The ERK and JNK pathways in the regulation of metabolic reprogramming.

Most tumor cells reprogram their glucose metabolism as a result of mutations in oncogenes and tumor suppressors, leading to the constitutive activation of signaling pathways involved in cell growth. This metabolic reprogramming, known as aerobic glycolysis or the Warburg effect, allows tumor cells to sustain their fast proliferation and evade apoptosis. Interfering with oncogenic signaling pathways that regulate the Warburg effect in cancer cells has therefore become an attractive anticancer strategy. However, evidence for the occurrence of the Warburg effect in physiological processes has also been documented. As such, close consideration of which signaling pathways are beneficial targets and the effect of their inhibition on physiological processes are essential. The MAPK/ERK and MAPK/JNK pathways, crucial for normal cellular responses to extracellular stimuli, have recently emerged as key regulators of the Warburg effect during tumorigenesis and normal cellular functions. In this review, we summarize our current understanding of the roles of the ERK and JNK pathways in controlling the Warburg effect in cancer and discuss their implication in controlling this metabolic reprogramming in physiological processes and opportunities for targeting their downstream effectors for therapeutic purposes.Brunel Research Initiative & Enterprise Fund, Brunel University of London (to CB), Kay Kendall Leukemia Fund (KKL443) (to CB), 250 Great Minds Fellowship, University of Leeds (to SP), AMMF Cholangiocarcinoma Charity (to SP and PMC), and Bloodwise (17014) (to SP and CB)

Assessing surface water consumption using remotely-sensed groundwater, evapotranspiration, and precipitation

Estimates of consumptive use of surface water by agriculture are vital for assessing food security, managing water rights, and evaluating anthropogenic impacts on regional hydrology. However, reliable, current, and public data on consumptive use can be difficult to obtain, particularly in international and less developed basins. We combine remotely-sensed precipitation and satellite observations of evapotranspiration and groundwater depletion to estimate surface water consumption by irrigated agriculture in California's Central Valley for the 2004–09 water years. We validated our technique against measured consumption data determined from streamflow observations and water export data in the Central Valley. Mean satellite-derived surface water consumption was 291.0 ± 32.4 mm/year while measured surface water consumption was 308.1 ± 6.5 mm/year. The results show the potential for remotely-sensed hydrologic data to independently observe irrigated agriculture's surface water consumption in contested or unmonitored basins. Improvements in the precision and spatial resolution of satellite precipitation, evapotranspiration and gravimetric groundwater observations are needed to reduce the uncertainty in this method and to allow its use on smaller basins and at shorter time scales