The Experts below are selected from a list of 327 Experts worldwide ranked by ideXlab platform
Collette Britton - One of the best experts on this subject based on the ideXlab platform.
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Small RNAs in Parasitic Nematodes - forms and functions.
Parasitology, 2019Co-Authors: Collette Britton, Roz Laing, Eileen DevaneyAbstract:: Small RNAs are important regulators of gene expression. They were first identified in Caenorhabditis elegans, but it is now apparent that the main small RNA silencing pathways are functionally conserved across diverse organisms. Availability of genome data for an increasing number of Parasitic Nematodes has enabled bioinformatic identification of small RNA sequences. Expression of these in different lifecycle stages is revealed by small RNA sequencing and microarray analysis. In this review we describe what is known of the three main small RNA classes in Parasitic Nematodes - microRNAs (miRNAs), Piwi-interacting RNAs (piRNAs) and small interfering RNAs (siRNAs) - and their proposed functions. miRNAs regulate development in C. elegans and the temporal expression of Parasitic nematode miRNAs suggest modulation of target gene levels as parasites develop within the host. miRNAs are also present in extracellular vesicles released by Nematodes in vitro, and in plasma from infected hosts, suggesting potential regulation of host gene expression. Roles of piRNAs and siRNAs in suppressing target genes, including transposable elements, are also reviewed. Recent successes in RNAi-mediated gene silencing, and application of small RNA inhibitors and mimics will continue to advance understanding of small RNA functions within the parasite and at the host-parasite interface.
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Ups and downs of RNA interference in Parasitic Nematodes
Experimental Parasitology, 2012Co-Authors: Collette Britton, Buddhini Samarasinghe, D P KnoxAbstract:RNA interference (RNAi) is widely used in Caenorhabiditis elegans to identify essential gene function. In Parasitic Nematodes RNAi has been reported to result in transcript knockdown of some target genes, but not others, thus limiting its use as a potential functional genomics tool. We recently extended work in Haemonchus contortus to examine why only some genes seem to be susceptible to RNAi and to test RNAi effects in vivo. Here we review our findings, which suggest that site of gene expression influences silencing. This most likely reflects limited uptake of dsRNA from the environment, a phenomenon also observed in other free-living Nematodes. We discuss new technologies to improve dsRNA delivery, such as nanoparticles being developed for therapeutic siRNA delivery, and methods to monitor RNAi effects. Alternative approaches will be important in progressing the application of RNAi to identify essential gene function in Parasitic Nematodes. © 2011 Elsevier Inc.
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micrornas a role in drug resistance in Parasitic Nematodes
Trends in Parasitology, 2010Co-Authors: Eileen Devaney, Alan D Winter, Collette BrittonAbstract:Drug resistance in Parasitic Nematodes is an increasing problem worldwide, with resistance reported to all three commonly used classes of anthelmintics. Most studies to date have sought to correlate the resistant phenotype with genotypic changes in putative target molecules. Although this approach has identified mutations in several relevant genes, resistance might result from a complex interaction of different factors. Here we propose an alternative mechanism underlying the development of drug resistance based on functional differences in microRNA activity in resistant parasites. microRNAs play an important role in resistance to chemotherapeutic agents in many tumour cells and here we discuss whether they might also be involved in anthelmintic resistance in Parasitic Nematodes.
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rna interference in Parasitic Nematodes of animals a reality check
Trends in Parasitology, 2007Co-Authors: D P Knox, Peter Geldhof, Aline Visser, Collette BrittonAbstract:RNA interference (RNAi) is widely used in Caenorhabditis elegans to identify gene function and has been adapted as a high-throughput screening method to identify genes involved in essential processes. The technique has been applied to Parasitic Nematodes with variable success and we believe that inconsistent outcomes preclude its use as a robust screen with which to identify potential control targets. In this article, key issues that require clarification are discussed, including the mode of delivery of double-stranded RNA to the parasite, the developmental stage targeted and, perhaps of most importance, whether the RNAi pathway (as defined by studies in C. elegans) is fully functional in some Parasitic Nematodes.
