins defined by a neutralizing monoclonal antibody. Infection and immunity 68, 5167-5175.
Chen, X.M., Huang, B.Q., Splinter, P.L., Orth, J.D., Billadeau, D.D., McNiven, M.A., LaRusso, N.F., 2004a. Cdc42 and the actin-related protein/neural Wiskott-Aldrich syndrome protein network mediate cellular invasion by Cryptosporidium parvum. Infection and immunity 72,3011-3021.
Chen, X.M., O'Hara, S.P., Huang, B.Q., Nelson, J.B., Lin, J.J., Zhu, G., Ward, H.D., LaRusso, N.F., 2004b. Apical organelle discharge by Cryptosporidium parvum is temperature, cytoskeleton, and intracellular calcium dependent and required for host cell invasion. Infection and immunity 72,6806-6816.
Chen, X.M., O'Hara, S.P., Huang, B.Q., Splinter, P.L., Nelson, J.B., LaRusso, N.F.,2005. Localized glucose and water influx facilitates Cryptosporidium parvum cellular invasion by means of modulation of host-cell membrane protrusion. Proceedings of the National Academy of Sciences of the United States of America 102,6338-6343.
Chen, Q., Rehman, S., Smant, G., Jones, J.T.,2005. Functional analysis of pathogenicity proteins of the potato cyst nematode Globodera rostochiensis using RNAi. Mol Plant Microbe Interact 18, 621-625.
Chu W.Y., Wei Y.W., Qian R.H.,2006. Characterization of the 5'-to-5'linked adult a-and β-globin genes from three sciaenid fish species(Pseudosciaena crocea, Sciaenops ocellatus, Nibea miichthioides). Comp Biochem Physiol, Part D 1:319-327.
Collins, S. M.,1996. The immunomodulation of enteric neuromuscular function:implications for motility and inflammatory disorders.Gastroenterology. 111,1683-99.
Convey, P., McInnes, S.J.,2005. Exceptional tardigrade-dominated ecosystems in Ellsworth Land, Antarctica. Ecology 86,519-527.
Cook, A.A., Bhadury, P., Debenham, N.J., MeldaL B.H.M., Blaxter, M.L., Smerdon, G., Austen, M.C., Lambshead, P.J.D., Rogers, A.D.,2005. Denaturing gradient gel electrophoresis (DGGE) as a tool for the identiWcation of marine nematodes. Mar. Ecol. Prog. Ser.291,103-113.
Coomans, A.,2000. Nematode systematics:past, present and future. Nematology 2(1),3-7.
Costa, J.C., Lilley, C.J., Atkinson, H.J., Urwin, P.E.,2009. Functional characterisation of a cyst nematode acetylcholinesterase gene using Caenorhabditis elegans as a heterologous system. International journal for parasitology 39,849-858.
Coyne, C.P., Brake, D.,2001. Characterisation of Haemonchus contortus-derived cell populations propagated in vitro in a tissue culture environment and their potential to induce protective immunity in sheep. International journal for parasitology 31,359-376.
Davey, K.G., Sommerville, R.I., Rogers, W.P.,1982. The effect of ethoxyzolamide, an analogue of insect juvenile hormone, nor-adrenaline and iodine on changes in the optical path difference in the excretory cells and oesophagus during exsheathment in Haemonchus contortus. International journal for parasitology 12,509-513.
Davis. M.W., Birnie, A.J., Chan, A.C., Page, A.P., Jorgensen, E.M., 2004. A conserved metalloprotease mediates ecdysis in Caenorhabditis elegans. Development (Cambridge, England) 131,6001-6008.
Del Rio, L., Bennouna, S., Salinas, J., Denkers, E.Y.,2001. CXCR2 deficiency confers impaired neutrophil recruitment and increased susceptibility during Toxoplasma gondii infection. J Immunol 167,6503-6509.
Dieterich, C., Clifton, S.W., Schuster, L.N., Chinwalla, A., Delehaunty, K., Dinkelacker, I., Fulton, L. Fulton, R., Godfrey, J.,minx, P., Mitreva, M., Roeseler, W., Tian, H., Witte, H., Yang, S.P., Wilson, R.K., Sommer, R.J.,2008. The Pristionchus pacificus genome provides a unique perspective on nematode lifestyle and parasitism. Nature genetics 40,1193-1198.
Dillon, S.R., Sprecher, C., Hammond, A., Bilsborough, J., Rosenfeld-Franklin, M., Presnell, S.R., Haugen, H.S., Maurer, M., Harder, B., Johnston, J., Bort, S., Mudri, S., Kuijper, J.L. Bukowski, T., Shea, P., Dong, D.L., Dasovich, M., Grant, F.J., Lockwood, L., Levin, S.D., LeCiel, C., Waggie, K., Day, H., Topouzis, S., Kramer, J., Kuestner, R., Chen, Z., Foster, D., Parrish-Novak, J., Gross, J.A.,2004. Interleukin 31, a cytokine produced by activated T cells, induces dermatitis in mice. Nature immunology 5,752-760.
Dowse, T., Soldati, D.,2004. Host cell invasion by the apicomplexans:the significance of microneme protein proteolysis. Current opinion in microbiology 7,388-396.
Elbashir, S.M., Martinez, J., Patkaniowska, A., Lendeckel, W., Tuschl, T.,2001. Functional anatomy of siRNAs for mediating efficient RNAi in Drosophila melanogaster embryo lysate. The EMBO journal 20,6877-6888.
Elliott, D.A., Clark, D.P.,2000. Cryptosporidium parvum induces host cell actin accumulation at the host-parasite interface. Infection and immunity 68,2315-2322.
Emmons, S.,1988. The genome. In: Wood W.B. (Ed.), The nematode Caenorhabditis elegans. Cold Spring Harbor, NY:Cold Spring Harbor Laboratory, pp.47-79.
Fanelli, E., Di Vito, M., Jones. J.T., De Giorgi, C.,2005. Analysis of chitin synthase function in a plant parasitic nematode, Meloidogyne artiellia, using RNAi. Gene 349,87-95.
Feinberg, E.H., Hunter, C.P.,2003. Transport of dsRNA into cells by the transmembrane protein SID-1. Science (New York, N.Y 301,1545-1547.
Files, J.G., Carr, S., Hirsh, D.,1983. Actin gene family of Caenorhabditis elegans. Journal of molecular biology 164,355-375.
Fire, A., Xu, S., Montgomery, M.K., Kostas, S.A., Driver, S.E., Mello, C.C.,1998. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 391,806-811.
Ford, L., Zhang, J., Liu, J., Hashmi, S., Fuhrman, J.A., Oksov, Y., Lustigman, S.,2009. Functional analysis of the cathepsin-like cysteine protease genes in adult Brugia malayi using RNA interference. PLoS neglected tropical diseases 3, e377.
Forney, J.R., Yang, S., Healey, M.C.,1996. Protease activity associated with excystation of Cryptosporidium parvum oocysts. The Journal of parasitology 82,889-892.
Fort, M.M., Cheung, J., Yen, D., Li, J., Zurawski, S.M., Lo, S., Menon, S., Clifford, T., Hunte, B., Lesley, R., Muchamuel, T., Hurst, S.D., Zurawski, G., Leach, M.W., Gorman, D.M., Rennick, D.M.,2001. IL-25 induces IL-4,IL-5, and IL-13 and Th2-associated pathologies in vivo. Immunity 15,985-995.
Fraser, A.,2004. Towards full employment:using RNAi to find roles for the redundant. Oncogene 23, 8346-8352.
Fraser, A.G., Kamath, R.S., Zipperlen, P., Martinez-Campos, M., Sohrmann, M., Ahringer, J.,2000. Functional genomic analysis of C. elegans chromosome I by systematic RNA interference. Nature 408,325-330.
Freeman, A.S., Nghiem, C., Li, J., Ashton, F.T., Guerrero, J., Shoop, W.L., Schad, G.A.,2003. Amphidial structure of ivermectin-resistant and susceptible laboratory and field strains of Haemonchus contortus. Veterinary parasitology 110,217-226.
Galbadage, T., Hartman, P.S.,2008. Repeated temperature fluctuation extends the life span of Caenorhabditis elegans in a daf-16-dependent fashion. Mechanisms of ageing and
development 129,507-514.
Gamble, H.R., Mansfield, L.S.,1996. Characterization of excretory-secretory products from larval stages of Haemonchus contortus cultured in vitro. Veterinary parasitology 62,291-305.
Gause, W.C., Urban, J.F., Jr., Stadecker, M.J.,2003. The immune response to parasitic helminths: insights from murine models. Trends in immunology 24,269-277.
Geary, T.G., Thompson, D.P.,2001. Caenorhabditis elegans:how good a model for veterinary parasites? Veterinary parasitology 101,371-386.
Geldhof, P., Newlands, G.F., Nyame, K., Cummings, R., Smith, W.D., Knox, D.P.,2005. Presence of the LDNF glycan on the host-protective H-gal-GP fraction from Haemonchus contortus. Parasite immunology 27,55-60.
Geldhof. P., Moloy, C., Knox, D.P.,2006a. Combinatorial RNAi on intestinal cathepsin B-like proteinases in Caenorhabditis elegans questions the perception of their role in nematode biology. Molecular and biochemical parasitology 145,128-132.
Geldhof, P., Murray, L., Couthier, A., Gilleard, J.S., McLauchlan, G., Knox, D.P., Britton, C.,2006b. Testing the efficacy of RNA interference in Haemonchus contortus. International journal for parasitology 36,801-810.
Geldhof, P., Clark, D., Molloy, C., Knox, D.P.,2007. Assessment of Caenorhabditis elegans as a model in Haemonchus contortus vaccine research. Molecular and biochemical parasitology 152.220-223.
Gheysen, G., Vanholme, B.,2007. RNAi from plants to nematodes. Trends in biotechnology 25,89-92.
Gonczy, P., Echeverri, C., Oegema, K., Coulson, A., Jones, S.J., Copley, R.R., Duperon, J., Oegema, J., Brehm, M., Cassin, E., Hannak, E., Kirkham, M., Pichler, S., Flohrs, K., Goessen, A., Leidel, S., Alleaume, A.M., Martin, C., Ozlu, N., Bork, P., Hyman, A.A.,2000. Functional genomic analysis of cell division in C. elegans using RNAi of genes on chromosome III. Nature 408, 331-336.
Goodman, S.J., Branda, C.S., Robinson, M.K., Burdine, R.D., Stern, M.J.,2003. Alternative splicing affecting a novel domain in the C. elegans EGL-15 FGF receptor confers functional specificity. Development (Cambridge, England) 130,3757-3766.
Graham M., Smith T.S.,Munn E.A. et al.,1993.Recombinant DNA molecules encoding aminopeptidase enzymes and their use in the preparation of vaccines against helminth infections. Patent Application No. WO 93/2354
Grossi, L., McHugh, K., Collins, S.M.,1993. On the specificity of altered muscle function in experimental colitis in rats. Gastroenterology 104,1049-1056.
Hansen, M., Hsu, A.L., Dillin, A., Kenyon, C.,2005. New genes tied to endocrine, metabolic, and dietary regulation of lifespan from a Caenorhabditis elegans genomic RNAi screen. PLoS genetics 1,119-128.
Harnett, W., Harnett, M. M.,2006. Molecular basis of worm-induced immunomodulation. Parasite Immunol.28,535-43.
Hartfelder, K.,2000. Insect juvenile hormone:from "status quo" to high society. Brazilian journal of
medical and biological research= Revista brasileira de pesquisas medicas e biologicas/ Sociedade Brasileira de Biofisica... [et al 33,157-177.
Hashmi, S., Britton, C., Liu, J., Guiliano, D.B., Oksov, Y., Lustigman, S.,2002. Cathepsin L is essential for embryogenesis and development of Caenorhabditis elegans. The Journal of biological chemistry 277,3477-3486.
Hashim, A., Mulcahy, G., Bourke, B., Clyne, M.,2006. Interaction of Cryptosporidium hominis and Cryptosporidium parvum with primary human and bovine intestinal cells. Infection and immunity 74,99-107.
Haslam, S.M., Coles, G.C., Munn, E.A., Smith, T.S., Smith, H.F., Morris, H.R., Dell, A.,1996. Haemonchus contortus glycoproteins contain N-linked oligosaccharides with novel highly fucosylated core structures. The Journal of biological chemistry 271,30561-30570.
Haslam, S.M., Coles, G.C., Reason, A.J., Morris, H.R., Dell, A.,1998. The novel core fucosylation of Haemonchus contortus N-glycans is stage specific. Molecular and biochemical parasitology 93,143-147.
Hijjawi, N.S., Meloni, B.P., Morgan, U.M., Thompson, R.C.,2001. Complete development and long-term maintenance of Cryptosporidium parvum human and cattle genotypes in cell culture. International journal for parasitology 31,1048-1055.
Holden-Dye, L., Walker, R. J.,2006. Actions of glutamate and ivermectin on the pharyngeal muscle of Ascaridia galli:a comparative study with Caenorhabditis elegans. International journal for parasitology 36,395-402.
Hu, M., Lok, J.B., Ranjit, N., Massey, H.C., Jr., Sternberg, P.W., Gasser, R.B.2010, Structural and functional characterisation of the fork head transcription factor-encoding gene, Hc-daf-16, from the parasitic nematode Haemonchus contortus (Strongylida). International journal for parasitology 40,405-415.
Hu, M., Zhong, W., Campbell, B.E., Sternberg, P.W., Pellegrino, M.W., Gasser, R.B.,2010. Elucidating ANTs in worms using genomic and bioinformatic tools--biotechnological prospects? Biotechnology advances 28,49-60.
Huang, B.Q., Chen, X.M., LaRusso, N.F.,2004. Cryptosporidium parvum attachment to and internalization by human biliary epithelia in vitro:a morphologic study. The Journal of parasitology 90,212-221.
Huang, G., Allen, R., Davis, E.L., Baum, T.J., Hussey, R.S.,2006. Engineering broad root-knot resistance in transgenic plants by RNAi silencing of a conserved and essential root-knot nematode parasitism gene. Proceedings of the National Academy of Sciences of the United States of America 103,14302-14306.
Hunt-Newbury, R., Viveiros, R., Johnsen, R., Mah, A., Anastas, D., Fang, L., Halfnight, E., Lee, D., Lin, J., Lorch, A., McKay, S., Okada, H.M., Pan, J., Schulz, A.K., Tu, D., Wong, K., Zhao, Z., Alexeyenko, A., Burglin, T., Sonnhammer, E., Schnabel, R., Jones, S.J., Marra, M.A., Baillie, D.L., Moerman, D.G.,2007. High-throughput in vivo analysis of gene expression in Caenorhabditis elegans. PLoS biology 5, e237.
Hurd, D.D., Kemphues, K.J.,2003. PAR-1 is required for morphogenesis of the Caenorhabditis elegans vulva. Developmental biology 253,54-65.
Hussein, A.S., Kichenin, K., Selkirk, M.E.,2002. Suppression of secreted acetylcholinesterase expression in Nippostrongylus brasiliensis by RNA interference. Molecular and biochemical parasitology 122,91-94.
Ince, M.N., Elliott, D.E., Setiawan, T., Blum, A., Metwali, A., Wang, Y., Urban, J.F., Jr., Weinstock, J.V.,2006. Heligmosomoides polygyrus induces TLR4 on murine mucosal T cells that produce TGFbeta after lipopolysaccharide stimulation. J Immunol 176,726-729.
