The role of microbial polysaccharides in host-pathogen interaction

Bacteria are capable of expressing a diverse range of cell surface polysaccharides from capsules and lipopolysaccharides through teichoic acid molecules to lipoarabinomannans. This review will focus on the expression of capsular polysaccharides and their interaction with the host. In particular, it will focus on the role of capsular polysaccharides as immunomodulatory molecules

Simple steps to develop trial follow-up procedures.

BACKGROUND: Loss to follow-up in randomised controlled trials reduces statistical power and increases the potential for bias. Almost half of all trials fail to achieve their follow-up target. Statistical methods have been described for handling losses to follow-up and systematic reviews have identified interventions that increase follow-up. However, there is little guidance on how to develop practical follow-up procedures. This paper describes the development of follow-up procedures in a pilot randomised controlled trial of a sexual health intervention that required participants to provide and return questionnaires and chlamydia test samples in the post. We identified effective methods to increase follow-up from systematic reviews. We developed and tested prototype procedures to identify barriers to follow-up completion. We asked trial participants about their views on our follow-up procedures and revised the methods accordingly. RESULTS: We identified 17 strategies to increase follow-up and employed all but five. We found that some postal test kits do not fit through letterboxes and that that the test instructions were complicated. After identifying the appropriate sized test kit and simplifying the instructions, we obtained user opinions. Users wanted kits to be sent in coloured envelopes (so that they could identify them easily), with simple instructions and questionnaires and wanted to be notified before we sent the kits. We achieved 92 % (183/200) overall follow-up for the postal questionnaire at 1 month and 82 % (163/200) at 12 months. We achieved 86 % (171/200) overall follow-up for the postal chlamydia test at 3 months and 80 % (160/200) at 12 months. CONCLUSIONS: By using established methods to increase follow-up, testing prototype procedures and seeking user opinions, we achieved higher follow-up than previous sexual health trials. However, it is not possible to determine if the increase in response was due to our follow-up procedures. TRIAL REGISTRATION: Current Controlled Trials ISRCTN02304709 Date of registration: 27 March 2013

Erratum to: Simple steps to develop trial follow-up procedures.

Unfortunately, the original version of this article [1] contained an error. There were errors in the reference numbers in Additional file 1. This has now been corrected and Additional file 1 is included here with the correct reference numbers

THE ROLE OF PRODUCT ATTRIBUTES IN THE AGRICULTURAL NEGOTIATIONS

Marketing, International Relations/Trade,

Caracterización genotípica y nuevos tipos de secuencia multilocus de exoU+ de Pseudomonas aeruginosa presente en diferentes infecciones clínicas y entornos

Introducción: The exoU gene, a marker for highly virulent strains of Pseudomonas aeruginosa, is the major contributor to a wide varietyof healthcare-associated infections. Methods: In this study, the antibiotic susceptibility profile, prevalence and genotyping of exoU+ P.aeruginosa were demonstrated. A total of 101 isolates of P. aeruginosa were analysed from different clinical and environmental sources. Results: The antibiotic susceptibility profile classified these isolates as extensively drug resistant (35.6%), multidrug resistant (40.5%) and non-multidrug resistant (23.7%). The prevalence of exoU gene was screened by PCR and 23 exoU+ genotypes were detected which all were clinical isolates. Multilocus sequence typing (MLST) analysis of seven loci assigned these exoU+ genotypes to 21 sequence types (STs) from which 16 new STs were identified. The prevalent STs were ST-308 and ST-235. Phylogenetic analysis using the concatenated nucleotide sequences of the seven housekeeping genes, exoU and the ITS region differentiated these exoU+ strains into five main groups. However, distinct evolutionary origins for some new sequence types were also indicated. Conclusions: The studied isolates showed the coexistence of exoU- and exoU+ genotypes of clinical P. aeruginosa in Kurdistan with a majority of MDR and XDR pattern. The prevalent STs found in other hospitals worldwide and at the international level

A new family of phosphoinositide phosphatases in microorganisms: identification and biochemical analysis

