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Mediator, a co-regulator complex required for RNA Polymerase II activity, interacts with tissue-specific transcription factors to regulate development and maintain homeostasis. We observe reduced Mediator subunit MED15 expression in endocrine hormone-producing pancreatic islets isolated from people living with type 2 diabetes and sought to understand how MED15 and Mediator control gene expression programs important for the function of insulin-producing β-cells. Here we show that Med15 is expressed during mouse β-cell development and maturation. Knockout of Med15 in mouse β-cells causes defects in β-cell maturation without affecting β-cell mass or insulin expression. ChIP-seq and co-immunoprecipitation analyses found that Med15 binds β-cell transcription factors Nkx6-1 and NeuroD1 to regulate key β-cell maturation genes. In support of a conserved role during human development, human embryonic stem cell-derived β-like cells, genetically engineered to express high levels of MED15, express increased levels of maturation markers. We provide evidence of a conserved role for Mediator in β-cell maturation and demonstrate an additional layer of control that tunes β-cell transcription factor function., (© 2024. The Author(s).)

Background: Gamification represents a promising approach for facilitating positive social interactions among groups of individuals and is increasingly being leveraged in physical activity (PA) interventions to promote enhanced intervention engagement and PA outcomes. Although African American (AA) adults experience disparities associated with health conditions that can be ameliorated with increased PA, little is known about how best to culturally target PA gamification strategies for this population. The purpose of this study was to gather perspectives from AA adults residing in the Southeast United States and subsequently identify themes to help inform the cultural adaptation of an existing electronic and mobile health (e/mHealth) gamification- and theory-based PA intervention for teams of insufficiently active AA adults., Methods: An AA moderator facilitated six online focus groups among AA adults (n=42; 93% female; 45.09±9.77 years; 34.40±57.38 minutes/week of reported moderate-intensity equivalent PA), using a semi-structured focus group guide. Drawing from a content analysis approach, transcripts were coded and salient themes were identified., Results: The focus groups revealed the following seven themes: (I) motivation (team-based gamification motivating); (II) accountability (team-based gamification promotes accountability); (III) competition (competitive elements attractive); (IV) weekly challenges (prefer to choose weekly PA challenges); (V) leaderboard feedback (preference for viewing steps and active minutes via a leaderboard); (VI) cultural relevancy (prefer elements reflective of their race and culture that promote team unity); (VII) teammate characteristics (mixed preferences regarding ideal sociodemographic characteristics and starting PA level of teammates)., Conclusions: Integrating team-based gamification in an e/mHealth-based PA intervention may be acceptable among AA adults. The identification of specific design preferences and perceptions of the value of the social environment points to the need to consider surface-level and deep structure cultural targeting when developing and further exploring best practices regarding gamified PA interventions for insufficiently active AAs., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://mhealth.amegroups.com/article/view/10.21037/mhealth-23-44/coif). All authors report that this project was funded by the Southeast Regional Pilot and Feasibility Program [Vanderbilt University School of Medicine/National Institute of Diabetes and Digestive and Kidney Diseases (No. DK020593 to Principal Investigator: C.M.M.)]. This funding provided monetary support for K.Z. and M.S. to fulfill their role in the proposed work. Effort on this project was provided in-kind by C.M.M., R.E.D., G.D., R.L.N., B.C., and D.S.W. C.M.M. reports receiving travel costs in 2022 from the University of South Carolina to present a portion of this work via a poster at the Society of Behavioral Medicine’s 2022 Annual Meeting. R.L.N. reports receiving NIH funding (R42MD014947) to work with Klein Buendel (a marketing and technology company), to develop a smartphone app to increase physical activity in African American men. The authors have no other conflicts of interest to declare., (2024 mHealth. All rights reserved.)