Photolysis of chlorantraniliprole and cyantraniliprole in water and soil: verification of degradation pathways via kinetics modeling.

Photodegradation of [(14)C]-chlorantraniliprole (CLAP) and [(14)C]-cyantraniliprole (CNAP) was investigated in sterile buffer solutions, in natural water, and on soil surfaces. Both compounds displayed rapid degradation in aqueous buffers when exposed to light at concentrations which could result from direct overspray to a shallow water body. While the main products observed had analogous structures, a substantial difference was noted in the rate of degradation of the two compounds despite minimal differences in their structures. Transformations observed were primarily intramolecular rearrangements and degradations resulting from addition of hydroxyl radicals leading to molecular cleavage. Some of the degradation products were transient, and several degradates had isomeric molecular compositions. The sequence of transformations was established definitively with the help of kinetics modeling. Utility of kinetics analysis in verification of the proposed pathways is illustrated.

Assessment of the environmental fate and effects of the PPARgamma receptor agonist, pioglitazone.

The environmental fate and effects of pioglitazone prescribed for the treatment of type 2 diabetes were evaluated in an environmental risk assessment following the European Medicines Agency (EMA) "Guideline on the Environmental Risk Assessment of Medicinal Products for Human Use"; EMEA/CHMP/SWP/4447/00. A predicted environment concentration (PEC) for surface water was estimated at 0.023µgL(-1), (action limit of 0.01µgL(-1)) triggering a comprehensive battery of laboratory evaluations. Pioglitazone and its major metabolites were determined not to significantly adsorb to sewage solids, were not persistent in the aquatic environment, did not bioaccumulate and were non-toxic to aquatic organisms. Pioglitazone does not pose an unacceptable risk to groundwater supplies, with concentrations not anticipated to be a risk to aquatic organisms or human drinking water supplies. Pioglitazone does not pose a risk of secondary poisoning.

Resolution of joint molecules by RuvABC and RecG following cleavage of the Escherichia coli chromosome by EcoKI.

DNA double-strand breaks can be repaired by homologous recombination involving the formation and resolution of Holliday junctions. In Escherichia coli, the RuvABC resolvasome and the RecG branch-migration enzyme have been proposed to act in alternative pathways for the resolution of Holliday junctions. Here, we have studied the requirements for RuvABC and RecG in DNA double-strand break repair after cleavage of the E. coli chromosome by the EcoKI restriction enzyme. We show an asymmetry in the ability of RuvABC and RecG to deal with joint molecules in vivo. We detect linear DNA products compatible with the cleavage-ligation of Holliday junctions by the RuvABC pathway but not by the RecG pathway. Nevertheless we show that the XerCD-mediated pathway of chromosome dimer resolution is required for survival regardless of whether the RuvABC or the RecG pathway is active, suggesting that crossing-over is a common outcome irrespective of the pathway utilised. This poses a problem. How can cells resolve joint molecules, such as Holliday junctions, to generate crossover products without cleavage-ligation? We suggest that the mechanism of bacterial DNA replication provides an answer to this question and that RecG can facilitate replication through Holliday junctions.

SbcCD regulation and localization in Escherichia coli.

The SbcCD complex and its homologues play important roles in DNA repair and in the maintenance of genome stability. In Escherichia coli, the in vitro functions of SbcCD have been well characterized, but its exact cellular role remains elusive. This work investigates the regulation of the sbcDC operon and the cellular localization of the SbcC and SbcD proteins. Transcription of the sbcDC operon is shown to be dependent on starvation and RpoS protein. Overexpressed SbcC protein forms foci that colocalize with the replication factory, while overexpressed SbcD protein is distributed through the cytoplasm.