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Trends in streamflow, rainfall and potential evapotranspiration (PET) time series, from 1970 to 2017, were assessed for five important hydrological basins in Southeastern Brazil. The concept of elasticity was also used to assess the streamflow sensitivity to changes in climate variables, for annual data and 5-, 10- and 20-year moving averages. Significant negative trends in streamflow and rainfall and significant increasing trend in PET were detected. For annual analysis, elasticity revealed that 1% decrease in rainfall resulted in 1.21-2.19% decrease in streamflow, while 1% increase in PET induced different reductions percentages in streamflow, ranging from 2.45% to 9.67%. When both PET and rainfall were computed to calculate the elasticity, results were positive for some basins. Elasticity analysis considering 20-year moving averages revealed that impacts on the streamflow were cumulative: 1% decrease in rainfall resulted in 1.83-4.75% decrease in streamflow, while 1% increase in PET induced 3.47-28.3% decrease in streamflow. This different temporal response may be associated with the hydrological memory of the basins. Streamflow appears to be more sensitive in less rainy basins. This study provides useful information to support strategic government decisions, especially when the security of water resources and drought mitigation are considered in face of climate change.
The mechanism of action of eprenetapopt (APR-246, PRIMA-1MET) as an anticancer agent remains unresolved, al-though the clinical development of eprenetapopt focuses on its reported mechanism of action as a mutant-p53 reactivator. Using unbiased approaches, this study demonstrates that eprenetapopt depletes cellular antioxidant glutathione levels by increasing its turnover, triggering a nonapoptotic, iron-dependent form of cell death known as ferroptosis. Deficiency in genes responsible for supplying cancer cells with the substrates for de novo glutathione synthesis (SLC7A11, SHMT2, and MTHFD1L), as well as the enzymes required to synthesize glutathione (GCLC and GCLM), augments the activity of eprenetapopt. Eprenetapopt also inhibits iron-sulfur cluster biogenesis by limit-ing the cysteine desulfurase activity of NFS1, which potentiates ferroptosis and may restrict cellular proliferation. The combination of eprenetapopt with dietary serine and glycine restriction synergizes to inhibit esophageal xenograft tumor growth. These findings reframe the canonical view of eprenetapopt from a mutant-p53 reactivator to a ferroptosis inducer.