Project description:Toxocariasis is an important, neglected zoonosis caused mainly by Toxocara canis. Although our knowledge of helminth molecular biology is improving through completed draft genome projects, there is limited detailed information on the molecular biology of Toxocara species. Here, transcriptomic sequencing of male and female adult T. canis and comparative analyses were conducted. For each sex, two-thirds (66-67%) of quality-filtered reads mapped to the gene set of T. canis, and at least five reads mapped to each of 16,196 (87.1%) of all 18,596 genes, and 321 genes were specifically transcribed in female and 1467 in male T. canis. Genes differentially transcribed between the two sexes were identified, enriched biological processes and pathways linked to these genes established, and molecules associated with reproduction and development predicted. In addition, small RNA pathways involved in reproduction were characterized, but there was no evidence for piwi RNA pathways in adult T. canis. The results of this transcriptomic study should provide a useful basis to support investigations of the reproductive biology of T. canis and related nematodes.
Project description:Migration and persistence of Toxocara canis and T. cati larvae in brains of paratenic hosts, including humans, may induce the disease neurotoxocarosis (NT). Along with various clinical symptoms, neurodegenerative and neuropsychiatric disorders have been described as a consequence of the disease. As most knowledge on NT is derived from only a few published clinical cases, information regarding underlying pathomechanisms and host’s response to Toxocara remain scarce. Therefore, it was aimed to characterize the general pathogenesis as well as the respective host's reaction on the transcriptional level in brains of T. canis- and T. cati C57BL/6J mice as a model for paratenic hosts.
Project description:Comparative oncology is a developing research discipline that is being used to assist our understanding of human neoplastic diseases. Companion canines are a preferred animal oncology model due to spontaneous tumor development and similarity to human disease at the pathophysiological level. We use a paired RNA sequencing (RNA-Seq)/microarray analysis of a set of four normal canine lymph nodes and ten canine lymphoma fine needle aspirates to identify technical biases and variation between the technologies and convergence on biological disease pathways. Surrogate Variable Analysis (SVA) provides a formal multivariate analysis of the combined RNA-Seq/microarray data set. Applying SVA to the data allows us to decompose variation into contributions associated with transcript abundance, differences between the technology, and latent variation within each technology. A substantial and highly statistically significant component of the variation reflects transcript abundance, and RNA-Seq proved more sensitive for detection of transcripts expressed at low levels. Latent random variation among RNA-Seq samples is also distinct in character from that impacting microarray samples. In particular, we observed variation between RNA-Seq samples that reflects transcript GC content. Platform-independent variable decomposition without a priori knowledge of the sources of variation using SVA represents a generalizable method for accomplishing cross-platform data analysis. We identified genes differentially expressed between normal lymph nodes of disease free dogs and a subset of the diseased dogs diagnosed with B-cell lymphoma using each technology. There is statistically significant overlap between the RNA-Seq and microarray sets of differentially expressed genes. Analysis of overlapping genes in the context of biological systems suggests elevated expression and activity of PI3K signaling in B-cell lymphoma biopsies compared with normal biopsies, consistent with literature describing successful use of drugs targeting this pathway in lymphomas. RNA was extracted from 10 lymphoma fine needle aspirates attained from companion canines. 4 normal lymph node samples were obtained from a Beagle breeding colony at Pfizer, including two samples that were taken from the same dog but different lymph nodes. This Series represents the Affymetrix gene expression only, not RNA-Seq referenced above. RNA-Seq data have been submitted to SRA as SRA059558.
Project description:Larvae of Toxocara canis and T. cati show affinities to different tissues within the paratenic host. T. canis preferably migrates to the CNS whereat T. cati prefers muscle tissue. As both species share many characteristics like antigen fractions, reasons for this behaviour as well as underlying pathomechanisms or host reactions towards the respective parasite are unknown. Therefore, it was aimed to characterize the general pathogenesis as well as the respective host's reaction on the transcriptional level to identify similarities and differences between T. canis- and T. cati-infected brains. Transcriptional changes in cerebra as well as cerebella of T. canis- and T. cati-infected C57Bl/6J mice were analysed 42 days post infection. In each infection group, 3 animals were included and 4 animals in the uninfected control.