Peter E. Urwin - One of the best experts on this subject based on the ideXlab platform.
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Caenorhabditis elegans as a model for plant-Parasitic Nematodes
Nematology, 2020Co-Authors: Joana C. Costa, Catherine J. Lilley, Peter E. UrwinAbstract:Many studies on aspects of the biology of plant-Parasitic Nematodes can be facilitated by using the information and resources available for the model species Caenorhabditis elegans. Comparative genomics of shared processes can provide insights into plant-Parasitic nematode biology that would otherwise be intractable. In this article we consider some of the resources available for C. elegans. We describe the practical utility of C. elegans and the use of available information to facilitate the characterisation of neurobiological processes in plant-Parasitic Nematodes.
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towards genetic modification of plant Parasitic Nematodes delivery of macromolecules to adults and expression of exogenous mrna in second stage juveniles
bioRxiv, 2020Co-Authors: Olaf Kranse, Catherine J. Lilley, Peter E. Urwin, David Mck. Bird, Helen Beasley, Sally Adams, Andre Pires Da Silva, Christopher A Bell, Eric A Miska, G SmantAbstract:Plant-Parasitic Nematodes are a continuing threat to food security, causing an estimated 100 billion USD in crop losses each year. The most problematic are the obligate sedentary endoparasites (primarily root knot Nematodes and cyst Nematodes). Progress in understanding their biology is held back by a lack of tools for functional genetics: forward genetics is largely restricted to studies of natural variation in populations, and reverse genetics is entirely reliant on RNA interference. There is an expectation that the development of functional genetic tools would accelerate the progress of research on plant-Parasitic Nematodes, and hence the development of novel control solutions. Here, we develop some of the foundational biology required to deliver a functional genetic tool kit in plant-Parasitic Nematodes. We characterise the gonads of male Heterodera schachtii and Meloidogyne hapla in the context of spermatogenesis. We test and optimise various methods for the delivery, expression, and/or detection of exogenous nucleic acids in plant-Parasitic Nematodes. We demonstrate that delivery of macromolecules to cyst and root knot nematode male germlines is difficult, but possible. Similarly, we demonstrate the delivery of oligonucleotides to root knot nematode gametes. Finally, we develop a transient expression system in plant-Parasitic Nematodes by demonstrating the delivery and expression of exogenous mRNA encoding various reporter genes throughout the body of H. schachtii juveniles using lipofectamine-based transfection. We anticipate these developments to be independently useful, will expedite the development of genetic modification tools for plant-Parasitic Nematodes, and ultimately catalyze research on a group of Nematodes that threaten global food security.
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rna interference in plant Parasitic Nematodes a summary of the current status
Parasitology, 2012Co-Authors: Catherine J. Lilley, Laura J Davies, Peter E. UrwinAbstract:: SUMMARYRNA interference (RNAi) has emerged as an invaluable gene-silencing tool for functional analysis in a wide variety of organisms, particularly the free-living model nematode Caenorhabditis elegans. An increasing number of studies have now described its application to plant Parasitic Nematodes. Genes expressed in a range of cell types are silenced when Nematodes take up double stranded RNA (dsRNA) or short interfering RNAs (siRNAs) that elicit a systemic RNAi response. Despite many successful reports, there is still poor understanding of the range of factors that influence optimal gene silencing. Recent in vitro studies have highlighted significant variations in the RNAi phenotype that can occur with different dsRNA concentrations, construct size and duration of soaking. Discrepancies in methodology thwart efforts to reliably compare the efficacy of RNAi between different Nematodes or target tissues. Nevertheless, RNAi has become an established experimental tool for plant Parasitic Nematodes and also offers the prospect of being developed into a novel control strategy when delivered from transgenic plants.
