Comparative genomics of the type VI secretion systems of Pantoea and Erwinia species reveals the presence of putative effector islands that may be translocated by the VgrG and Hcp proteins

<p>Abstract</p> <p>Background</p> <p>The Type VI secretion apparatus is assembled by a conserved set of proteins encoded within a distinct locus. The putative effector proteins Hcp and VgrG are also encoded within these loci. We have identified numerous distinct Type VI secretion system (T6SS) loci in the genomes of several ecologically diverse <it>Pantoea </it>and <it>Erwinia </it>species and detected the presence of putative effector islands associated with the <it>hcp </it>and <it>vgrG </it>genes.</p> <p>Results</p> <p>Between two and four T6SS loci occur among the <it>Pantoea </it>and <it>Erwinia </it>species. While two of the loci (T6SS-1 and T6SS-2) are well conserved among the various strains, the third (T6SS-3) locus is not universally distributed. Additional orthologous loci are present in <it>Pantoea </it>sp. aB-valens and <it>Erwinia billingiae </it>Eb661. Comparative analysis of the T6SS-1 and T6SS-3 loci showed non-conserved islands associated with the <it>vgrG </it>and <it>hcp</it>, and <it>vgrG </it>genes, respectively. These regions had a G+C content far lower than the conserved portions of the loci. Many of the proteins encoded within the <it>hcp </it>and <it>vgrG </it>islands carry conserved domains, which suggests they may serve as effector proteins for the T6SS. A number of the proteins also show homology to the C-terminal extensions of evolved VgrG proteins.</p> <p>Conclusions</p> <p>Extensive diversity was observed in the number and content of the T6SS loci among the <it>Pantoea </it>and <it>Erwinia </it>species. Genomic islands could be observed within some of T6SS loci, which are associated with the <it>hcp </it>and <it>vgrG </it>proteins and carry putative effector domain proteins. We propose new hypotheses concerning a role for these islands in the acquisition of T6SS effectors and the development of novel evolved VgrG and Hcp proteins.</p

STK295900, a Dual Inhibitor of Topoisomerase 1 and 2, Induces G<inf>2</inf> Arrest in the Absence of DNA Damage

STK295900, a small synthetic molecule belonging to a class of symmetric bibenzimidazoles, exhibits antiproliferative activity against various human cancer cell lines from different origins. Examining the effect of STK295900 in HeLa cells indicates that it induces G2 phase arrest without invoking DNA damage. Further analysis shows that STK295900 inhibits DNA relaxation that is mediated by topoisomerase 1 (Top 1) and topoisomerase 2 (Top 2) in vitro. In addition, STK295900 also exhibits protective effect against DNA damage induced by camptothecin. However, STK295900 does not affect etoposide-induced DNA damage. Moreover, STK295900 preferentially exerts cytotoxic effect on cancer cell lines while camptothecin, etoposide, and Hoechst 33342 affected both cancer and normal cells. Therefore, STK295900 has a potential to be developed as an anticancer chemotherapeutic agent. © 2013 Kim et al

Metabolic Versatility and Antibacterial Metabolite Biosynthesis Are Distinguishing Genomic Features of the Fire Blight Antagonist Pantoea vagans C9-1

Smits THM, Rezzonico F, Kamber T, et al. Metabolic Versatility and Antibacterial Metabolite Biosynthesis Are Distinguishing Genomic Features of the Fire Blight Antagonist Pantoea vagans C9-1. PLoS ONE. 2011;6(7): e22247.Background: Pantoea vagans is a commercialized biological control agent used against the pome fruit bacterial disease fire blight, caused by Erwinia amylovora. Compared to other biocontrol agents, relatively little is currently known regarding Pantoea genetics. Better understanding of antagonist mechanisms of action and ecological fitness is critical to improving efficacy. Principal Findings: Genome analysis indicated two major factors contribute to biocontrol activity: competition for limiting substrates and antibacterial metabolite production. Pathways for utilization of a broad diversity of sugars and acquisition of iron were identified. Metabolism of sorbitol by P. vagans C9-1 may be a major metabolic feature in biocontrol of fire blight. Biosynthetic genes for the antibacterial peptide pantocin A were found on a chromosomal 28-kb genomic island, and for dapdiamide E on the plasmid pPag2. There was no evidence of potential virulence factors that could enable an animal or phytopathogenic lifestyle and no indication of any genetic-based biosafety risk in the antagonist. Conclusions: Identifying key determinants contributing to disease suppression allows the development of procedures to follow their expression in planta and the genome sequence contributes to rationale risk assessment regarding the use of the biocontrol strain in agricultural systems

