@article{orton_arasu_hammerberg_2007, title={A novel gene from Brugia sp that encodes a cytotoxic fatty acid binding protein allergen recognized by canine monoclonal IgE and serum IgE from infected dogs}, volume={93}, ISSN={["0022-3395"]}, DOI={10.1645/GE-1217.1}, abstractNote={Brugia pahangi infection of dogs is a well characterized model of human lymphatic filariasis in which sera consistently show IgG or IgE reactivity to a 35-kDa antigen. Using dog lymph node B cells, we previously established a heterohybridoma cell line producing canine monoclonal IgE (cmAb 2.39) that activates and degranulates canine mast cells, and specifically recognizes a 35-kDa B. pahangi antigen. By affinity purification and sequencing of the native protein from B. pahangi adults, a 19-amino acid sequence was obtained; the derived nucleotide sequence showed homology to a Brugia malayi and 2 related Onchocerca volvulus expressed sequence tag (EST) clones from the Filarial Genome Project database. Consensus primers amplified a 244-bp product from adult and infective larval stage cDNA libraries of B. malayi, O. volvulus, and Wuchereria bancrofti, but not from those of nonfilarial nematodes. The B. malayi EST clone only showed nucleotide sequence homology to O. volvulus EST sequences. A 684-bp region from the open reading frame was expressed as a glutathione S-transferase fusion protein designated BmAl-1. CmAb 2.39, as well as serum IgE from dogs infected with B. pahangi and canine filarial heartworm, Dirofilaria immitis, recognized BmAl-1 on enzyme-linked immunosorbent assay and Western blots. BmAl-1 showed high binding affinity for a fatty acid; however, a search for sequence homology with known fatty acid binding proteins indicated that BmAl-1 is a unique fatty acid binding protein. This 35-kDa protein seems to be highly conserved in different stages and species of filarids, and it represents a previously unknown allergen that is possibly involved in the pathogenesis of filarial disease.}, number={6}, journal={JOURNAL OF PARASITOLOGY}, author={Orton, Susan M. and Arasu, Prema and Hammerberg, Bruce}, year={2007}, month={Dec}, pages={1378–1387} }
 @article{moser_carbone_arasu_gibson_2007, title={Impact of population structure on genetic diversity of a potential vaccine target in the canine hookworm (Ancylostoma caninum)}, volume={93}, ISSN={["1937-2345"]}, DOI={10.1645/GE-1096R.1}, abstractNote={Ancylostoma caninum is a globally distributed canine parasitic nematode. To test whether positive selection, population structure, or both affect genetic variation at the candidate vaccine target Ancylostoma secreted protein 1 (asp-1), we have quantified the genetic variation in A. caninum at asp-1 and a mitochondrial gene, cytochrome oxidase subunit 1 (cox-1), using the statistical population analysis tools found in the SNAP Workbench. The mitochondrial gene cox-1 exhibits moderate diversity within 2 North American samples, comparable to the level of variation observed in other parasitic nematodes. The protein coding portion for the C-terminal half of asp-1 shows similar levels of genetic variation in a Wake County, North Carolina, sample as cox-1. Standard tests of neutrality provide little formal evidence for selection acting on this locus, but haplotype networks for 2 of the exon regions have significantly different topologies, consistent with different evolutionary forces shaping variation at either end of a 1.3-kilobase stretch of sequence. Evidence for gene flow among geographically distinct samples suggests that the mobility of hosts of A. caninum is an important contributing factor to the population structure of the parasite.}, number={4}, journal={JOURNAL OF PARASITOLOGY}, author={Moser, Jennifer M. and Carbone, Ignazio and Arasu, Prema and Gibson, Greg}, year={2007}, month={Aug}, pages={796–805} }
