179 research outputs found

    Sequencing and Genetic Variation of Multidrug Resistance Plasmids in Klebsiella pneumoniae

    Get PDF
    BACKGROUND: The development of multidrug resistance is a major problem in the treatment of pathogenic microorganisms by distinct antimicrobial agents. Characterizing the genetic variation among plasmids from different bacterial species or strains is a key step towards understanding the mechanism of virulence and their evolution. RESULTS: We applied a deep sequencing approach to 206 clinical strains of Klebsiella pneumoniae collected from 2002 to 2008 to understand the genetic variation of multidrug resistance plasmids, and to reveal the dynamic change of drug resistance over time. First, we sequenced three plasmids (70 Kb, 94 Kb, and 147 Kb) from a clonal strain of K. pneumoniae using Sanger sequencing. Using the Illumina sequencing technology, we obtained more than 17 million of short reads from two pooled plasmid samples. We mapped these short reads to the three reference plasmid sequences, and identified a large number of single nucleotide polymorphisms (SNPs) in these pooled plasmids. Many of these SNPs are present in drug-resistance genes. We also found that a significant fraction of short reads could not be mapped to the reference sequences, indicating a high degree of genetic variation among the collection of K. pneumoniae isolates. Moreover, we identified that plasmid conjugative transfer genes and antibiotic resistance genes are more likely to suffer from positive selection, as indicated by the elevated rates of nonsynonymous substitution. CONCLUSION: These data represent the first large-scale study of genetic variation in multidrug resistance plasmids and provide insight into the mechanisms of plasmid diversification and the genetic basis of antibiotic resistance

    Mesoporous nitrogen-doped TiO2 sphere applied for quasi-solid-state dye-sensitized solar cell

    Get PDF
    A mesoscopic nitrogen-doped TiO2 sphere has been developed for a quasi-solid-state dye-sensitized solar cell [DSSC]. Compared with the undoped TiO2 sphere, the quasi-solid-state DSSC based on the nitrogen-doped TiO2 sphere shows more excellent photovoltaic performance. The photoelectrochemistry of electrodes based on nitrogen-doped and undoped TiO2 spheres was characterized with Mott-Schottky analysis, intensity modulated photocurrent spectroscopy, and electrochemical impedance spectroscopy, which indicated that both the quasi-Fermi level and the charge transport of the photoelectrode were improved after being doped with nitrogen. As a result, a photoelectric conversion efficiency of 6.01% was obtained for the quasi-solid-state DSSC

    The Protection of Midazolam Against Immune Mediated Liver Injury Induced by Lipopolysaccharide and Galactosamine in Mice

    Get PDF
    Objectives: Liver macrophages agitated by Lipopolysaccharide (LPS) can enhance immuno-inflammatory responses in the liver which mediate liver injury and result in dysfunction. Midazolam has been reported to have inhibitory effects on activated immunity and escalated inflammation, however, what the effects of midazolam on the liver injury caused by excessive immuno-inflammatory response in sepsis, and what influence it will exert on inflamed liver macrophages need to be elucidated.Methods: In the present study, LPS and galactosamine-induced acute liver injury mice were used to observe the effect of midazolam in vivo. LPS-stimulated bone marrow cells were used to evaluate the influence of midazolam on monocytes in vitro.Results: Midazolam prevented liver tissue injury and decreased serum alanine transaminase (ALT) level in LPS plus galactosamine treated mice. Mechanistically, midazolam suppressed tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) produced by LPS stimulated liver macrophages in vivo and bone marrow monocytes in vitro, and reduced the expression of major histocompatibility complex class II (MHC II), cluster of differentiation 40 and 86 (CD40 and CD86) on the cell surface. These results could be reversed by PK-11195, a peripheral benzodiazepine receptor (PBR) blocker.Conclusion: Midazolam can prevent liver from LPS-induced immune mediated liver injury by inhibiting inflammation and immune activation in liver macrophages

    Impacts of Hypoxia-Inducible Factor-1 Knockout in the Retinal Pigment Epithelium on Choroidal Neovascularization

    Get PDF
    PURPOSE. Hypoxia-inducible factor (HIF)-1 is a key oxygen sensor and is believed to play an important role in neovascularization (NV). The purpose of this study is to determine the role of retinal pigment epithelium (RPE)-derived HIF-1a on ocular NV. METHODS. Conditional HIF-1a knockout (KO) mice were generated by crossing transgenic mice expressing Cre in the RPE with HIF-1a floxed mice, confirmed by immunohistochemistry, Western blot analysis, and fundus fluorescein angiography. The mice were used for the oxygen-induced retinopathy (OIR) and laser-induced choroidal neovascularization (CNV) models. RESULTS. HIF-1a levels were significantly decreased in the RPE layer of ocular sections and in primary RPE cells from the HIF1a KO mice. Under normal conditions, the HIF-1a KO mice exhibited no apparent abnormalities in retinal histology or visual function as shown by light microscopy and electroretinogram recording, respectively. The HIF-1a KO mice with OIR showed no significant difference from the wild-type (WT) mice in retinal levels of HIF-1a and VEGF as well as in the number of preretinal neovascular cells. In the laser-induced CNV model, however, the disruption of HIF-1a in the RPE attenuated the over expression of VEGF and the intercellular adhesion molecule 1 (ICAM-1), and reduced vascular leakage and CNV area. CONCLUSIONS. RPE-derived HIF-1a plays a key role in CNV, but not in ischemia-induced retinal NV. (Invest Ophthalmol Vis Sci

    The role of RhoA/Rho kinase pathway in endothelial dysfunction

    Get PDF
    Endothelial dysfunction is a key event in the development of vascular disease, and it precedes clinically obvious vascular pathology. Abnormal activation of the RhoA/Rho kinase (ROCK) pathway has been found to elevate vascular tone through unbalancing the production of vasodilating and vasoconstricting substances. Inhibition of the RhoA/ROCK pathway can prevent endothelial dysfunction in a variety of pathological conditions. This review, based on recent molecular, cellular, and animal studies, focuses on the current understanding of the ROCK pathway and its roles in endothelial dysfunction

    Cassava genome from a wild ancestor to cultivated varieties

    Get PDF
    Cassava is a major tropical food crop in the Euphorbiaceae family that has high carbohydrate production potential and adaptability to diverse environments. Here we present the draft genome sequences of a wild ancestor and a domesticated variety of cassava and comparative analyses with a partial inbred line. We identify 1,584 and 1,678 gene models specific to the wild and domesticated varieties, respectively, and discover high heterozygosity and millions of single-nucleotide variations. Our analyses reveal that genes involved in photosynthesis, starch accumulation and abiotic stresses have been positively selected, whereas those involved in cell wall biosynthesis and secondary metabolism, including cyanogenic glucoside formation, have been negatively selected in the cultivated varieties, reflecting the result of natural selection and domestication. Differences in microRNA genes and retrotransposon regulation could partly explain an increased carbon flux towards starch accumulation and reduced cyanogenic glucoside accumulation in domesticated cassava. These results may contribute to genetic improvement of cassava through better understanding of its biology

    TOR kinase complexes and cell migration

    Get PDF
    Cell migration is a fundamental process in a wide array of biological and pathological responses. It is regulated by complex signal transduction pathways in response to external cues that couple to growth factor and chemokine receptors. In recent years, the target of rapamycin (TOR) kinase, as part of either TOR complex 1 (TORC1) or TOR complex 2 (TORC2), has been shown to be an important signaling component linking external signals to the cytoskeletal machinery in a variety of cell types and organisms. Thus, these complexes have emerged as key regulators of cell migration and chemotaxis
    • …
    corecore