Nitric oxide production by Biomphalaria glabrata haemocytes: effects of Schistosoma mansoni ESPs and regulation through the extracellular signal-regulated kinase pathway

BACKGROUND: Schistosoma mansoni uses Biomphalaria glabrata as an intermediate host during its complex life cycle. In the snail, the parasite initially transforms from a miracidium into a mother sporocyst and during this process excretory-secretory products (ESPs) are released. Nitric oxide (NO) and its reactive intermediates play an important role in host defence responses against pathogens. This study therefore aimed to determine the effects of S. mansoni ESPs on NO production in defence cells (haemocytes) from schistosome-susceptible and schistosome-resistant B. glabrata strains. As S. mansoni ESPs have previously been shown to inhibit extracellular signal-regulated kinase (ERK) phosphorylation (activation) in haemocytes from susceptible, but not resistant, B. glabrata the regulation of NO output by ERK in these cells was also investigated. RESULTS: Haemocytes from resistant snails challenged with S. mansoni ESPs (20 mug/ml) over 5 h displayed an increase in NO production that was 3.3 times greater than that observed for unchallenged haemocytes; lower concentrations of ESPs (0.1-10 mug/ml) did not significantly increase NO output. In contrast, haemocytes from susceptible snails showed no significant change in NO output following challenge with ESPs at any concentration used (0.1-20 mug/ml). Western blotting revealed that U0126 (1 muM or 10 muM) blocked the phosphorylation (activation) status of ERK in haemocytes from both snail strains. Inhibition of ERK signalling by U0126 attenuated considerably intracellular NO production in haemocytes from both susceptible and resistant B. glabrata strains, identifying ERK as a key regulator of NO output in these cells. CONCLUSION: S. mansoni ESPs differentially influence intracellular NO levels in susceptible and resistant B. glabrata haemocytes, possibly through modulation of the ERK signalling pathway. Such effects might facilitate survival of S. mansoni in its intermediate host

Mineralogical report on ceramics

Appendix A in Report on the Mineralogy of Sample Sherds from Taunton CastleCopyright © 2015 Somerset Archaeological & Natural History SocietyMineralogical analysis was carried out by QEMS-CAN using the methodology described by Andersen et al. (in press). Four major mineralogical types were recognised and the key mineralogical characteristics of these types are listed in Table A.1 on the next page. A list of potential minerals included in the QEMSCAN mineral groups is given in Table A.2 on page 29

Moving from control to elimination of schistosomiasis in sub-Saharan Africa: time to change and adapt strategies.

Schistosomiasis is a water borne parasitic disease of global importance and with ongoing control the disease endemic landscape is changing. In sub-Saharan Africa, for example, the landscape is becoming ever more heterogeneous as there are several species of Schistosoma that respond in different ways to ongoing preventive chemotherapy and the inter-sectoral interventions currently applied. The major focus of preventive chemotherapy is delivery of praziquantel by mass drug administration to those shown to be, or presumed to be, at-risk of infection and disease. In some countries, regional progress may be uneven but in certain locations there are very real prospects to transition from control into interruption of transmission, and ultimately elimination. To manage this transition requires reconsideration of some of the currently deployed diagnostic tools used in surveillance and downward realignment of existing prevalence thresholds to trigger mass treatment. A key challenge will be maintaining and if possible, expanding the current donation of praziquantel to currently overlooked groups, then judging when appropriate to move from mass drug administration to selective treatment. In so doing, this will ensure the health system is adapted, primed and shown to be cost-effective to respond to these changing disease dynamics as we move forward to 2020 targets and beyond

Simultaneous infection of Schistosoma mansoni and S. rodhaini in Biomphalaria glabrata: impact on chronobiology and cercarial behaviour