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recent progress in the development of rna interference for plant Parasitic Nematodes
Molecular Plant Pathology, 2007Co-Authors: Catherine J. Lilley, Manjula Bakhetia, Wayne L Charlton, Peter E. UrwinAbstract:: SUMMARY RNA interference (RNAi), first described for Caenorhabditis elegans, has emerged as a powerful gene silencing tool for investigating gene function in a range of organisms. Recent studies have described its application to plant Parasitic Nematodes. Genes expressed in a range of cell types are silenced when preParasitic juvenile Nematodes take up double-stranded (ds)RNA that elicits a systemic RNAi response. Important developments over the last year have shown that in planta expression of a dsRNA targeting a nematode gene can successfully induce silencing in parasitizing Nematodes. When the targeted gene has an essential function, a resistance effect is observed paving the way for the potential use of RNAi technology to control plant Parasitic Nematodes.
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rna interference and plant Parasitic Nematodes
Trends in Plant Science, 2005Co-Authors: Manjula Bakhetia, Peter E. Urwin, Wayne L Charlton, Michael J Mcpherson, Howard J. AtkinsonAbstract:RNA interference (RNAi) has recently been demonstrated in plant Parasitic Nematodes. It is a potentially powerful investigative tool for the genome-wide identification of gene function that should help improve our understanding of plant Parasitic Nematodes. RNAi should help identify gene and, hence, protein targets for nematode control strategies. Prospects for novel resistance depend on the plant generating an effective form of double-stranded RNA in the absence of an endogenous target gene without detriment to itself. These RNA molecules must then become available to the nematode and be capable of ingestion via its feeding tube. If these requirements can be met, crop resistance could be achieved by a plant delivering a dsRNA that targets a nematode gene and induces a lethal or highly damaging RNAi effect on the parasite.
Angela J Russell - One of the best experts on this subject based on the ideXlab platform.
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an automated high throughput system for phenotypic screening of chemical libraries on c elegans and Parasitic Nematodes
International Journal for Parasitology-Drugs and Drug Resistance, 2018Co-Authors: Frederick A Partridge, Anwen E Brown, Steven D Buckingham, Nicky J Willis, Graham Michael Wynne, Ruth Forman, Kathryn J Else, Alison A Morrison, Jacqueline B Matthews, Angela J RussellAbstract:Parasitic Nematodes infect hundreds of millions of people and farmed livestock. Further, plant Parasitic Nematodes result in major crop damage. The pipeline of therapeutic compounds is limited and parasite resistance to the existing anthelmintic compounds is a global threat. We have developed an INVertebrate Automated Phenotyping Platform (INVAPP) for high-throughput, plate-based chemical screening, and an algorithm (Paragon) which allows screening for compounds that have an effect on motility and development of Parasitic worms. We have validated its utility by determining the efficacy of a panel of known anthelmintics against model and Parasitic Nematodes: Caenorhabditis elegans, Haemonchus contortus, Teladorsagia circumcincta, and Trichuris muris. We then applied the system to screen the Pathogen Box chemical library in a blinded fashion and identified compounds already known to have anthelmintic or anti-Parasitic activity, including tolfenpyrad, auranofin, and mebendazole; and 14 compounds previously undescribed as anthelmintics, including benzoxaborole and isoxazole chemotypes. This system offers an effective, high-throughput system for the discovery of novel anthelmintics.
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an automated high throughput system for phenotypic screening of chemical libraries on c elegans and Parasitic Nematodes
bioRxiv, 2017Co-Authors: Frederick A Partridge, Anwen E Brown, Steven D Buckingham, Nicky J Willis, Graham Michael Wynne, Ruth Forman, Kathryn J Else, Alison A Morrison, Jacqueline B Matthews, Angela J RussellAbstract:Parasitic Nematodes infect hundreds of millions of people and farmed livestock. Further, plant Parasitic Nematodes result in major crop damage. The pipeline of therapeutic compounds is limited and parasite resistance to the existing anthelmintic compounds is a global threat. We have developed an INVertebrate Automated Phenotyping Platform (INVAPP) for high-throughput, plate-based chemical screening, and an algorithm (Paragon) which allows screening for compounds that have an effect on motility and development of Parasitic worms. We have validated its utility by determining the efficacy of a panel of known anthelmintics against model and Parasitic Nematodes: Caenorhabditis elegans, Haemonchus contortus, Teladorsagia circumcincta, and Trichuris muris. We then applied the system to screen the Pathogen Box chemical library in a blinded fashion and identified known anthelmintics, including tolfenpyrad, auranofin, and mebendazole and 14 compounds previously undescribed as anthelmintics, including benzoxaborole and isoxazole chemotypes. This system offers an effective, high-throughput system for the discovery of novel anthelmintics.