 @article{freitas_arasu_2005, title={Cloning and characterisation of genes encoding two transforming growth factor-beta-like ligands from the hookworm, Ancylostoma caninum}, volume={35}, ISSN={["0020-7519"]}, DOI={10.1016/j.ijpara.2005.07.005}, abstractNote={To elucidate the role of transforming growth factor beta (TGF-beta) signalling in the arrest/reactivation pathway of the Ancylostoma caninum hookworm, two parasite-encoded TGF-beta-like ligands were cloned and characterised. Ac-dbl-1 showed 60% amino acid identity to the Caenorhabditis elegansdbl-1 gene, which regulates growth while Ac-daf-7 showed 46% amino acid identity to Ce-daf-7 which regulates arrested development. Exon/intron organisation of the genes for Ac-dbl-1 and Ac-daf-7 were different from that of the corresponding C. elegans genes with nine and 10 exons, respectively, and introns ranging in size from 56 to 2,556 bp. Based on real-time reverse transcriptase (RT)-PCR, Ac-dbl-1 and Ac-daf-7 were expressed in all stages tested, i.e. egg, first/second stage larvae (L1/L2), infective third stage larvae (iL3), serum-stimulated third stage larvae (ssL3), and male and female adult worms. Expression of Ac-dbl-1 peaked in the adult male stage suggesting a similar role to Ce-dbl-1 in regulating male tail patterning. Ac-daf-7 expression was at a maximum in the arrested iL3 and reactivated ssL3 stages, which differs from that of Ce-daf-7 expression and may be unique to parasitic nematodes that have an obligate requirement to undergo developmental arrest. In support of the PCR results, antibodies to the A. caninum TGF-beta-like ligands detected proteins in iL3, ssL3, and adult worm extracts. Immunofluorescent studies showed that Ac-daf-7 is expressed in the anterior region of the iL3 similar to Ce-daf-7, which is localised to the ASI chemosensory neurons.}, number={14}, journal={INTERNATIONAL JOURNAL FOR PARASITOLOGY}, author={Freitas, TC and Arasu, P}, year={2005}, month={Dec}, pages={1477–1487} }
 @article{trivedi_arasu_2005, title={Evaluation of endogenous reference genes for real-time PCR quantification of gene expression in Ancylostoma caninum}, volume={143}, ISSN={["1872-9428"]}, DOI={10.1016/j.molbiopara.2005.05.011}, number={2}, journal={MOLECULAR AND BIOCHEMICAL PARASITOLOGY}, author={Trivedi, S and Arasu, P}, year={2005}, month={Oct}, pages={241–244} }
 @article{moser_freitas_arasu_gibson_2005, title={Gene expression profiles associated with the transition to parasitism in Ancylostoma caninum larvae}, volume={143}, DOI={10.1016/j.molbiopran.2005.04.012}, number={1}, journal={Molecular and Biochemical Parasitology}, author={Moser, J. M. and Freitas, T. and Arasu, P. and Gibson, G.}, year={2005}, pages={39–48} }
 @article{mitreva_mccarter_arasu_hawdon_martin_dante_wylie_xu_stajich_kapulkin_et al._2005, title={Investigating hookworm genomes by comparative analysis of two Ancylostoma species}, volume={6}, journal={BMC Genomics}, author={Mitreva, M. and McCarter, J. P. and Arasu, P. and Hawdon, J. and Martin, J. and Dante, M. and Wylie, T. and Xu, J. and Stajich, J. E. and Kapulkin, W. and et al.}, year={2005} }
 @article{arasu_2001, title={In vitro reactivation of Ancylostoma caninum tissue-arrested third-stage larvae by transforming growth factor-beta}, volume={87}, ISSN={["0022-3395"]}, DOI={10.1645/0022-3395(2001)087[0733:IVROAC]2.0.CO;2}, abstractNote={Developmental arrest in Ancylostoma caninum is associated with preparasitic, free-living third-stage (L3) larvae, as well as anthelmintic-resilient hypobiotic L3 larvae within the tissues of an infected dog. With the tissue-arrested larvae, pregnancy and, more specifically, the hormonal effects of estrogen and prolactin mediate reactivation resulting in transmammary transmission of infection to nursing puppies. Estrogen and prolactin have been shown to be critically involved in upregulation of transforming growth factor (TGF)-β2 during pregnancy, and studies on the soil nematode Caenorhabditis elegans further implicate TGF-β and insulin-like signaling pathways with larval arrest and reactivation. In this report, an in vitro assay was used to show that neither estrogen, prolactin, nor insulin had a direct effect on the feeding/reactivation response of tissue-arrested larvae; however, TGF-β isoforms 1 and 2 both had significant stimulatory effects that were comparable to the effects of dog serum. The stimulatory effects of serum could be blocked by preincubation with anti-TGF-β antibodies. Taken together, the results support the hypothesis that during pregnancy, host-derived TGF-β can signal a parasite-encoded receptor to trigger the reactivation of tissue-arrested larvae. TGF-β had no effect on preparasitic larvae, suggesting that different signals may be involved in reactivation of the 2 different arrested forms of A. caninum L3 larvae.}, number={4}, journal={JOURNAL OF PARASITOLOGY}, author={Arasu, P}, year={2001}, month={Aug}, pages={733–738} }
