13 research outputs found

    Genome of Herbaspirillum seropedicae Strain SmR1, a Specialized Diazotrophic Endophyte of Tropical Grasses

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    The molecular mechanisms of plant recognition, colonization, and nutrient exchange between diazotrophic endophytes and plants are scarcely known. Herbaspirillum seropedicae is an endophytic bacterium capable of colonizing intercellular spaces of grasses such as rice and sugar cane. The genome of H. seropedicae strain SmR1 was sequenced and annotated by The Paraná State Genome Programme—GENOPAR. The genome is composed of a circular chromosome of 5,513,887 bp and contains a total of 4,804 genes. The genome sequence revealed that H. seropedicae is a highly versatile microorganism with capacity to metabolize a wide range of carbon and nitrogen sources and with possession of four distinct terminal oxidases. The genome contains a multitude of protein secretion systems, including type I, type II, type III, type V, and type VI secretion systems, and type IV pili, suggesting a high potential to interact with host plants. H. seropedicae is able to synthesize indole acetic acid as reflected by the four IAA biosynthetic pathways present. A gene coding for ACC deaminase, which may be involved in modulating the associated plant ethylene-signaling pathway, is also present. Genes for hemagglutinins/hemolysins/adhesins were found and may play a role in plant cell surface adhesion. These features may endow H. seropedicae with the ability to establish an endophytic life-style in a large number of plant species

    Transport and consumption rate of O2 in alginate gel beads entrapping hepatocytes

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    Experiments carried out with hepatocytes entrapped in alginate gel particles with a cell density of about 107 cells ml-1 showed an oxygen consumption rate of about 2.2 x 10-16 mol cell-1 s-1. Under these conditions, no inner anoxic core is present in 1.8 mm diameter beads. From these data, the maximum bead size consistent with noncritical O2 concentration at the bead center has been evaluated for different cell densities and O2 concentrations in the medium.Experiments carried out with hepatocytes entrapped in alginate gel particles with a cell density of about 107cells ml-1showed an oxygen consumption rate of about 2.2 x 10-16mol cell-1s-1. Under these conditions, no inner anoxic core is present in 1.8 mm diameter beads. From these data, the maximum bead size consistent with noncritical O2concentration at the bead center has been evaluated for different cell densities and O2concentrations in the medium

    The 3′UTR NFKBIA Variant Is Associated with Extensive Colitis in Hungarian IBD Patients

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    Purpose In previous studies the NFKBIA 3'alleles did not predict response to medical therapy or need for surgery.UTR (untranslated region) AA genotype was associated with Crohn's disease (CD), while the NFKB1-94ins/del-ATTG mutation increased the risk for ulcerative colitis (UC). The aim of our study was to investigate these two polymorphisms and patients' response to medical therapy and/or disease phenotype in Hungarian inflammatory bowel disease (IBD) patients. Methods NFKBIA 3'UTR- and NFKB1-94ins/delATTG polymorphisms were investigated in 415 unrelated IBD patients (CD: 266 patients, mean age 35.2 +/- 12.1 years, duration 8.7 +/- 7.5 years; UC patients: 149, mean age 44.4 +/- 15.4 years, duration 10.7 +/- 8.9 years) and 149 controls by PCR-restriction fragment length polymorphism (RFLP) analysis. Detailed clinical phenotypes were determined by reviewing the medical charts. Results The NFKBIA 3'UTR and NFKB1-94ins/ delATTG genotypes and allele frequencies were not significantly different among IBD and controls. In patients with UC, the 3'UTR GG genotype was associated with extensive colitis (55.3 vs. 29.4%, odds ratio 2.97, 95% confidence interval 1.45-6.08). The presence of variant alleles did not predict response to steroids, infliximab, or need for surgery. Conclusions The NFKBIA 3'UTR GG genotype was associated with an increased risk for extensive colitis in Hungarian patients. In contrast, variant alleles did not predict response to medical therapy or need for surgery

    Design of Substituted Imidazolidinylpiperidinylbenzoic Acids as Chemokine Receptor 5 Antagonists: Potent Inhibitors of R5 HIV‑1 Replication

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    The redesign of the previously reported thiophene-3-yl-methyl urea series, as a result of potential cardiotoxicity, was successfully accomplished, resulting in the identification of a novel potent series of CCR5 antagonists containing the imidazolidinylpiperidinyl scaffold. The main redesign criteria were to reduce the number of rotatable bonds and to maintain an acceptable lipophilicity to mitigate hERG inhibition. The structure–activity relationship (SAR) that was developed was used to identify compounds with the best pharmacological profile to inhibit HIV-1. As a result, five advanced compounds, <b>6d</b>, <b>6e</b>, <b>6i</b>, <b>6h</b>, and <b>6k</b>, were further evaluated for receptor selectivity, antiviral activity against CCR5 using (R5) HIV-1 clinical isolates, and in vitro and in vivo safety. On the basis of these results, <b>6d</b> and <b>6h</b> were selected for further development

    Molecular mechanisms probably involved in plant colonization and plant growth promotion identified in the <i>H. seropedicae</i> SmR1 genome.

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    <p>Plant signals can modulate the expression of bacterial genes coding for adhesins, type IV <i>pili</i> and enzymes of lipopolysaccharide (LPS) synthesis, triggering bacterial attachment to root surfaces. The molecular communication involves bacterial protein secretion and phytohormones to stimulate plant growth and modulate plant defense response. In addition, modulation of plant ethylene levels by ACC deaminase may contribute to plant growth promotion. The success of the endophytic association depends on a compatible genetic background that leads to benefits for both organisms.</p

    General features of the genome of <i>Herbaspirillum seropedicae</i> SmR1.

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    <p>General features of the genome of <i>Herbaspirillum seropedicae</i> SmR1.</p

    Proposed pathways for aromatic compounds metabolism in <i>H. seropedicae</i> SmR1.

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    <p>Proposed pathways for aromatic compounds metabolism in <i>H. seropedicae</i> SmR1.</p

    The type III secretion system gene cluster of <i>H. seropedicae</i> SmR1 and other organisms.

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    <p>Genes of the same color in different organisms are homologous. Genes colored in black have no counterpart in the genomic regions shown.</p

    The genome of <i>Herbaspirillum seropedicae</i> SmR1.

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    <p>From inside to outside 1) G+C content; 2) GC skew; 3) genes color-coded according the COG functional categories; genes in the + strand and − strand are represented in the inside and outside circles respectively; 4) rRNAS operons; 5) putative horizontally transferred regions identified using IVOM: light red indicates low score and dark red indicates high score; 6) regions of <i>H. seropedicae</i> genome identical to castor bean (<i>Ricinus communis</i>) sequences (minimum of 200 bp in length and higher than 90% in identity).</p

    Safety and efficacy of MD1003 (high-dose biotin) in patients with progressive multiple sclerosis (SPI2) : a randomised, double-blind, placebo-controlled, phase 3 trial

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