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Biology subjects

Stewart, E. L.

Publications and source records attributed to Stewart, E. L..

2 recordsLinked to original sources

Contextual effects and the components of reward sensitivity: Sucrose consumption, discrimination and incentive contrast

Reward sensitivity (RS) has been a moving target because the majority of experimental work utilizes different measures and distinct outcomes in a variety of contexts. Moreover, studies focus on individual components of RS such as intake or reward discrimination or relative valuation. Pinpointing how consistent or variable these distinct components of RS are would be highly beneficial, so we tested identical subjects between two well-established contexts (home cage and operant chamber) using identical sucrose solutions to assess key elements of RS (e.g., intake and reward discrimination and incentive contrast). Previous work has found context invariance for specific components of RS and consistency across contexts could be highly adaptive. Interestingly, the current study found significant discrimination and contrast effects in the home environment and reduced or weaker effects in the operant testing chamber environment. Negative contrast effect was observed only in the homecage and not in the operant chamber. Surprisingly, relative to home, rats consumed significantly more sucrose in the operant box for 1% and 10% but not 30% sucrose. The results support a substantial environmental gating influence whereby context may work to induce alterations in reward value. Contextual factors such as arousal, stress or effort could influence the intensity or expression of RS. Careful consideration to context is highly warranted when generalizing reward processing functions among distinct environmental-experimental settings. Moreover, contextual factors should be recognized as interactive forces that can guide RS as a dynamic state as opposed to a static trait-like indicator of the reward process.

animal behavior and cognition↗

Recapitulating idiopathic pulmonary fibrosis related alveolar epithelial dysfunction in an iPSC-derived air-liquid interface model

An abnormal emergence of airway epithelial-like cells within the alveolar compartments of the lung, herein termed bronchiolization, is a process often observed in patients suffering from idiopathic pulmonary fibrosis (IPF), a fatal disease characterized by progressive fibrotic lung remodeling. However, the origin of this dysfunctional epithelium remains unknown.\n\nIn this study, we aimed to investigate the effects of a pro-fibrotic milieu, similar to that found in an IPF lung, on human alveolar epithelial progenitor cell differentiation. We developed an induced pluripotent stem cell (iPSC)-derived air-liquid interface (ALI) model of alveolar type II (ATII)-like cell differentiation and stimulated it with an IPF-relevant cocktail (IPF-RC), composed of cytokines previously reported to be elevated in IPF lungs. iPSC-derived cultures express ATII markers and contain lamellar body-like structures. Stimulation with IPF-RC during the last two weeks of differentiation increases secretion of IPF biomarkers. Transcriptome analysis of IPF-RC treated cultures reveals significant overlap with human IPF data and enrichment of transcripts associated with extracellular matrix organization. IPF-RC stimulation further impairs ATII differentiation by driving a shift towards an airway epithelial-like expression signature.\n\nIn conclusion, we show for the first time, the establishment of a human model system that recapitulates aspects of IPF-associated bronchiolization in vitro. Our findings reveal how aberrant alveolar epithelial progenitor cell differentiation in a pro-fibrotic environment could contribute to alveolar bronchiolization in the distal IPF lung.\n\nSOURCE OF SUPPORTThe research was funded by Boehringer Ingelheim Pharma GmbH & Co. KG.

cell biology↗