 @article{arasu_heller_1999, title={Antibody responses in pregnancy-induced transmammary transmission of Ancylostoma caninum hookworm larvae}, volume={70}, ISSN={["0165-2427"]}, DOI={10.1016/s0165-2427(99)00081-1}, abstractNote={Third stage larvae of the Ancylostoma caninum hookworm nematode have the capacity to infect a dog, abort the normal maturation pathway to become blood-feeding intestinal worms, and instead distribute throughout the body in a developmentally arrested state that is relatively resilient to most chemotherapeutic agents. During pregnancy, a percentage of the arrested larvae reactivate and transmit via the mammary glands to infect the nursing puppies with resulting iron-deficiency anemia and potential mortality. To determine if the suppression of parasite-specific antibody responses during pregnancy facilitates the reactivation and transmammary transfer of hookworm larvae, a murine model of A. caninum infection was used to compare the infected versus uninfected animals that were either bred or not bred. Initial comparisons of genetically divergent BALB/c versus C57BL/6 mice showed that both the strains mounted strong Th2 biased IgG1 and IgE antibody responses to A. caninum infection. Using the BALB/c strain for the breeding analyses, it was confirmed that larval transfer to the mouse pups only occurred during the post-partum lactational period. In the dams, levels of total and antigen-specific IgG1 and total IgE were highly correlated with parasite burden. During most phases of pregnancy and lactation, infected dams had lower total IgG1, IgG2a and IgE levels as compared to unbred mice at comparable times post-infection; this downward modulation of antibody responses supports the established dogma of a generalized immunosuppression associated with pregnancy. However, at parturition and post-partum lactation, antigen-specific IgG1 levels measured at 1:5000 serum dilutions were comparable between bred and unbred mice, and antigen-specific IgG2a levels at 1:100 serum dilutions were also not significantly different except for a marginal reduction in the bred mice at the lactational timepoint. The comparable anti-A. caninum IgG1 levels between bred and unbred mice, and low correlation between IgG2a levels and larval burden suggest that parasite-specific antibody responses do not play a major role in the pregnancy-associated transmammary transmission of A. caninum larvae. This conclusion does not rule out the possibility that underlying fluxes in the levels of specific cytokines associated with pregnancy and infection may be involved in the process of larval reactivation and transmission.}, number={3-4}, journal={VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY}, author={Arasu, P and Heller, A}, year={1999}, month={Sep}, pages={289–298} }
 @article{howell_luginbuhl_grice_anderson_arasu_flowers_1999, title={Control of gastrointestinal parasite larvae of ruminant using nitrogen fertilizer, limestone and sodium hypochlorite solutions}, volume={32}, ISSN={["1879-0941"]}, DOI={10.1016/S0921-4488(98)00186-2}, abstractNote={Gastrointestinal parasites are considered to be one of the most prominent health problems of small ruminants. Additional concerns are associated with parasite resistance to traditional anthelmintics and drug withdrawal times. Solutions of commercial fertilizers, bleach and limestone were used to examine their effect on the motility of infective Haemonchus contortus larvae (L3) in vitro. Infective larvae were cultured from feces of one Suffolk ram lamb infected with 5000 L3. Infective larvae (500 L3/100 μl) were then pipetted into individual petri dishes with 400 μl of a known concentration of either urea (U), ammonium nitrate (AN), liquid nitrogen fertilizer (LNF), a mixture of ammonium nitrate + urea (ANU), dolomitic limestone (DLM), limestone (LM) and sodium hypochlorite (SH). Percent