30 research outputs found

    100K Pathogen Genome Project: 306 Listeria Draft Genome Sequences for Food Safety and Public Health.

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    Listeria monocytogenes is a food-associated bacterium that is responsible for food-related illnesses worldwide. This is the initial public release of 306 L. monocytogenes genome sequences as part of the 100K Pathogen Genome Project. These isolates represent global genomic diversity in L. monocytogenes

    Salmonella typhimurium and Escherichia coli dissimilarity: closely related bacteria with distinct metabolic profiles

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    Live attenuated strains of Salmonella typhimurium have been extensively investigated as vaccines for a number of infectious diseases. However, there is still little information available concerning aspects of their metabolism. S. typhimurium and Escherichia coli show a high degree of similarity in terms of their genome contents and metabolic networks. However, this work presents experimental evidence showing that significant differences exist in their abilities to direct carbon fluxes to biomass and energy production. It is important to study the metabolism of Salmonella in order to elucidate the formation of acetate and other metabolites involved in optimizing the production of biomass, essential for the development of recombinant vaccines. The metabolism of Salmonella under aerobic conditions was assessed using continuous cultures performed at dilution rates ranging from 0.1 to 0.67 h1, with glucose as main substrate. Acetate assimilation and glucose metabolism under anaerobic conditions were also investigated using batch cultures. Chemostat cultivations showed deviation of carbon towards acetate formation, starting at dilution rates above 0.1 h1. This differed from previous findings for E. coli, where acetate accumulation was only detected at dilution rates exceeding 0.4 h1, and was due to the lower rate of acetate assimilation by S. typhimurium under aerobic conditions. Under anaerobic conditions, both microorganisms mainly produced ethanol, acetate, and formate. A genome-scale metabolic model, reconstructed for Salmonella based on an E. coli model, provided a poor description of the mixed fermentation pattern observed during Salmonella cultures, reinforcing the different patterns of carbon utilization exhibited by these closely related bacteria. This article is protected by copyright. All rights reserved.Special thanks to Amadeus Azevedo for the HPLC analyses and technical assistance. The authors acknowledge the national funding received from CNPq (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico, Brazil), the international cooperation project CAPES-FCT (Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior/Brazil-Fundacao para a Ciencia e a Tecnologia/Portugal-Process 315/11), CAPES (Atracao de Jovens Talentos-Process 064922/2014-01) and to Fundacao para a Ciencia e Tecnologia the strategic funding of UID/BIO/04469/2013 unit

    Genetic Dissection of Epidermal Growth Factor Receptor Signaling during Luteinizing Hormone-Induced Oocyte Maturation

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    Recent evidence that luteinizing hormone (LH) stimulation of ovulatory follicles causes transactivation of the epidermal growth factor receptor (EGFR) has provided insights into the mechanisms of ovulation. However, the complete array of signals that promote oocyte reentry into the meiotic cell cycle in the follicle are still incompletely understood. To elucidate the signaling downstream of EGFR involved in oocyte maturation, we have investigated the LH responses in granulosa cells with targeted ablation of EGFR. Oocyte maturation and ovulation is disrupted when EGFR expression is progressively reduced. In granulosa cells from mice with either global or granulosa cell-specific disruption of EGFR signaling, LH-induced phosphorylation of MAPK3/1, p38MAPK, and connexin-43 is impaired. Although the LH-induced decrease in cGMP is EGFR-dependent in wild type follicles, LH still induces a decrease in cGMP in Egfrdelta/f Cyp19-Cre follicles. Thus compensatory mechanisms appear activated in the mutant. Spatial propagation of the LH signal in the follicle also is dependent on the EGF network, and likely is important for the control of signaling to the oocyte. Thus, multiple signals and redundant pathways contribute to regulating oocyte reentry into the cell cycle

    Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

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    Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

    The Intersection of Person and Practice: A Bundle of Narratives, Learnings, and Offerings

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    https://scholarworks.umt.edu/grad_portfolios/1106/thumbnail.jp

    Inhibition of LH-induced connexin-43 phosphorylation by the EGFR inhibitor AG1478 and the p38MAPK inhibitor SB202190.

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    <p><b>A and B,</b> LH-induced Cx43 phosphorylation on S262 and S255 was examined by Western blot analyses using protein extracts from preovulatory follicles that were pre-incubated for 30 min with or without the EGFR tyrosine kinase inhibitor AG1478 (0.5 µM), and then stimulated for 2 h with rLH (5 IU). The ratio of phosphorylated S262 or S255 to total Cx43 was normalized to the control and expressed as fold induction. Data are the mean ± range of two separate experiments, and are shown in the immunoblots. <b>C and D,</b> Western blot analyses to detect LH-induced phosphorylation of Cx43 on S262 and S255 was performed using protein extracts from preovulatory follicles pre-incubated for 30 min with or without SB202190 (10 µM) and stimulated for 2 h with rLH (5 IU). The ratio of phosphorylated S262 or S255 to total Cx43 was normalized to the control and expressed as fold induction. Data are the mean ± SEM of three separate experiments. Representative blots are shown.</p

    Comparison of cGMP levels in wild type and <i>Egfr<sup>delta/f</sup> Cyp19-Cre</i> preovulatory follicles.

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    <p>WT and <i>Egfr<sup>delta/f</sup> Cyp19-Cre</i> preovulatory follicles were preincubated with or without AG1478 (0.5 µM) for 30 min, and then stimulated with or without rLH (5 IU/mL) for 2 h. Cyclic GMP levels were measured as described in the <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0021574#s2" target="_blank">Materials and Methods</a>. Data are shown as the mean ± SEM of three or four separate samples for each treatment group.</p
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