Barger, C. | bioRxiv Science

bioRxiv2021

Pan-cancer imaging of TERT expression using deuterium magnetic resonance spectroscopy-based assessment of pyruvate metabolism

Telomerase reverse transcriptase (TERT) expression is indispensable for tumor immortality. Non-invasive methods of imaging TERT can, therefore, report on tumor proliferation and response to therapy. Here, we show that TERT expression is associated with elevated levels of the redox metabolite NADH in multiple cancers, including glioblastoma, oligodendroglioma, melanoma, neuroblastoma, and hepatocellular carcinoma. Mechanistically, TERT acts via the metabolic regulator FOXO1 to upregulate nicotinamide phosphoribosyl transferase, which is the key enzyme for NADH biosynthesis. Importantly, deuterium magnetic resonance spectroscopy (2H-MRS), which is a novel, clinically translatable metabolic imaging modality, can be leveraged for imaging TERT-linked NADH in preclinical tumor models in vivo. Since NADH is essential for pyruvate flux to lactate, 2H-MRS following administration of 2H-labeled pyruvate non-invasively visualizes TERT expression and reports on early response to therapy. Collectively, our study provides insights into the mechanisms of TERT-linked metabolic reprogramming and, importantly, establishes 2H-MRS as a pan-cancer strategy for imaging tumor immortality.

cancer biology↗

bioRxiv2018

Complex stopover and migratory behavior revealed using mechanistic movement models with environmentally driven dynamic parameters

AstractLong distance migration can increase lifetime fitness, but can be costly, incurring increased energetic expenses and higher mortality risks. Stopover and other en route behaviors allow animals to rest and replenish energy stores and avoid or mitigate other hazards during migration. Some animals, such as soaring birds, can subsidize the energetic costs of migration by extracting energy from flowing air. However, it is unclear how these energy sources affect or interact with behavioral processes and stopover in long-distance soaring migrants. To understand these behaviors and the effects of processes that might enhance use of flight subsidies, we developed a flexible mechanistic model to predict how flight subsidies drive migrant behavior and movement processes. The novel modelling framework incorporated time-varying parameters informed by environmental covariates to characterize a continuous range of behaviors during migration. This model framework was fit to GPS satellite telemetry data collected from a large soaring and opportunist foraging bird, the golden eagle (Aquila chrysaetos), during migration in western North America. Fitted dynamic model parameters revealed a clear circadian rhythm in eagle movement and behavior, which was directly related to thermal uplift. Behavioral budgets were complex, however, with evidence for a joint migrating/foraging behavior, resembling a slower paced fly-and-forage migration, which could facilitate efficient refueling while still ensuring migration progress. In previous work, ecological and foraging conditions are normally considered to be the key aspects of stopover location quality, but taxa that can tap energy sources from moving fluids to drive migratory locomotion, such as the golden eagle, may pace migration based on both foraging opportunities and available flight subsidies.

ecology↗