non-motile L3 increased (p < 0.05) as they were exposed to increasing concentrations of nitrogen (N) sources and SH. However, DLM and LM were not effective. Another trial compared the highest concentrations of the four N sources (18 g N/100 ml) and SH (10%). Percent non-motile L3 were: U, 81.3; AN, 96.8; LNF, 93.3; ANU, 89.2; SH, 99.8. Larvicidal properties of N sources and SH could decrease gastrointestinal parasite loads, may reduce producers dependency on traditional anthelmintics to control infective larvae and may reduce the potential of anthelmintic resistance when used strategically with pasture fertilization and other agricultural practices. Field studies are needed to corroborate results presented herein.}, number={3}, journal={SMALL RUMINANT RESEARCH}, author={Howell, JM and Luginbuhl, JM and Grice, MJ and Anderson, KL and Arasu, P and Flowers, JR}, year={1999}, month={May}, pages={197–204} }
 @article{arasu_kwak_1999, title={Developmental arrest and pregnancy-induced transmammary transmission of Ancylostoma caninum larvae in the murine model}, volume={85}, ISSN={["1937-2345"]}, DOI={10.2307/3285811}, abstractNote={Pregnancy is associated with reactivation of latent infections of many protozoal and helminthic parasites. To facilitate in vivo studies on the process of transmammary transmission of hookworm infection to nursing newborns, we established an experimental model of infection of BALB/c mice with infective larvae of the canine nematode Ancylostoma caninum. To establish latency with a significant reservoir of tissue larvae and achieve acceptable pregnancy success rates, mice were subcutaneously infected at day 5 postimpregnation; similar larval distribution profiles were observed at the end of the gestational period for bred compared to correspondingly infected unbred animals. No larvae were detected in fetuses or neonatal pups. Significant numbers of larvae were not detected in mammary tissue during the periparturient or postpartum lactational periods although about 8% of a dam's reservoir of tissue larvae was transferred to her nursing pups; this suggests that larvae reaching the mammary glands are rapidly transmitted through the milk sinuses, as was documented by histopathological analyses. Comparison of BALB/c with C57BL/6 mice that typically display divergent immune responses to infection showed no difference in tissue larval burden or in numbers transferred to pups. A hypothesis for the molecular mechanism of larval reactivation and transmission is discussed.}, number={5}, journal={JOURNAL OF PARASITOLOGY}, author={Arasu, P and Kwak, D}, year={1999}, month={Oct}, pages={779–784} }
 @article{arasu_1998, title={Anthelmintic efficacy against tissue-arrested larvae of Ancylostoma caninum in murine hosts}, volume={84}, ISSN={["1937-2345"]}, DOI={10.2307/3284686}, abstractNote={Third-stage larvae of the major human and canine Ancylostoma hookworm species have the capacity to undergo developmental arrest in the somatic tissues of an infected host. Arrested larvae reactivate at opportune periods such as pregnancy, which results in the transmammary transmission of infection to the nursing neonates. Using murine paratenic hosts to focus specifically on tissue-arrested stages of Ancylostoma caninum, the present study found that neither recommended nor elevated doses of commonly used anthelmintics were effective in eliminating latent infections at the accepted standard of greater than 90% reduction in parasite burden. Of the drugs tested, i.e., pyrantel, fenbendazole, ivermectin, and milbemycin, ivermectin was the most effective and engendered an 80% reduction in the burden of tissue-arrested A. caninum larvae but only if administered repeatedly or at elevated doses. Studies in 2 inbred mouse strains, BALB/c (H-2b) and C57BL/6 (H-2d), that typically display divergent immune responses to various infections showed no significant differences in the efficacies of the drugs tested. The results of this study indicate that there is still a need for effective strategies of eradicating latent infections with tissue-arrested hookworm larvae.}, number={6}, journal={JOURNAL OF PARASITOLOGY}, author={Arasu, P}, year={1998}, month={Dec}, pages={1263–1267} }