Irimia, M., Rukov, J.L., Roy, S.W., Vinther, J., Garcia-Fernandez, J.,2009. Quantitative regulation of alternative splicing in evolution and development. Bioessays 31,40-50.
Ishikawa, N., Wakelin, D., Mahida, Y.R.,1997. Role of T helper 2 cells in intestinal goblet cell hyperplasia in mice infected with Trichinella spiralis. Gastroenterology 113,542-549.
Issa, Z., Grant, W.N., Stasiuk, S., Shoemaker, C.B.,2005. Development of methods for RNA interference in the sheep gastrointestinal parasite, Trichostrongylus colubriformis. International journal for parasitology 35,935-940.
Jacobs, H.J., Wiltshire, C., Ashman, K., Meeusen, E.N.,1999. Vaccination against the gastrointestinal nematode, Haemonchus contortus, using a purified larval surface antigen. Vaccine 17,362-368.
Jiang, H., Chess, L.,2004. An integrated view of suppressor T cell subsets in immunoregulation. J Clin Invest.114,1198-208.
Jimenez, J.C., Fontaine, J., Grzych, J.M., Dei-Cas, E., Capron, M.,2004. Systemic and mucosal responses to oral administration of excretory and secretory antigens from Giardia intestinalis. Clinical and diagnostic laboratory immunology 11,152-160.
Johnson, J.M., Castle, J., Garrett-Engele, P., Kan, Z., Loerch, P.M., Armour, C.D., Santos, R., Schadt, E.E., Stoughton, R., Shoemaker, D.D.,2003. Genome-wide survey of human alternative pre-mRNA splicing with exon junction microarrays. Science (New York, N.Y 302,2141-2144.
Joshua, G.W.,2001. Functional analysis of leucine aminopeptidase in Caenorhabditis elegans. Molecular and biochemical parasitology 113,223-232.
Kamath, R.S., Fraser, A.G., Dong, Y., Poulin, G., Durbin, R., Gotta, M., Kanapin, A., Le Bot, N., Moreno, S., Sohrmann, M., Welchman, D.P., Zipperlen, P., Ahringer, J.,2003. Systematic functional analysis of the Caenorhabditis elegans genome using RNAi. Nature 421,231-237.
Kampkotter, A., Volkmann, T.E., de Castro, S.H., Leiers, B., Klotz, L.O., Johnson, T.E., Link, C.D., Henkle-Duhrsen, K.,2003. Functional analysis of the glutathione S-transferase 3 from Onchocerca volvulus (Ov-GST-3):a parasite GST confers increased resistance to oxidative stress in Caenorhabditis elegans. Journal of molecular biology 325,25-37.
Kan, Z., Rouchka, E.C., Gish, W.R., States, D.J.,2001. Gene structure prediction and alternative splicing analysis using genomically aligned ESTs. Genome research 11,889-900.
Kaplan, R.M.,2004. Drug resistance in nematodes of veterinary importance:a status report. Trends in parasitology 20,477-481.
Kappe, S.H., Buscaglia, C.A., Bergman, L.W., Coppens, I., Nussenzweig, V.,2004. Apicomplexan gliding motility and host cell invasion:overhauling the motor model. Trends in parasitology 20,13-16.
Kawano, T., Fujita, M., Sakamoto, H.,2000. Unique and redundant functions of SR proteins, a conserved family of splicing factors, in Caenorhabditis elegans development. Mechanisms of development 95,67-76.
Kelsall, B. L., Rescigno, M.,2004. Mucosal dendritic cells in immunity and inflammation. Nat Immunol.5,1091-5.
Kelsall, B. L., Strober, W.,1996. The role of dendritic cells in antigen processing in the Peyer's patch. Ann N Y Acad Sci.778,47-54.
Kennerdell, J.R., Carthew, R.W.,1998. Use of dsRNA-mediated genetic interference to demonstrate that frizzled and frizzled 2 act in the wingless pathway. Cell 95,1017-1026.
Khalife, J., Godin, C., Capron, A.,1995. Transcriptional regulation of Schistosoma mansoni calreticulin:possible role of AP-1. Parasitology 111 (Pt 4),469-475.
Khan, W. I.,2008. Physiological changes in the gastrointestinal tract and host protective immunity: learning from the mouse-Trichinella spiralis model. Parasitology.135,671-82.
Khan, W.I., Blennerhasset, P., Ma, C., Matthaei, K.I., Collins, S.M.,2001. Stat6 dependent goblet cell hyperplasia during intestinal nematode infection. Parasite immunology 23,39-42.
Kim, E., Magen, A., Ast, G.,2007. Different levels of alternative splicing among eukaryotes. Nucleic acids research 35,125-131.
Kimber, M.J., McKinney, S., McMaster, S., Day, T.A., Fleming, C.C., Maule, A.G.,2007. flp gene disruption in a parasitic nematode reveals motor dysfunction and unusual neuronal sensitivity to RNA interference. Faseb J 21,1233-1243.
Knox, D.P., Smith, W.D.,2001. Vaccination against gastrointestinal nematode parasites of ruminants using gut-expressed antigens. Veterinary parasitology 100,21-32.
Knox D.P., Smith S K, Smith W D,1995. Vaccines against helminthic parasites:thiol binding proteins: International Patent Application, PCT/GB95/00665[P].1995-03-24.
Knox, D.P., Redmond, D.L., Newlands, G.F., Skuce, P.J., Pettit, D., Smith, W.D.,2003. The nature and prospects for gut membrane proteins as vaccine candidates for Haemonchus contortus and other ruminant trichostrongyloids. International journal for parasitology 33,1129-1137.
Knox, D.P., Geldhof, P., Visser, A., Britton, C.,2007. RNA interference in parasitic nematodes of animals:a reality check? Trends in parasitology 23,105-107.
Kotze, A.C., Bagnall, N.H.,2006. RNA interference in Haemonchus contortus:suppression of beta-tubulin gene expression in L3, L4 and adult worms in vitro. Molecular and biochemical parasitology 145,101-110.
Krause, S., Sommer, A., Fischer, P., Brophy, P.M., Walter, R.D., Liebau, E.,2001. Gene structure of the extracellular glutathione S-transferase from Onchocerca volvulus and its overexpression and promoter analysis in transgenic Caenorhabditis elegans. Molecular and biochemical parasitology 117,145-154.
Kreider, T., Anthony, R.M., Urban, J.F., Jr., Gause, W.C.,2007. Alternatively activated macrophages in helminth infections. Current opinion in immunology 19,448-453.
Kuznar, Z. A., Elimelech, M.,2005. Role of surface proteins in the deposition kinetics of Cryptosporidium parvum oocysts. Langmuir.21,710-6.
Kwa, M.S., Veenstra, J.G., Van Dijk, M., Roos, M.H.,1995. Beta-tubulin genes from the parasitic nematode Haemonchus contortus modulate drug resistance in Caenorhabditis elegans. Journal of molecular biology 246,500-510.
Lambshead, P.J.D.,2004. Marine nematode biodiversity. In:Chen, Z.X., Chen, W.Y., Chen, S.Y., Dickson, D.W. (Eds.), Nematology:Advances and Perspectives Vol 1:Nematode Morphology, Physiology and Ecology. CABI Publishing, pp.436-467.
Laurent, V., Brooks, D.R., Coates, D., Isaac, R.E.,2001. Functional expression and characterization of the cytoplasmic aminopeptidase P of Caenorhabditis elegans. European journal of biochemistry/FEBS 268,5430-5438.
Lebrun, M., Michelin, A., El Hajj, H., Poncet, J., Bradley, P.J., Vial, H., Dubremetz, J.F.,2005. The rhoptry neck protein RON4 re-localizes at the moving junction during Toxoplasma gondii invasion. Cellular microbiology 7,1823-1833.
LeJambre, L.F., Windon, R.G., Smith, W.D.,2008. Vaccination against Haemonchus contortus: performance of native parasite gut membrane glycoproteins in Merino lambs grazing contaminated pasture. Veterinary parasitology 153,302-312.
Lendner, M., Doligalska, M., Lucius, R., Hartmann, S.,2008. Attempts to establish RNA interference in the parasitic nematode Heligmosomoides polygyrus. Molecular and biochemical parasitology 161,21-31.
Levy-Holtzman, R., Schechter, I.,1995. Activity of the promoter of the hsp70 gene of the parasitic helminth Schistosoma mansoni in the mammalian CHO cell-line. Biochimica et biophysica acta 1263,96-98.
Li, C., Wei, X., Xu, L., Li, X.,2007a. Recombinant galectins of male and female Haemonchus contortus do not hemagglutinate erythrocytes of their natural host. Veterinary parasitology 144,299-303.
Li, J., Zhu, X., Ashton, F.T., Gamble, H.R., Schad, GA.,2001. Sensory neuroanatomy of a passively ingested nematode parasite, Haemonchus contortus:amphidial neurons of the third-stage larva. The Journal of parasitology 87,65-72.
Li, X., Du, A., Cai, W., Hou, Y., Pang, L., Gao, X.,2007b. Evaluation of a recombinant excretory secretory Haemonchus contortus protein for use in a diagnostic enzyme-linked immunosorbent assay. Experimental parasitology 115,242-246.
Lieberman, L. A., Hunter, C. A.,2002. The role of cytokines and their signaling pathways in the regulation of immunity to Toxoplasma gondii. Int Rev Immunol.21,373-403.
Liu, J., Dent, J.A., Beech, R.N., Prichard, R.K.,2004. Genomic organization of an avermectin receptor subunit from Haemonchus contortus and expression of its putative promoter region in Caenorhabditis elegans. Molecular and biochemical parasitology 134,267-274.
Lojda, Z., Gossrau, R.,1980. Study on aminopeptidase A. Histochemistry 67,267-290.
Longman, D., Johnstone, I.L., Caceres, J.F.,2000. Functional characterization of SR and SR-related genes in Caenorhabditis elegans. The EMBO journal 19,1625-1637.
Lopez de Mendoza, M.E., Modha, J., Roberts, M.C., Curtis, R., Kusel, J.R.,2000. Changes in the lipophilicity of the surfaces of Meloidogyne incognita and Haemonchus contortus during exposure to host signals. Parasitology 120 (Pt 2),203-209.
Luangsay, S., Kasper, L.H., Rachinel, N., Minns, L.A., Mennechet, F.J., Vandewalle, A., Buzoni-Gatel, D.,2003. CCR5 mediates specific migration of Toxoplasma gondii-primed CD8 lymphocytes to inflammatory intestinal epithelial cells. Gastroenterology 125,491-500.
Lumaret J.P., Ganlante E., Lumbreras C.,1993. Fields effects of ivermectin residues on drug beetles. Journal for Applied Ecology,30:428-436
Lu, R., Maduro, M., Li, F., Li, H.W., Broitman-Maduro, G., Li, W.X., Ding, S.W.,2005. Animal virus replication and RNAi-mediated antiviral silencing in Caenorhabditis elegans. Nature 436, 1040-1043.
Lustigman, S., Zhang, J., Liu, J., Oksov, Y., Hashmi, S.,2004. RNA interference targeting cathepsin L and Z-like cysteine proteases of Onchocerca volvulus confirmed their essential function during L3 molting. Molecular and biochemical parasitology 138,165-170.
Lynch, K.W.,2007. Regulation of alternative splicing by signal transduction pathways. Advances in experimental medicine and biology 623,161-174.
Mckay S.J., Johnsen R., Khattra J.,2004. Gene expression profiling of cells, tissues and developmental stages of the nematode C. elegans. Cold Spring Harbor Symposium on Quantitative Biology,68:159-169.
Madsen M.B., Neelsen B.O., Holter P., et al,1990. Treating cattle with ivermectin:the effects on the fauna and decomposition of dung pats. Journal for Applied Ecology,27:1-15
Maeda, I., Kohara, Y., Yamamoto, M., Sugimoto, A.,2001. Large-scale analysis of gene function in Caenorhabditis elegans by high-throughput RNAi. Curr Biol 11,171-176.
Makeyev, E.V., Zhang, J., Carrasco, M.A., Maniatis, T.,2007. The MicroRNA miR-124 promotes neuronal differentiation by triggering brain-specific alternative pre-mRNA splicing. Molecular cell 27,435-448.
Manzanilla-Lopes, R.H., Evans, K., Bridge, J.,2004. Plant diseases caused by nematodes. In:Chen, Z.X., Chen, W.Y., Chen, S.Y., Dickson, D.W. (Eds.), Nematology:Advances and Perspectives Vol 2:Nematode Management and Utilization. CABI Publishing, pp.637-716.
McDonald, V.,2003. Parasites in the gastrointestinal tract. Parasite immunology 25,231-234.
Mello, C., Fire, A.,1995. DNA transformation. Methods in cell biology 48,451-482.
Mello, C.C., Kramer, J.M., Stinchcomb, D., Ambros, V.,1991. Efficient gene transfer in C.elegans: extrachromosomal maintenance and integration of transforming sequences. The EMBO journal 10,3959-3970.
Metwali, A., Setiawan, T., Blum, A.M., Urban, J., Elliott, D.E., Hang, L., Weinstock, J.V.,2006.
Induction of CD8+ regulatory T cells in the intestine by Heligmosomoides polygyrus infection. American journal of physiology 291, G253-259.
Miller, H. R.,1987. Gastrointestinal mucus, a medium for survival and for elimination of parasitic nematodes and protozoa. Parasitology.94 Suppl, S77-100.
Mironov, A.A., Fickett, J.W., Gelfand, M.S.,1999. Frequent alternative splicing of human genes. Genome research 9,1288-1293.
Mital, J., Meissner, M., Soldati, D., Ward, GE.,2005. Conditional expression of Toxoplasma gondii apical membrane antigen-1 (TgAMAl) demonstrates that TgAMA1 plays a critical role in host cell invasion. Molecular biology of the cell 16,4341-4349.
Mitreva, M., Blaxter, M.L., Bird, D.M., McCarter, J.P.,2005. Comparative genomics of nematodes. Trends Genet 21, 573-581.
Modrek, B., Resch, A., Grasso, C., Lee, C.,2001. Genome-wide detection of alternative splicing in expressed sequences of human genes. Nucleic acids research 29,2850-2859.
Modrek, B., Lee, C.,2002. A genomic view of alternative splicing. Nature genetics 30,13-19.
Morrissette, N. S., Sibley, L. D.,2002. Cytoskeleton of apicomplexan parasites. Microbiol Mol Biol Rev.66,21-38; table of contents.
Mount, S.M.,1982. A catalogue of splice junction sequences. Nucleic acids research 10,459-472.
Munn, E.A., Smith, T.S., Smith, H., James, F.M., Smith, F.C., Andrews, S.J.,1997. Vaccination against Haemonchus contortus with denatured forms of the protective antigen H11. Parasite immunology 19,243-248.
Murray, L., Geldhof, P., Clark, D., Knox, D.P., Britton, C.,2007. Expression and purification of an active cysteine protease of Haemonchus contortus using Caenorhabditis elegans. International journal for parasitology 37,1117-1125.
Natsuka, S., Adachi, J., Kawaguchi, M., Nakakita, S., Hase, S., Ichikawa, A., Ikura, K.,2002. Structural analysis of N-linked glycans in Caenorhabditis elegans. Journal of biochemistry 131,807-813.
Nelson, J.B., O'Hara, S.P., Small, A.J., Tietz, P.S., Choudhury, A.K., Pagano, R.E., Chen, X.M., LaRusso, N.F.,2006. Cryptosporidium parvum infects human cholangiocytes via sphingolipid-enriched membrane microdomains. Cellular microbiology 8,1932-1945.
