Decay rates of faecal indicator bacteria from sewage and ovine faeces in brackish and freshwater microcosms with contrasting suspended particulate matter concentrations.

To safeguard human health, legislative measures require the monitoring of faecal indicator bacteria (FIB) concentrations in recreational and shellfish waters. Consequently, numerous studies have focussed on FIB survival in the water column and more recently in estuarine sediments. However, there is a paucity of information regarding the influence of contrasting suspended particulate matter (SPM) concentrations on the survival of FIB in the water column of estuaries.

Iterative conversion of cyclin binding groove peptides into druglike CDK inhibitors with antitumor activity.

The cyclin groove is an important recognition site for substrates of the cell cycle cyclin dependent kinases and provides an opportunity for highly selective inhibition of kinase activity through a non-ATP competitive mechanism. The key peptide residues of the cyclin binding motif have been studied in order to precisely define the structure-activity relationship for CDK kinase inhibition. Through this information, new insights into the interactions of peptide CDK inhibitors with key subsites of the cyclin binding groove provide for the replacement of binding determinants with more druglike functionality through REPLACE, a strategy for the iterative conversion of peptidic blockers of protein-protein interactions into pharmaceutically relevant compounds.

Sediment composition influences spatial variation in the abundance of human pathogen indicator bacteria within an estuarine environment.

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.

The interaction of human microbial pathogens, particulate material and nutrients in estuarine environments and their impacts on recreational and shellfish waters.

Anthropogenic activities have increased the load of faecal bacteria, pathogenic viruses and nutrients in rivers, estuaries and coastal areas through point and diffuse sources such as sewage discharges and agricultural runoff. These areas are used by humans for both commercial and recreational activities and are therefore protected by a range of European Directives. If water quality declines in these zones, significant economic losses can occur.

Optimization of non-ATP competitive CDK/cyclin groove inhibitors through REPLACE-mediated fragment assembly.

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.