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Sarkies P.,Imperial College London | Selkirk M.E.,Imperial College London | Jones J.T.,James Hutton Institute | Blok V.,James Hutton Institute | And 11 more authors.
PLoS Biology | Year: 2015

Small RNA pathways act at the front line of defence against transposable elements across the Eukaryota. In animals, Piwi interacting small RNAs (piRNAs) are a crucial arm of this defence. However, the evolutionary relationships among piRNAs and other small RNA pathways targeting transposable elements are poorly resolved. To address this question we sequenced small RNAs from multiple, diverse nematode species, producing the first phylum-wide analysis of how small RNA pathways evolve. Surprisingly, despite their prominence in Caenorhabditis elegans and closely related nematodes, piRNAs are absent in all other nematode lineages. We found that there are at least two evolutionarily distinct mechanisms that compensate for the absence of piRNAs, both involving RNA-dependent RNA polymerases (RdRPs). Whilst one pathway is unique to nematodes, the second involves Dicer-dependent RNA-directed DNA methylation, hitherto unknown in animals, and bears striking similarity to transposon-control mechanisms in fungi and plants. Our results highlight the rapid, context-dependent evolution of small RNA pathways and suggest piRNAs in animals may have replaced an ancient eukaryotic RNA-dependent RNA polymerase pathway to control transposable elements. © 2015 Sarkies et al. Source


Mendonca L.R.,Federal University of Bahia | Veiga R.V.,Federal University of Bahia | Dattoli V.C.C.,Federal University of Bahia | Figueiredo C.A.,Federal University of Bahia | And 7 more authors.
PLoS Neglected Tropical Diseases | Year: 2012

Background: Toxocara canis and T. cati are parasites of dogs and cats, respectively, that infect humans and cause human toxocariasis. Infection may cause asthma-like symptoms but is often asymptomatic and is associated with a marked eosinophilia. Previous epidemiological studies indicate that T. canis infection may be associated with the development of atopy and asthma. Objectives: To investigate possible associations between Toxocara spp. seropositivity and atopy and childhood wheezing in a population of children living in non-affluent areas of a large Latin American city. Methods: The study was conducted in the city of Salvador, Brazil. Data on wheezing symptoms were collected by questionnaire, and atopy was measured by the presence of aeroallergen-specific IgE (sIgE). Skin prick test (SPT), total IgE and peripheral eosinophilia were measured. Toxocara seropositivity was determined by the presence of anti-Toxocara IgG antibodies, and intestinal helminth infections were determined by stool microscopy. Findings: Children aged 4 to 11 years were studied, of whom 47% were seropositive for anti-Toxocara IgG; eosinophilia >4% occurred in 74.2% and >10% in 25.4%; 59.6% had elevated levels of total IgE; 36.8% had sIgE≥0.70 kU/L and 30.4% had SPT for at least one aeroallergen; 22.4% had current wheezing symptoms. Anti-Toxocara IgG was positively associated with elevated eosinophils counts, total IgE and the presence of specific IgE to aeroallergens but was inversely associated with skin prick test reactivity. Conclusion: The prevalence of Toxocara seropositivity was high in the studied population of children living in conditions of poverty in urban Brazil. Toxocara infection, although associated with total IgE, sIgE and eosinophilia, may prevent the development of skin hypersensitivity to aeroallergens, possibly through increased polyclonal IgE and the induction of a modified Th2 immune reaction. © 2012 Mendonça et al. Source


Fatih F.A.,St Georges, University of London | Siner A.,University Malaysia Sarawak | Ahmed A.,University Malaysia Sarawak | Woon L.C.,Pathology Laboratory | And 6 more authors.
Malaria Journal | Year: 2012

