A unique homologue of the eukaryotic protein-modifier ubiquitin present in the bacterium Bacteroides fragilis, a predominant resident of the human gastro-intestinal tract

In the complete genome sequences of Bacteroides fragilis NCTC9343 and 638R, we have discovered a gene, ubb, the product of which has 63% identity to human ubiquitin and cross-reacts with antibodies raised against bovine ubiquitin. The sequence of ubb is closest in identity (76%) to the ubiquitin gene from a Migratory Grasshopper entomopoxvirus, suggesting acquisition by inter-kingdom horizontal gene transfer. We have screened clinical isolates of B. fragilis from diverse geographical regions and found that ubb is present in some, but not all strains. The gene is transcribed and the mRNA translated in B. fragilis, but deletion of ubb did not have a detrimental effect on growth. BfUbb has a predicted signal sequence; both full length and processed forms were detected in whole cell extracts, while the processed form was found in concentrated culture supernatants. Purified recombinant BfUbb inhibited in vitro ubiquitination and was able to covalently bind the human E1 activating enzyme, suggesting it could act as a suicide substrate in vivo. B. fragilis is one of the predominant members of the normal human resident gastro-intestinal microbiota with estimates up to >1011 cells g-1 of faeces by culture. These data indicate that the gastro-intestinal tract of some individuals could contain a significant amount of aberrant ubiquitin with the potential to inappropriately activate the host immune system and/or interfere with eukaryotic ubiquitin activity. This discovery could have profound implications in relation to our understanding of human diseases such as inflammatory bowel and autoimmune diseases.

The contours of memory in post-conflict societies: enacting public remembrance of the bomb in Omagh, Northern Ireland

Drawing on the theoretical insights of Paul Ricoeur this paper investigates the geographies of public remembrance in a post-conflict society. In Northern Ireland, where political divisions have found expression through acts of extreme violence over the past 30 years, questions of memory and an amnesty for forgetting have particular resonance both at the individual and societal level, and render Ricoeur’s framework particularly prescient. Since the signing of the Belfast Agreement in 1998, initiating the Peace Process through consociational structures, discovering a nomenclature and set of practices which would aid in the rapprochement of a deeply divided society has presented a complex array of issues. In this paper I examine the various practices of public remembrance of the 1998 bombing of Omagh as a means of understanding how memory-spaces evolve in a post-conflict context. In Omagh there were a variety of commemorative practices instituted and each, in turn, adopted a different contour towards achieving reconciliation with the violence and grief of the bombing. In particular the Garden of Light project is analysed as a collective monument which, with light as its metaphysical centre, invited the populace to reflect backward on the pain of the bombing while at the same time enabling the society to look forward toward a peaceful future where a politics of hope might eclipse a politics of despair.

Sequential antimicrobial therapy: treatment of severe lower respiratory tract infections in children

Although there have been a number of studies in adults, to date there has been little research into sequential antimicrobial therapy (SAT) in paediatric populations. The present study evaluates the impact of a SAT protocol for the treatment of severe lower respiratory tract infection in paediatric patients. The study involved 89 paediatric patients (44 control and 45 SAT). The SAT patients had a shorter length of hospital stay (4.0 versus 8.3 days), shorter duration of inpatient antimicrobial therapy (4.0 versus 7.9 days) with the period of iv therapy being reduced from a mean of 5.6 to 1.7 days. The total healthcare costs were reduced by 52%. The resolution of severe lower respiratory tract infection with a short course of iv antimicrobials, followed by conversion to oral therapy yielded clinical outcomes comparable to those achieved using longer term iv therapy. SAT proved to be an important cost-minimizing tool for realizing substantial healthcare costs savings.