<p>Abstract</p> <p>Background</p> <p>Phosphoinositide metabolism is essential to membrane dynamics and impinges on many cellular processes, including phagocytosis. Modulation of phosphoinositide metabolism is important for pathogenicity and virulence of many human pathogens, allowing them to survive and replicate in the host cells. Phosphoinositide phosphatases from bacterial pathogens are therefore key players in this modulation and constitute attractive targets for chemotherapy. MptpB, a virulence factor from <it>Mycobacterium tuberculosis</it>, has phosphoinositide phosphatase activity and a distinct active site P-loop signature HCXXGKDR that shares characteristics with eukaryotic lipid phosphatases and protein tyrosine phosphatases. We used this P-loop signature as a "diagnostic motif" to identify related putative phosphatases with phosphoinositide activity in other organisms.</p> <p>Results</p> <p>We found more than 200 uncharacterised putative phosphatase sequences with the conserved signature in bacteria, with some related examples in fungi and protozoa. Many of the sequences identified belong to recognised human pathogens. Interestingly, no homologues were found in any other organisms including Archaea, plants, or animals. Phylogenetic analysis revealed that these proteins are unrelated to classic eukaryotic lipid phosphatases. However, biochemical characterisation of those from <it>Listeria monocytogenes </it>and <it>Leishmania major</it>, demonstrated that, like MptpB, they have phosphatase activity towards phosphoinositides. Mutagenesis studies established that the conserved Asp and Lys in the P-loop signature (HCXXG<b>KD</b>R) are important in catalysis and substrate binding respectively. Furthermore, we provide experimental evidence that the number of basic residues in the P-loop is critical in determining activity towards poly-phosphoinositides.</p> <p>Conclusion</p> <p>This new family of enzymes in microorganisms shows distinct sequence and biochemical characteristics to classic eukaryotic lipid phosphatases and they have no homologues in humans. This study provides a foundation for examining the biological role of this new family of phosphatases and their potential as pharmaceutical targets against infectious diseases.</p

Pherotype polymorphism in Streptococcus pneumoniae has no obvious effects on population structure and recombination

Natural transformation in the Gram-positive pathogen Streptococcus pneumoniae occurs when cells become “competent”, a state that is induced in response to high extracellular concentrations of a secreted peptide signal called CSP (Competence Stimulating Peptide) encoded by the comC locus. Two main CSP signal types (pherotypes) are known to dominate the pherotype diversity across strains. Using 4,089 fully sequenced pneumococcal genomes, we confirm that pneumococcal populations are highly genetically structured and that there is significant variation among diverged populations in pherotype frequencies; most carry only a single pherotype. Moreover, we find that the relative frequencies of the two dominant pherotypes significantly vary within a small range across geographical sites. It has been variously proposed that pherotypes either promote genetic exchange among cells expressing the same pherotype, or conversely that they promote recombination between strains bearing different pherotypes. We attempt to distinguish these hypotheses using a bioinformatics approach by estimating recombination frequencies within and between pherotypes across 4,089 full genomes. Despite underlying population structure, we observe extensive recombination between populations; additionally, we found significantly higher (although marginal) rates of genetic exchange between strains expressing different pherotypes than among isolates carrying the same pherotype. Our results indicate that pherotypes do not restrict, and may even slightly facilitate, recombination between strains; however, these marginal effects suggest the more likely possibility that the cause of CSP polymorphism lies outside of its effects on transformation. Our results suggest that the CSP balanced polymorphism does not causally underlie population differentiation. Therefore, when strains carrying different pherotypes encounter one another during co-colonization, genetic exchange can occur without restriction

Simulating multiple quantum well solar cells

The quantum well solar cell (QWSC) has been proposed as a route to higher efficiency than that attainable by homojunction devices. Previous studies have established that carriers escape the quantum wells with high efficiency in forward bias and contribute to the photocurrent. Progress in resolving the efficiency limits of these cells has been dogged by the lack of a theoretical model reproducing both the enhanced carrier gen- eration and enhanced recombination due to the quantum wells. Here we present a model which calculates the incremental generation and recombination due to the QWs and is verified by modelling the experimental light and dark current-voltage characteristics of a range of III-V quantum well structures. We find that predicted dark currents are significantly greater than experiment if we use lifetimes derived from homostructure devices. Successful simulation of light and dark currents can be obtained only by introducing a parameter which represents a reduction in the quasi-Fermi level separation.Comment: Preprint submitted to the 28th IEEE Photovoltaic Specialists Conference, Anchorage, Alaska, USA, Sept. 2000, pp. 1304-130