Historical and Operational Monitoring of Surface Sediments in the Lower Mekong Basin Using Landsat and Google Earth Engine Cloud Computing

Reservoir construction and land use change are altering sediment transport within river systems at a global scale. Changes in sediment transport can impact river morphology, aquatic ecosystems, and ultimately the growth and retreat of delta environments. The Lower Mekong Basin is crucial to five neighboring countries for transportation, energy production, sustainable water supply, and food production. In response, countries have coordinated to develop programs for regional scale water quality monitoring that including surface sediment concentrations (SSSC); however, these programs are based on a limited number of point measurements and due to resource limitations, cannot provide comprehensive insights into sediment transport across all strategic locations within the Lower Mekong Basin. To augment in situ SSSC data from the current monitoring program, we developed an empirical model to estimate SSSC across the Lower Mekong Basin from Landsat observations. Model validation revealed that remotely sensed SSSC estimates captured the spatial and temporal dynamics in a range of aquatic environments (main stem of Mekong river, tributary systems, Mekong Floodplain, and reservoirs) while, on average, slightly underestimating SSSC by about 2 mg·L−1 across all settings. The operational SSSC model was developed and implemented using Google Earth Engine and Google App Engine was used to host an online application that allows users, without any knowledge of remote sensing, to access SSSC data across the region. Expanded access to SSSC data should be particularly helpful for resource managers and other stakeholders seeking to understand the dynamics between surface sediment concentrations and land use conversions, water policy, and energy production in a globally strategic region

Translation Termination Factor GSPT1 Is a Phenotypically Relevant Off-Target of Heterobifunctional Phthalimide Degraders

Protein degradation is an emerging therapeutic strategy with a unique molecular pharmacology that enables the disruption of all functions associated with a target. This is particularly relevant for proteins depending on molecular scaffolding, such as transcription factors or receptor tyrosine kinases (RTKs). To address tractability of multiple RTKs for chemical degradation by the E3 ligase CUL4-RBX1-DDB1-CRBN (CRL4^CRBN), we synthesized a series of phthalimide degraders based on the promiscuous kinase inhibitors sunitinib and PHA665752. While both series failed to induce degradation of their consensus targets, individual molecules displayed pronounced efficacy in leukemia cell lines. Orthogonal target identification supported by molecular docking led us to identify the translation termination factor G1 to S phase transition 1 (GSPT1) as a converging off-target, resulting from inadvertent E3 ligase modulation. This research highlights the importance of monitoring degradation events that are independent of the respective targeting ligand as a unique feature of small-molecule degraders