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Chen, W (Ed.)Therapeutic recombinant protein production relies on industrial scale culture of mammalian cells to produce active proteins in quantities sufficient for clinical use. The combination of stresses from industrial cell culture environment and recombinant protein production can overwhelm the protein synthesis machinery in the endoplasmic reticulum (ER). This leads to a buildup of improperly folded proteins which induces ER stress. Cells respond to ER stress by activating the Unfolded Protein Response (UPR). To restore proteostasis, ER sensor proteins reduce global protein synthesis and increase chaperone protein synthesis, and if that is insufficient the proteins are degraded. If proteostasis is still not restored, apoptosis is initiated. Increasing evidence suggests crosstalk between ER proteostasis and DNA damage repair (DDR) pathways. External factors (e.g., metabolites) from the cellular environment as well as internal factors (e.g., transgene copy number) can impact genome stability. Failure to maintain genome integrity reduces cell viability and in turn protein production. This review focuses on the association between ER stress and processes that affect protein production and secretion. The processes mediated by ER stress, including inhibition of global protein translation, chaperone protein production, degradation of misfolded proteins, DNA repair, and protein secretion, impact recombinant protein production. Recombinant protein production can be reduced by ER stress through increased autophagy and protein degradation, reduced protein secretion, and reduced DDR response.more » « less
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Students, instructors, and policy makers are in need of research-based recommendations for supporting students’ motivation to pursue STEM fields. The present study addressed this need by examining relations between perceived motivational supports, year-long trajectories of expectancy for success and three task values, and grades among students ( N = 1,021) in a large, gateway engineering course. Results indicated that students with higher motivation at the beginning of the year tended to perceive their class as more motivationally supportive. Controlling for relations between initial motivation and perceptions, perceived instructional supports for mastery goals, autonomy, and competence predicted more positive trajectories of all three task values. Conversely, higher perceived instructor performance goals negatively predicted grades and the slopes of self-efficacy and interest value. Results contribute key understanding about the interconnectedness of individual motivation and climate perceptions, while indicating the importance students place on certain motivationally supportive practices in promoting students’ STEM motivation trajectories.more » « less
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