Complete genome sequence of the proteolytic Clostridium botulinum type A5 (B3') strain H04402 065

H04402 065 is one of a very small group of strains of proteolytic Clostridium botulinum that form type A5 neurotoxin. Here, we report the complete 3.9-Mb genome sequence and annotation of strain H04402 065, which was isolated from a botulism patient in the United Kingdom in 2004.     

Draft genome sequence of Streptomyces strain S4, a symbiont of the leaf-cutting ant Acromyrmex octospinosus

Streptomyces spp. are common symbionts of the leaf-cutting ant species Acromyrmex octospinosus, which feeds on basidiomycete fungus leaf matter and harvests the lipid- and carbohydrate-rich gongylidia as a food source. A. octospinosus and other ant genera use antifungal compounds produced by Streptomyces spp. and other actinomycetes in order to help defend their fungal gardens from parasitic fungi. Herein, we report the draft genome sequence of Streptomyces strain S4, an antifungal-producing symbiont of A. octospinosus.     

Evaluation of the Clinical and Cost Effectiveness of Intermediate Care Clinics for Diabetes (ICCD): A Multicentre Cluster Randomised Controlled Trial

Background

Configuring high quality care for the rapidly increasing number of people with type 2 diabetes (T2D) is a major challenge worldwide for both providers and commissioners. In the UK, about two thirds of people with T2D are managed entirely in primary care, with wide variation in management strategies and achievement of targets. Pay for performance, introduced in 2004, initially resulted in improvements but disparities exist in ethnic minorities and the improvements are levelling off. Community based, intermediate care clinics for diabetes (ICCDs) were considered one solution and are functioning across the UK. However, there is no randomised trial evidence for the effectiveness of such clinics.

Trial Design, Methods and Findings

This is a cluster-randomised trial, involving 3 primary care trusts, with 49 general practices randomised to usual care (n = 25) or intervention (ICCDs; n = 24). All eligible adult patients with T2D were invited; 1997 were recruited and 1280 followed-up after 18-months intervention. Primary outcome: achievement of all three of the NICE targets [(HbA1c≤7.0%/53 mmol/mol; Blood Pressure <140/80 mmHg; cholesterol <154 mg/dl (4 mmol/l)]. Primary outcome was achieved in 14.3% in the intervention arm vs. 9.3% in the control arm (p = 0.059 after adjustment for covariates). The odds ratio (95% CI) for achieving primary outcome in the intervention group was 1.56 (0.98, 2.49). Primary care and community clinic costs were significantly higher in the intervention group, but there were no significant differences in hospital costs or overall healthcare costs. An incremental cost-effectiveness ratio (ICER) of +£7,778 per QALY gained, indicated ICCD was marginally more expensive at producing health gain.

Conclusions

Intermediate care clinics can contribute to improving target achievement in patients with diabetes. Further work is needed to investigate the optimal scale and organisational structure of ICCD services and whether, over time, their role may change as skill levels in primary care increase.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00945204","term_id":"NCT00945204"}}NCT00945204; National Research Register (NRR) M0014178167.     

Conversion of erythro-D-sphinganine to its [1-2H1] and [1-3H1] derivatives

A convenient chemical synthesis of erythro-D-[1-2H1] sphinganine and erythro-D-[1-3H1]sphinganine is described. The approach utilizes a stereospecific starting material (natural sphinganine prepared from bovine brain sphingomyelin) and applies a sequence of selective protection of functional groups yielding 2-acetamido-3-O-benzoyloctadecan-1-ol. Oxidation of the primary alcohol to an aldehyde followed by NaB2H4 or NaB3H4 reduction and hydrolysis of the protective groups yields erythro-D-[1-2H1]sphinganine or erythro-D-[1-3H1]sphinganine. The synthetic intermediates and isotopically labeled sphinganines are characterized by infrared analysis, 1H-nuclear magnetic resonance, optical rotation, and gas-liquid radiochromatographic and mass spectral fragmentation analyses. The [1-2H1] and [1-3H1] derivatives were obtained with overall yields (and isotope enrichments) of 11% (min. 84 mol% 2H1) and 8% (60 mCi/mmol), respectively.     

Land use efficiency: anticipating future demand for land‐sector greenhouse gas emissions abatement and managing trade‐offs with agriculture,water, and biodiversity

Competition for land is increasing, and policy needs to ensure the efficient supply of multiple ecosystem services from land systems. We modelled the spatially explicit potential future supply of ecosystem services in Australia's intensive agricultural land in response to carbon markets under four global outlooks from 2013 to 2050. We assessed the productive efficiency of greenhouse gas emissions abatement, agricultural production, water resources, and biodiversity services and compared these to production possibility frontiers (PPFs). While interacting commodity markets and carbon markets produced efficient outcomes for agricultural production and emissions abatement, more efficient outcomes were possible for water resources and biodiversity services due to weak price signals. However, when only two objectives were considered as per typical efficiency assessments, efficiency improvements involved significant unintended trade‐offs for the other objectives and incurred substantial opportunity costs. Considering multiple objectives simultaneously enabled the identification of land use arrangements that were efficient over multiple ecosystem services. Efficient land use arrangements could be selected that meet society's preferences for ecosystem service provision from land by adjusting the metric used to combine multiple services. To effectively manage competition for land via land use efficiency, market incentives are needed that effectively price multiple ecosystem services.     

