RESCALE: Review and Simulate Climate and Catchment Responses at Burrishoole

The climate of the Burrishoole catchment is projected to change significantly over the present century. Previous research of the catchment identified a scientific gap in knowledge in terms of understanding the implications of present and projected future changes in stream flow, water temperature, pH levels and DO concentrations on fish productivity in the catchment. To address this, a multidisciplinary team of scientists undertook an analysis of both present and likely future climate impacts on the catchment with a view to furthering the understanding of the inter-linkages between climate, climate change, and the freshwater ecosystem. The research findings outlined in the report provide climate change information at the catchment scale to assist catchment stakeholders in integrating climate change considerations into their decision-making processes. The report presents an in-depth assessment of the climate and environmental datasets from the catchment to establish if changes have occurred over the period of record. In order to assess the likely impacts of future changes in climate on the catchment, regional climate projections were developed and subsequently employed to simulate likely responses in stream flow and temperature, DOC and DO for the present century. The projected changes in both the climate and water-quality were then used to provide a basis for assessing impacts on fish growth and survival rates of salmonid and eel species in the catchment. The report provides a useful template for future studies, not just in the Burrishoole catchment but for other ecologically important catchments. The findings from the report are relevant to policy makers at the national scale; catchment managers at the regional scale; and, specifically, to stakeholders in the Burrishoole catchment, in developing adaptive responses to climate change.Funded under the Marine Research Sub-programme of the National Development Plan (2007-’13), as part of the Sea Change Strategy.Funder: Marine Institut

Consideration of metabolite efflux in radiolabelled choline kinetics

Hypoxia is a complex microenvironmental condition known to regulate choline kinase α (CHKA) activity and choline transport through transcription factor hypoxia-inducible factor-1α (HIF-1α) and, therefore may confound uptake of choline radiotracer [ 18F]fluoromethyl-[1,2- 2H4]-choline ([ 18 F]-D4-FCH). The aim of this study was to investigate how hypoxia affects choline radiotracer dynamics. Three underlying mechanisms by which hypoxia could potentially alter the uptake of the choline radiotracer, [ 18 F]-D4-FCH, were investigated: 18F-D4-FCH import, CHKA phosphorylation activity, and efflux of [18 F]-D4-FCH and its phosphorylated product [ 18F]-D4-FCHP. Effects of hypoxia on [18 F]-D4-FCH uptake were studied in CHKA-overexpressing cell lines of prostate cancer, PC-3, and breast cancer, MDA-MB-231 cells. Mechanisms of radiotracer efflux were assessed by cell uptake and immunofluorescence in vitro, and examined in vivo (N=24). Mathematical modelling methodology was further developed to verify efflux hypothesis using [18 F]-D4-FCH dynamic PET scans from non-small cell lung cancer (NSCLC) patients (N=17). We report a novel finding involving export of phosphorylated [18F]-D4-FCH, [18 F]-D4-FCHP, via HIF-1α-responsive efflux transporters including ABCB4 when HIF-1α level is augmented. This is supported by graphical analysis of human data with a compartmental model (M2T6k+k5) that accounts for efflux. Hypoxia/HIF-1α increases the efflux of phosphorylated radiolabelled choline species, thus supporting consideration of efflux in modelling of radiotracer dynamics