Vibrio vulnificus Type 6 Secretion System 1 contains anti-Bacterial properties.

This is the final version of the article. Available from Public Library of Science via the DOI in this record.Vibrio vulnificus is a bacterium responsible for severe gastroenteritis, sepsis and wound infections. Gastroenteritis and sepsis are commonly associated with the consumption of raw oysters, whereas wound infection is often associated with the handling of contaminated fish. Although classical virulence factors of this emerging pathogen are well characterised, there remains a paucity of knowledge regarding the general biology of this species. To investigate the presence of previously unreported virulence factors, we applied whole genome sequencing to a panel of ten V. vulnificus strains with varying virulence potentials. This identified two novel type 6 secretion systems (T6SSs), systems that are known to have a role in bacterial virulence and population dynamics. By utilising a range of molecular techniques and assays we have demonstrated the functionality of one of these T6SSs. Furthermore, we have shown that this system is subject to thermoregulation and is negatively regulated by increasing salinity concentrations. This secretion system was also shown to be involved in the killing of V. vulnificus strains that did not possess this system and a model is proposed as to how this interaction may contribute to population dynamics within V. vulnificus strains. In addition to this intra-species killing, this system also contributes to the killing of inter bacterial species and may have a role in the general composition of Vibrio species in the environment.This work was funded by a CEFAS-Exeter University Alliance PhD Studentship awarded to SRC and SLM. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Polymorphisms in the Mn-SOD and EC-SOD Genes and Their Relationship to Diabetic Neuropathy in Type 1 Diabetes Mellitus

BACKGROUND: Oxidative stress, resulting in a marked increase in the level of oxygen free radicals (OFR), has been implicated in the etiology of diabetic neuropathy (DN). Antioxidant enzymes may protect against the rapid onset and progression of DN, by reducing the excess of OFR and peroxide. Mutations and polymorphisms in the genes encoding such enzymes may therefore result in predisposition to DN. We investigated the role of genes encoding two antioxidant enzymes, mitochondrial (Mn-SOD) and extracellular (EC-SOD) superoxide dismutase, in DN pathogenesis in a Russian population. We studied Ala(-9)Val and Ile58Thr polymorphisms of the Mn-SOD gene and Arg213Gly dimorphism of the EC-SOD gene in type 1 diabetic patients with (n = 82) and without DN (n = 84). RESULTS: We developed and used a new polymerase chain reaction (PCR) assays for rapid detection of polymorphisms. These assays involved the use of mismatch PCR primers to create restriction sites in the amplified product only in presence of the polymorphic base. The PCR product was than digested with BshTI, Eco32I or Eco52I to detect Ala(-9)Val, Ile58Thr or Arg213Gly polymorphic site respectively. The frequencies of the Ala allele (50.6% vs. 68.5%, p < 0.002) and the Ala/Ala genotype (17.1% vs. 39.3%, p < 0.005) of the Mn-SOD gene were significantly lower in DN patients than in diabetic subjects without DN. In contrast, the Val allele (49.4% vs. 31.5%, p < 0.002) and the Val/Val genotype (15.9% vs. 2.4%, p < 0.01) were significantly more frequent in the DN patients than in the control group. CONCLUSIONS: Ala(-9)Val substitution in the Mn-SOD gene was associated with DN in a Russian populatio

Population-based laboratory surveillance for Giardia sp. and Cryptosporidium sp. infections in a large Canadian health region

