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73 result(s) for "Jex, Aaron R."
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Impact of gastrointestinal parasitic nematodes of sheep, and the role of advanced molecular tools for exploring epidemiology and drug resistance - an Australian perspective
Parasitic nematodes (roundworms) of small ruminants and other livestock have major economic impacts worldwide. Despite the impact of the diseases caused by these nematodes and the discovery of new therapeutic agents (anthelmintics), there has been relatively limited progress in the development of practical molecular tools to study the epidemiology of these nematodes. Specific diagnosis underpins parasite control, and the detection and monitoring of anthelmintic resistance in livestock parasites, presently a major concern around the world. The purpose of the present article is to provide a concise account of the biology and knowledge of the epidemiology of the gastrointestinal nematodes (order Strongylida), from an Australian perspective, and to emphasize the importance of utilizing advanced molecular tools for the specific diagnosis of nematode infections for refined investigations of parasite epidemiology and drug resistance detection in combination with conventional methods. It also gives a perspective on the possibility of harnessing genetic, genomic and bioinformatic technologies to better understand parasites and control parasitic diseases.
3, 2, 1, go! Cryptosporidium counts down to sex
Cryptosporidium is a leading cause of death from childhood diarrhea, but its biology is poorly understood. A recent study in PLOS Biology reveals hitherto unknown aspects of the parasite's life cycle that may lead to improvements in ex vivo culture.
Phylogenomic and biogeographic reconstruction of the Trichinella complex
Trichinellosis is a globally important food-borne parasitic disease of humans caused by roundworms of the Trichinella complex. Extensive biological diversity is reflected in substantial ecological and genetic variability within and among Trichinella taxa, and major controversy surrounds the systematics of this complex. Here we report the sequencing and assembly of 16 draft genomes representing all 12 recognized Trichinella species and genotypes, define protein-coding gene sets and assess genetic differences among these taxa. Using thousands of shared single-copy orthologous gene sequences, we fully reconstruct, for the first time, a phylogeny and biogeography for the Trichinella complex, and show that encapsulated and non-encapsulated Trichinella taxa diverged from their most recent common ancestor ∼21 million years ago (mya), with taxon diversifications commencing ∼10−7 mya. Trichinellosis is a globally important food-borne disease caused by roundworms of the Trichinella complex. Here the authors present genomic sequences representing all 12 recognized Trichinella species and genotypes, and reconstruct their phylogeny and biogeography.
Hookworms dynamically respond to loss of Type 2 immune pressure
The impact of the host immune environment on parasite transcription and fitness is currently unknown. It is widely held that hookworm infections have an immunomodulatory impact on the host, but whether the converse is true remains unclear. Immunity against adult-stage hookworms is largely mediated by Type 2 immune responses driven by the transcription factor Signal Transducer and Activator of Transcription 6 (STAT6). This study investigated whether serial passage of the rodent hookworm Nippostrongylus brasiliensis in STAT6-deficient mice (STAT6 KO) caused changes in parasites over time. After adaptation to STAT6 KO hosts, N . brasiliensis increased their reproductive output, feeding capacity, energy content, and body size. Using an improved N . brasiliensis genome, we found that these physiological changes corresponded with a dramatic shift in the transcriptional landscape, including increased expression of gene pathways associated with egg production, but a decrease in genes encoding neuropeptides, proteases, SCP/TAPS proteins, and transthyretin-like proteins; the latter three categories have been repeatedly observed in hookworm excreted/secreted proteins (ESPs) implicated in immunosuppression. Although transcriptional changes started to appear in the first generation of passage in STAT6 KO hosts for both immature and mature adult stages, downregulation of the genes putatively involved in immunosuppression was only observed after multiple generations in this immunodeficient environment. When STAT6 KO-adapted N . brasiliensis were reintroduced to a naive WT host after up to 26 generations, this progressive change in host-adaptation corresponded to increased production of inflammatory cytokines by the WT host. Surprisingly, however, this single exposure of STAT6 KO-adapted N . brasiliensis to WT hosts resulted in worms that were morphologically and transcriptionally indistinguishable from WT-adapted parasites. This work uncovers remarkable plasticity in the ability of hookworms to adapt to their hosts, which may present a general feature of parasitic nematodes.