<p>Abstract</p> <p>Background</p> <p>The chances of a schistosome cercaria encountering a suitable definitive host may be enhanced by emergence from the molluscan intermediate host with maximal glycogen stores and by an appropriate chronobiological rhythm. This study aimed to identify and characterize the effects of potential competitive interactions in the snail host <it>Biomphalaria glabrata</it>, between the closely-related <it>Schistosoma mansoni </it>and <it>S. rodhaini</it>, on phenotypic behavioural traits. It was predicted that inter-specific competition would affect chronobiological emergence rhythms and reduce the activity of schistosome swimming behavioural traits. <it>Biomphalaria glabrata </it>snails (120) were exposed to either <it>S. mansoni </it>or <it>S. rodhaini </it>single infections, or a mixed infection of both species simultaneously and the resulting cercarial phenotypic traits were characterised. Cercariae were identified from co-exposed snails by amplification and sequencing of the mitochondrial cytochrome oxidase subunit 1 (CO1).</p> <p>Results</p> <p><it>S. mansoni </it>and <it>S. rodhaini </it>largely maintained their distinct chronobiological rhythms after mixed exposures and infections. However, inter-specific competition appeared to result in a restriction of the shedding pattern of <it>S. rodhaini </it>and slight shift in the shedding pattern of <it>S. mansoni</it>. Inter-specific competition also significantly lowered hourly cercarial production for both parasite species in comparison to single exposures and infections and reduced cercarial swimming activity.</p> <p>Conclusion</p> <p>Inter-specific competition was shown to influence cercarial production, chronobiology and activity and should therefore be investigated further in field situations to determine the effects of these changes on parasite fitness (incorporating both host finding and infectivity) where these two species overlap. Importantly this competition did not result in a large change in chronobiological emergence of cercariae for either species indicating that it would not have a large influence on the species of hosts available for infection at time of emergence. This study has furthermore demonstrated the potential for phenotypic measures to provide markers for species-specific identification even in conditions of co-infection.</p

Community Knowledge, Perceptions, and Practices Associated with Urogenital Schistosomiasis among School-Aged Children in Zanzibar, United Republic of Tanzania

Background: On the Zanzibar islands, United Republic of Tanzania, elimination of urogenital schistosomiasis is strived for in the coming years. This qualitative study aimed to better understand community knowledge, perceptions, and practices associated with schistosomiasis among school-aged children on Unguja and Pemba islands, in order to inform the development of behavior change interventions contributing to eliminate urogenital schistosomiasis. Methodology: In 2011, we conducted 35 children’s discussion groups, 41 in-depth interviews with parents and teachers, and 5 focus group discussions with community members in Zanzibar. Using a modified-grounded theory approach, we transcribed and coded the narrative data followed by thematic analysis of the emergent themes. Principal Findings: Urogenital schistosomiasis is a common experience among children in Zanzibar and typically considered a boys’ disease. Children engage in multiple high-risk behaviors for acquiring schistosomiasis because of poor knowledge on disease transmission, lack of understanding on severity of disease-associated consequences, and lack of alternative options for water related activities of daily living and recreational play. Local primary school teachers had little to no training about the disease and no teaching tools or materials for students. Conclusions/Significance: Conducting activities in open natural freshwater contaminated by S. haematobium larvae compromises the health of school-aged children in Zanzibar. The perception of urogenital schistosomiasis as a minor illness rather than a serious threat to a child’s well-being contributes to the spread of disease. Understanding community perceptions of disease along with the barriers and facilitators to risk reduction behaviors among children can inform health promotion activities, campaigns, and programs for the prevention, control, and elimination of urogenital schistosomiasis in Zanzibar

Genomes and geography: genomic insights into the evolution and phylogeography of the genus Schistosoma

Blood flukes within the genus 'Schistosoma' still remain a major cause of disease in the tropics and subtropics and the study of their evolution has been an area of major debate and research. With the advent of modern molecular and genomic approaches deeper insights have been attained not only into the divergence and speciation of these worms, but also into the historic movement of these parasites from Asia into Africa, via migration and dispersal of definitive and snail intermediate hosts. This movement was subsequently followed by a radiation of Schistosoma species giving rise to the S. mansoni and S. haematobium groups, as well as the S. indicum group that reinvaded Asia. Each of these major evolutionary events has been marked by distinct changes in genomic structure evident in differences in mitochondrial gene order and nuclear chromosomal architecture between the species associated with Asia and Africa. Data from DNA sequencing, comparative molecular genomics and karyotyping are indicative of major constitutional genomic events which would have become fixed in the ancestral populations of these worms. Here we examine how modern genomic techniques may give a more in depth understanding of the evolution of schistosomes and highlight the complexity of speciation and divergence in this group

Molecular characterization of freshwater snails in the genus Bulinus: a role for barcodes?