Elissa A Hallem - One of the best experts on this subject based on the ideXlab platform.
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mechanisms of host seeking by Parasitic Nematodes
Molecular and Biochemical Parasitology, 2016Co-Authors: Spencer S Gang, Elissa A HallemAbstract:The phylum Nematoda comprises a diverse group of roundworms that includes parasites of vertebrates, invertebrates, and plants. Human-Parasitic Nematodes infect more than one billion people worldwide and cause some of the most common neglected tropical diseases, particularly in low-resource countries [1]. Parasitic Nematodes of livestock and crops result in billions of dollars in losses each year [1]. Many nematode infections are treatable with low-cost anthelmintic drugs, but repeated infections are common in endemic areas and drug resistance is a growing concern with increasing therapeutic and agricultural administration [1]. Many Parasitic Nematodes have an environmental infective larval stage that engages in host seeking, a process whereby the infective larvae use sensory cues to search for hosts. Host seeking is a complex behavior that involves multiple sensory modalities, including olfaction, gustation, thermosensation, and humidity sensation. As the initial step of the parasite-host interaction, host seeking could be a powerful target for preventative intervention. However, host-seeking behavior remains poorly understood. Here we review what is currently known about the host-seeking behaviors of different Parasitic Nematodes, including insect-Parasitic Nematodes, mammalian-Parasitic Nematodes, and plant-Parasitic Nematodes. We also discuss the neural bases of these behaviors.
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olfaction shapes host parasite interactions in Parasitic Nematodes
Proceedings of the National Academy of Sciences of the United States of America, 2012Co-Authors: Adler R Dillman, Manon L Guillermin, Paul W Sternberg, Elissa A HallemAbstract:Many Parasitic Nematodes actively seek out hosts in which to complete their lifecycles. Olfaction is thought to play an important role in the host-seeking process, with parasites following a chemical trail toward host-associated odors. However, little is known about the olfactory cues that attract Parasitic Nematodes to hosts or the behavioral responses these cues elicit. Moreover, what little is known focuses on easily obtainable laboratory hosts rather than on natural or other ecologically relevant hosts. Here we investigate the olfactory responses of six diverse species of entomopathogenic Nematodes (EPNs) to seven ecologically relevant potential invertebrate hosts, including one known natural host and other potential hosts collected from the environment. We show that EPNs respond differentially to the odor blends emitted by live potential hosts as well as to individual host-derived odorants. In addition, we show that EPNs use the universal host cue CO2 as well as host-specific odorants for host location, but the relative importance of CO2 versus host-specific odorants varies for different parasite–host combinations and for different host-seeking behaviors. We also identified host-derived odorants by gas chromatography-mass spectrometry and found that many of these odorants stimulate host-seeking behaviors in a species-specific manner. Taken together, our results demonstrate that Parasitic Nematodes have evolved specialized olfactory systems that likely contribute to appropriate host selection.
