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Saber, A.

Publications and source records attributed to Saber, A..

2 recordsLinked to original sources

Complex trait responses to complex environments: how do larval amphibians navigate co-occurring ecological demands that influence the same traits?

O_LIMany organisms alter phenotypically plastic traits in response to environmental cues to match their phenotypes with variable environments. In larval amphibians, development and growth rates respond to spatiotemporally variable mortality risk from predation, wetland drying, or resource limitation. However, these rates are also temperature-dependent for ectotherms. Although wild animals experience these factors simultaneously (e.g., thermal regimes, predation risk, resource limitation), most studies investigate their impacts in isolation, limiting our understanding of how they interact across ecological contexts. C_LIO_LIHere we simultaneously exposed larval Plains Leopard Frogs (Lithobates blairi) to varying resource levels and predation risk treatments across a thermal regime to investigate the joint effects of these ecological drivers on growth and development rates and their consequences for size and vagility after metamorphosis. We crossed two predation treatments (waterborne cues from Procambarus gracilis fed L. blairi larvae, control water) with three food resource levels (5%, 25%, 50% of body mass) and six thermal regimes (diel {+/-} 3{degrees}C cycles of 15, 20, 22, 24, 26, 28{degrees}C), replicating each combination five times for a total of 180 individuals. We recorded growth and development rates and completion of metamorphosis, then measured juvenile body size and jumping performance. C_LIO_LIThe number of larvae completing metamorphosis was primarily determined by temperature and temperature-dependent effects of resource limitation. Percent metamorphosis peaked at intermediate temperatures when resources were high and were higher in predation-risk treatments at the warmest temperatures. Under high resources, development and growth rates showed unimodal thermal responses that were absent when resources were constrained. Higher resources increased development rates, but proportional increases in growth maintained constant body size across temperatures. Post-metamorphic body size differed only by predation treatment, with predator-exposed individuals being smaller. Juvenile jumping performance increased with body size and individuals raised with high resources without predator cues exhibited the highest performance. C_LIO_LIThe absence of temperature effects on size at metamorphosis reflected unexpected coupling of growth and development rates across treatments, producing uniform body sizes. This pattern contrasts with the temperature-size rule and suggests that plastic responses may exhibit selection for a minimum viable size at metamorphosis. C_LI

ecology↗

Transcriptional activation of cyclin D1 via HER2/HER3 contributes to cell survival and EGFR tyrosine kinase inhibitor resistance in non-small cell lung carcinoma

Several different mechanisms are implicated in the resistance of lung cancer cells to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), and only few have been functionally investigated. Here, using genetically knocked out EGFR and TKI-resistant lung cancer cells, we show that loss of wild-type EGFR attenuates cell proliferation, migration and 3D-spherid formation, whereas loss of mutant EGFR or resistance to TKIs reinforces those processes. Consistently, disruption of wild-type EGFR leads to suppression of HER2/HER3, while mutant EGFR ablation or resistance to TKIs increases HER2/HER3 expression, compensating for EGFR loss. Furthermore, HER2/HER3 nuclear translocation mediates overexpression of cyclin D1, leading to tumor cell survival and drug resistance. Cyclin D1/CDK4/6 inhibition resensitizes erlotinib-resistant (ER) cells to erlotinib. Analysis of cyclin D1 expression in patients with non-small cell lung carcinoma (NSCLC) showed that its expression is negatively associated with overall survival and disease-free survival. Our results provide biological and mechanistic insights into targeting EGFR and TKI resistance.

cancer biology↗