<p>Abstract</p> <p>Background</p> <p>Reliable and consistent methods are required for the identification and classification of freshwater snails belonging to the genus <it>Bulinus </it>(Gastropoda, Planorbidae) which act as intermediate hosts for schistosomes of both medical and veterinary importance. The current project worked towards two main objectives, the development of a cost effective, simple screening method for the routine identification of <it>Bulinus </it>isolates and the use of resultant sequencing data to produce a model of relationships within the group.</p> <p>Results</p> <p>Phylogenetic analysis of the DNA sequence for a large section (1009 bp) of the mitochondrial gene cytochrome oxidase subunit 1 (<it>cox1</it>) for isolates of <it>Bulinus </it>demonstrated superior resolution over that employing the second internal transcribed spacer <it>(its2</it>) of the ribosomal gene complex. Removal of transitional substitutions within <it>cox1 </it>because of saturation effects still allowed identification of snails at species group level. Within groups, some species could be identified with ease but there were regions where the high degree of molecular diversity meant that clear identification of species was problematic, this was particularly so within the <it>B. africanus </it>group.</p> <p>Conclusion</p> <p>The sequence diversity within <it>cox1 </it>is such that a barcoding approach may offer the best method for characterization of populations and species within the genus from different geographical locations. The study has confirmed the definition of some accepted species within the species groups but additionally has revealed some unrecognized isolates which underlines the need to use molecular markers in addition to more traditional methods of identification. A barcoding approach based on part of the <it>cox1 </it>gene as defined by the Folmer primers is proposed.</p

Adaptive maternal investment in the wild? Links between maternal growth trajectory and offspring size, growth, and survival in contrasting environments

Life history theory predicts that investment per offspring should correlate negatively with the quality of environment offspring are anticipated to encounter; parents may use their own experience as juveniles to predict this environment and may modulate offspring traits such as growth capacity as well as initial size. We manipulated nutrient levels in the juvenile habitat of wild Atlantic salmon Salmo salar to investigate the hypothesis that the egg size maximizing juvenile growth and survival depends on environmental quality. We also tested whether offspring traits were related to parental growth trajectory. Mothers that grew fast when young produced more, smaller offspring than mothers that had grown slowly to reach the same size. Despite their size disadvantage, offspring of faster-growing mothers grew faster than those of slow-growing mothers in all environments, counter to the expectation that they would be competitively disadvantaged. However, they had lower relative survival in environments where the density of older predatory/competitor fish was relatively high. These links between maternal (but not paternal) growth trajectory and offspring survival rate were independent of egg size, underscoring that mothers may be adjusting egg traits other than size to suit the anticipated environment faced by their offspring

Molecular characterization of host-parasite cell signalling in 'Schistosoma mansoni' during early development

During infection of their human definitive host, schistosomes transform rapidly from free-swimming infective cercariae in freshwater to endoparasitic schistosomules. The 'somules' next migrate within the skin to access the vasculature and are surrounded by host molecules that might activate intracellular pathways that influence somule survival, development and/or behaviour. However, such 'transactivation' by host factors in schistosomes is not well defined. In the present study, we have characterized and functionally localized the dynamics of protein kinase C (PKC) and extracellular signal-regulated kinase (ERK) activation during early somule development in vitro and demonstrate activation of these protein kinases by human epidermal growth factor, insulin, and insulin-like growth factor I, particularly at the parasite surface. Further, we provide evidence that support the existence of specialized signalling domains called lipid rafts in schistosomes and propose that correct signalling to ERK requires proper raft organization. Finally, we show that modulation of PKC and ERK activities in somules affects motility and reduces somule survival. Thus, PKC and ERK are important mediators of host-ligand regulated transactivation events in schistosomes, and represent potential targets for anti-schistosome therapy aimed at reducing parasite survival in the human host