Background: Cytoadherence of infected red blood cells to brain endothelium is causally implicated in malarial coma, one of the severe manifestations of falciparum malaria. Cytoadherence is mediated by specific binding of variant parasite antigens, expressed on the surface of infected erythrocytes, to endothelial receptors including, ICAM-1, VCAM and CD36. In fatal cases of severe falciparum malaria with coma, blood vessels in the brain are characteristically congested with infected erythrocytes. Brain sections from a fatal case of knowlesi malaria, but without coma, were similarly congested with infected erythrocytes. The objective of this study was to determine the binding phenotype of Plasmodium knowlesi infected human erythrocytes to recombinant human ICAM-1, VCAM and CD36. Methods. Five patients with PCR-confirmed P. knowlesi malaria were recruited into the study with consent between April and August 2010. Pre-treatment venous blood was washed and cultured ex vivo to increase the proportion of schizont-infected erythrocytes. Cultured blood was seeded into Petri dishes with triplicate areas coated with ICAM-1, VCAM and CD36. Following incubation at 37°C for one hour the dishes were washed and the number of infected erythrocytes bound/mm 2 to PBS control areas and to recombinant human ICAM-1 VCAM and CD36 coated areas were recorded. Each assay was performed in duplicate. Assay performance was monitored with the Plasmodium falciparum clone HB3. Results: Blood samples were cultured ex vivo for up to 14.5 h (mean 11.3 ± 1.9 h) to increase the relative proportion of mature trophozoite and schizont-infected red blood cells to at least 50% (mean 65.8 17.51%). Three (60%) isolates bound significantly to ICAM-1 and VCAM, one (20%) isolate bound to VCAM and none of the five bound significantly to CD36. Conclusions: Plasmodium knowlesi infected erythrocytes from human subjects bind in a specific but variable manner to the inducible endothelial receptors ICAM-1 and VCAM. Binding to the constitutively-expressed endothelial receptor CD36 was not detected. Further work will be required to define the pathological consequences of these interactions. © 2012 Fatih et al; licensee BioMed Central Ltd. Source


Hastings I.M.,Molecular and Biochemical Parasitology | Nsanzabana C.,University of California at San Francisco | Smith T.A.,Swiss Tropical and Public Health Institute
American Journal of Tropical Medicine and Hygiene | Year: 2010

We compare, contrast, and evaluate methods to quantify genetic markers of antimalarial drug resistance. Frequency estimates should be reported along with crude prevalence. There are four main potential methods to estimate frequencies in blood samples: simple counting of single nucleotide polymorphisms (SNPs) and haplotypes in samples with multiplicity of infection (MOI) = 1; SNP counting in samples with MOI ≤ 2; SNP and haplotypes counting in samples with unambiguous genotypes; statistical inference using SNP and MOI data from all samples. Large differences between the methods became apparent when analyzing field data with high MOI. Simple counting dramatically reduced sample size and estimate precision, and we show that analysis of unambiguous samples is biased, leaving maximum likelihood or similar statistical inference as the only practical option. It is essential to account for genotyping missing minor clones; ignoring this phenomenon resulted in a 2-fold underestimation of SNPs and haplotypes present at low frequencies. Copyright © 2010 by The American Society of Tropical Medicine and Hygiene. Source


Antao T.,Molecular and Biochemical Parasitology | Beaumont M.A.,University of Bristol
Bioinformatics | Year: 2011

Motivation: Dominant markers (DArTs and AFLPs) are commonly used for genetic analysis in the fields of evolutionary genetics, ecology and conservation of genetic resources. The recent prominence of these markers has coincided with renewed interest in detecting the effects of local selection and adaptation at the level of the genome.Results: We present Mcheza, an application for detecting loci under selection based on a well-evaluated FST-outlier method. The application allows robust estimates to be made of model parameters (e.g. genome-wide average, neutral FST), provides data import and export functions, iterative contour smoothing and generation of graphics in an easy to use graphical user interface with a computation engine that supports multicore processors for enhanced performance. Mcheza also provides functionality to mitigate common analytical errors when scanning for loci under selection. © The Author 2011. Published by Oxford University Press. Source

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