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a sensory code for host seeking in Parasitic Nematodes
Current Biology, 2011Co-Authors: Elissa A Hallem, Adler R Dillman, Annie V Hong, Yuanjun Zhang, Jessica M Yano, Stephanie F Demarco, Paul W SternbergAbstract:Parasitic nematode species often display highly specialized host-seeking behaviors that reflect their specific host preferences. Many such behaviors are triggered by host odors, but little is known about either the specific olfactory cues that trigger these behaviors or the underlying neural circuits. Heterorhabditis bacteriophora and Steinernema carpocapsae are phylogenetically distant insect-Parasitic Nematodes whose host-seeking and host-invasion behavior resembles that of some devastating human- and plant-Parasitic Nematodes. We compare the olfactory responses of Heterorhabditis and Steinernema infective juveniles (IJs) to those of Caenorhabditis elegans dauers, which are analogous life stages [1]. The broad host range of these parasites results from their ability to respond to the universally produced signal carbon dioxide (CO_2), as well as a wide array of odors, including host-specific odors that we identified using thermal desorption-gas chromatography-mass spectroscopy. We find that CO_2 is attractive for the Parasitic IJs and C. elegans dauers despite being repulsive for C. elegans adults [2–4], and we identify a sensory neuron that mediates CO_2 response in both Parasitic and free-living species, regardless of whether CO_2 is attractive or repulsive. The parasites’ odor response profiles are more similar to each other than to that of C. elegans despite their greater phylogenetic distance, likely reflecting evolutionary convergence to insect parasitism.
Robin B Gasser - One of the best experts on this subject based on the ideXlab platform.
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elucidating the molecular and developmental biology of Parasitic Nematodes moving to a multiomics paradigm
Advances in Parasitology, 2020Co-Authors: Tao Wang, Paul W Sternberg, Pasi K Korhonen, Andreas Hofmann, Neil D Young, Robin B GasserAbstract:Abstract In the past two decades, significant progress has been made in the sequencing, assembly, annotation and analyses of genomes and transcriptomes of Parasitic worms of socioeconomic importance. This progress has somewhat improved our knowledge and understanding of these pathogens at the molecular level. However, compared with the free-living nematode Caenorhabditis elegans, the areas of functional genomics, transcriptomics, proteomics and metabolomics of Parasitic Nematodes are still in their infancy, and there are major gaps in our knowledge and understanding of the molecular biology of Parasitic Nematodes. The information on signalling molecules, molecular pathways and microRNAs (miRNAs) that are known to be involved in developmental processes in C. elegans and the availability of some molecular resources (draft genomes, transcriptomes and some proteomes) for selected Parasitic Nematodes provide a basis to start exploring the developmental biology of Parasitic Nematodes. Indeed, some studies have identified molecules and pathways that might associate with developmental processes in related, Parasitic Nematodes, such as Haemonchus contortus (barber's pole worm). However, detailed information is often scant and ‘omics resources are limited, preventing a proper integration of ‘omic data sets and comprehensive analyses. Moreover, little is known about the functional roles of pheromones, hormones, signalling pathways and post-transcriptional/post-translational regulations in the development of key Parasitic Nematodes throughout their entire life cycles. Although C. elegans is an excellent model to assist molecular studies of Parasitic Nematodes, its use is limited when it comes to explorations of processes that are specific to parasitism within host animals. A deep understanding of Parasitic Nematodes, such as H. contortus, requires substantially enhanced resources and the use of integrative ‘omics approaches for analyses. The improved genome and well-established in vitro larval culture system for H. contortus provide unprecedented opportunities for comprehensive studies of the transcriptomes (mRNA and miRNA), proteomes (somatic, excretory/secretory and phosphorylated proteins) and lipidomes (e.g., polar and neutral lipids) of this nematode. Such resources should enable in-depth explorations of its developmental biology at a level, not previously possible. The main aims of this review are (i) to provide a background on the development of Nematodes, with a particular emphasis on the molecular aspects involved in the dauer formation and exit in C. elegans; (ii) to critically appraise the current state of knowledge of the developmental biology of Parasitic Nematodes and identify key knowledge gaps; (iii) to cover salient aspects of H. contortus, with a focus on the recent advances in genomics, transcriptomics, proteomics and lipidomics as well as in vitro culturing systems; (iv) to review recent advances in our knowledge and understanding of the molecular and developmental biology of H. contortus using an integrative multiomics approach, and discuss the implications of this approach for detailed explorations of signalling molecules, molecular processes and pathways likely associated with nematode development, adaptation and parasitism, and for the identification of novel intervention targets against these pathogens. Clearly, the multiomics approach established recently is readily applicable to exploring a wide range of interesting and socioeconomically significant Parasitic worms (including also trematodes and cestodes) at the molecular level, and to elucidate host–parasite interactions and disease processes.