A Commensal Gone Bad: Complete Genome Sequence of the Prototypical Enterotoxigenic Escherichia coli Strain H10407

In most cases, Escherichia coli exists as a harmless commensal organism, but it may on occasion cause intestinal and/or extraintestinal disease. Enterotoxigenic E. coli (ETEC) is the predominant cause of E. coli-mediated diarrhea in the developing world and is responsible for a significant portion of pediatric deaths. In this study, we determined the complete genomic sequence of E. coli {"type":"entrez-nucleotide","attrs":{"text":"H10407","term_id":"875229","term_text":"H10407"}}H10407, a prototypical strain of enterotoxigenic E. coli, which reproducibly elicits diarrhea in human volunteer studies. We performed genomic and phylogenetic comparisons with other E. coli strains, revealing that the chromosome is closely related to that of the nonpathogenic commensal strain E. coli HS and to those of the laboratory strains E. coli K-12 and C. Furthermore, these analyses demonstrated that there were no chromosomally encoded factors unique to any sequenced ETEC strains. Comparison of the E. coli {"type":"entrez-nucleotide","attrs":{"text":"H10407","term_id":"875229","term_text":"H10407"}}H10407 plasmids with those from several ETEC strains revealed that the plasmids had a mosaic structure but that several loci were conserved among ETEC strains. This study provides a genetic context for the vast amount of experimental and epidemiological data that have been published.Current dogma suggests the Gram-negative motile bacterium Escherichia coli colonizes the infant gut within hours of birth and establishes itself as the predominant facultative anaerobe of the colon for the remainder of life (3, 59). While the majority of E. coli strains maintain this harmless existence, some strains have adopted a pathogenic lifestyle. Contemporary tenets suggest that pathogenic strains of E. coli have acquired genetic elements that encode virulence factors and enable the organism to cause disease (12). The large repertoire of virulence factors enables E. coli to cause a variety of clinical manifestations, including intestinal infections mediating diarrhea and extraintestinal infections, such as urinary tract infections, septicemia, and meningitis. Based on clinical manifestation of disease, the repertoire of virulence factors, epidemiology, and phylogenetic profiles, the strains causing intestinal infections can be divided into six separate pathotypes, viz., enteroaggregative E. coli (EAEC), enteroinvasive E. coli (EIEC), enteropathogenic E. coli (EPEC), enterohemorrhagic E. coli (EHEC), diffuse adhering E. coli (DAEC), and enterotoxigenic E. coli (ETEC) (33, 35, 39).ETEC is responsible for the majority of E. coli-mediated cases of human diarrhea worldwide. It is particularly prevalent among children in developing countries, where sanitation and clean supplies of drinking water are inadequate, and in travelers to such regions. It is estimated that there are 200 million incidences of ETEC infection annually, resulting in hundreds of thousands of deaths in children under the age of 5 (55, 64). The essential determinants of ETEC virulence are traditionally considered to be colonization of the host small-intestinal epithelium via plasmid-encoded colonization factors (CFs) and subsequent release of plasmid-encoded heat-stable (ST) and/or heat-labile (LT) enterotoxins that induce a net secretory state leading to profuse watery diarrhea (20, 62). More recently, additional plasmid-encoded factors have been implicated in the pathogenesis of ETEC, namely, the EatA serine protease autotransporter (SPATE) and the EtpA protein, which acts as an intermediate in the adhesion between bacterial flagella and host cells (23, 32, 42, 46). Furthermore, a number of chromosomal factors are thought to be involved in virulence, e.g., the invasin Tia; the TibA adhesin/invasin; and LeoA, a GTPase with unknown function (14, 21, 22). E. coli {"type":"entrez-nucleotide","attrs":{"text":"H10407","term_id":"875229","term_text":"H10407"}}H10407 is considered a prototypical ETEC strain; it expresses colonization factor antigen 1 (CFA/I) and the heat-stable and heat labile toxins. Loss of a 94.8-kb plasmid encoding CFA/I and a gene for ST enterotoxin from E. coli strain {"type":"entrez-nucleotide","attrs":{"text":"H10407","term_id":"875229","term_text":"H10407"}}H10407 leads to reduced ability to cause diarrhea (17).Here, we report the complete genome sequence and virulence factor repertoire of the prototypical ETEC strain {"type":"entrez-nucleotide","attrs":{"text":"H10407","term_id":"875229","term_text":"H10407"}}H10407 and the nucleotide sequence and gene repertoire of the plasmids from ETEC strain E1392/75, and we describe a novel conserved secretion system associated with the sequenced ETEC strains.