The Biomphalaria glabrata DNA methylation machinery displays spatial tissue expression, is differentially active in distinct snail populations and is modulated by interactions with Schistosoma mansoni

BBSRC Grant (BB/K005448/1)Background The debilitating human disease schistosomiasis is caused by infection with schistosome parasites that maintain a complex lifecycle alternating between definitive (human) and intermediate (snail) hosts. While much is known about how the definitive host responds to schistosome infection, there is comparably less information available describing the snail?s response to infection. Methodology/Principle findings Here, using information recently revealed by sequencing of the Biomphalaria glabrata intermediate host genome, we provide evidence that the predicted core snail DNA methylation machinery components are associated with both intra-species reproduction processes and inter-species interactions. Firstly, methyl-CpG binding domain protein (Bgmbd2/3) and DNA methyltransferase 1 (Bgdnmt1) genes are transcriptionally enriched in gonadal compared to somatic tissues with 5-azacytidine (5-AzaC) treatment significantly inhibiting oviposition. Secondly, elevated levels of 5-methyl cytosine (5mC), DNA methyltransferase activity and 5mC binding in pigmented hybrid- compared to inbred (NMRI)- B. glabrata populations indicate a role for the snail?s DNA methylation machinery in maintaining hybrid vigour or heterosis. Thirdly, locus-specific detection of 5mC by bisulfite (BS)-PCR revealed 5mC within an exonic region of a housekeeping protein-coding gene (Bg14-3-3), supporting previous in silico predictions and whole genome BS-Seq analysis of this species? genome. Finally, we provide preliminary evidence for parasite-mediated host epigenetic reprogramming in the schistosome/snail system, as demonstrated by the increase in Bgdnmt1 and Bgmbd2/3 transcript abundance following Bge (B. glabrata embryonic cell line) exposure to parasite larval transformation products (LTP). Conclusions/Significance The presence of a functional DNA methylation machinery in B. glabrata as well as the modulation of these gene products in response to schistosome products, suggests a vital role for DNA methylation during snail development/oviposition and parasite interactions. Further deciphering the role of this epigenetic process during Biomphalaria/Schistosoma co-evolutionary biology may reveal key factors associated with disease transmission and, moreover, enable the discovery of novel lifecycle intervention strategiespublishersversionPeer reviewe

A systematic review of electrical stimulation for pressure ulcer prevention and treatment in people with spinal cord injuries

Context: Electrical stimulation (ES) can confer benefit to pressure ulcer (PU) prevention and treatment in spinal cord injuries (SCI). However, clinical guidelines regarding the use of ES for PU management in SCI remain limited. Objectives: To critically appraise and synthesize the research evidence on ES for PU prevention and treatment in SCI. Method: Review was limited to peer-reviewed studies published in English from 1970 to July 2013. Studies included randomized controlled trials (RCTs), non-RCTs, prospective cohort studies, case series, case control and case report studies. Target population included adults with SCI. Interventions of any type of ES were accepted. Any outcome measuring effectiveness of PU prevention and treatment was included. Methodological quality was evaluated using established instruments. Results: Twenty-seven studies were included, 9/27 studies were RCTs. Six RCTs were therapeutic trials. ES enhanced PU healing in all eleven therapeutic studies. Two types of ES modalities were identified in therapeutic studies (surface electrodes, anal probe), 4 types of modalities in preventive studies (surface electrodes, ES shorts, sacral anterior nerve root implant, neuromuscular electrical stimulation implant). Conclusion: The methodological quality of the studies was poor, in particular for prevention studies. A significant effect of ES on enhancement of PU healing is shown in limited Grade I evidence. The great variability in ES parameters, stimulating locations and outcome measure leads to an inability to advocate any one standard approach for PU therapy or prevention. Future research is suggested to improve the design of ES devices, standardize ES parameters and conduct more rigorous trials