Newlands, G.F., Skuce, P.J., Knox, D.P., Smith, S.K., Smith, W.D.,1999. Cloning and characterization of a beta-galactoside-binding protein (galectin) from the gut of the gastrointestinal nematode parasite Haemonchus contortus. Parasitology 119 (Pt 5),483-490.
Newmark, P.A., Reddien, P.W., Cebria, F., Sanchez Alvarado, A.,2003. Ingestion of bacterially expressed double-stranded RNA inhibits gene expression in planarians. Proceedings of the National Academy of Sciences of the United States of America 100 Suppl 1,11861-11865.
Newton, S.E., Morrish, L.E., Martin, P.J., Montague, P.E., Rolph, T.P.,1995. Protection against multiply drug-resistant and geographically distant strains of Haemonchus contortus by vaccination with Hll, a gut membrane-derived protective antigen. International journal for parasitology 25,511-521.
Newton, S.E., Munn, E.A.,1999. The development of vaccines against gastrointestinal nematode parasites, particularly Haemonchus contortus. Parasitology today (Personal ed 15,116-122.
Newton, S.E., Meeusen, E.N.,2003. Progress and new technologies for developing vaccines against gastrointestinal nematode parasites of sheep. Parasite immunology 25,283-296.
Ngo, H., Tschudi, C., Gull, K., Ullu, E.,1998. Double-stranded RNA induces mRNA degradation in Trypanosoma brucei. Proceedings of the National Academy of Sciences of the United States of America 95,14687-14692.
Nikolaou, S., Hartman, D., Presidente, P.J., Newton, S.E., Gasser, R.B.,2002. HcSTK, a Caenorhabditis elegans PAR-1 homologue from the parasitic nematode, Haemonchus contortus. International journal for parasitology 32,749-758.
Nikolaou. S., Gasser, R.B.,2006. Prospects for exploring molecular developmental processes in Haemonchus contortus. International journal for parasitology 36,859-868.
Nilsen, T.W., Graveley, B.R., Expansion of the eukaryotic proteome by alternative splicing. Nature 463,457-463.
Novelli, J., Ahrned, S., Hodgkin, J.,2004. Gene interactions in Caenorhabditis elegans define DPY-31 as a candidate procollagen C-proteinase and SQT-3/ROL-4 as its predicted major target. Genetics 168,1259-1273.
Novelli, J., Page, A.P., Hodgkin, J.,2006. The C terminus of collagen SQT-3 has complex and essential functions in nematode collagen assembly. Genetics 172,2253-2267.
Oka, T., Toyomura, T., Honjo, K., Wada, Y., Futai, M.,2001. Four subunit a isoforms of Caenorhabditis elegans vacuolar H+-ATPase. Cell-specific expression during development. The Journal of biological chemistry 276,33079-33085.
Okhuysen, P.C., DuPont, H.L., Sterling, C.R., Chappell, C.L.,1994. Arginine aminopeptidase, an integral membrane protein of the Cryptosporidium parvum sporozoite. Infection and immunity 62,4667-4670.
Page, A.P., Winter, A.D.,2003. Enzymes involved in the biogenesis of the nematode cuticle. Advances in parasitology 53,85-148.
Page, A.P., Johnstone, I.L.,2007. The cuticle. WormBook,1-15.
Paschinger, K., Rendic, D., Lochnit, G., Jantsch, V., Wilson, I.B.,2004. Molecular basis of anti-horseradish peroxidase staining in Caenorhabditis elegans. The Journal of biological chemistry 279,49588-49598.
Perkins, M.E., Riojas, Y.A., Wu, T.W., Le Blancq, S.M.,1999. CpABC, a Cryptosporidium parvum ATP-binding cassette protein at the host-parasite boundary in intracellular stages. Proceedings of the National Academy of Sciences of the United States of America 96,5734-5739.
Petronijevic, T., Rogers, W.P.,1983. Gene activity and the development of early parasitic stages of nematodes. International journal for parasitology 13,197-199.
Pfarr, K., Heider, U., Hoerauf, A.,2006. RNAi mediated silencing of actin expression in adult Litomosoides sigmodontis is specific, persistent and results in a phenotype. International journal for parasitology 36,661-669.
Piano, F., Schetter, A.J., Mangone, M., Stein, L., Kemphues, K.J.,2000. RNAi analysis of genes expressed in the ovary of Caenorhabditis elegans. Curr Biol 10,1619-1622.
Pillai, S., Kalinna, B.H., Liebau, E., Hartmann, S., Theuring, F., Lucius, R.,2005. Studies on Acanthocheilonema viteae cystatin:genomic organization, promoter studies and expression in Caenorhabditis elegans. Filaria journal 4,9.
Pollok, R.C., McDonald, V., Kelly, P., Farthing, M.J.,2003. The role of Cryptosporidium parvum-derived phospholipase in intestinal epithelial cell invasion. Parasitology research 90,181-186.
Pujol, N., Bonnerot, C., Ewbank, J.J., Kohara, Y., Thierry-Mieg, D.,2001. The Caenorhabditis elegans unc-32 gene encodes alternative forms of a vacuolar ATPase a subunit. The Journal of biological chemistry 276,11913-11921.
Qin, L., Smant, G, Stokkermans, J., Bakker, J., Schots, A., Helder, J.,1998. Cloning of a trans-spliced glyceraldehyde-3-phosphate-dehydrogenase gene from the potato cyst nematode Globodera rostochiensis and expression of its putative promoter region in Caenorhabditis elegans. Molecular and biochemical parasitology 96,59-67.
Rachinel, N., Buzoni-Gatel, D., Dutta, C., Mennechet, F.J., Luangsay, S., Minns, L.A., Grigg, M.E., Tomavo, S., Boothroyd, J.C., Kasper, L.H.,2004. The induction of acute ileitis by a single microbial antigen of Toxoplasma gondii. J Immunol 173,2725-2735.
Rathore, D.K., Suchitra, S., Saini, M., Singh, B.P., Joshi, P.,2006. Identification of a 66 kDa Haemonchus contortus excretory/secretory antigen that inhibits host monocytes. Veterinary parasitology 138,291-300.
Rawlings, N.D., Barrett, A.J.,1995. Evolutionary families of metallopeptidases. Methods in enzymology 248,183-228.
Redmond, D.L., Knox, D.P., Newlands, G., Smith, W.D.,1997. Molecular cloning and characterisation of a developmentally regulated putative metallopeptidase present in a host protective extract of Haemonchus contortus. Molecular and biochemical parasitology 85,77-87.
Redmond, D.L., Clucas, C., Johnstone, I.L., Knox, D.P.,2001. Expression of Haemonchus contortus pepsinogen in Caenorhabditis elegans. Molecular and biochemical parasitology 112,125-131.
Redmond, D.L., Geldhof, P., Knox, D.P.,2004. Evaluation of Caenorhabditis elegans glycoproteins as protective immunogens against Haemonchus contortus challenge in sheep. International Journal for Parasitology 34,1347-1353.
Reszka. N., Rijsewijk, F.A., Zelnik, V., Moskwa, B., Bienkowska-Szewczyk, K.,2007. Haemonchus contortus:characterization of the baculovirus expressed form of aminopeptidase H11. Experimental parasitology 117,208-213.
Rogers, W.P., Petronijevic, T.,1982. The infective stage and the development of nematodes. In: Symons, L.E.A., Donald, A.D., Dineen, J.K. (Eds.), Biology and Control of Endoparasites. Academic Press, Australia, pp.3-28.
Roos, M.H., Tielens, A.G,1994. Differential expression of two succinate dehydrogenase subunit-B genes and a transition in energy metabolism during the development of the parasitic nematode Haemonchus contortus. Molecular and biochemical parasitology 66,273-281.
Rosso, M.N., Dubrana, M.P., Cimbolini, N., Jaubert, S., Abad, P.,2005. Application of RNA interference to root-knot nematode genes encoding esophageal gland proteins. Mol Plant Microbe Interact 18,615-620.
Rosso, M.N., Jones, J.T., Abad, P.,2009. RNAi and functional genomics in plant parasitic nematodes. Annual review of phytopathology 47,207-232.
Rothwell, T.L.,1989. Immune expulsion of parasitic nematodes from the alimentary tract. International journal for parasitology 19,139-168.
Sagar, M., Padol, I., Khan, W.I., Bonin, R.P., Blennerhassett, P.A., Hunt, R.H.,2004. Establishment of T-Helper-2 immune response based gerbil model of enteric infection. Scandinavian journal of gastroenterology 39,668-673.
Sague, S.L., Tato, C., Pure, E., Hunter, C.A.,2004. The regulation and activation of CD44 by natural killer (NK) cells and its role in the production of IFN-gamma. J Interferon Cytokine Res 24, 301-309.
Sanchez, L.,2008. Sex-determining mechanisms in insects. The International journal of developmental biology 52,837-856.
Sasagawa, Y., Urano, T., Kohara, Y., Takahashi, H., Higashitani, A.,2003. Caenorhabditis elegans RBX1 is essential for meiosis, mitotic chromosomal condensation and segregation, and cytokinesis. Genes Cells 8,857-872.
Schallig, H.D., Van Leeuwen, M.A.,1997. Protective immunity to the blood-feeding nematode Haemonchus contortus induced by vaccination with parasite low molecular weight antigens. Parasitology 114 (Pt 3),293-299.
Schallig, H.D., van Leeuwen, M.A., Cornelissen, A.W.,1997. Protective immunity induced by vaccination with two Haemonchus contortus excretory secretory proteins in sheep. Parasite immunology 19,447-453.
Schratt, G.M., Tuebing, F., Nigh, E.A., Kane, C.G., Sabatini, M.E., Kiebler, M, Greenberg, M.E.,2006. A brain-specific microRNA regulates dendritic spine development. Nature 439,283-289.
Sciacca, J., Forbes, W.M., Ashton, F.T., Lombardini, E., Gamble, H.R., Schad, G.A.,2002. Response to carbon dioxide by the infective larvae of three species of parasitic nematodes. Parasitology international 51,53-62.
Serra, E., Zemzoumi, K., Trolet, J., Capron, A., Dissous, C.,1996. Functional analysis of the Schistosoma mansoni 28 kDa glutathione S-transferase gene promoter:involvement of SMNF-Y transcription factor in multimeric complexes. Molecular and biochemical parasitology 83,69-80.
Setiawan, T., Metwali, A., Blum, A.M., Ince, M.N., Urban, J.F., Jr., Elliott, D.E., Weinstock, J.V.,2007. Heligmosomoides polygyrus promotes regulatory T-cell cytokine production in the murine normal distal intestine. Infection and immunity 75,4655-4663.
Shamansky, L.M., Pratt, D., Boisvenue, R.J., Cox, G.N.,1989. Cuticle collagen genes of Haemonchus contortus and Caenorhabditis elegans are highly conserved. Molecular and biochemical parasitology 37,73-85.
Shin, C., Manley, J.L.,2004. Cell signalling and the control of pre-mRNA splicing. Nature reviews 5, 727-738.
Shingles, J., Lilley, C.J., Atkinson, H.J., Urwin, P.E.,2007. Meloidogyne incognita:molecular and biochemical characterisation of a cathepsin L cysteine proteinase and the effect on parasitism following RNAi. Experimental parasitology 115,114-120.
Siddiqui, S.Z., Brown, D.D., Rao, V.T., Forrester, S.G., AN UNC-49 GABA RECEPTOR SUBUNIT FROM THE PARASITIC NEMATODE Haemonchus contortus IS ASSOCIATED WITH ENHANCED GABA SENSITIVITY IN NEMATODE HETEROMERIC CHANNELS. Journal of neurochemistry. (In press)
Simmer, F., Moorman, C., van der Linden, A.M., Kuijk, E., van den Berghe, P.V., Kamath, R.S., Fraser, A.G., Ahringer, J., Plasterk, R.H.,2003. Genome-wide RNAi of C. elegans using the hypersensitive rrf-3 strain reveals novel gene functions. PLoS biology 1, E12.
Sinai, A.P., Webster, P., Joiner, K.A.,1997. Association of host cell endoplasmic reticulum and mitochondria with the Toxoplasma gondii parasitophorous vacuole membrane:a high affinity interaction. Journal of cell science 110 (Pt 17),2117-2128.
Skuce, P.J., Redmond, D.L., Liddell, S., Stewart, E.M., Newlands, G.F., Smith, W.D., Knox, D.P., 1999a. Molecular cloning and characterization of gut-derived cysteine proteinases associated with a host protective extract from Haemonchus contortus. Parasitology 119 (Pt 4),405-412.
Skuce, P.J., Stewart, E.M., Smith, W.D., Knox, D.P.,1999b. Cloning and characterization of glutamate dehydrogenase (GDH) from the gut of Haemonchus contortus. Parasitology 118 (Pt 3),297-304.
Skuce, P.J., Newlands, G.F., Stewart, E.M., Pettit, D., Smith, S.K., Smith, W.D., Knox, D.P.,2001. Cloning and characterisation of thrombospondin, a novel multidomain glycoprotein found in association with a host protective gut extract from Haemonchus contortus. Molecular and biochemical parasitology 117,241-244.
Smith, H.V., Nichols, R.A., Grimason, A.M.,2005. Cryptosporidium excystation and invasion:getting to the guts of the matter. Trends in parasitology 21,133-142.
Smith, S.K., Smith, W.D.,1996. Immunisation of sheep with an integral membrane glycoprotein complex of Haemonchus contortus and with its major polypeptide components. Research in veterinary science 60,1-6.
Smith, T.S., Munn, E.A., Graham, M., Tavernor, A.S., Greenwood, C.A.,1993. Purification and evaluation of the integral membrane protein H11 as a protective antigen against Haemonchus contortus. International journal for parasitology 23,271-280.
Smith, T.S., Graham, M., Munn, E.A., Newton, S.E., Knox, D.P., Coadwell, W.J., McMichael-Phillips, D., Smith, H., Smith, W.D., Oliver, J.J.,1997. Cloning and characterization of a microsomal aminopeptidase from the intestine of the nematode Haemonchus contortus. Biochimica et biophysica acta 1338,295-306.
Smith, W.D., Jackson, F., Jackson, E., Williams, J.,1983. Local immunity and Ostertagia circumcincta: changes in the gastric lymph of sheep after a primary infection. Journal of comparative pathology 93,471-478.
Smith, W.D., Jackson, F., Jackson, E., Williams, J., Miller, H.R.,1984. Manifestations of resistance to ovine ostertagiasis associated with immunological responses in the gastric lymph. Journal of comparative pathology 94,591-601.
Smith, W.D., Jackson, F., Jackson, E., Williams, J.,1985. Age immunity to Ostertagia circumcincta: comparison of the local immune responses of 4 1/2- and 10-month-old lambs. Journal of comparative pathology 95,235-245.
Smith, W.D.,2007. Some observations on immunologically mediated inhibited Teladorsagia circumcincta and their subsequent resumption of development in sheep. Veterinary parasitology 147,103-109.
Smith, W.D., Smith, S.K., Murray, J.M.,1994. Protection studies with integral membrane fractions of Haemonchus contortus. Parasite immunology 16,231-241.
Smith, W.D.,1999. Prospects for vaccines of helminth parasites of grazing ruminants. International journal for parasitology 29,17-24.
Smith, W.D., Smith, S.K., Pettit, D., Newlands, G.F., Skuce, P.J.,2000. Relative protective properties of three membrane glycoprotein fractions from Haemonchus contortus. Parasite immunology 22,63-71.