Integrated Surveys of Neglected Tropical Diseases in Southern Sudan: How Much Do They Cost and Can They Be Refined?

Control of neglected tropical diseases (NTDs) is suggested to be more cost-effective when drugs are co-administered through a single integrated delivery system rather than separate systems. An essential prerequisite for such efficiency gains is sufficient geographical overlap of the targeted diseases – lymphatic filariasis (LF), onchocerciasis, schistosomiasis, soil-transmitted helminth infection and trachoma. Lack of data on geographical NTD distribution currently hampers the implementation of integrated control in many African countries. To generate the required data quickly and efficiently, integrated surveys of several NTDs simultaneously have been recommended. However, experience with integrated surveys is limited and requires additional research on cost and effectiveness to inform improvements in methodology and to guide scale-up. Here we analyse costs of the first integrated NTD survey round in Southern Sudan, generating average costs per implementation unit surveyed. Cost estimates are presented for use of the existing survey method and for modified versions. Key cost drivers were survey consumables and personnel, both of which are recurrent costs. These inputs could be reduced or put to more efficient use by modifying sampling for LF. To generate comparable cost estimates and identify key cost drivers in other settings we provide detailed cost data and guidance on how to replicate this work

Erwinia amylovora Novel Plasmid pEI70: Complete Sequence, Biogeography, and Role in Aggressiveness in the Fire Blight Phytopathogen

Comparative genomics of several strains of Erwinia amylovora, a plant pathogenic bacterium causal agent of fire blight disease, revealed that its diversity is primarily attributable to the flexible genome comprised of plasmids. We recently identified and sequenced in full a novel 65.8 kb plasmid, called pEI70. Annotation revealed a lack of known virulence-related genes, but found evidence for a unique integrative conjugative element related to that of other plant and human pathogens. Comparative analyses using BLASTN showed that pEI70 is almost entirely included in plasmid pEB102 from E. billingiae, an epiphytic Erwinia of pome fruits, with sequence identities superior to 98%. A duplex PCR assay was developed to survey the prevalence of plasmid pEI70 and also that of pEA29, which had previously been described in several E. amylovora strains. Plasmid pEI70 was found widely dispersed across Europe with frequencies of 5–92%, but it was absent in E. amylovora analyzed populations from outside of Europe. Restriction analysis and hybridization demonstrated that this plasmid was identical in at least 13 strains. Curing E. amylovora strains of pEI70 reduced their aggressiveness on pear, and introducing pEI70 into low-aggressiveness strains lacking this plasmid increased symptoms development in this host. Discovery of this novel plasmid offers new insights into the biogeography, evolution and virulence determinants in E. amylovora

Social class origin and assortative mating in Britain, 1949-2010

This article examines trends in assortative mating in Britain over the last 60 years. Assortative mating is the tendency for like to form a conjugal partnership with like. Our focus is on the association between the social class origins of the partners. The propensity towards assortative mating is taken as an index of the openness of society which we regard as a macro level aspect of social inequality. There is some evidence that the propensity for partners to come from similar class backgrounds declined during the 1960s. Thereafter, there was a period of 40 years of remarkable stability during which the propensity towards assortative mating fluctuated trendlessly within quite narrow limits. This picture of stability over time in social openness parallels the well-established facts about intergenerational social class mobility in Britain

