10 research outputs found

    Thymine starvation causes abortive initiation of chromosome replication critical for cell death in Escherichia coli

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    Presentado en: XXXVI Congreso SEBBM (Sociedad Española de Bioquímica y Biología Molecular), Madrid, 4-6 septiembre, 2013Thymineless death (TLD), a phenomenon in which thymine auxotrophy becomes lethal when cells are starved for thymine, can be prevented by rifampicin addition. In this work, we have obtained evidence indicating that among the effects of RNA polymerase inhibition by rifampicin, the inhibition of chromosomal replication initiation is the process responsible for TLD suppression. We show that diminishing, abolishing or increasing the transcription level around oriC alleviates TLD by limiting the chromosomal initiation capacity (ChIC) generated under thymine starvation. TLD suppression was eliminated by DnaA inactivation or the deletion in the left half of the replication origin or deletion of the DnaA-boxes located in the right half of the oriC region. In accordance with these data, two-dimensional DNA electrophoresis gels showed an accumulation of simple-Y and bubble arc replication intermediates, as well as recombination structures at the oriC region during thymine starvation. None of these structures were observed under genetic or physiological conditions that suppress TLD. These results demonstrate that abortive initiations of chromosome replication occur under thymine starvation, supporting the idea that these events are a critical target for the lethal damage caused by thymine starvation and that results in TLD.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tec

    Long-Term Burden and Respiratory Effects of Respiratory Syncytial Virus Hospitalization in Preterm Infants—The SPRING Study

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    <div><p>The health status of premature infants born 32<sup>1</sup>-35<sup>0</sup> weeks’ gestational age (wGA) hospitalized for RSV infection in the first year of life (cases; n = 125) was compared to that of premature infants not hospitalized for RSV (controls; n = 362) through 6 years. The primary endpoints were the percentage of children with wheezing between 2-6 years and lung function at 6 years of age. Secondary endpoints included quality of life, healthcare resource use, and allergic sensitization. A significantly higher proportion of cases than controls experienced recurrent wheezing through 6 years of age (46.7% vs. 27.4%; p = 0.001). The vast majority of lung function tests appeared normal at 6 years of age in both cohorts. In children with pulmonary function in the lower limit of normality (FEV<sub>1</sub> Z-score [-2; -1]), wheezing was increased, particularly for cases vs. controls (72.7% vs. 18.9%, p = 0.002). Multivariate analysis revealed the most important factor for wheezing was RSV hospitalization. Quality of life on the respiratory subscale of the TAPQOL was significantly lower (p = 0.001) and healthcare resource utilization was significantly higher (p<0.001) in cases than controls. This study confirms RSV disease is associated with wheezing in 32-35 wGA infants through 6 years of age.</p></div

    Respiratory scores for TAPQOL questionnaire through 6 years of age.

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    <p>†Scores range from 0–100, where higher scores indicate better quality of life for patients. Mann-Whitney <i>U</i> test. SD: standard deviation, NS: not significant. Patient numbers at years 2 and 3 reflect patients entering the study at different ages. For each patient, the mean score was calculated across the years they completed the questionnaire (e.g. if TAPQOL completed from 2 to 6 years, mean was calculated over 5 years).</p

    Wheezing through 6 years of age<sup>a</sup>.

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    <p>Wheezing through 6 years of age<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0125422#t002fn002" target="_blank"><sup>a</sup></a>.</p

    Logistic regression analysis<sup>*</sup> of risk factors associated with wheezing through 1–6 years.

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    <p>Logistic regression analysis<sup><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0125422#t003fn002" target="_blank">*</a></sup> of risk factors associated with wheezing through 1–6 years.</p

    Respiratory function Z-score<sup>a</sup> FEV<sub>1</sub> ranking [-2; -1] stratified by wheezing.

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    <p>Respiratory function Z-score<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0125422#t004fn002" target="_blank"><sup>a</sup></a> FEV<sub>1</sub> ranking [-2; -1] stratified by wheezing.</p

    Long-Term Burden and Respiratory Effects of Respiratory Syncytial Virus Hospitalization in Preterm Infants — The SPRING Study

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    The health status of premature infants born 32(1)-35(0) weeks' gestational age (wGA) hospitalized for RSV infection in the first year of life (cases; n = 125) was compared to that of premature infants not hospitalized for RSV (controls; n = 362) through 6 years. The primary endpoints were the percentage of children with wheezing between 2-6 years and lung function at 6 years of age. Secondary endpoints included quality of life, healthcare resource use, and allergic sensitization. A significantly higher proportion of cases than controls experienced recurrent wheezing through 6 years of age (46.7% vs. 27.4%; p = 0.001). The vast majority of lung function tests appeared normal at 6 years of age in both cohorts. In children with pulmonary function in the lower limit of normality (FEV1 Z-score [-2; -1]), wheezing was increased, particularly for cases vs. controls (72.7% vs. 18.9%, p = 0.002). Multivariate analysis revealed the most important factor for wheezing was RSV hospitalization. Quality of life on the respiratory subscale of the TAPQOL was significantly lower (p = 0.001) and healthcare resource utilization was significantly higher (p<0.001) in cases than controls. This study confirms RSV disease is associated with wheezing in 32-35 wGA infants through 6 years of age.This study was funded by AbbVie Farmaceutica S.L.U. Madrid, Spain. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
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