Beneficial modulation of the gut microbiota

peer-reviewedThe human gut microbiota comprises approximately 100 trillion microbial cells and has a significant effect on many aspects of human physiology including metabolism, nutrient absorption and immune function. Disruption of this population has been implicated in many conditions and diseases, including examples such as obesity, inflammatory bowel disease and colorectal cancer that are highlighted in this review. A logical extension of these observations suggests that the manipulation of the gut microbiota can be employed to prevent or treat these conditions. Thus, here we highlight a variety of options, including the use of changes in diet (including the use of prebiotics), antimicrobial-based intervention, probiotics and faecal microbiota transplantation, and discuss their relative merits with respect to modulating the intestinal community in a beneficial way.C.J.W, C.M.G. and P.D.C are supported by a SFI PI award “Obesibiotics” (11/PI/1137

Governing through trust: community-based link workers and parental engagement in education

This article seeks to further understandings of contemporary patterns of parental government. Parenting has emerged as a key policy domain in twenty-first century Britain and we explore the politicisation of family life by examining a pilot programme tasked with enhancing parental engagement in education amongst ‘hard-to-reach’ families within the white British community of a large inner-London borough. Concentrating upon the programme’s signature device – the deployment of community-based ‘link workers’ to bridge home and school – ‘governmentality’ (Foucault, 2009) is used as a theoretical lens through which to foreground the link workers’ role in governing parents. We draw on qualitative data collected from link workers, parents, and school leaders, to argue that link workers represent a mode of governmentality that privileges the instrumental use of trust to achieve strategic objectives, rather than coercive authority. The aim being to produce responsible, self-disciplined parents who act freely in accordance with normative expectations as to what constitutes ‘good’ parenting and effective parental support. As such, the article highlights the link workers’ role in (re)producing the ideal, neoliberal parent. However, governing through trust comes at the cost of being unable to firmly secure desired outcomes. We thereby conclude that this gentle art of parental government affords parents some latitude in resisting institutional agendas

The MultiSite Spectroscopic Telescope campaign: 2m spectroscopy of the V361 Hya variable PG1605+072

We present results and analysis for the 2m spectroscopic part of the MultiSite Spectroscopic Telescope (MSST) campaign undertaken in May/June 2002. The goal of the project was to observe the pulsating subdwarf B star PG1605+072 simultaneously in velocity and photometry and to resolve as many of the >50 known modes as possible, which will allow a detailed asteroseismological analysis. We have obtained over 150 hours of spectroscopy, leading to an unprecedented noise level of only 207m/s. We report here the detection of 20 frequencies in velocity, with two more likely just below our detection threshold. In particular, we detect 6 linear combinations, making PG1605+072 only the second star known to show such frequencies in velocity. We investigate the phases of these combinations and their parent modes and find relationships between them that cannot be easily understood based on current theory. These observations, when combined with our simultaneous photometry, should allow asteroseismology of this most complicated of sdB pulsators.Comment: 9 pages, 5 figures, accepted for publication in A&A; Figure 1 at lower resolution than accepted versio

In silico identification of bacteriocin gene clusters in the gastrointestinal tract, based on the Human Microbiome Project’s reference genome database

peer-reviewedBackground The human gut microbiota comprises approximately 100 trillion microbial cells which significantly impact many aspects of human physiology - including metabolism, nutrient absorption and immune function. Disturbances in this population have been implicated in many conditions and diseases, including obesity, type-2 diabetes and inflammatory bowel disease. This suggests that targeted manipulation or shaping of the gut microbiota, by bacteriocins and other antimicrobials, has potential as a therapeutic tool for the prevention or treatment of these conditions. With this in mind, several studies have used traditional culture-dependent approaches to successfully identify bacteriocin-producers from the mammalian gut. In silico-based approaches to identify novel gene clusters are now also being utilised to take advantage of the vast amount of data currently being generated by next generation sequencing technologies. In this study, we employed an in silico screening approach to mine potential bacteriocin clusters in genome-sequenced isolates from the gastrointestinal tract (GIT). More specifically, the bacteriocin genome-mining tool BAGEL3 was used to identify potential bacteriocin producers in the genomes of the GIT subset of the Human Microbiome Project’s reference genome database. Each of the identified gene clusters were manually annotated and potential bacteriocin-associated genes were evaluated. Results We identified 74 clusters of note from 59 unique members of the Firmicutes, Bacteroidetes, Actinobacteria, Fusobacteria and Synergistetes. The most commonly identified class of bacteriocin was the >10 kDa class, formerly known as bacteriolysins, followed by lantibiotics and sactipeptides. Conclusions Multiple bacteriocin gene clusters were identified in a dataset representative of the human gut microbiota. Interestingly, many of these were associated with species and genera which are not typically associated with bacteriocin production.CJW, CMG and PDC are supported by a SFI PI award to PDC “Obesibiotics” (11/PI/1137)

Summary of the 1st Annual Biodiscovery Research Workshop

This publication presents the background and aims of the inaugural Marine Biodiscovery Workshop 2008. Presentations relating to progress achieved in the marine biodiscovery research area through the Irish Beaufort Marine Biodiscovery Research Awards have been captured in extended abstracts.Marine research Sub-Programme 2007-'13Funder: Marine Institut

Enhanced Integrin α4β1-Mediated Adhesion Contributes to a Mobilization Defect of Endothelial Progenitor Cells in Diabetes.