Smith, W.D., Newlands, G.F., Smith, S.K., Pettit, D., Skuce, P.J.,2003a. Metalloendopeptidases from the intestinal brush border of Haemonchus contortus as protective antigens for sheep. Parasite immunology 25,313-323.
Smith, W.D., Skuce, P.J., Newlands, G.F., Smith, S.K., Pettit, D.,2003b. Aspartyl proteases from the intestinal brush border of Haemonchus contortus as protective antigens for sheep. Parasite immunology 25,521-530.
Smith, W.D., Zarlenga, D.S.,2006. Developments and hurdles in generating vaccines for controlling helminth parasites of grazing ruminants. Veterinary parasitology 139,347-359.
Snelling, W.J., Lin, Q., Moore, J.E., Millar, B.C., Tosini, F., Pozio, E., Dooley, J.S., Lowery, C.J.,2007. Proteomics analysis and protein expression during sporozoite excystation of Cryptosporidium parvum (Coccidia, Apicomplexa). Mol Cell Proteomics 6,346-355.
Stear, M.J., Strain, S., Bishop, S.C.,1999. Mechanisms underlying resistance to nematode infection. International journal for parasitology 29,51-56; discussion 73-55.
Stepek, G., McCormack, G., Page, A.P.,2010. Collagen processing and cuticle formation is catalysed by the astacin metalloprotease DPY-31 in free-living and parasitic nematodes. International journal for parasitology 40,533-542.
Stinchcomb, D.T., Mello, C., Hirsh, D.,1985. Caenorhabditis elegans DNA that directs segregation in yeast cells. Proceedings of the National Academy of Sciences of the United States of America 82,4167-4171.
Streit, A.,2008. Reproduction in Strongyloides (Nematoda):a life between sex and parthenogenesis. Parasitology 135,285-294.
Strong, W.B., Gut, J., Nelson, R.G.,2000. Cloning and sequence analysis of a highly polymorphic
Cryptosporidium parvum gene encoding a 60-kilodalton glycoprotein and characterization of its 15-and 45-kilodalton zoite surface antigen products. Infection and immunity 68,4117-4134.
Sulston, J.E., Horvitz, H.R.,1977. Post-embryonic cell lineages of the nematode, Caenorhabditis elegans. Developmental biology 56,110-156.
Sulston, J.E., Schierenberg, E., White, J.G., Thomson, J.N.,1983. The embryonic cell lineage of the nematode Caenorhabditis elegans. Developmental biology 100,64-119.
Suss-Toby, E., Zimmerberg, J., Ward, GE.,1996. Toxoplasma invasion:the parasitophorous vacuole is formed from host cell plasma membrane and pinches off via a fission pore. Proceedings of the National Academy of Sciences of the United States of America 93,8413-8418.
Tabara, H., Grishok, A., Mello, C.C.,1998. RNAi in C. elegans:soaking in the genome sequence. Science (New York, N.Y 282,430-431.
Tavernarakis, N., Wang, S.L., Dorovkov, M., Ryazanov, A., Driscoll, M.,2000. Heritable and inducible genetic interference by double-stranded RNA encoded by transgenes. Nature genetics 24,180-183.
Tato, C.M., Villarino, A., Caamano, J.H., Boothby, M., Hunter, C.A.,2003. Inhibition of NF-kappa B activity in T and NK cells results in defective effector cell expansion and production of IFN-gamma required for resistance to Toxoplasma gondii. J Immunol 170,3139-3146.
Tavernor, A.S., Smith, T.S., Langford, C.F., Munn, E.A., Graham, M.,1992. Vaccination of young Dorset lambs against haemonchosis. Parasite immunology 14,645-655.
Tetley, L., Brown, S.M., McDonald, V., Coombs, GH.,1998. Ultrastructural analysis of the sporozoite of Cryptosporidium parvum. Microbiology (Reading, England) 144 (Pt 12),3249-3255.
Thein, M.C., Winter, A.D., Stepek, G, McCormack, G, Stapleton, G, Johnstone, I.L., Page, A.P.,2009. Combined extracellular matrix cross-linking activity of the peroxidase MLT-7 and the dual oxidase BLI-3 is critical for post-embryonic viability in Caenorhabditis elegans. The Journal of biological chemistry 284,17549-17563.
Thompson, R.C., Olson, M.E., Zhu, G, Enomoto, S., Abrahamsen, M.S., Hijjawi, N.S.,2005. Cryptosporidium and cryptosporidiosis. Advances in parasitology 59,77-158.
Tijsterman, M., May, R.C., Simmer, F., Okihara, K.L., Plasterk, R.H.,2004. Genes required for systemic RNA interference in Caenorhabditis elegans. Curr Biol 14,111-116.
Urban, J.F., Jr., Noben-Trauth, N., Donaldson, D.D., Madden, K.B., Morris, S.C., Collins, M., Finkelman, F.D.,1998. IL-13, IL-4Ralpha, and Stat6 are required for the expulsion of the gastrointestinal nematode parasite Nippostrongylus brasiliensis. Immunity 8,255-264.
Urwin, P.E., Lilley, C.J., Atkinson, H.J.,2002. Ingestion of double-stranded RNA by preparasitic juvenile cyst nematodes leads to RNA interference. Mol Plant Microbe Interact 15,747-752.
Valigurova, A., Jirku, M., Koudela, B., Gelnar, M., Modry, D., Slapeta, J.,2008. Cryptosporidia: epicellular parasites embraced by the host cell membrane. International journal for parasitology 38,913-922.
Vallance, B.A., Galeazzi, F., Collins, S.M., Snider, D.P.,1999. CD4 T cells and major histocompatibility complex class II expression influence worm expulsion and increased intestinal muscle contraction during Trichinella spiralis infection. Infection and immunity 67, 6090-6097.
van Wyk, J.A., Malan, F.S., Randles, J.L.,1997. How long before resistance makes it impossible to control some field strains of Haemonchus contortus in South Africa with any of the modern anthelmintics? Veterinary parasitology 70,111-122.
Vasudevan, S., Tong, Y., Steitz, J.A.,2007. Switching from repression to activation:microRNAs can up-regulate translation. Science (New York, N.Y 318,1931-1934.
Vermillion, D.L., Collins, S.M.,1988. Increased responsiveness of jejunal longitudinal muscle in Trichinella-infected rats. The American journal of physiology 254, G124-129.
Vervelde, L., Kooyman, F.N., Van Leeuwen. M.A, Schallig, H.D., MacKellar, A., Huntley, J.F., Cornelissen, A.W.,2001. Age-related protective immunity after vaccination with Haemonchus contortus excretory/secretory proteins. Parasite immunology 23,419-426.
Vervelde, L., Van Leeuwen, M.A., Kruidenier, M., Kooyman, F.N., Huntley, J.F., Van Die, I., Cornelissen, A.W.,2002. Protection studies with recombinant excretory/secretory proteins of Haemonchus contortus. Parasite immunology 24,189-201.
Viney, M.E., Thompson, F.J.,2008. Two hypotheses to explain why RNA interference does not work in animal parasitic nematodes. International journal for parasitology 38,43-47.
Waller, P.J.,1994. The development of anthelmintic resistance in ruminant livestock. Acta tropica 56, 233-243.
Wang, J., Yan, R., Xu, L., Li, X.,2007. The second glutamic acid in the C-terminal CRD affects the carbohydrate-binding properties of recombinant galectins of Haemonchus contortus. Veterinary parasitology 148,247-255.
Wetzel, D.M., Schmidt, J., Kuhlenschmidt, M.S., Dubey, J.P., Sibley, L.D.,2005. Gliding motility leads to active cellular invasion by Cryptosporidium parvum sporozoites. Infection and immunity 73,5379-5387.
Wilkins, C., Dishongh, R., Moore. S.C., Whitt, M.A., Chow, M., Machaca, K.,2005. RNA interference is an antiviral defence mechanism in Caenorhabditis elegans. Nature 436,1044-1047.
Willis, J.H., Munro, E., Lyczak, R., Bowerman, B.,2006. Conditional dominant mutations in the Caenorhabditis elegans gene act-2 identify cytoplasmic and muscle roles for a redundant actin isoform. Molecular biology of the cell 17,1051-1064.
Wilson, M.S., Taylor, M.D., Balic, A., Finney, C.A., Lamb, J.R., Maizels, R.M.,2005. Suppression of allergic airway inflammation by helminth-induced regulatory T cells. The Journal of experimental medicine 202,1199-1212.
Winston, W.M., Molodowitch, C., Hunter, C.P.,2002. Systemic RNAi in C. elegans requires the putative transmembrane protein SID-1. Science (New York, N.Y 295,2456-2459.
Winston, W.M., Sutherlin, M., Wright, A.J., Feinberg, E.H., Hunter, C.P.,2007. Caenorhabditis elegans SID-2 is required for environmental RNA interference. Proceedings of the National Academy of Sciences of the United States of America 104,10565-10570.
Wolstenholme, A.J., Fairweather, I., Prichard, R., von Samson-Himmelstjerna, G, Sangster, N.C., 2004. Drug resistance in veterinary helminths. Trends in parasitology 20,469-476.
Wynn, T.A., Thompson, R.W., Cheever, A.W., Mentink-Kane, M.M.,2004. Immunopathogenesis of schistosomiasis. Immunological reviews 201,156-167.
Xie, J., Black, D.L.,2001. A CaMK IV responsive RNA element mediates depolarization-induced alternative splicing of ion channels. Nature 410,936-939.
Yanming, S., Ruofeng, Y, Muleke, C.I., Guangwei, Z., Lixin, X., Xiangrui, L.,2007. Vaccination of goats with recombinant galectin antigen induces partial protection against Haemonchus contortus infection. Parasite immunology 29,319-326.
Yao, L., Yin, J., Zhang, X., Liu, Q., Li, J., Chen, L., Zhao, Y, Gong, P., Liu, C.,2007. Cryptosporidium parvum:identification of a new surface adhesion protein on sporozoite and oocyst by screening of a phage-display cDNA library. Experimental parasitology 115,333-338.
Yates, D.M., Portillo, V., Wolstenholme, A.J.,2003. The avermectin receptors of Haemonchus contortus and Caenorhabditis elegans. International journal for parasitology 33,1183-1193.
Yeates, G.W., Boag, B.,2004. Background for Nematode Ecology in the 21st Century. In:Chen, Z.X., Chen, W.Y., Chen, S.Y., Dickson, D.W. (Eds.), Nematology:Advances and Perspectives vol 1: Nematode Morphology, Physiology and Ecology. CABI Publishing, pp.406-437.
Yin, Y., Martin, J., Abubucker, S., Scott, A.L., McCarter, J.P., Wilson, R.K., Jasmer, D.P., Mitreva, M., 2008. Intestinal transcriptomes of nematodes:comparison of the parasites Ascaris suum and Haemonchus contortus with the free-living Caenorhabditis elegans. PLoS neglected tropical diseases 2, e269.
Zorio, D.A., Blumenthal, T.,1999. U2AF35 is encoded by an essential gene clustered in an operon with RRM/cyclophilin in Caenorhabditis elegans. RNA (New York, N.Y 5,487-494.
郑润宽,郝文俊.冬季舍内捻转血矛线虫的生态学研究[J].内蒙古畜牧科学,1994,11(1)：1-4.
Abbas, A.K., Murphy, K.M., Sher, A.,1996. Functional diversity of helper T lymphocytes. Nature 383, 787-793.
Aboobaker, A.A., Blaxter, M.L.,2003. Use of RNA interference to investigate gene function in the human filarial nematode parasite Brugia malayi. Molecular and biochemical parasitology 129, 41-51.
Alexander, D.L., Mital. J., Ward, G.E., Bradley, P., Boothroyd, J.C.,2005. Identification of the moving junction complex of Toxoplasma gondii:a collaboration between distinct secretory organelles. PLoS pathogens 1,e17.
Alfonso, A., Grundahl, K., McManus, J.R., Asbury, J.M., Rand, J.B.,1994. Alternative splicing leads to two cholinergic proteins in Caenorhabditis elegans. Journal of molecular biology 241,627-630.
Aliberti, J., Jankovic, D., Sher, A.,2004. Turning it on and off:regulation of dendritic cell function in Toxoplasma gondii infection. Immunological reviews 201,26-34.
Anonymous,1998. Genome sequence of the nematode C. elegans:a platform for investigating biology. Science (New York, N.Y 282,2012-2018.
Ashton, F.T., Li, J., Schad, G.A.,1999. Chemo-and thermosensory neurons:structure and function in animal parasitic nematodes. Veterinary parasitology 84,297-316.
Babu, S., Blauvelt, C.P., Kumaraswami, V., Nutman, T.B.,2006. Regulatory networks induced by live parasites impair both Thl and Th2 pathways in patent lymphatic filariasis:implications for parasite persistence. J Immunol 176,3248-3256.
Bakker, N., Vervelde, L., Kanobana, K., Knox, D.P., Cornelissen, A.W., de Vries, E., Yatsuda, A.P., 2004. Vaccination against the nematode Haemonchus contortus with a thiol-binding fraction from the excretory/secretory products (ES). Vaccine 22,618-628.
Balic, A., Bowles, V.M., Meeusen, E.N.,2000. The immunobiology of gastrointestinal nematode infections in ruminants. Advances in parasitology 45,181-241.
Balic, A., Bowles, V.M., Meeusen, E.N.,2002. Mechanisms of immunity to Haemonchus contortus infection in sheep. Parasite immunology 24,39-46.
Banchereau, J., Steinman, R.M.,1998. Dendritic cells and the control of immunity. Nature 392,245-252.
Bancroft, A.J., Artis, D., Donaldson, D.D., Sypek, J.P., Grencis, R.K.,2000. Gastrointestinal nematode expulsion in IL-4 knockout mice is IL-13 dependent. European journal of immunology 30, 2083-2091.
Barnes, D.A., Bonnin, A., Huang, J.X., Gousset, L., Wu, J., Gut, J., Doyle, P., Dubremetz, J.F., Ward, H., Petersen, C.,1998. A novel multi-domain mucin-like glycoprotein of Cryptosporidium parvum mediates invasion. Molecular and biochemical parasitology 96,93-110.
Barta, J.R., Thompson, R.C.,2006. What is Cryptosporidium? Reappraising its biology and phylogenetic affinities. Trends in parasitology 22,463-468.
Belkaid, Y., Rouse, B.T.,2005. Natural regulatory T cells in infectious disease. Nature immunology 6, 353-360.
Bhat, N., Joe, A., PereiraPerrin, M., Ward, H.D.,2007. Cryptosporidium p30, a galactose/N-acetylgalactosamine-specific lectin, mediates infection in vitro. The Journal of biological chemistry 282,34877-34887.
Blaxter, M.L., De Ley. P., Garey, J.R., Liu, L.X.. Scheldeman, P., Vierstraete, A., Vanfleteren, J.R., Mackey, L.Y., Dorris, M., Frisse, L.M.,Vida, J.T., Thomas, W.K.,1998. A molecular evolutionary framework for the phylum Nematoda. Nature 392,71-75.
Bliss, S.K., Gavrilescu, L.C., Alcaraz, A., Denkers, E.Y.,2001. Neutrophil depletion during Toxoplasma gondii infection leads to impaired immunity and lethal systemic pathology. Infection and immunity 69,4898-4905.
Bonnin, A., Lapillonne, A., Petrella, T., Lopez, J., Chaponnier, C., Gabbiani, G., Robine, S., Dubremetz, J.F.,1999. Immunodetection of the microvillous cytoskeleton molecules villin and ezrin in the parasitophorous vacuole wall of Cryptosporidium parvum (Protozoa: Apicomplexa). European journal of cell biology 78,794-801.
