BarA-UvrY Two-Component System Regulates Virulence of Uropathogenic E. coli CFT073

Uropathogenic Escherichia coli (UPEC), a member of extraintestinal pathogenic E. coli, cause ∼80% of community-acquired urinary tract infections (UTI) in humans. UPEC initiates its colonization in epithelial cells lining the urinary tract with a complicated life cycle, replicating and persisting in intracellular and extracellular niches. Consequently, UPEC causes cystitis and more severe form of pyelonephritis. To further understand the virulence characteristics of UPEC, we investigated the roles of BarA-UvrY two-component system (TCS) in regulating UPEC virulence. Our results showed that mutation of BarA-UvrY TCS significantly decreased the virulence of UPEC CFT073, as assessed by mouse urinary tract infection, chicken embryo killing assay, and cytotoxicity assay on human kidney and uroepithelial cell lines. Furthermore, mutation of either barA or uvrY gene reduced the production of hemolysin, lipopolysaccharide (LPS), proinflammatory cytokines (TNF-α and IL-6) and chemokine (IL-8). The virulence phenotype was restored similar to that of wild-type by complementation of either barA or uvrY gene in trans. In addition, we discussed a possible link between the BarA-UvrY TCS and CsrA in positively and negatively controlling virulence in UPEC. Overall, this study provides the evidences for BarA-UvrY TCS regulates the virulence of UPEC CFT073 and may point to mechanisms by which virulence regulations are observed in different ways may control the long-term survival of UPEC in the urinary tract

Optimising construction with self-compacting concrete

Winner of the 2018 ICE Publishing Awards (Thomas Howard Medal) for the best paper of the year in the Construction Materials journal. Permission is granted by ICE Publishing to print one copy for personal use. Any other use of these PDF files is subject to reprint fees.Self-compacting concrete or self-consolidating concrete (as it is known in North America) (SCC) is used on the basis of its unique properties of flowability, passability and resistance to segregation. It requires no external energy to achieve full compaction, so is advantageous on site, but there is evidence that its higher cost is a significant barrier to greater adoption. The research entailed work measurement of 14 UK single-family home residential projects (eliciting data on construction time and labour productivity) and cost modelling of three slab scenarios (exploring the relationship between material and labour costs). The study found SCC was placed up to 73% faster than conventional concrete and, when labour and material costs are included, the supplier is able to price SCC to closely match conventional concrete, hence making SCC more viable for the contractor. This relationship between as-built costs for SCC and conventional concrete is clarified by developing Pmax, providing a new mechanism for understanding project profitability and viability of SCC

<i>rahu</i> is a mutant allele of <i>Dnmt3c</i>, encoding a DNA methyltransferase homolog required for meiosis and transposon repression in the mouse male germline

<div><p>Transcriptional silencing by heritable cytosine-5 methylation is an ancient strategy to repress transposable elements. It was previously thought that mammals possess four DNA methyltransferase paralogs—<i>Dnmt1</i>, <i>Dnmt3a</i>, <i>Dnmt3b</i> and <i>Dnmt3l</i>—that establish and maintain cytosine-5 methylation. Here we identify a fifth paralog, <i>Dnmt3c</i>, that is essential for retrotransposon methylation and repression in the mouse male germline. From a phenotype-based forward genetics screen, we isolated a mutant mouse called ‘<i>rahu</i>’, which displays severe defects in double-strand-break repair and homologous chromosome synapsis during male meiosis, resulting in sterility. <i>rahu</i> is an allele of a transcription unit (<i>Gm14490</i>, renamed <i>Dnmt3c</i>) that was previously mis-annotated as a <i>Dnmt3-</i>family pseudogene. <i>Dnmt3c</i> encodes a cytosine methyltransferase homolog, and <i>Dnmt3c</i>^<i>rahu</i> mutants harbor a non-synonymous mutation of a conserved residue within one of its cytosine methyltransferase motifs, similar to a mutation in human DNMT3B observed in patients with immunodeficiency, centromeric instability and facial anomalies syndrome. The <i>rahu</i> mutation lies at a potential dimerization interface and near the potential DNA binding interface, suggesting that it compromises protein-protein and/or protein-DNA interactions required for normal DNMT3C function. <i>Dnmt3c</i>^<i>rahu</i> mutant males fail to establish normal methylation within LINE and LTR retrotransposon sequences in the germline and accumulate higher levels of transposon-derived transcripts and proteins, particularly from distinct L1 and ERVK retrotransposon families. Phylogenetic analysis indicates that <i>Dnmt3c</i> arose during rodent evolution by tandem duplication of <i>Dnmt3b</i>, after the divergence of the Dipodoidea and Muroidea superfamilies. These findings provide insight into the evolutionary dynamics and functional specialization of the transposon suppression machinery critical for mammalian sexual reproduction and epigenetic regulation.</p></div