Diabetes is associated with a deficit of circulating endothelial progenitor cells (EPCs), which has been attributed to their defective mobilization from the bone marrow. The basis for this mobilization defect is not completely understood, and we sought to determine if hyperglycemic conditions enhanced EPC adhesion. We found that culturing EPCs in high glucose media increased adhesion to bone marrow stromal cells. This enhanced adhesion was associated with decreased expression of protein kinase A regulatory subunit 1β (PRKAR1β), activation of protein kinase A (PKA), and phosphorylation of α4-integrin on serine 988. This potentiated adhesion was reversed by treatment with a PKA inhibitor, overexpression of PRKAR1β, or expression of a phosphorylation-defective α4-integrin variant (α4[S988A]). Using a model of type 1 diabetes, we showed that α4(S988A)-expressing mice have more circulating EPCs than their wild-type counterparts. Moreover, diabetic α4(S988A) mice demonstrate enhanced revascularization after hind limb ischemia. Thus, we have identified a novel signaling mechanism activating PKA in diabetes (downregulation of an inhibitory regulatory subunit) that leads to deficits of circulating EPCs and impaired vascular repair, which could be reversed by α4-integrin mutation

Characterization of Pro-Inflammatory Flagellin Proteins Produced by Lactobacillus ruminis and Related Motile Lactobacilli

peer-reviewedLactobacillus ruminis is one of at least twelve motile but poorly characterized species found in the genus Lactobacillus. Of these, only L. ruminis has been isolated from mammals, and this species may be considered as an autochthonous member of the gastrointestinal microbiota of humans, pigs and cows. Nine L. ruminis strains were investigated here to elucidate the biochemistry and genetics of Lactobacillus motility. Six strains isolated from humans were non-motile while three bovine isolates were motile. A complete set of flagellum biogenesis genes was annotated in the sequenced genomes of two strains, ATCC25644 (human isolate) and ATCC27782 (bovine isolate), but only the latter strain produced flagella. Comparison of the L. ruminis and L. mali DSM20444T motility loci showed that their genetic content and gene-order were broadly similar, although the L. mali motility locus was interrupted by an 11.8 Kb region encoding rhamnose utilization genes that is absent from the L. ruminis motility locus. Phylogenetic analysis of 39 motile bacteria indicated that Lactobacillus motility genes were most closely related to those of motile carnobacteria and enterococci. Transcriptome analysis revealed that motility genes were transcribed at a significantly higher level in motile L. ruminis ATCC27782 than in non-motile ATCC25644. Flagellin proteins were isolated from L. ruminis ATCC27782 and from three other Lactobacillus species, while recombinant flagellin of aflagellate L. ruminis ATCC25644 was expressed and purified from E. coli. These native and recombinant Lactobacillus flagellins, and also flagellate L. ruminis cells, triggered interleukin-8 production in cultured human intestinal epithelial cells in a manner suppressed by short interfering RNA directed against Toll-Like Receptor 5. This study provides genetic, transcriptomic, phylogenetic and immunological insights into the trait of flagellum-mediated motility in the lactobacilli.This work was supported by a Principal Investigator Award (07/IN.1/B1780) from Science Foundation Ireland to PWOT. BAN was the recipient of an Embark studentship from the Irish Research Council for Science Engineering and Technology. TD and KN were supported by the Alimentary Pharmabiotic Centre, funded by Science Foundation Ireland

The molecular genetic analysis of the expanding pachyonychia congenita case collection

BACKGROUND: Pachyonychia congenita (PC) is a rare autosomal dominant keratinizing disorder characterized by severe, painful, palmoplantar keratoderma and nail dystrophy, often accompanied by oral leucokeratosis, cysts and follicular keratosis. It is caused by mutations in one of five keratin genes: KRT6A, KRT6B, KRT6C, KRT16 or KRT17. OBJECTIVES: To identify mutations in 84 new families with a clinical diagnosis of PC, recruited by the International Pachyonychia Congenita Research Registry during the last few years. METHODS: Genomic DNA isolated from saliva or peripheral blood leucocytes was amplified using primers specific for the PC-associated keratin genes and polymerase chain reaction products were directly sequenced. RESULTS: Mutations were identified in 84 families in the PC-associated keratin genes, comprising 46 distinct keratin mutations. Fourteen were previously unreported mutations, bringing the total number of different keratin mutations associated with PC to 105. CONCLUSIONS: By identifying mutations in KRT6A, KRT6B, KRT6C, KRT16 or KRT17, this study has confirmed, at the molecular level, the clinical diagnosis of PC in these families