Arterial line pressure control enhanced extracorporeal blood flow prescription in hemodialysis patients

<p>Abstract</p> <p>Background</p> <p>In hemodialysis, extracorporeal blood flow (Qb) recommendation is 300–500 mL/min. To achieve the best Qb, we based our prescription on dynamic arterial line pressure (DALP).</p> <p>Methods</p> <p>This prospective study included 72 patients with catheter Group 1 (G1), 1877 treatments and 35 arterio-venous (AV) fistulae Group 2 (G2), 1868 treatments. The dialysis staff was trained to prescribe Qb sufficient to obtain DALP between -200 to -250 mmHg. We measured ionic clearance (IK: mL/min), access recirculation, DALP (mmHg) and Qb (mL/min). Six prescription zones were identified: from an optimal A zone (Qb > 400, DALP -200 to -250) to zones with lower Qb E (Qb < 300, DALP -200 to -250) and F (Qb < 300, DALP > -199).</p> <p>Results</p> <p>Treatments distribution in A was 695 (37%) in G1 vs. 704 (37.7%) in G2 (<it>P </it>= 0.7). In B 150 (8%) in G1 vs. 458 (24.5%) in G2 (<it>P </it>< 0.0001). Recirculation in A was 10.0% (Inter quartile rank, IQR 6.5, 14.2) in G1 vs. 9.8% (IQR 7.5, 14.1) in G2 (<it>P </it>= 0.62). IK in A was 214 ± 34 (G1) vs. 213 ± 35 (G2) (<it>P </it>= 0.65). IK Anova between G2 zones was: A vs. C and D (<it>P </it>< 0.000001). Staff prescription adherence was 81.3% (G1) vs. 84.1% (G2) (<it>P </it>= 0.02).</p> <p>Conclusion</p> <p>In conclusion, an optimal Qb can de prescribed with DALP of -200 mmHg. Staff adherence to DLAP treatment prescription could be reached up to 81.3% in catheters and 84.1% in AV fistulae.</p

Association of Dietary Factors with Presence and Severity of Tinnitus in a Middle-Aged UK Population

Objective The impact of dietary factors on tinnitus has received limited research attention, despite being a considerable concern among people with tinnitus and clinicians. The objective was to examine the link between dietary factors and presence and severity of tinnitus. Design This study used the UK Biobank resource, a large cross-sectional study of adults aged 40–69. 171,722 eligible participants were asked questions specific to tinnitus (defined as noises such as ringing or buzzing in the head or ears). Dietary factors included portions of fruit and vegetables per day, weekly fish consumption (oily and non-oily), bread type, cups of caffeinated coffee per day, and avoidance of dairy, eggs, wheat and sugar. We controlled for lifestyle, noise exposure, hearing, personality and comorbidity factors. Results Persistent tinnitus, defined as present at least a lot of the time, was elevated with increased: (i) fruit/vegetable intake (OR = 1.01 per portion/day), (ii) bread (wholemeal/wholegrain, OR = 1.07; other bread, 1.20) and (iii) dairy avoidance (OR = 1.27). Persistent tinnitus was reduced with: (i) fish consumption (non-oily, OR = 0.91; oily, 0.95), (ii) egg avoidance (OR = 0.87) and (iii) caffeinated coffee consumption (OR = 0.99 per cup/day). Reports of “bothersome” tinnitus (moderate-severe handicap) increased with wholemeal/wholegrain bread intake (OR = 0.86). Reports of less frequent transient tinnitus increased with dairy avoidance (OR = 1.18) and decreased with caffeinated coffee (OR = 0.98 per cup/day) and brown bread (OR = 0.94). Conclusions This is the first population study to report the association between dietary factors and tinnitus. Although individually dietary associations are mostly modest, particular changes in diet, such as switching between foodstuffs, may result in stronger associations. These findings offer insights into possible dietary associations with tinnitus, and this may be useful when discussing management options in combination with other lifestyle changes and therapies