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transcriptomic resources for Parasitic Nematodes of veterinary importance
Trends in Parasitology, 2019Co-Authors: Robin B Gasser, Erich M SchwarzAbstract:Parasitic Nematodes are important pathogens of animals, causing diseases that impact on agricultural production worldwide. Research on these worms has been constrained by a lack of genetic and genomic tools. Nonetheless, over the past decade this field has made substantial advances, many of which have been led by transcriptomic sequencing. The present review summarises major transcriptomic studies of veterinary Parasitic Nematodes in recent years, and comments on overarching themes stemming from this work that inform our understanding of parasitism. Finally, we comment on current, state-of-the-art informatic tools for the analysis of complex worm transcriptomes to extract maximum the molecular information from them.
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toward practical dna based diagnostic methods for Parasitic Nematodes of livestock bionomic and biotechnological implications
Biotechnology Advances, 2008Co-Authors: Robin B Gasser, Nathan J Bott, Neil B Chilton, Peter W Hunt, Ian BeveridgeAbstract:Parasitic Nematodes of livestock have a major economic impact worldwide. In spite of the health problems caused by Nematodes and advances toward the development of vaccines and new therapeutic agents against some of them, relatively limited attention has been paid to the need for improved, practical methods of diagnosis. Accurate diagnosis and genetic characterization of Parasitic Nematodes of livestock are central to their effective control, particularly given the current, serious problems with anthelmintic resistance in nematode populations. Traditional diagnostic techniques have considerable limitations, and there have been some advances toward the development of molecular-diagnostic tools. This article provides a brief account of the significance of Parasitic Nematodes (order Strongylida), reviews the techniques that have been evaluated or used for diagnosis and describes developments in polymerase chain reaction (PCR)-based methods for the specific diagnosis of nematode infection/s and the genetic characterisation of the causative agents. The advances made in recent years provide a solid foundation for the development of practical, highly sensitive and specific diagnostic tools for epidemiological investigations and for use in control programmes.
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mitochondrial genomes of Parasitic Nematodes progress and perspectives
Trends in Parasitology, 2006Co-Authors: Min Hu, Robin B GasserAbstract:Mitochondria are subcellular organelles in which oxidative phosphorylation and other important biochemical functions take place within the cell. Within these organelles is a mitochondrial (mt) genome, which is distinct from, but cooperates with, the nuclear genome of the cell. Studying mt genomes has implications for various fundamental areas, including mt biochemistry, physiology and molecular biology. Importantly, the mt genome is a rich source of markers for population genetic and systematic studies. To date, more than 696 mt genomes have been sequenced for a range of metazoan organisms. However, few of these are from Parasitic Nematodes, despite their socioeconomic importance and the need for fundamental investigations into areas such as nematode genetics, systematics and ecology. In this article, we review knowledge and recent progress in mt genomics of Parasitic Nematodes, summarize applications of mt gene markers to the study of population genetics, systematics, epidemiology and evolution of key Nematodes, and highlight some prospects and opportunities for future research.
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Genomics of reproduction in Parasitic Nematodes-fundamental and biotechnological implications.
Biotechnology Advances, 2003Co-Authors: Peter R. Boag, Robin B Gasser, Alasdair J. Nisbet, Susan E NewtonAbstract:Understanding reproductive and developmental processes of socioeconomically important Parasitic Nematodes is of fundamental scientific interest and could have important implications for developing novel methods for parasite control via the disruption or interruption of such processes. Central to investigating reproductive molecular biology is the identification and characterisation of genes with sex-specific expression profiles. However, there is currently a paucity of information on such genes and their expression patterns in Parasitic Nematodes. This article describes recent progress on the characterisation of sex-specific genes from a Parasitic nematode of veterinary importance, and discusses the fundamental scientific and applied implications of this work.