Borgsteede, F.H., Pekelder, J.J., Dercksen, D.P., Sol, J., Vellema, P., Gaasenbeek, C.P., van der Linden, J.N.,1997. A survey of anthelmintic resistance in nematodes of sheep in The Netherlands. The Veterinary quarterly 19,167-172.
Boutz, P.L., Stoilov, P., Li, Q., Lin, C.H., Chawla, G., Ostrow, K., Shiue, L., Ares, M., Jr., Black, D.L. 2007. A post-transcriptional regulatory switch in polypyrimidine tract-binding proteins reprograms alternative splicing in developing neurons. Genes& development 21,1636-1652.
Boxem, M., Tsai, C.W., Zhang, Y., Saito, R.M., Liu, J.O.,2004. The C. elegans methionine aminopeptidase 2 analog map-2 is required for germ cell proliferation. FEBS letters 576,245-250.
Brett, D., Pospisil, H., Valcarcel, J., Reich, J., Bork, P.,2002. Alternative splicing and genome complexity. Nature genetics 30,29-30.
Britton, C., Redmond, D.L., Knox, D.F., McKerrow, J.H., Barry, J.D.,1999. Identification of promoter elements of parasite nematode genes in transgenic Caenorhabditis elegans. Molecular and biochemical parasitology 103,171-181.
Britton, C., Murray, L.,2002. A cathepsin L protease essential for Caenorhabditis elegans embryogenesis is functionally conserved in parasitic nematodes. Molecular and biochemical parasitology 122,21-33.
Britton, C., Murray, L.,2004. Cathepsin L protease (CPL-1) is essential for yolk processing during embryogenesis in Caenorhabditis elegans. Journal of cell science 117,5133-5143.
Britton, C., Murray, L.,2006. Using Caenorhabditis elegans for functional analysis of genes of parasitic nematodes. International journal for parasitology 36,651-659.
Brooks, D.R., Isaac, R. E. (ed.),2004. Nematode Aminopeptidases. Kluwer Academic/Plenum Press, New York.
Burglin, T.R., Lobos, E., Blaxter, M.L.,1998. Caenorhabditis elegans as a model for parasitic nematodes. International journal for parasitology 28,395-411.
Butaeva, F., Paskerova, G., Entzeroth, R.,2006. Ditrypanocystis sp. (Apicomplexa, Gregarinia, Selenidiidae):the mode of survival in the gut of Enchytraeus albidus (Annelida, Oligochaeta, Enchytraeidae) is close to that of the coccidian genus Cryptosporidium. Tsitologiia 48,695-704.
Butcher, B.A., Greene, R.I., Henry, S.C., Annecharico, K.L., Weinberg, J.B.. Denkers, E.Y., Sher, A.. Taylor, G.A.,2005a. p47 GTPases regulate Toxoplasma gondii survival in activated macrophages. Infection and immunity 73,3278-3286.
Butcher, B.A., Kim, L., Panopoulos, A.D., Watowich, S.S., Murray, P.J., Denkers, E.Y.,2005b. IL-10-independent STAT3 activation by Toxoplasma gondii mediates suppression of IL-12 and TNF-alpha in host macrophages. J Immunol 174,3148-3152.
Buzoni-Gatel, D., Schulthess, J., Menard, L.C., Kasper, L.H.,2006. Mucosal defences against orally acquired protozoan parasites, emphasis on Toxoplasma gondii infections. Cellular microbiology 8,535-544.
Campbell, B.E., Nagaraj, S.H., Hu, M., Zhong, W., Sternberg, P.W., Ong, E.K., Loukas, A., Ranganathan, S., Beveridge, I., McInnes, R.L., Hutchinson, G.W., Gasser, R.B.,2008. Gender-enriched transcripts in Haemonchus contortus--predicted functions and genetic interactions based on comparative analyses with Caenorhabditis elegans. International journal for parasitology 38,65-83.
Carruthers, V.B., Sibley, L.D.,1997. Sequential protein secretion from three distinct organelles of Toxoplasma gondii accompanies invasion of human fibroblasts. European journal of cell biology 73,114-123.
Cevallos, A.M., Bhat, N., Verdon, R., Hamer, D.H., Stein, B., Tzipori, S., Pereira, M.E., Keusch, G.T., Ward, H.D.,2000. Mediation of Cryptosporidium parvum infection in vitro by mucin-like glycoproteins defined by a neutralizing monoclonal antibody. Infection and immunity 68, 5167-5175.
Chen, X.M., Huang, B.Q., Splinter, P.L., Orth, J.D., Billadeau, D.D., McNiven, M.A., LaRusso, N.F., 2004a. Cdc42 and the actin-related protein/neural Wiskott-Aldrich syndrome protein network mediate cellular invasion by Cryptosporidium parvum. Infection and immunity 72,3011-3021.
Chen, X.M., O'Hara, S.P., Huang, B.Q., Nelson, J.B., Lin, J.J., Zhu, G., Ward, H.D., LaRusso, N.F., 2004b. Apical organelle discharge by Cryptosporidium parvum is temperature, cytoskeleton, and intracellular calcium dependent and required for host cell invasion. Infection and immunity 72,6806-6816.
Chen, X.M., O'Hara, S.P., Huang, B.Q., Splinter, P.L., Nelson, J.B., LaRusso, N.F.,2005. Localized glucose and water influx facilitates Cryptosporidium parvum cellular invasion by means of modulation of host-cell membrane protrusion. Proceedings of the National Academy of Sciences of the United States of America 102,6338-6343.
Chen, Q., Rehman, S., Smant, G., Jones, J.T.,2005. Functional analysis of pathogenicity proteins of the potato cyst nematode Globodera rostochiensis using RNAi. Mol Plant Microbe Interact 18, 621-625.
Chu W.Y., Wei Y.W., Qian R.H.,2006. Characterization of the 5'-to-5'linked adult a-and β-globin genes from three sciaenid fish species(Pseudosciaena crocea, Sciaenops ocellatus, Nibea miichthioides). Comp Biochem Physiol, Part D 1:319-327.
Collins, S. M.,1996. The immunomodulation of enteric neuromuscular function:implications for motility and inflammatory disorders.Gastroenterology. 111,1683-99.
Convey, P., McInnes, S.J.,2005. Exceptional tardigrade-dominated ecosystems in Ellsworth Land, Antarctica. Ecology 86,519-527.
Cook, A.A., Bhadury, P., Debenham, N.J., MeldaL B.H.M., Blaxter, M.L., Smerdon, G., Austen, M.C., Lambshead, P.J.D., Rogers, A.D.,2005. Denaturing gradient gel electrophoresis (DGGE) as a tool for the identiWcation of marine nematodes. Mar. Ecol. Prog. Ser.291,103-113.
Coomans, A.,2000. Nematode systematics:past, present and future. Nematology 2(1),3-7.
Costa, J.C., Lilley, C.J., Atkinson, H.J., Urwin, P.E.,2009. Functional characterisation of a cyst nematode acetylcholinesterase gene using Caenorhabditis elegans as a heterologous system. International journal for parasitology 39,849-858.
Coyne, C.P., Brake, D.,2001. Characterisation of Haemonchus contortus-derived cell populations propagated in vitro in a tissue culture environment and their potential to induce protective immunity in sheep. International journal for parasitology 31,359-376.
Davey, K.G., Sommerville, R.I., Rogers, W.P.,1982. The effect of ethoxyzolamide, an analogue of insect juvenile hormone, nor-adrenaline and iodine on changes in the optical path difference in the excretory cells and oesophagus during exsheathment in Haemonchus contortus. International journal for parasitology 12,509-513.
Davis. M.W., Birnie, A.J., Chan, A.C., Page, A.P., Jorgensen, E.M., 2004. A conserved metalloprotease mediates ecdysis in Caenorhabditis elegans. Development (Cambridge, England) 131,6001-6008.
Del Rio, L., Bennouna, S., Salinas, J., Denkers, E.Y.,2001. CXCR2 deficiency confers impaired neutrophil recruitment and increased susceptibility during Toxoplasma gondii infection. J Immunol 167,6503-6509.
Dieterich, C., Clifton, S.W., Schuster, L.N., Chinwalla, A., Delehaunty, K., Dinkelacker, I., Fulton, L. Fulton, R., Godfrey, J.,minx, P., Mitreva, M., Roeseler, W., Tian, H., Witte, H., Yang, S.P., Wilson, R.K., Sommer, R.J.,2008. The Pristionchus pacificus genome provides a unique perspective on nematode lifestyle and parasitism. Nature genetics 40,1193-1198.
Dillon, S.R., Sprecher, C., Hammond, A., Bilsborough, J., Rosenfeld-Franklin, M., Presnell, S.R., Haugen, H.S., Maurer, M., Harder, B., Johnston, J., Bort, S., Mudri, S., Kuijper, J.L. Bukowski, T., Shea, P., Dong, D.L., Dasovich, M., Grant, F.J., Lockwood, L., Levin, S.D., LeCiel, C., Waggie, K., Day, H., Topouzis, S., Kramer, J., Kuestner, R., Chen, Z., Foster, D., Parrish-Novak, J., Gross, J.A.,2004. Interleukin 31, a cytokine produced by activated T cells, induces dermatitis in mice. Nature immunology 5,752-760.
Dowse, T., Soldati, D.,2004. Host cell invasion by the apicomplexans:the significance of microneme protein proteolysis. Current opinion in microbiology 7,388-396.
Elbashir, S.M., Martinez, J., Patkaniowska, A., Lendeckel, W., Tuschl, T.,2001. Functional anatomy of siRNAs for mediating efficient RNAi in Drosophila melanogaster embryo lysate. The EMBO journal 20,6877-6888.
Elliott, D.A., Clark, D.P.,2000. Cryptosporidium parvum induces host cell actin accumulation at the host-parasite interface. Infection and immunity 68,2315-2322.
Emmons, S.,1988. The genome. In: Wood W.B. (Ed.), The nematode Caenorhabditis elegans. Cold Spring Harbor, NY:Cold Spring Harbor Laboratory, pp.47-79.
Fanelli, E., Di Vito, M., Jones. J.T., De Giorgi, C.,2005. Analysis of chitin synthase function in a plant parasitic nematode, Meloidogyne artiellia, using RNAi. Gene 349,87-95.
Feinberg, E.H., Hunter, C.P.,2003. Transport of dsRNA into cells by the transmembrane protein SID-1. Science (New York, N.Y 301,1545-1547.
Files, J.G., Carr, S., Hirsh, D.,1983. Actin gene family of Caenorhabditis elegans. Journal of molecular biology 164,355-375.
Fire, A., Xu, S., Montgomery, M.K., Kostas, S.A., Driver, S.E., Mello, C.C.,1998. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 391,806-811.
Ford, L., Zhang, J., Liu, J., Hashmi, S., Fuhrman, J.A., Oksov, Y., Lustigman, S.,2009. Functional analysis of the cathepsin-like cysteine protease genes in adult Brugia malayi using RNA interference. PLoS neglected tropical diseases 3, e377.
Forney, J.R., Yang, S., Healey, M.C.,1996. Protease activity associated with excystation of Cryptosporidium parvum oocysts. The Journal of parasitology 82,889-892.
Fort, M.M., Cheung, J., Yen, D., Li, J., Zurawski, S.M., Lo, S., Menon, S., Clifford, T., Hunte, B., Lesley, R., Muchamuel, T., Hurst, S.D., Zurawski, G., Leach, M.W., Gorman, D.M., Rennick, D.M.,2001. IL-25 induces IL-4,IL-5, and IL-13 and Th2-associated pathologies in vivo. Immunity 15,985-995.
Fraser, A.,2004. Towards full employment:using RNAi to find roles for the redundant. Oncogene 23, 8346-8352.
Fraser, A.G., Kamath, R.S., Zipperlen, P., Martinez-Campos, M., Sohrmann, M., Ahringer, J.,2000. Functional genomic analysis of C. elegans chromosome I by systematic RNA interference. Nature 408,325-330.
Freeman, A.S., Nghiem, C., Li, J., Ashton, F.T., Guerrero, J., Shoop, W.L., Schad, G.A.,2003. Amphidial structure of ivermectin-resistant and susceptible laboratory and field strains of Haemonchus contortus. Veterinary parasitology 110,217-226.
Galbadage, T., Hartman, P.S.,2008. Repeated temperature fluctuation extends the life span of Caenorhabditis elegans in a daf-16-dependent fashion. Mechanisms of ageing and
development 129,507-514.
Gamble, H.R., Mansfield, L.S.,1996. Characterization of excretory-secretory products from larval stages of Haemonchus contortus cultured in vitro. Veterinary parasitology 62,291-305.
Gause, W.C., Urban, J.F., Jr., Stadecker, M.J.,2003. The immune response to parasitic helminths: insights from murine models. Trends in immunology 24,269-277.
Geary, T.G., Thompson, D.P.,2001. Caenorhabditis elegans:how good a model for veterinary parasites? Veterinary parasitology 101,371-386.
Geldhof, P., Newlands, G.F., Nyame, K., Cummings, R., Smith, W.D., Knox, D.P.,2005. Presence of the LDNF glycan on the host-protective H-gal-GP fraction from Haemonchus contortus. Parasite immunology 27,55-60.
Geldhof. P., Moloy, C., Knox, D.P.,2006a. Combinatorial RNAi on intestinal cathepsin B-like proteinases in Caenorhabditis elegans questions the perception of their role in nematode biology. Molecular and biochemical parasitology 145,128-132.
Geldhof, P., Murray, L., Couthier, A., Gilleard, J.S., McLauchlan, G., Knox, D.P., Britton, C.,2006b. Testing the efficacy of RNA interference in Haemonchus contortus. International journal for parasitology 36,801-810.
Geldhof, P., Clark, D., Molloy, C., Knox, D.P.,2007. Assessment of Caenorhabditis elegans as a model in Haemonchus contortus vaccine research. Molecular and biochemical parasitology 152.220-223.
Gheysen, G., Vanholme, B.,2007. RNAi from plants to nematodes. Trends in biotechnology 25,89-92.
Gonczy, P., Echeverri, C., Oegema, K., Coulson, A., Jones, S.J., Copley, R.R., Duperon, J., Oegema, J., Brehm, M., Cassin, E., Hannak, E., Kirkham, M., Pichler, S., Flohrs, K., Goessen, A., Leidel, S., Alleaume, A.M., Martin, C., Ozlu, N., Bork, P., Hyman, A.A.,2000. Functional genomic analysis of cell division in C. elegans using RNAi of genes on chromosome III. Nature 408, 331-336.
Goodman, S.J., Branda, C.S., Robinson, M.K., Burdine, R.D., Stern, M.J.,2003. Alternative splicing affecting a novel domain in the C. elegans EGL-15 FGF receptor confers functional specificity. Development (Cambridge, England) 130,3757-3766.
Graham M., Smith T.S.,Munn E.A. et al.,1993.Recombinant DNA molecules encoding aminopeptidase enzymes and their use in the preparation of vaccines against helminth infections. Patent Application No. WO 93/2354
Grossi, L., McHugh, K., Collins, S.M.,1993. On the specificity of altered muscle function in experimental colitis in rats. Gastroenterology 104,1049-1056.
Hansen, M., Hsu, A.L., Dillin, A., Kenyon, C.,2005. New genes tied to endocrine, metabolic, and dietary regulation of lifespan from a Caenorhabditis elegans genomic RNAi screen. PLoS genetics 1,119-128.