BACKGROUND: Giardia lamblia (intestinalis) and Cryptosporidium parvum are the two most important intestinal parasites infecting North Americans but there is a paucity of active population-based surveillance data from Canada. This study determined the incidence of and demographic risk factors for developing Giardia sp. and Cryptosporidium sp. infections in a general Canadian population. METHODS: Population-based laboratory surveillance was conducted among all residents of the Calgary Health Region (CHR; population ≅ 1 million) during May 1, 1999 and April 30, 2002. RESULTS: Giardia sp. infection occurred at a rate of 19.6 per 100,000 populations per year. Although the yearly incidence was stable, a significant seasonal variation was observed with a peak in late summer to early fall. Males were at higher risk for development of this infection as compared to females (21.2 vs. 17.9 per 100,000/yr; relative risk (RR) 1.19; 95% confidence interval (CI), 1.00–1.40, p = 0.047), and there was a significant decrease in risk associated with an increasing age. Cryptosporidium sp. infection occurred at an overall rate of 6.0 per 100,000 populations per year although a large outbreak of Cryptosporidium sp. infections occurred in the second half of the summer of 2001. During August and September of 2001, the incidence of cryptosporidiosis was 55.1 per 100,000 per year as compared to 3.1 per 100,000 per year for the remainder of the surveillance period (p < 0.0001). Cryptosporidiosis was largely a disease of children with an incidence of 17.8 per 100,000 per year occurring among those aged < 20 years of age compared to 1.25 per 100,000 per year for adults ≥ 20 years of age (RR 14.19; 95% CI, 9.77–21.11; p < 0.0001). CONCLUSION: This study provides important information on the occurrence and demographic risk groups for acquisition of giardiasis and cryptosporidiosis in a non-selected Canadian population

Potential climatic transitions with profound impact on Europe

We discuss potential transitions of six climatic subsystems with large-scale impact on Europe, sometimes denoted as tipping elements. These are the ice sheets on Greenland and West Antarctica, the Atlantic thermohaline circulation, Arctic sea ice, Alpine glaciers and northern hemisphere stratospheric ozone. Each system is represented by co-authors actively publishing in the corresponding field. For each subsystem we summarize the mechanism of a potential transition in a warmer climate along with its impact on Europe and assess the likelihood for such a transition based on published scientific literature. As a summary, the ‘tipping’ potential for each system is provided as a function of global mean temperature increase which required some subjective interpretation of scientific facts by the authors and should be considered as a snapshot of our current understanding. <br/

Hypoxia and oxidative stress in breast cancer: Oxidative stress: its effects on the growth, metastatic potential and response to therapy of breast cancer

Reactive oxygen species (ROS) damage DNA, but the role of ROS in breast carcinoma may not be limited to the mutagenic activity that drives carcinoma initiation and progression. Carcinoma cells in vitro and in vivo are frequently under persistent oxidative stress. In the present review, we outline potential causes of oxygen radical generation within carcinoma cells and explore the possible impact of oxidative stress on the clinical outcome of breast carcinoma

Evaluation of Methods for De Novo Genome Assembly from High-Throughput Sequencing Reads Reveals Dependencies That Affect the Quality of the Results

Recent developments in high-throughput sequencing technology have made low-cost sequencing an attractive approach for many genome analysis tasks. Increasing read lengths, improving quality and the production of increasingly larger numbers of usable sequences per instrument-run continue to make whole-genome assembly an appealing target application. In this paper we evaluate the feasibility of de novo genome assembly from short reads (≤100 nucleotides) through a detailed study involving genomic sequences of various lengths and origin, in conjunction with several of the currently popular assembly programs. Our extensive analysis demonstrates that, in addition to sequencing coverage, attributes such as the architecture of the target genome, the identity of the used assembly program, the average read length and the observed sequencing error rates are powerful variables that affect the best achievable assembly of the target sequence in terms of size and correctness

Limits to scale invariance in alluvial rivers

Assumptions about fluvial processes and process–form relations are made in general models and in many site‐specific applications. Many standard assumptions about reach‐scale flow resistance, bed‐material entrainment thresholds and transport rates, and downstream hydraulic geometry involve one or other of two types of scale invariance: a parameter (e.g. critical Shields number) has the same value in all rivers, or doubling one variable causes a fixed proportional change in another variable in all circumstances (e.g. power‐law hydraulic geometry). However, rivers vary greatly in size, gradient, and bed material, and many geomorphologists regard particular types of river as distinctive. This review examines the tension between universal scaling assumptions and perceived distinctions between different types of river. It identifies limits to scale invariance and departures from simple scaling, and illustrates them using large data sets spanning a wide range of conditions. Scaling considerations and data analysis support the commonly made distinction between coarse‐bed and fine‐bed reaches, whose different transport regimes can be traced to the different settling‐velocity scalings for coarse and fine grains. They also help identify two end‐member sub‐types: steep shallow coarse‐bed ‘torrents’ with distinctive flow‐resistance scaling and increased entrainment threshold, and very large, low‐gradient ‘mega rivers’ with predominantly suspended load, subdued secondary circulation, and extensive backwater conditions