Host range expansion of asexual parasite can be explained by loss of adaptions in Muller’s Ratchet
Sexual recombination is a hallmark of eukaryotic evolution. Without recombination, asexual eukaryotes should succumb to deleterious mutations and more rapidly evolving pathogens. Giardia duodenalis , a parasitic protist, sits within one of the earliest-branching eukaryotic lineages and has no known sexual stage. Whether Giardia are ‘ancient asexuals’ has been long explored but is unresolved. Here, we find clear evidence of sex in Giardia and also discover an asexual sublineage that has a broader host range than its sexual ancestor. This asexual lineage is not ancient, and is accumulating deleterious mutations. Unlike its sexual counterparts, its genetic variation lacks the signatures of selection and Red Queen coevolution. We propose a new hypothesis that explains how a mutational meltdown during Muller’s Ratchet might enable asexual pathogens to expand their host ranges transiently. Fittingly, our results suggest that Giardia is not the last exception to, but rather further evidence of, the essentiality of eukaryotic sex. Sexual reproduction is thought to be essential for long-term survival of eukaryotes. This study shows that Giardia, once suspected to be anciently asexual, retains evidence of sex while a newly derived asexual lineage is accumulating mutations and expanding its host range.
Field evaluation of the gut microbiome composition of pre-school and school-aged children in Tha Song Yang, Thailand, following oral MDA for STH infections
Soil-transmitted helminths, such as roundworms ( Ascaris lumbricoides ), whipworms ( Trichuris trichiura ) and hookworms ( Necator americanus and Ancylostoma spp.), are gastrointestinal parasites that occur predominantly in low- to middle-income countries worldwide and disproportionally impact children. Depending on the STH species, health status of the host and infection intensity, direct impacts of these parasites include malnutrition, anaemia, diarrhoea and physical and cognitive stunting. The indirect consequences of these infections are less well understood. Specifically, gastrointestinal infections may exert acute or chronic impacts on the natural gut microfauna, leading to increased risk of post-infectious gastrointestinal disorders, and reduced gut and overall health through immunomodulating mechanisms. To date a small number of preliminary studies have assessed the impact of helminths on the gut microbiome, but these studies are conflicting. Here, we assessed STH burden in 273 pre-school and school-aged children in Tha Song Yang district, Tak province, Thailand receiving annual oral mebendazole treatment. Ascaris lumbricoides (107/273) and Trichuris trichiura (100/273) were the most prevalent species and often occurred as co-infections (66/273). Ancylostoma ceylanicum was detected in a small number of children as well ( n = 3). All of these infections were of low intensity (<4,999 or 999 eggs per gram for Ascaris and Trichuris respectively). Using this information, we characterised the baseline gut microbiome profile and investigated acute STH-induced alterations, comparing infected with uninfected children at the time of sampling. We found no difference between these groups in bacterial alpha-diversity, but did observe differences in beta-diversity and specific differentially abundant OTUs, including increased Akkermansia muciniphila and Bacteroides coprophilus , and reduced Bifidobacterium adolescentis , each of which have been previously implicated in STH-associated changes in the gut microfauna.
Genetic blueprint of the zoonotic pathogen Toxocara canis
Toxocara canis is a zoonotic parasite of major socioeconomic importance worldwide. In humans, this nematode causes disease (toxocariasis) mainly in the under-privileged communities in developed and developing countries. Although relatively well studied from clinical and epidemiological perspectives, to date, there has been no global investigation of the molecular biology of this parasite. Here we use next-generation sequencing to produce a draft genome and transcriptome of T. canis to support future biological and biotechnological investigations. This genome is 317 Mb in size, has a repeat content of 13.5% and encodes at least 18,596 protein-coding genes. We study transcription in a larval, as well as adult female and male stages, characterize the parasite’s gene-silencing machinery, explore molecules involved in development or host–parasite interactions and predict intervention targets. The draft genome of T. canis should provide a useful resource for future molecular studies of this and other, related parasites. Toxocara canis is a zoonotic parasite of major worldwide socioeconomic importance. Here, the authors sequence the genome and transcriptome of T. canis , and highlight potential mechanisms involved in development and host–parasite interactions that could support the pursuit of new drug interventions.