Harnett, W., Harnett, M. M.,2006. Molecular basis of worm-induced immunomodulation. Parasite Immunol.28,535-43.
Hartfelder, K.,2000. Insect juvenile hormone:from "status quo" to high society. Brazilian journal of
medical and biological research= Revista brasileira de pesquisas medicas e biologicas/ Sociedade Brasileira de Biofisica... [et al 33,157-177.
Hashmi, S., Britton, C., Liu, J., Guiliano, D.B., Oksov, Y., Lustigman, S.,2002. Cathepsin L is essential for embryogenesis and development of Caenorhabditis elegans. The Journal of biological chemistry 277,3477-3486.
Hashim, A., Mulcahy, G., Bourke, B., Clyne, M.,2006. Interaction of Cryptosporidium hominis and Cryptosporidium parvum with primary human and bovine intestinal cells. Infection and immunity 74,99-107.
Haslam, S.M., Coles, G.C., Munn, E.A., Smith, T.S., Smith, H.F., Morris, H.R., Dell, A.,1996. Haemonchus contortus glycoproteins contain N-linked oligosaccharides with novel highly fucosylated core structures. The Journal of biological chemistry 271,30561-30570.
Haslam, S.M., Coles, G.C., Reason, A.J., Morris, H.R., Dell, A.,1998. The novel core fucosylation of Haemonchus contortus N-glycans is stage specific. Molecular and biochemical parasitology 93,143-147.
Hijjawi, N.S., Meloni, B.P., Morgan, U.M., Thompson, R.C.,2001. Complete development and long-term maintenance of Cryptosporidium parvum human and cattle genotypes in cell culture. International journal for parasitology 31,1048-1055.
Holden-Dye, L., Walker, R. J.,2006. Actions of glutamate and ivermectin on the pharyngeal muscle of Ascaridia galli:a comparative study with Caenorhabditis elegans. International journal for parasitology 36,395-402.
Hu, M., Lok, J.B., Ranjit, N., Massey, H.C., Jr., Sternberg, P.W., Gasser, R.B.2010, Structural and functional characterisation of the fork head transcription factor-encoding gene, Hc-daf-16, from the parasitic nematode Haemonchus contortus (Strongylida). International journal for parasitology 40,405-415.
Hu, M., Zhong, W., Campbell, B.E., Sternberg, P.W., Pellegrino, M.W., Gasser, R.B.,2010. Elucidating ANTs in worms using genomic and bioinformatic tools--biotechnological prospects? Biotechnology advances 28,49-60.
Huang, B.Q., Chen, X.M., LaRusso, N.F.,2004. Cryptosporidium parvum attachment to and internalization by human biliary epithelia in vitro:a morphologic study. The Journal of parasitology 90,212-221.
Huang, G., Allen, R., Davis, E.L., Baum, T.J., Hussey, R.S.,2006. Engineering broad root-knot resistance in transgenic plants by RNAi silencing of a conserved and essential root-knot nematode parasitism gene. Proceedings of the National Academy of Sciences of the United States of America 103,14302-14306.
Hunt-Newbury, R., Viveiros, R., Johnsen, R., Mah, A., Anastas, D., Fang, L., Halfnight, E., Lee, D., Lin, J., Lorch, A., McKay, S., Okada, H.M., Pan, J., Schulz, A.K., Tu, D., Wong, K., Zhao, Z., Alexeyenko, A., Burglin, T., Sonnhammer, E., Schnabel, R., Jones, S.J., Marra, M.A., Baillie, D.L., Moerman, D.G.,2007. High-throughput in vivo analysis of gene expression in Caenorhabditis elegans. PLoS biology 5, e237.
Hurd, D.D., Kemphues, K.J.,2003. PAR-1 is required for morphogenesis of the Caenorhabditis elegans vulva. Developmental biology 253,54-65.
Hussein, A.S., Kichenin, K., Selkirk, M.E.,2002. Suppression of secreted acetylcholinesterase expression in Nippostrongylus brasiliensis by RNA interference. Molecular and biochemical parasitology 122,91-94.
Ince, M.N., Elliott, D.E., Setiawan, T., Blum, A., Metwali, A., Wang, Y., Urban, J.F., Jr., Weinstock, J.V.,2006. Heligmosomoides polygyrus induces TLR4 on murine mucosal T cells that produce TGFbeta after lipopolysaccharide stimulation. J Immunol 176,726-729.
Irimia, M., Rukov, J.L., Roy, S.W., Vinther, J., Garcia-Fernandez, J.,2009. Quantitative regulation of alternative splicing in evolution and development. Bioessays 31,40-50.
Ishikawa, N., Wakelin, D., Mahida, Y.R.,1997. Role of T helper 2 cells in intestinal goblet cell hyperplasia in mice infected with Trichinella spiralis. Gastroenterology 113,542-549.
Issa, Z., Grant, W.N., Stasiuk, S., Shoemaker, C.B.,2005. Development of methods for RNA interference in the sheep gastrointestinal parasite, Trichostrongylus colubriformis. International journal for parasitology 35,935-940.
Jacobs, H.J., Wiltshire, C., Ashman, K., Meeusen, E.N.,1999. Vaccination against the gastrointestinal nematode, Haemonchus contortus, using a purified larval surface antigen. Vaccine 17,362-368.
Jiang, H., Chess, L.,2004. An integrated view of suppressor T cell subsets in immunoregulation. J Clin Invest.114,1198-208.
Jimenez, J.C., Fontaine, J., Grzych, J.M., Dei-Cas, E., Capron, M.,2004. Systemic and mucosal responses to oral administration of excretory and secretory antigens from Giardia intestinalis. Clinical and diagnostic laboratory immunology 11,152-160.
Johnson, J.M., Castle, J., Garrett-Engele, P., Kan, Z., Loerch, P.M., Armour, C.D., Santos, R., Schadt, E.E., Stoughton, R., Shoemaker, D.D.,2003. Genome-wide survey of human alternative pre-mRNA splicing with exon junction microarrays. Science (New York, N.Y 302,2141-2144.
Joshua, G.W.,2001. Functional analysis of leucine aminopeptidase in Caenorhabditis elegans. Molecular and biochemical parasitology 113,223-232.
Kamath, R.S., Fraser, A.G., Dong, Y., Poulin, G., Durbin, R., Gotta, M., Kanapin, A., Le Bot, N., Moreno, S., Sohrmann, M., Welchman, D.P., Zipperlen, P., Ahringer, J.,2003. Systematic functional analysis of the Caenorhabditis elegans genome using RNAi. Nature 421,231-237.
Kampkotter, A., Volkmann, T.E., de Castro, S.H., Leiers, B., Klotz, L.O., Johnson, T.E., Link, C.D., Henkle-Duhrsen, K.,2003. Functional analysis of the glutathione S-transferase 3 from Onchocerca volvulus (Ov-GST-3):a parasite GST confers increased resistance to oxidative stress in Caenorhabditis elegans. Journal of molecular biology 325,25-37.
Kan, Z., Rouchka, E.C., Gish, W.R., States, D.J.,2001. Gene structure prediction and alternative splicing analysis using genomically aligned ESTs. Genome research 11,889-900.
Kaplan, R.M.,2004. Drug resistance in nematodes of veterinary importance:a status report. Trends in parasitology 20,477-481.
Kappe, S.H., Buscaglia, C.A., Bergman, L.W., Coppens, I., Nussenzweig, V.,2004. Apicomplexan gliding motility and host cell invasion:overhauling the motor model. Trends in parasitology 20,13-16.
Kawano, T., Fujita, M., Sakamoto, H.,2000. Unique and redundant functions of SR proteins, a conserved family of splicing factors, in Caenorhabditis elegans development. Mechanisms of development 95,67-76.
Kelsall, B. L., Rescigno, M.,2004. Mucosal dendritic cells in immunity and inflammation. Nat Immunol.5,1091-5.
Kelsall, B. L., Strober, W.,1996. The role of dendritic cells in antigen processing in the Peyer's patch. Ann N Y Acad Sci.778,47-54.
Kennerdell, J.R., Carthew, R.W.,1998. Use of dsRNA-mediated genetic interference to demonstrate that frizzled and frizzled 2 act in the wingless pathway. Cell 95,1017-1026.
Khalife, J., Godin, C., Capron, A.,1995. Transcriptional regulation of Schistosoma mansoni calreticulin:possible role of AP-1. Parasitology 111 (Pt 4),469-475.
Khan, W. I.,2008. Physiological changes in the gastrointestinal tract and host protective immunity: learning from the mouse-Trichinella spiralis model. Parasitology.135,671-82.
Khan, W.I., Blennerhasset, P., Ma, C., Matthaei, K.I., Collins, S.M.,2001. Stat6 dependent goblet cell hyperplasia during intestinal nematode infection. Parasite immunology 23,39-42.
Kim, E., Magen, A., Ast, G.,2007. Different levels of alternative splicing among eukaryotes. Nucleic acids research 35,125-131.
Kimber, M.J., McKinney, S., McMaster, S., Day, T.A., Fleming, C.C., Maule, A.G.,2007. flp gene disruption in a parasitic nematode reveals motor dysfunction and unusual neuronal sensitivity to RNA interference. Faseb J 21,1233-1243.
Knox, D.P., Smith, W.D.,2001. Vaccination against gastrointestinal nematode parasites of ruminants using gut-expressed antigens. Veterinary parasitology 100,21-32.
Knox D.P., Smith S K, Smith W D,1995. Vaccines against helminthic parasites:thiol binding proteins: International Patent Application, PCT/GB95/00665[P].1995-03-24.
Knox, D.P., Redmond, D.L., Newlands, G.F., Skuce, P.J., Pettit, D., Smith, W.D.,2003. The nature and prospects for gut membrane proteins as vaccine candidates for Haemonchus contortus and other ruminant trichostrongyloids. International journal for parasitology 33,1129-1137.
Knox, D.P., Geldhof, P., Visser, A., Britton, C.,2007. RNA interference in parasitic nematodes of animals:a reality check? Trends in parasitology 23,105-107.
Kotze, A.C., Bagnall, N.H.,2006. RNA interference in Haemonchus contortus:suppression of beta-tubulin gene expression in L3, L4 and adult worms in vitro. Molecular and biochemical parasitology 145,101-110.
Krause, S., Sommer, A., Fischer, P., Brophy, P.M., Walter, R.D., Liebau, E.,2001. Gene structure of the extracellular glutathione S-transferase from Onchocerca volvulus and its overexpression and promoter analysis in transgenic Caenorhabditis elegans. Molecular and biochemical parasitology 117,145-154.
Kreider, T., Anthony, R.M., Urban, J.F., Jr., Gause, W.C.,2007. Alternatively activated macrophages in helminth infections. Current opinion in immunology 19,448-453.
Kuznar, Z. A., Elimelech, M.,2005. Role of surface proteins in the deposition kinetics of Cryptosporidium parvum oocysts. Langmuir.21,710-6.
Kwa, M.S., Veenstra, J.G., Van Dijk, M., Roos, M.H.,1995. Beta-tubulin genes from the parasitic nematode Haemonchus contortus modulate drug resistance in Caenorhabditis elegans. Journal of molecular biology 246,500-510.
Lambshead, P.J.D.,2004. Marine nematode biodiversity. In:Chen, Z.X., Chen, W.Y., Chen, S.Y., Dickson, D.W. (Eds.), Nematology:Advances and Perspectives Vol 1:Nematode Morphology, Physiology and Ecology. CABI Publishing, pp.436-467.
Laurent, V., Brooks, D.R., Coates, D., Isaac, R.E.,2001. Functional expression and characterization of the cytoplasmic aminopeptidase P of Caenorhabditis elegans. European journal of biochemistry/FEBS 268,5430-5438.
Lebrun, M., Michelin, A., El Hajj, H., Poncet, J., Bradley, P.J., Vial, H., Dubremetz, J.F.,2005. The rhoptry neck protein RON4 re-localizes at the moving junction during Toxoplasma gondii invasion. Cellular microbiology 7,1823-1833.
LeJambre, L.F., Windon, R.G., Smith, W.D.,2008. Vaccination against Haemonchus contortus: performance of native parasite gut membrane glycoproteins in Merino lambs grazing contaminated pasture. Veterinary parasitology 153,302-312.
Lendner, M., Doligalska, M., Lucius, R., Hartmann, S.,2008. Attempts to establish RNA interference in the parasitic nematode Heligmosomoides polygyrus. Molecular and biochemical parasitology 161,21-31.
Levy-Holtzman, R., Schechter, I.,1995. Activity of the promoter of the hsp70 gene of the parasitic helminth Schistosoma mansoni in the mammalian CHO cell-line. Biochimica et biophysica acta 1263,96-98.
Li, C., Wei, X., Xu, L., Li, X.,2007a. Recombinant galectins of male and female Haemonchus contortus do not hemagglutinate erythrocytes of their natural host. Veterinary parasitology 144,299-303.
Li, J., Zhu, X., Ashton, F.T., Gamble, H.R., Schad, GA.,2001. Sensory neuroanatomy of a passively ingested nematode parasite, Haemonchus contortus:amphidial neurons of the third-stage larva. The Journal of parasitology 87,65-72.
Li, X., Du, A., Cai, W., Hou, Y., Pang, L., Gao, X.,2007b. Evaluation of a recombinant excretory secretory Haemonchus contortus protein for use in a diagnostic enzyme-linked immunosorbent assay. Experimental parasitology 115,242-246.
Lieberman, L. A., Hunter, C. A.,2002. The role of cytokines and their signaling pathways in the regulation of immunity to Toxoplasma gondii. Int Rev Immunol.21,373-403.
Liu, J., Dent, J.A., Beech, R.N., Prichard, R.K.,2004. Genomic organization of an avermectin receptor subunit from Haemonchus contortus and expression of its putative promoter region in Caenorhabditis elegans. Molecular and biochemical parasitology 134,267-274.
Lojda, Z., Gossrau, R.,1980. Study on aminopeptidase A. Histochemistry 67,267-290.
Longman, D., Johnstone, I.L., Caceres, J.F.,2000. Functional characterization of SR and SR-related genes in Caenorhabditis elegans. The EMBO journal 19,1625-1637.
Lopez de Mendoza, M.E., Modha, J., Roberts, M.C., Curtis, R., Kusel, J.R.,2000. Changes in the lipophilicity of the surfaces of Meloidogyne incognita and Haemonchus contortus during exposure to host signals. Parasitology 120 (Pt 2),203-209.
Luangsay, S., Kasper, L.H., Rachinel, N., Minns, L.A., Mennechet, F.J., Vandewalle, A., Buzoni-Gatel, D.,2003. CCR5 mediates specific migration of Toxoplasma gondii-primed CD8 lymphocytes to inflammatory intestinal epithelial cells. Gastroenterology 125,491-500.
Lumaret J.P., Ganlante E., Lumbreras C.,1993. Fields effects of ivermectin residues on drug beetles. Journal for Applied Ecology,30:428-436
Lu, R., Maduro, M., Li, F., Li, H.W., Broitman-Maduro, G., Li, W.X., Ding, S.W.,2005. Animal virus replication and RNAi-mediated antiviral silencing in Caenorhabditis elegans. Nature 436, 1040-1043.
Lustigman, S., Zhang, J., Liu, J., Oksov, Y., Hashmi, S.,2004. RNA interference targeting cathepsin L and Z-like cysteine proteases of Onchocerca volvulus confirmed their essential function during L3 molting. Molecular and biochemical parasitology 138,165-170.
