4 research outputs found

    Sediment Composition Influences Spatial Variation in the Abundance of Human Pathogen Indicator Bacteria within an Estuarine Environment

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    <div><p>Faecal contamination of estuarine and coastal waters can pose a risk to human health, particularly in areas used for shellfish production or recreation. Routine microbiological water quality testing highlights areas of faecal indicator bacteria (FIB) contamination within the water column, but fails to consider the abundance of FIB in sediments, which under certain hydrodynamic conditions can become resuspended. Sediments can enhance the survival of FIB in estuarine environments, but the influence of sediment composition on the ecology and abundance of FIB is poorly understood. To determine the relationship between sediment composition (grain size and organic matter) and the abundance of pathogen indicator bacteria (PIB), sediments were collected from four transverse transects of the Conwy estuary, UK. The abundance of culturable <i>Escherichia coli</i>, total coliforms, enterococci, <i>Campylobacter</i>, <i>Salmonella</i> and <i>Vibrio</i> spp. in sediments was determined in relation to sediment grain size, organic matter content, salinity, depth and temperature. Sediments that contained higher proportions of silt and/or clay and associated organic matter content showed significant positive correlations with the abundance of PIB. Furthermore, the abundance of each bacterial group was positively correlated with the presence of all other groups enumerated. <i>Campylobacter</i> spp. were not isolated from estuarine sediments. Comparisons of the number of culturable <i>E. coli</i>, total coliforms and <i>Vibrio</i> spp. in sediments and the water column revealed that their abundance was 281, 433 and 58-fold greater in sediments (colony forming units (CFU)/100<b> </b>g) when compared with the water column (CFU/100<b> </b>ml), respectively. These data provide important insights into sediment compositions that promote the abundance of PIB in estuarine environments, with important implications for the modelling and prediction of public health risk based on sediment resuspension and transport.</p></div

    Optimization of Non-ATP Competitive CDK/Cyclin Groove Inhibitors through REPLACE-Mediated Fragment Assembly

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    A major challenge in drug discovery is to develop and improve methods for targeting protein–protein interactions. Further exemplification of the REPLACE (REplacement with Partial Ligand Alternatives through Computational Enrichment) strategy for generating inhibitors of protein–protein interactions demonstrated that it can be used to optimize fragment alternatives of key determinants, to combine these in an effective way, and this was achieved for compounds targeting the cyclin-dependent kinase 2 (CDK2) substrate recruitment site on the cyclin regulatory subunit. Phenylheterocyclic isosteres replacing a critical charge–charge interaction provided new structural insights for binding to the cyclin groove. In particular, these results shed light onto the key contributions of a H-bond observed in crystal structures of N-terminally capped peptides. Furthermore, the structure–activity relationship of a bis­(aryl) ether C-terminal capping group mimicking dipeptide interactions was probed through ring substitutions, allowing increased complementarity with the primary hydrophobic pocket. This study further validates REPLACE as an effective strategy for converting peptidic compounds to more pharmaceutically relevant compounds

    Bacterial abundance (CFU/100 g wet weight) compared to sediment grain size, organic matter content in sediments and bacterial abundance in the water column (CFU/100 ml), across four transverse transects.

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    <p>(A) Transect 1, (B) Transect 2, (C) Transect 3, (D) Transect 4. The X-axis represents sample points (n = 3 replicate samples for A, B, C and D except for sediment samples site 13, n = 2), mean values are plotted and error bars represent the SEM).</p
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