Population structure, gene flow and genetic diversity of sheep blowfly (Lucilia cuprina dorsalis) in Australia
Background Flystrike (cutaneous myiasis) is caused by blowfly larvae of the genus Lucilia . This disease is a major obstacle to sustainable global sheep and wool production. Flystrike control relies primarily on breech modification surgery (mulesing) and insecticidal treatment; however, control is constantly compromised by the emergence and spread of insecticide-resistance. Preventing the spread of resistance is severely hindered by a limited understanding of genetic variation, structure and gene flow within and among Lucilia populations. Australia is one of the world’s largest producers of sheep and wool products, where Lucilia cuprina dorsalis is the major cause of flystrike. Results Here, we collected 2,034 Lucilia cuprina dorsalis individuals among 86 populations from sheep-grazing regions across the continent. Each fly was genetically characterised at 20,000 loci using DArTseq, a reduced complexity genome sequencing strategy. Three genetically distinct population clusters (i.e., Western Australia, Eastern Australia and Tasmania) were revealed through population structure analyses. Conclusions This investigation into population structure and gene flow yields significant insights into the genetic composition of diverse L. c. dorsalis populations throughout Australia. These findings will be essential for the sustainable management of flystrike on a global scale and for addressing the ongoing challenge of insecticide resistance.
Development and validation of a multiplexed-tandem qPCR tool for diagnostics of human soil-transmitted helminth infections
Soil-transmitted helminths (STH) are a major cause of morbidity in tropical developing countries with a global infection prevalence of more than one billion people and disease burden of around 3.4 million disability adjusted life years. Infection prevalence directly correlates to inadequate sanitation, impoverished conditions and limited access to public health systems. Underestimation of infection prevalence using traditional microscopy-based diagnostic techniques is common, specifically in populations with access to benzimidazole mass treatment programs and a predominance of low intensity infections. In this study, we developed a multiplexed-tandem qPCR (MT-PCR) tool to identify and quantify STH eggs in stool samples. We have assessed this assay by measuring infection prevalence and intensity in field samples of two cohorts of participants from Timor-Leste and Cambodia, which were collected as part of earlier epidemiological studies. MT-PCR diagnostic parameters were compared to a previously published multiplexed qPCR for STH detection. The MT-PCR assay agreed strongly with qPCR data and showed a diagnostic specificity of 99.60-100.00% (sensitivity of 83.33-100.00%) compared to qPCR and kappa agreement exceeding 0.85 in all tests. In addition, the MT-PCR has the added advantage of distinguishing Ancylostoma spp. species, namely Ancylostoma duodenale and Ancylostoma ceylanicum. This semi-automated platform uses a standardized, manufactured reagent kit, shows excellent run-to-run consistency/repeatability and supports high-throughput detection and quantitation at a moderate cost.
Genome and transcriptome of the porcine whipworm Trichuris suis
Aaron Jex and colleagues report whole-genome sequencing of adult male and female whipworm, Trichuris suis , from experimentally infected pigs. They also report stage-, sex- and tissue-specific transcriptomes and provide insights into host-parasite interactions. Trichuris (whipworm) infects 1 billion people worldwide and causes a disease (trichuriasis) that results in major socioeconomic losses in both humans and pigs. Trichuriasis relates to an inflammation of the large intestine manifested in bloody diarrhea, and chronic disease can cause malnourishment and stunting in children. Paradoxically, Trichuris of pigs has shown substantial promise as a treatment for human autoimmune disorders, including inflammatory bowel disease (IBD) and multiple sclerosis. Here we report whole-genome sequencing at ∼140-fold coverage of adult male and female T. suis and ∼80-Mb draft assemblies. We explore stage-, sex- and tissue-specific transcription of mRNAs and small noncoding RNAs.