Lynch, K.W.,2007. Regulation of alternative splicing by signal transduction pathways. Advances in experimental medicine and biology 623,161-174.
Mckay S.J., Johnsen R., Khattra J.,2004. Gene expression profiling of cells, tissues and developmental stages of the nematode C. elegans. Cold Spring Harbor Symposium on Quantitative Biology,68:159-169.
Madsen M.B., Neelsen B.O., Holter P., et al,1990. Treating cattle with ivermectin:the effects on the fauna and decomposition of dung pats. Journal for Applied Ecology,27:1-15
Maeda, I., Kohara, Y., Yamamoto, M., Sugimoto, A.,2001. Large-scale analysis of gene function in Caenorhabditis elegans by high-throughput RNAi. Curr Biol 11,171-176.
Makeyev, E.V., Zhang, J., Carrasco, M.A., Maniatis, T.,2007. The MicroRNA miR-124 promotes neuronal differentiation by triggering brain-specific alternative pre-mRNA splicing. Molecular cell 27,435-448.
Manzanilla-Lopes, R.H., Evans, K., Bridge, J.,2004. Plant diseases caused by nematodes. In:Chen, Z.X., Chen, W.Y., Chen, S.Y., Dickson, D.W. (Eds.), Nematology:Advances and Perspectives Vol 2:Nematode Management and Utilization. CABI Publishing, pp.637-716.
McDonald, V.,2003. Parasites in the gastrointestinal tract. Parasite immunology 25,231-234.
Mello, C., Fire, A.,1995. DNA transformation. Methods in cell biology 48,451-482.
Mello, C.C., Kramer, J.M., Stinchcomb, D., Ambros, V.,1991. Efficient gene transfer in C.elegans: extrachromosomal maintenance and integration of transforming sequences. The EMBO journal 10,3959-3970.
Metwali, A., Setiawan, T., Blum, A.M., Urban, J., Elliott, D.E., Hang, L., Weinstock, J.V.,2006.
Induction of CD8+ regulatory T cells in the intestine by Heligmosomoides polygyrus infection. American journal of physiology 291, G253-259.
Miller, H. R.,1987. Gastrointestinal mucus, a medium for survival and for elimination of parasitic nematodes and protozoa. Parasitology.94 Suppl, S77-100.
Mironov, A.A., Fickett, J.W., Gelfand, M.S.,1999. Frequent alternative splicing of human genes. Genome research 9,1288-1293.
Mital, J., Meissner, M., Soldati, D., Ward, GE.,2005. Conditional expression of Toxoplasma gondii apical membrane antigen-1 (TgAMAl) demonstrates that TgAMA1 plays a critical role in host cell invasion. Molecular biology of the cell 16,4341-4349.
Mitreva, M., Blaxter, M.L., Bird, D.M., McCarter, J.P.,2005. Comparative genomics of nematodes. Trends Genet 21, 573-581.
Modrek, B., Resch, A., Grasso, C., Lee, C.,2001. Genome-wide detection of alternative splicing in expressed sequences of human genes. Nucleic acids research 29,2850-2859.
Modrek, B., Lee, C.,2002. A genomic view of alternative splicing. Nature genetics 30,13-19.
Morrissette, N. S., Sibley, L. D.,2002. Cytoskeleton of apicomplexan parasites. Microbiol Mol Biol Rev.66,21-38; table of contents.
Mount, S.M.,1982. A catalogue of splice junction sequences. Nucleic acids research 10,459-472.
Munn, E.A., Smith, T.S., Smith, H., James, F.M., Smith, F.C., Andrews, S.J.,1997. Vaccination against Haemonchus contortus with denatured forms of the protective antigen H11. Parasite immunology 19,243-248.
Murray, L., Geldhof, P., Clark, D., Knox, D.P., Britton, C.,2007. Expression and purification of an active cysteine protease of Haemonchus contortus using Caenorhabditis elegans. International journal for parasitology 37,1117-1125.
Natsuka, S., Adachi, J., Kawaguchi, M., Nakakita, S., Hase, S., Ichikawa, A., Ikura, K.,2002. Structural analysis of N-linked glycans in Caenorhabditis elegans. Journal of biochemistry 131,807-813.
Nelson, J.B., O'Hara, S.P., Small, A.J., Tietz, P.S., Choudhury, A.K., Pagano, R.E., Chen, X.M., LaRusso, N.F.,2006. Cryptosporidium parvum infects human cholangiocytes via sphingolipid-enriched membrane microdomains. Cellular microbiology 8,1932-1945.
Newlands, G.F., Skuce, P.J., Knox, D.P., Smith, S.K., Smith, W.D.,1999. Cloning and characterization of a beta-galactoside-binding protein (galectin) from the gut of the gastrointestinal nematode parasite Haemonchus contortus. Parasitology 119 (Pt 5),483-490.
Newmark, P.A., Reddien, P.W., Cebria, F., Sanchez Alvarado, A.,2003. Ingestion of bacterially expressed double-stranded RNA inhibits gene expression in planarians. Proceedings of the National Academy of Sciences of the United States of America 100 Suppl 1,11861-11865.
Newton, S.E., Morrish, L.E., Martin, P.J., Montague, P.E., Rolph, T.P.,1995. Protection against multiply drug-resistant and geographically distant strains of Haemonchus contortus by vaccination with Hll, a gut membrane-derived protective antigen. International journal for parasitology 25,511-521.
Newton, S.E., Munn, E.A.,1999. The development of vaccines against gastrointestinal nematode parasites, particularly Haemonchus contortus. Parasitology today (Personal ed 15,116-122.
Newton, S.E., Meeusen, E.N.,2003. Progress and new technologies for developing vaccines against gastrointestinal nematode parasites of sheep. Parasite immunology 25,283-296.
Ngo, H., Tschudi, C., Gull, K., Ullu, E.,1998. Double-stranded RNA induces mRNA degradation in Trypanosoma brucei. Proceedings of the National Academy of Sciences of the United States of America 95,14687-14692.
Nikolaou, S., Hartman, D., Presidente, P.J., Newton, S.E., Gasser, R.B.,2002. HcSTK, a Caenorhabditis elegans PAR-1 homologue from the parasitic nematode, Haemonchus contortus. International journal for parasitology 32,749-758.
Nikolaou. S., Gasser, R.B.,2006. Prospects for exploring molecular developmental processes in Haemonchus contortus. International journal for parasitology 36,859-868.
Nilsen, T.W., Graveley, B.R., Expansion of the eukaryotic proteome by alternative splicing. Nature 463,457-463.
Novelli, J., Ahrned, S., Hodgkin, J.,2004. Gene interactions in Caenorhabditis elegans define DPY-31 as a candidate procollagen C-proteinase and SQT-3/ROL-4 as its predicted major target. Genetics 168,1259-1273.
Novelli, J., Page, A.P., Hodgkin, J.,2006. The C terminus of collagen SQT-3 has complex and essential functions in nematode collagen assembly. Genetics 172,2253-2267.
Oka, T., Toyomura, T., Honjo, K., Wada, Y., Futai, M.,2001. Four subunit a isoforms of Caenorhabditis elegans vacuolar H+-ATPase. Cell-specific expression during development. The Journal of biological chemistry 276,33079-33085.
Okhuysen, P.C., DuPont, H.L., Sterling, C.R., Chappell, C.L.,1994. Arginine aminopeptidase, an integral membrane protein of the Cryptosporidium parvum sporozoite. Infection and immunity 62,4667-4670.
Page, A.P., Winter, A.D.,2003. Enzymes involved in the biogenesis of the nematode cuticle. Advances in parasitology 53,85-148.
Page, A.P., Johnstone, I.L.,2007. The cuticle. WormBook,1-15.
Paschinger, K., Rendic, D., Lochnit, G., Jantsch, V., Wilson, I.B.,2004. Molecular basis of anti-horseradish peroxidase staining in Caenorhabditis elegans. The Journal of biological chemistry 279,49588-49598.
Perkins, M.E., Riojas, Y.A., Wu, T.W., Le Blancq, S.M.,1999. CpABC, a Cryptosporidium parvum ATP-binding cassette protein at the host-parasite boundary in intracellular stages. Proceedings of the National Academy of Sciences of the United States of America 96,5734-5739.
Petronijevic, T., Rogers, W.P.,1983. Gene activity and the development of early parasitic stages of nematodes. International journal for parasitology 13,197-199.
Pfarr, K., Heider, U., Hoerauf, A.,2006. RNAi mediated silencing of actin expression in adult Litomosoides sigmodontis is specific, persistent and results in a phenotype. International journal for parasitology 36,661-669.
Piano, F., Schetter, A.J., Mangone, M., Stein, L., Kemphues, K.J.,2000. RNAi analysis of genes expressed in the ovary of Caenorhabditis elegans. Curr Biol 10,1619-1622.
Pillai, S., Kalinna, B.H., Liebau, E., Hartmann, S., Theuring, F., Lucius, R.,2005. Studies on Acanthocheilonema viteae cystatin:genomic organization, promoter studies and expression in Caenorhabditis elegans. Filaria journal 4,9.
Pollok, R.C., McDonald, V., Kelly, P., Farthing, M.J.,2003. The role of Cryptosporidium parvum-derived phospholipase in intestinal epithelial cell invasion. Parasitology research 90,181-186.
Pujol, N., Bonnerot, C., Ewbank, J.J., Kohara, Y., Thierry-Mieg, D.,2001. The Caenorhabditis elegans unc-32 gene encodes alternative forms of a vacuolar ATPase a subunit. The Journal of biological chemistry 276,11913-11921.
Qin, L., Smant, G, Stokkermans, J., Bakker, J., Schots, A., Helder, J.,1998. Cloning of a trans-spliced glyceraldehyde-3-phosphate-dehydrogenase gene from the potato cyst nematode Globodera rostochiensis and expression of its putative promoter region in Caenorhabditis elegans. Molecular and biochemical parasitology 96,59-67.
Rachinel, N., Buzoni-Gatel, D., Dutta, C., Mennechet, F.J., Luangsay, S., Minns, L.A., Grigg, M.E., Tomavo, S., Boothroyd, J.C., Kasper, L.H.,2004. The induction of acute ileitis by a single microbial antigen of Toxoplasma gondii. J Immunol 173,2725-2735.
Rathore, D.K., Suchitra, S., Saini, M., Singh, B.P., Joshi, P.,2006. Identification of a 66 kDa Haemonchus contortus excretory/secretory antigen that inhibits host monocytes. Veterinary parasitology 138,291-300.
Rawlings, N.D., Barrett, A.J.,1995. Evolutionary families of metallopeptidases. Methods in enzymology 248,183-228.
Redmond, D.L., Knox, D.P., Newlands, G., Smith, W.D.,1997. Molecular cloning and characterisation of a developmentally regulated putative metallopeptidase present in a host protective extract of Haemonchus contortus. Molecular and biochemical parasitology 85,77-87.
Redmond, D.L., Clucas, C., Johnstone, I.L., Knox, D.P.,2001. Expression of Haemonchus contortus pepsinogen in Caenorhabditis elegans. Molecular and biochemical parasitology 112,125-131.
Redmond, D.L., Geldhof, P., Knox, D.P.,2004. Evaluation of Caenorhabditis elegans glycoproteins as protective immunogens against Haemonchus contortus challenge in sheep. International Journal for Parasitology 34,1347-1353.
Reszka. N., Rijsewijk, F.A., Zelnik, V., Moskwa, B., Bienkowska-Szewczyk, K.,2007. Haemonchus contortus:characterization of the baculovirus expressed form of aminopeptidase H11. Experimental parasitology 117,208-213.
Rogers, W.P., Petronijevic, T.,1982. The infective stage and the development of nematodes. In: Symons, L.E.A., Donald, A.D., Dineen, J.K. (Eds.), Biology and Control of Endoparasites. Academic Press, Australia, pp.3-28.
Roos, M.H., Tielens, A.G,1994. Differential expression of two succinate dehydrogenase subunit-B genes and a transition in energy metabolism during the development of the parasitic nematode Haemonchus contortus. Molecular and biochemical parasitology 66,273-281.
Rosso, M.N., Dubrana, M.P., Cimbolini, N., Jaubert, S., Abad, P.,2005. Application of RNA interference to root-knot nematode genes encoding esophageal gland proteins. Mol Plant Microbe Interact 18,615-620.
Rosso, M.N., Jones, J.T., Abad, P.,2009. RNAi and functional genomics in plant parasitic nematodes. Annual review of phytopathology 47,207-232.
Rothwell, T.L.,1989. Immune expulsion of parasitic nematodes from the alimentary tract. International journal for parasitology 19,139-168.
Sagar, M., Padol, I., Khan, W.I., Bonin, R.P., Blennerhassett, P.A., Hunt, R.H.,2004. Establishment of T-Helper-2 immune response based gerbil model of enteric infection. Scandinavian journal of gastroenterology 39,668-673.
Sague, S.L., Tato, C., Pure, E., Hunter, C.A.,2004. The regulation and activation of CD44 by natural killer (NK) cells and its role in the production of IFN-gamma. J Interferon Cytokine Res 24, 301-309.
Sanchez, L.,2008. Sex-determining mechanisms in insects. The International journal of developmental biology 52,837-856.
Sasagawa, Y., Urano, T., Kohara, Y., Takahashi, H., Higashitani, A.,2003. Caenorhabditis elegans RBX1 is essential for meiosis, mitotic chromosomal condensation and segregation, and cytokinesis. Genes Cells 8,857-872.
Schallig, H.D., Van Leeuwen, M.A.,1997. Protective immunity to the blood-feeding nematode Haemonchus contortus induced by vaccination with parasite low molecular weight antigens. Parasitology 114 (Pt 3),293-299.
Schallig, H.D., van Leeuwen, M.A., Cornelissen, A.W.,1997. Protective immunity induced by vaccination with two Haemonchus contortus excretory secretory proteins in sheep. Parasite immunology 19,447-453.
Schratt, G.M., Tuebing, F., Nigh, E.A., Kane, C.G., Sabatini, M.E., Kiebler, M, Greenberg, M.E.,2006. A brain-specific microRNA regulates dendritic spine development. Nature 439,283-289.
Sciacca, J., Forbes, W.M., Ashton, F.T., Lombardini, E., Gamble, H.R., Schad, G.A.,2002. Response to carbon dioxide by the infective larvae of three species of parasitic nematodes. Parasitology international 51,53-62.
Serra, E., Zemzoumi, K., Trolet, J., Capron, A., Dissous, C.,1996. Functional analysis of the Schistosoma mansoni 28 kDa glutathione S-transferase gene promoter:involvement of SMNF-Y transcription factor in multimeric complexes. Molecular and biochemical parasitology 83,69-80.
Setiawan, T., Metwali, A., Blum, A.M., Ince, M.N., Urban, J.F., Jr., Elliott, D.E., Weinstock, J.V.,2007. Heligmosomoides polygyrus promotes regulatory T-cell cytokine production in the murine normal distal intestine. Infection and immunity 75,4655-4663.
Shamansky, L.M., Pratt, D., Boisvenue, R.J., Cox, G.N.,1989. Cuticle collagen genes of Haemonchus contortus and Caenorhabditis elegans are highly conserved. Molecular and biochemical parasitology 37,73-85.
Shin, C., Manley, J.L.,2004. Cell signalling and the control of pre-mRNA splicing. Nature reviews 5, 727-738.
