Pathogenicity and other genomic islands in plant pathogenic bacteria

Pathogenicity islands (PAIs) were first described in uropathogenic E. coli. They are now defined as regions of DNA that contain virulence genes and are present in the genome of pathogenic strains, but absent from or only rarely present in non-pathogenic variants of the same or related strains. Other features include a variable G+C content, distinct boundaries from the rest of the genome and the presence of genes related to mobile elements such as insertion sequences, integrases and transposases. Although PAIs have now been described in a wide range of both plant and animal pathogens it has become evident that the general features of PAIs are displayed by a number of regions of DNA with functions other than pathogenicity, such as symbiosis and antibiotic resistance, and the general term genomic islands has been adopted. This review will describe a range of genomic islands in plant pathogenic bacteria including those that carry effector genes, phytotoxins and the type III protein secretion cluster. The review will also consider some medically important bacteria in order to discuss the range, acquisition and stabilization of genomic islands.

Contributory negligence involving overseas European banks in property valuation negligence cases in the UK

This paper examines the phenomenon of cross-border property lending and examines a number of issues regarding lending procedures and decision making processes in the context of the relationship between lender and professional advisor. It commences by placing these procedures and processes in the context of the development of cross border European property investment and finance. The UK has been a popular destination for overseas investors and lenders over the last decade and is therefore used as a case study to examine the additional institutional risk that overseas lenders may face when operating outside of their own country and obtaining advice from home professionals. The UK market was the subject of a boom period during the late 1980s, followed by a recession in the early 1990s. The losses triggered a number of professional negligence actions by lenders against valuers. These include a number of overseas lenders mainly from Europe and these cases have been examined for any particular features which, coupled with other data gained from overseas lenders as part of an interview survey, could be used to isolate any significant problems for European lenders in overseas markets. The research identified a lack of clarity in roles and relationships between lender and advisor, difficulties in communications both internally and between overseas branches and headquarters and failures in provision and interpretation of advice. The paper concludes by identifying the issues which may need to be addressed generally by lenders and their advisors, when the lenders are operating in overseas markets.

The Genomic Threading Database: a comprehensive resource for structural annotations of the genomes from key organisms

Currently, the Genomic Threading Database (GTD) contains structural assignments for the proteins encoded within the genomes of nine eukaryotes and 101 prokaryotes. Structural annotations are carried out using a modified version of GenTHREADER, a reliable fold recognition method. The Gen THREADER annotation jobs are distributed across multiple clusters of processors using grid technology and the predictions are deposited in a relational database accessible via a web interface at http://bioinf.cs.ucl.ac.uk/GTD. Using this system, up to 84% of proteins encoded within a genome can be confidently assigned to known folds with 72% of the residues aligned. On average in the GTD, 64% of proteins encoded within a genome are confidently assigned to known folds and 58% of the residues are aligned to structures.

The Genomic Threading Database

The Genomic Threading Database currently contains structural annotations for the genomes of over 100 recently sequenced organisms. Annotations are carried out by using our modified GenTHREADER software and through implementing grid technology.

Improvement of the GenTHREADER method for genomic fold recognition

Motivation: In order to enhance genome annotation, the fully automatic fold recognition method GenTHREADER has been improved and benchmarked. The previous version of GenTHREADER consisted of a simple neural network which was trained to combine sequence alignment score, length information and energy potentials derived from threading into a single score representing the relationship between two proteins, as designated by CATH. The improved version incorporates PSI-BLAST searches, which have been jumpstarted with structural alignment profiles from FSSP, and now also makes use of PSIPRED predicted secondary structure and bi-directional scoring in order to calculate the final alignment score. Pairwise potentials and solvation potentials are calculated from the given sequence alignment which are then used as inputs to a multi-layer, feed-forward neural network, along with the alignment score, alignment length and sequence length. The neural network has also been expanded to accommodate the secondary structure element alignment (SSEA) score as an extra input and it is now trained to learn the FSSP Z-score as a measurement of similarity between two proteins. Results: The improvements made to GenTHREADER increase the number of remote homologues that can be detected with a low error rate, implying higher reliability of score, whilst also increasing the quality of the models produced. We find that up to five times as many true positives can be detected with low error rate per query. Total MaxSub score is doubled at low false positive rates using the improved method.

