Minneapolis Institute of Arts

Introduction and Objective: Inadequate maternal nutrition during pregnancy affects millions in the United States, increasing the risk of cognitive, metabolic, and neurodevelopmental disorders later in life. During late gestation, maternal glucose utilization declines, and ketogenesis increases (i.e., “accelerated starvation”), while neonates exhibit high ketone turnover. Despite this, no guidelines exist for monitoring ketones during pregnancy or lactation. Contrary to the notion that all ketosis should be avoided in pregnancy, gestational physical activity, which induces mild ketosis, has been shown to enhance offspring metabolic health and cognitive function. Ketones are a key energy source for fetal and neonatal growth, but their role in early development remains unclear. Methods: To investigate the effects of enhanced maternal ketone availability during gestation and/or lactation, breeder drinking water was supplemented with 3% 1,3-butanediol (BD), a precursor of the predominant ketone body, D-β-hydroxybutyrate (βOHB), during these two developmental stages. Maternal weight, blood glucose, ketones, and NEFA levels were assessed. Offspring development was tracked via neonatal weight, ketone levels, and organ mass at 3 weeks. Long-term metabolic impacts were assessed with GTT and KTT along with fed/fasted serum ketone levels Results: BD had no significant impact on weight or glucose but increased maternal ketones in late gestation (2.4 ± 0.69 mM vs. 0.6 ± 0.07 mM in non-pregnant dams). Pups exposed to BD only during lactation had lower weight gain but increased brain and heart mass at weaning, suggesting altered energy allocation. At 12 weeks, male offspring from BD-treated mothers during both stages displayed sex-specific glucose metabolism impairments, not observed in lactation-only exposure. Further studies are needed to assess systemic metabolic adaptations Conclusion: Findings suggest maternal ketone supplementation alters early growth and glucose regulation in offspring without impacting maternal health. Disclosure A.A. Hayir: None. R.E. Ankeriasniemi: None. K. Fulghum: None. P.A. Crawford: None. P. Puchalska: None. Funding National Institutes of Health (DK091538); National Institutes of Health (AG069781 ); Minnesota Postbaccalaureate Research Education Program in Diabetes, Endocrinology and Metabolic Diseases (1R25DK140753); Internal Masonic Institute for the Developing Brain (MIDB) seed grant

Introduction and Objective: Bone disease is a major type of complication of diabetes. However, the molecular and metabolic basis of how insulin deficiency or resistance affects bone is still incompletely known. Here, we tested if O-linked N-Acetylglucosamine (O-GlcNAc) signaling prevents diabetic osteoporosis in preclinical models. Methods: Post-translational modification of intracellular proteins by a single O-GlcNAc moiety at serine or threonine residues is mediated by O-GlcNAc transferase (OGT). We first used single-cell RNA sequencing and Flow Cytometry to examine the levels of Ogt gene expression and protein O-GlcNAc modification in osteogenic bone marrow stromal cells (BMSCs). We then generated adult perivascular BMSC-specific OGT knockout (OgtΔLepr) mice and characterized their bone microstructure at the steady state and during streptozotocin (STZ)-induced diabetes. Finally, we treated cultured BMSCs with chemicals to induce O-GlcNAcylation or overexpressed OGT in BMSCs in mice to test whether O-GlcNAc augmentation alleviates diabetes-induced osteopathy. Results: OGT and protein O-GlcNAcylation are enriched in adipo-osteogenic BMSCs that are marked by the leptin receptor gene (Lepr). LeprCre-mediated deletion of OGT in adult BMSCs (OgtΔLepr) did not evidently change bone microarchitecture or mineral density in young or old mice. Instead, STZ-induced diabetes diminished stromal O-GlcNAcylation and OgtΔLepr mice showed exacerbated bone loss during diabetes. In culture, OGT was required for insulin and intermittent parathyroid hormone (iPTH) to stimulate BMSC proliferation and osteogenic differentiation. In mice, OGT overexpression in BMSCs alleviated induced bone loss. Mechanistically, OGT modified and activated RUNX2 to stimulate osteogenesis. Conclusion: Protein O-GlcNAcylation modulates the differentiation fate and metabolic fitness of BMSCs, thus impeding diabetic osteopathy. Disclosure C. Gu: None. H. Ruan: None.

Bedroom pop, as a subgenre of indie pop, has recently grown rapidly in popularity.The primary characteristics of bedroom pop encompass the self-or home-production of musical material, digital production techniques, layering, limited instrumentation, and, most notably, the use of a stylized breathy, quiet vocal timbre that we call the "bedroom pop mixed voice."This article applies music theory and analysis, media and gender studies, and vocal science studies to two ends.First, we describe how the bedroom pop mixed voice is produced, offering both physical and anatomical definitions of it.Grounded in embodiment, mimesis, and physiology, we show how the bedroom pop mixed voice is used for stylistic and narrative purposes through the analysis of recent popular bedroom pop artists such as Billie Eilish, dodie, Lizzy McAlpine, and Olivia Rodrigo.Second, in tracing the use and propagation of the bedroom pop mixed voice through social media, we aim to discover bedroom pop's social and cultural impact on Gen-Z music makers.Through the lenses of antiphony and mimicry (Shelley 2020, Cox 2016), we show how amateur performances and covers of bedroom pop songs replicate this vocal production style.These covers have proliferated through social media platforms like TikTok and Instagram, and they have influenced a new generation of (primarily female-identifying) singers (Wolfe 2012, Barna 2022).

Our studies with a monoclonal antibody (mAb) to serpinB13, a protease inhibitor of cathepsin L, and serpinB13-deficient mice, demonstrated that during development, this serpin molecule downregulates the number of Ngn3-positive pancreatic endocrine progenitor cells and their conversion to insulin-producing cells. Establishing the precise role of serpinB13 in the pancreas after birth is important, as its inhibition with a mAb may provide a novel approach to augment beta cell neogenesis, proliferation, and survival in diabetes. To address this, we injected 10 micrograms of low-endotoxin, recombinant serpinB13 (or chicken ovalbumin as a control [OVA]) once a week for 4 weeks into healthy 3-week old immunodeficient Balb/c SCID mice. In addition, during the same period, these mice received 5-EdU in two i.p. injections per week (8 injections in total). At 8 weeks of age the animals were sacrificed for microscopic examination of the percentage of EdU+/insulin+ cells. In an alternative approach, to measure the impact of serpinB13 on cell survival in vitro, immortalized MIN6 beta cells were cultured with a 4 micromolar solution of staurosporine in the presence or absence of serpinB13 at 1 microgram/mL for four hours. Early and late apoptosis was examined with antibodies to Annexin V and caspase 3 antibody, respectively. We found that female mice injected with serpinB13 had significantly reduced proliferation of beta cells with a similar trend for alpha cells. This difference was observed in females rather than males and was particularly prominent for pancreatic islets less than 180 microns in diameter. Moreover, our in vitro studies revealed a significant augmentation of apoptosis and death events following exposure of MIN6 cells to serpinB13. Together our data suggest that serpinB13 has detrimental effects on beta-cell biology, both during embryogenesis and after birth, and further suggests that impeding serpinB13 function is potentially desirable to achieve improved clinical outcomes in the treatment of diabetes. Disclosure Y. Kryvalap: None. J. Czyzyk: None.