Shingles, J., Lilley, C.J., Atkinson, H.J., Urwin, P.E.,2007. Meloidogyne incognita:molecular and biochemical characterisation of a cathepsin L cysteine proteinase and the effect on parasitism following RNAi. Experimental parasitology 115,114-120.
Siddiqui, S.Z., Brown, D.D., Rao, V.T., Forrester, S.G., AN UNC-49 GABA RECEPTOR SUBUNIT FROM THE PARASITIC NEMATODE Haemonchus contortus IS ASSOCIATED WITH ENHANCED GABA SENSITIVITY IN NEMATODE HETEROMERIC CHANNELS. Journal of neurochemistry. (In press)
Simmer, F., Moorman, C., van der Linden, A.M., Kuijk, E., van den Berghe, P.V., Kamath, R.S., Fraser, A.G., Ahringer, J., Plasterk, R.H.,2003. Genome-wide RNAi of C. elegans using the hypersensitive rrf-3 strain reveals novel gene functions. PLoS biology 1, E12.
Sinai, A.P., Webster, P., Joiner, K.A.,1997. Association of host cell endoplasmic reticulum and mitochondria with the Toxoplasma gondii parasitophorous vacuole membrane:a high affinity interaction. Journal of cell science 110 (Pt 17),2117-2128.
Skuce, P.J., Redmond, D.L., Liddell, S., Stewart, E.M., Newlands, G.F., Smith, W.D., Knox, D.P., 1999a. Molecular cloning and characterization of gut-derived cysteine proteinases associated with a host protective extract from Haemonchus contortus. Parasitology 119 (Pt 4),405-412.
Skuce, P.J., Stewart, E.M., Smith, W.D., Knox, D.P.,1999b. Cloning and characterization of glutamate dehydrogenase (GDH) from the gut of Haemonchus contortus. Parasitology 118 (Pt 3),297-304.
Skuce, P.J., Newlands, G.F., Stewart, E.M., Pettit, D., Smith, S.K., Smith, W.D., Knox, D.P.,2001. Cloning and characterisation of thrombospondin, a novel multidomain glycoprotein found in association with a host protective gut extract from Haemonchus contortus. Molecular and biochemical parasitology 117,241-244.
Smith, H.V., Nichols, R.A., Grimason, A.M.,2005. Cryptosporidium excystation and invasion:getting to the guts of the matter. Trends in parasitology 21,133-142.
Smith, S.K., Smith, W.D.,1996. Immunisation of sheep with an integral membrane glycoprotein complex of Haemonchus contortus and with its major polypeptide components. Research in veterinary science 60,1-6.
Smith, T.S., Munn, E.A., Graham, M., Tavernor, A.S., Greenwood, C.A.,1993. Purification and evaluation of the integral membrane protein H11 as a protective antigen against Haemonchus contortus. International journal for parasitology 23,271-280.
Smith, T.S., Graham, M., Munn, E.A., Newton, S.E., Knox, D.P., Coadwell, W.J., McMichael-Phillips, D., Smith, H., Smith, W.D., Oliver, J.J.,1997. Cloning and characterization of a microsomal aminopeptidase from the intestine of the nematode Haemonchus contortus. Biochimica et biophysica acta 1338,295-306.
Smith, W.D., Jackson, F., Jackson, E., Williams, J.,1983. Local immunity and Ostertagia circumcincta: changes in the gastric lymph of sheep after a primary infection. Journal of comparative pathology 93,471-478.
Smith, W.D., Jackson, F., Jackson, E., Williams, J., Miller, H.R.,1984. Manifestations of resistance to ovine ostertagiasis associated with immunological responses in the gastric lymph. Journal of comparative pathology 94,591-601.
Smith, W.D., Jackson, F., Jackson, E., Williams, J.,1985. Age immunity to Ostertagia circumcincta: comparison of the local immune responses of 4 1/2- and 10-month-old lambs. Journal of comparative pathology 95,235-245.
Smith, W.D.,2007. Some observations on immunologically mediated inhibited Teladorsagia circumcincta and their subsequent resumption of development in sheep. Veterinary parasitology 147,103-109.
Smith, W.D., Smith, S.K., Murray, J.M.,1994. Protection studies with integral membrane fractions of Haemonchus contortus. Parasite immunology 16,231-241.
Smith, W.D.,1999. Prospects for vaccines of helminth parasites of grazing ruminants. International journal for parasitology 29,17-24.
Smith, W.D., Smith, S.K., Pettit, D., Newlands, G.F., Skuce, P.J.,2000. Relative protective properties of three membrane glycoprotein fractions from Haemonchus contortus. Parasite immunology 22,63-71.
Smith, W.D., Newlands, G.F., Smith, S.K., Pettit, D., Skuce, P.J.,2003a. Metalloendopeptidases from the intestinal brush border of Haemonchus contortus as protective antigens for sheep. Parasite immunology 25,313-323.
Smith, W.D., Skuce, P.J., Newlands, G.F., Smith, S.K., Pettit, D.,2003b. Aspartyl proteases from the intestinal brush border of Haemonchus contortus as protective antigens for sheep. Parasite immunology 25,521-530.
Smith, W.D., Zarlenga, D.S.,2006. Developments and hurdles in generating vaccines for controlling helminth parasites of grazing ruminants. Veterinary parasitology 139,347-359.
Snelling, W.J., Lin, Q., Moore, J.E., Millar, B.C., Tosini, F., Pozio, E., Dooley, J.S., Lowery, C.J.,2007. Proteomics analysis and protein expression during sporozoite excystation of Cryptosporidium parvum (Coccidia, Apicomplexa). Mol Cell Proteomics 6,346-355.
Stear, M.J., Strain, S., Bishop, S.C.,1999. Mechanisms underlying resistance to nematode infection. International journal for parasitology 29,51-56; discussion 73-55.
Stepek, G., McCormack, G., Page, A.P.,2010. Collagen processing and cuticle formation is catalysed by the astacin metalloprotease DPY-31 in free-living and parasitic nematodes. International journal for parasitology 40,533-542.
Stinchcomb, D.T., Mello, C., Hirsh, D.,1985. Caenorhabditis elegans DNA that directs segregation in yeast cells. Proceedings of the National Academy of Sciences of the United States of America 82,4167-4171.
Streit, A.,2008. Reproduction in Strongyloides (Nematoda):a life between sex and parthenogenesis. Parasitology 135,285-294.
Strong, W.B., Gut, J., Nelson, R.G.,2000. Cloning and sequence analysis of a highly polymorphic
Cryptosporidium parvum gene encoding a 60-kilodalton glycoprotein and characterization of its 15-and 45-kilodalton zoite surface antigen products. Infection and immunity 68,4117-4134.
Sulston, J.E., Horvitz, H.R.,1977. Post-embryonic cell lineages of the nematode, Caenorhabditis elegans. Developmental biology 56,110-156.
Sulston, J.E., Schierenberg, E., White, J.G., Thomson, J.N.,1983. The embryonic cell lineage of the nematode Caenorhabditis elegans. Developmental biology 100,64-119.
Suss-Toby, E., Zimmerberg, J., Ward, GE.,1996. Toxoplasma invasion:the parasitophorous vacuole is formed from host cell plasma membrane and pinches off via a fission pore. Proceedings of the National Academy of Sciences of the United States of America 93,8413-8418.
Tabara, H., Grishok, A., Mello, C.C.,1998. RNAi in C. elegans:soaking in the genome sequence. Science (New York, N.Y 282,430-431.
Tavernarakis, N., Wang, S.L., Dorovkov, M., Ryazanov, A., Driscoll, M.,2000. Heritable and inducible genetic interference by double-stranded RNA encoded by transgenes. Nature genetics 24,180-183.
Tato, C.M., Villarino, A., Caamano, J.H., Boothby, M., Hunter, C.A.,2003. Inhibition of NF-kappa B activity in T and NK cells results in defective effector cell expansion and production of IFN-gamma required for resistance to Toxoplasma gondii. J Immunol 170,3139-3146.
Tavernor, A.S., Smith, T.S., Langford, C.F., Munn, E.A., Graham, M.,1992. Vaccination of young Dorset lambs against haemonchosis. Parasite immunology 14,645-655.
Tetley, L., Brown, S.M., McDonald, V., Coombs, GH.,1998. Ultrastructural analysis of the sporozoite of Cryptosporidium parvum. Microbiology (Reading, England) 144 (Pt 12),3249-3255.
Thein, M.C., Winter, A.D., Stepek, G, McCormack, G, Stapleton, G, Johnstone, I.L., Page, A.P.,2009. Combined extracellular matrix cross-linking activity of the peroxidase MLT-7 and the dual oxidase BLI-3 is critical for post-embryonic viability in Caenorhabditis elegans. The Journal of biological chemistry 284,17549-17563.
Thompson, R.C., Olson, M.E., Zhu, G, Enomoto, S., Abrahamsen, M.S., Hijjawi, N.S.,2005. Cryptosporidium and cryptosporidiosis. Advances in parasitology 59,77-158.
Tijsterman, M., May, R.C., Simmer, F., Okihara, K.L., Plasterk, R.H.,2004. Genes required for systemic RNA interference in Caenorhabditis elegans. Curr Biol 14,111-116.
Urban, J.F., Jr., Noben-Trauth, N., Donaldson, D.D., Madden, K.B., Morris, S.C., Collins, M., Finkelman, F.D.,1998. IL-13, IL-4Ralpha, and Stat6 are required for the expulsion of the gastrointestinal nematode parasite Nippostrongylus brasiliensis. Immunity 8,255-264.
Urwin, P.E., Lilley, C.J., Atkinson, H.J.,2002. Ingestion of double-stranded RNA by preparasitic juvenile cyst nematodes leads to RNA interference. Mol Plant Microbe Interact 15,747-752.
Valigurova, A., Jirku, M., Koudela, B., Gelnar, M., Modry, D., Slapeta, J.,2008. Cryptosporidia: epicellular parasites embraced by the host cell membrane. International journal for parasitology 38,913-922.
Vallance, B.A., Galeazzi, F., Collins, S.M., Snider, D.P.,1999. CD4 T cells and major histocompatibility complex class II expression influence worm expulsion and increased intestinal muscle contraction during Trichinella spiralis infection. Infection and immunity 67, 6090-6097.
van Wyk, J.A., Malan, F.S., Randles, J.L.,1997. How long before resistance makes it impossible to control some field strains of Haemonchus contortus in South Africa with any of the modern anthelmintics? Veterinary parasitology 70,111-122.
Vasudevan, S., Tong, Y., Steitz, J.A.,2007. Switching from repression to activation:microRNAs can up-regulate translation. Science (New York, N.Y 318,1931-1934.
Vermillion, D.L., Collins, S.M.,1988. Increased responsiveness of jejunal longitudinal muscle in Trichinella-infected rats. The American journal of physiology 254, G124-129.
Vervelde, L., Kooyman, F.N., Van Leeuwen. M.A, Schallig, H.D., MacKellar, A., Huntley, J.F., Cornelissen, A.W.,2001. Age-related protective immunity after vaccination with Haemonchus contortus excretory/secretory proteins. Parasite immunology 23,419-426.
Vervelde, L., Van Leeuwen, M.A., Kruidenier, M., Kooyman, F.N., Huntley, J.F., Van Die, I., Cornelissen, A.W.,2002. Protection studies with recombinant excretory/secretory proteins of Haemonchus contortus. Parasite immunology 24,189-201.
Viney, M.E., Thompson, F.J.,2008. Two hypotheses to explain why RNA interference does not work in animal parasitic nematodes. International journal for parasitology 38,43-47.
Waller, P.J.,1994. The development of anthelmintic resistance in ruminant livestock. Acta tropica 56, 233-243.
Wang, J., Yan, R., Xu, L., Li, X.,2007. The second glutamic acid in the C-terminal CRD affects the carbohydrate-binding properties of recombinant galectins of Haemonchus contortus. Veterinary parasitology 148,247-255.
Wetzel, D.M., Schmidt, J., Kuhlenschmidt, M.S., Dubey, J.P., Sibley, L.D.,2005. Gliding motility leads to active cellular invasion by Cryptosporidium parvum sporozoites. Infection and immunity 73,5379-5387.
Wilkins, C., Dishongh, R., Moore. S.C., Whitt, M.A., Chow, M., Machaca, K.,2005. RNA interference is an antiviral defence mechanism in Caenorhabditis elegans. Nature 436,1044-1047.
Willis, J.H., Munro, E., Lyczak, R., Bowerman, B.,2006. Conditional dominant mutations in the Caenorhabditis elegans gene act-2 identify cytoplasmic and muscle roles for a redundant actin isoform. Molecular biology of the cell 17,1051-1064.
Wilson, M.S., Taylor, M.D., Balic, A., Finney, C.A., Lamb, J.R., Maizels, R.M.,2005. Suppression of allergic airway inflammation by helminth-induced regulatory T cells. The Journal of experimental medicine 202,1199-1212.
Winston, W.M., Molodowitch, C., Hunter, C.P.,2002. Systemic RNAi in C. elegans requires the putative transmembrane protein SID-1. Science (New York, N.Y 295,2456-2459.
Winston, W.M., Sutherlin, M., Wright, A.J., Feinberg, E.H., Hunter, C.P.,2007. Caenorhabditis elegans SID-2 is required for environmental RNA interference. Proceedings of the National Academy of Sciences of the United States of America 104,10565-10570.
Wolstenholme, A.J., Fairweather, I., Prichard, R., von Samson-Himmelstjerna, G, Sangster, N.C., 2004. Drug resistance in veterinary helminths. Trends in parasitology 20,469-476.
Wynn, T.A., Thompson, R.W., Cheever, A.W., Mentink-Kane, M.M.,2004. Immunopathogenesis of schistosomiasis. Immunological reviews 201,156-167.
Xie, J., Black, D.L.,2001. A CaMK IV responsive RNA element mediates depolarization-induced alternative splicing of ion channels. Nature 410,936-939.
Yanming, S., Ruofeng, Y, Muleke, C.I., Guangwei, Z., Lixin, X., Xiangrui, L.,2007. Vaccination of goats with recombinant galectin antigen induces partial protection against Haemonchus contortus infection. Parasite immunology 29,319-326.
Yao, L., Yin, J., Zhang, X., Liu, Q., Li, J., Chen, L., Zhao, Y, Gong, P., Liu, C.,2007. Cryptosporidium parvum:identification of a new surface adhesion protein on sporozoite and oocyst by screening of a phage-display cDNA library. Experimental parasitology 115,333-338.
Yates, D.M., Portillo, V., Wolstenholme, A.J.,2003. The avermectin receptors of Haemonchus contortus and Caenorhabditis elegans. International journal for parasitology 33,1183-1193.
Yeates, G.W., Boag, B.,2004. Background for Nematode Ecology in the 21st Century. In:Chen, Z.X., Chen, W.Y., Chen, S.Y., Dickson, D.W. (Eds.), Nematology:Advances and Perspectives vol 1: Nematode Morphology, Physiology and Ecology. CABI Publishing, pp.406-437.
Yin, Y., Martin, J., Abubucker, S., Scott, A.L., McCarter, J.P., Wilson, R.K., Jasmer, D.P., Mitreva, M., 2008. Intestinal transcriptomes of nematodes:comparison of the parasites Ascaris suum and Haemonchus contortus with the free-living Caenorhabditis elegans. PLoS neglected tropical diseases 2, e269.
Zorio, D.A., Blumenthal, T.,1999. U2AF35 is encoded by an essential gene clustered in an operon with RRM/cyclophilin in Caenorhabditis elegans. RNA (New York, N.Y 5,487-494.