Traditional Chinese medicine research in the post-genomic era: good practice, priorities, challenges and opportunities

Background and aims: GP-TCM is the 1st EU-funded Coordination Action consortium dedicated to traditional Chinese medicine (TCM) research. This paper aims to summarise the objectives, structure and activities of the consortium and introduces the position of the consortium regarding good practice, priorities, challenges and opportunities in TCM research. Serving as the introductory paper for the GPTCM Journal of Ethnopharmacology special issue, this paper describes the roadmap of this special issue and reports how the main outputs of the ten GP-TCM work packages are integrated, and have led to consortium-wide conclusions. Materials and methods: Literature studies, opinion polls and discussions among consortium members and stakeholders. Results: By January 2012, through 3 years of team building, the GP-TCM consortium had grown into a large collaborative network involving ∼200 scientists from 24 countries and 107 institutions. Consortium members had worked closely to address good practice issues related to various aspects of Chinese herbal medicine (CHM) and acupuncture research, the focus of this Journal of Ethnopharmacology special issue, leading to state-of-the-art reports, guidelines and consensus on the application of omics technologies in TCM research. In addition, through an online survey open to GP-TCM members and non-members, we polled opinions on grand priorities, challenges and opportunities in TCM research. Based on the poll, although consortium members and non-members had diverse opinions on the major challenges in the field, both groups agreed that high-quality efficacy/effectiveness and mechanistic studies are grand priorities and that the TCM legacy in general and its management of chronic diseases in particular represent grand opportunities. Consortium members cast their votes of confidence in omics and systems biology approaches to TCM research and believed that quality and pharmacovigilance of TCM products are not only grand priorities, but also grand challenges. Non-members, however, gave priority to integrative medicine, concerned on the impact of regulation of TCM practitioners and emphasised intersectoral collaborations in funding TCM research, especially clinical trials. Conclusions: The GP-TCM consortium made great efforts to address some fundamental issues in TCM research, including developing guidelines, as well as identifying priorities, challenges and opportunities. These consortium guidelines and consensus will need dissemination, validation and further development through continued interregional, interdisciplinary and intersectoral collaborations. To promote this, a new consortium, known as the GP-TCM Research Association, is being established to succeed the 3-year fixed term FP7 GP-TCM consortium and will be officially launched at the Final GP-TCM Congress in Leiden, the Netherlands, in April 2012.

Investigation into the adoption intention of social CRM in Saudi banks

The growth of Web 2.0 generation will have influence on developing strong relationships with customers. Even though Web 2.0 technologies and applications have gained significant attention recently by academics and practitioners, research into its potential integration with CRM system remains a poorly investigated subject. This paper aims to investigate the adoption intention of social CRM system, focusing on Saudi banks. A conceptual model was proposed based on technology organisation and environment (TOE) framework. A qualitative approach was applied to validate the research model. The finding suggests that technology infrastructure, and competitive pressures tend to be the most influential drivers to adopt social CRM. In contrast, the limited number of IT experts, security concerns, and organisational structure were found to negatively affect social CRM adoption intention.

Comparative genomic indexing reveals the phylogenomics of Escherichia coli pathogens

The Escherichia coli O26 serogroup includes important food-borne pathogens associated with human and animal diarrheal disease. Current typing methods have revealed great genetic heterogeneity within the O26 group; the data are often inconsistent and focus only on verotoxin (VT)-positive O26 isolates. To improve current understanding of diversity within this serogroup, the genomic relatedness of VT-positive and -negative O26 strains was assessed by comparative genomic indexing. Our results clearly demonstrate that irrespective of virulence characteristics and pathotype designation, the O26 strains show greater genomic similarity to each other than to any other strain included in this study. Our data suggest that enteropathogenic and VT-expressing E. coli O26 strains represent the same clonal lineage and that W-expressing E. coli O26 strains have gained additional virulence characteristics. Using this approach, we established the core genes which are central to the E. coli species and identified regions of variation from the E. coli K-12 chromosomal backbone.

Mapping the platelet profile for functional genomic studies and demonstration of the effect size of the GP6 locus

BACKGROUND: Evidence suggests the wide variation in platelet response within the population is genetically controlled. Unraveling the complex relationship between sequence variation and platelet phenotype requires accurate and reproducible measurement of platelet response. OBJECTIVE: To develop a methodology suitable for measuring signaling pathway-specific platelet phenotype, to use this to measure platelet response in a large cohort, and to demonstrate the effect size of sequence variation in a relevant model gene. METHODS: Three established platelet assays were evaluated: mobilization of [Ca(2+)](i), aggregometry and flow cytometry, each in response to adenosine 5'-diphosphate (ADP) or the glycoprotein (GP) VI-specific crosslinked collagen-related peptide (CRP). Flow cytometric measurement of fibrinogen binding and P-selectin expression in response to a single, intermediate dose of each agonist gave the best combination of reproducibility and inter-individual variability and was used to measure the platelet response in 506 healthy volunteers. Pathway specificity was ensured by blocking the main subsidiary signaling pathways. RESULTS: Individuals were identified who were hypo- or hyper-responders for both pathways, or who had differential responses to the two agonists, or between outcomes. 89 individuals, retested three months later using the same methodology, showed high concordance between the two visits in all four assays (r(2) = 0.872, 0.868, 0.766 and 0.549); all subjects retaining their phenotype at recall. The effect of sequence variation at the GP6 locus accounted for approximately 35% of the variation in the CRP-XL response. CONCLUSION: Genotyping-phenotype association studies in a well-characterized, large cohort provides a powerful strategy to measure the effect of sequence variation in genes regulating the platelet response.