IL-4 Amplifies the Pro-Inflammatory Effect of Adenosine in Human Mast Cells by Changing Expression Levels of Adenosine Receptors

Adenosine inhalation produces immediate bronchoconstriction in asthmatics but not in normal subjects. The bronchospastic effect of adenosine is largely mediated through adenosine-induced mast cell activation, the mechanism of which is poorly understood due to limitations in culturing human primary mast cells. Here, we show that human umbilical cord blood -derived mast cells incubated with the Th2 cytokine IL-4 develop increased sensitivity to adenosine. Potentiation of anti-IgE- induced and calcium ionophore/PMA-induced degranulation was augmented in mast cells cultured with IL-4, and this effect was reduced or abolished by pre-treatment with A2BsiRNA and selective A2B receptor antagonists, respectively. IL-4 incubation resulted in the increased expression of A2B and reduced expression of A2A adenosine receptors on human mast cells. These results suggest that Th2 cytokines in the asthmatic lung may alter adenosine receptor expression on airway mast cells to promote increased responsiveness to adenosine

Carbonic anhydrase IX in oligodendroglial brain tumors

Background Carbonic anhydrase IX is a hypoxia-induced enzyme that has many biologically important functions, including its role in cell adhesion and invasion. Methods This study was set out to investigate the role of CA IX in a series of 86 oligodendroglial brain tumors (71 primary and 15 recurrent; 48 pure oligodendrogliomas and 40 mixed oligoastrocytomas). Results 80% of the tumors showed CA IX expression by immunohistochemistry. Tumors with moderate or strong CA IX expression had decreased level of cell proliferation compared to weak or no CA IX expression (median 2.9 vs. 5.8, p = 0.015). CA IX correlated with two antioxidative enzymes, manganese superoxide dismutase (MnSOD) and regulatory gammaglutamylcysteine synthetase (GLCL-R): CA IX expression was significantly higher in MnSOD-positive tumors (p = 0.008) and decreased in GLCL-R-positive tumors (p = 0.044). In Cox multivariate analysis CA IX expression, patient age and histological component (pure oligodendroglioma vs. mixed oligoastrocytoma) showed independent prognostic values (p = 0.009, p = 0.003 and p = 0.022, respectively), CA IX positivity predicting poorer outcome. Conclusion CA IX was proved to be an independent prognostic indicator in oligodendroglial brain tumors, and it also correlates reversely with cell proliferation. It may have a role in the biology of oligodendrogliomas, and most interestingly, as it is mainly expressed in tumor tissue, CA IX could serve as a target molecule for anticancer treatments.BioMed Central Open acces

NLRP3 Inflammasome: Key Mediator of Neuroinflammation in Murine Japanese Encephalitis

Background: Japanese Encephalitis virus (JEV) is a common cause of acute and epidemic viral encephalitis. JEV infection is associated with microglial activation resulting in the production of pro-inflammatory cytokines including Interleukin-1 b (IL-1b) and Interleukin-18 (IL-18). The Pattern Recognition Receptors (PRRs) and the underlying mechanism by which microglia identify the viral particle leading to the production of these cytokines is unknown. Methodology/Principal Findings: For our studies, we have used murine model of JEV infection as well as BV-2 mouse microglia cell line. In this study, we have identified a signalling pathway which leads to the activation of caspase-1 as the key enzyme responsible for the maturation of both IL-1b and IL-18 in NACHT, LRR and PYD domains-containing protein-3 (NLRP3) dependent manner. Depletion of NLRP3 results in the reduction of caspase-1 activity and subsequent production of these cytokines. Conclusion/Significance: Our results identify a mechanism mediated by Reactive Oxygen Species (ROS) production and potassium efflux as the two danger signals that link JEV infection to caspase-1 activation resulting in subsequent IL-1b an