bluuebunny/crossref_metadata_2025_split huggingface dataset:
Belonging and Representation in Physiology Teaching
Authors: Co Elizabeth 
Published: May 2024

We teach in a discipline that should be agnostic to race, class, gender and ability, as we are literally in the work of learning about all bodies. Yet, so often we hold up one example and call it “normal.” By presenting images, using language and communicating an understanding that lacks representation we are committing a double failure. We uniquely have the opportunity to help raise awareness and ultimately contribute to a reduction in health care disparities by presenting more equitable and representative information to our students during their journey to become health care providers and researchers. Two, we have the ability to increase student beloning and reduce stereotype threat when we provide examples that include our students' identities. In this talk we will discuss some of the ways that representation and belonging can be addressed within undergraduate physiology curriculum. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Feasibility of Improving Glycemic Control via Heat Therapy in individuals at risk for Alzheimer’s Disease (FIGHT-AD): a pilot study
Authors: Blankenship Anneka , Kueck Paul , Vitztum Michelle , Jensen Reilly , Kemna Riley , John Casey , Vidoni Eric 
Published: May 2024

Impaired glycemic control increases the risk for type 2 diabetes and Alzheimer’s Disease (AD). Mechanisms such as impaired energy metabolism, cellular bioenergetic function, reduced intracellular protein homeostasis, and inflammation are all potential contributors to AD pathology. Heat therapy, via hot water immersion, has been shown to improve blood glucose regulation, insulin resistance, and inflammation. Given the potential contribution of these factors to brain health, heat therapy could offer immense clinical benefit to individuals at risk for AD. We performed a pilot study to test the feasibility of utilizing heat therapy in older individuals at risk for AD due to metabolic risk. The study intervention involved two pre-visits which included a cognitive function screen, sleep, diet, and physical activity questionnaires, as well as a glucose tolerance test and MRI scan. The intervention consisted of four weeks of heat therapy (3 visits/wk) for a total of 12 visits, followed by two post-intervention study visits identical to the pre-study visits. A total of 18 individuals (9 male, 9 female), average age 71.1 ± 3.9 y completed the intervention. Participants demonstrated metabolic risk based on average HbA1c values of 6.6 ± 0.67, Body Mass Index (BMI) of 29.1 ± 5.4, and 15 of the 18 participants were on hypertensive medications. Our cohort was highly diverse, with 33% underrepresented minority group representation. We had 96% participant adherence for the study (8 missed visits out of 216 total visits), and 1 study related Adverse Event (mild dizziness/nausea) that was mild. Overall, the research participants responded to a post-intervention survey saying they enjoyed participating in the study and it was not a burden on their schedules. In addition, we obtained preliminary data demonstrating a significant effect of the heat therapy intervention on body mass index, mean arterial pressure, and cerebral perfusion (p<0.05), and a trend for improved self-reported sleep quality (Pittsburgh Sleep Quality Index; p=0.06). Future studies of longer duration are needed to provide a comprehensive understanding of the impact of heat therapy on glucose homeostasis and brain health. NIH P30 AG035982 (KU ADRC), pilot funds to PCG. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Therapeutic potential of hiPSC-derived cardiomyocytes for Duchenne Muscular Dystrophy
Authors: Wang Ruchen , Perlingeiro Rita , van Berlo Jop 
Published: May 2024

Duchenne Muscular Dystrophy (DMD) results in progressive and incurable cardiomyopathy, leading to significant morbidity and mortality due to heart failure. There is currently no effective cure for DMD that can correct the genetic defects and compensate for the lack of dystrophin. Therefore, the therapeutic strategies that focus on the transplantation of induced pluripotent stem cells (iPSCs) derived cardiomyocytes are promising options, and remain to be investigated to which extent they can restrain the cardiomyocyte loss phenotype and improve cardiac function. There has been significant progress in the differentiation of cardiomyocytes (CMs) from hiPSCs (human iPSCs). Three hiPSC lines: AICS-0011, 029 iPS clone 4-PCBC, and PCBC16iPS were investigated based on previously published culture and differentiation methods. We will inject differentiated CMs into the heart of Mdx mice that are mutated or deficient for NOD-scid, IL2Rg to allow for xenotransplantation engraftment. Having confirmed the effcient differentiation of CMs from all three hiPSC lines, the next step will be to transplant CMs. The engraftment rate after transplantation will be quantified by IHC staining for human lamin A/C and the relative level of genomic human DNA from isolated hearts. Correction of dystrophin expression will be measured via IHC for dystrophin. Echocardiography will be performed to measure improvement in cardiac systolic or diastolic function. If therapeutic transplantation of hiPSC-CMs is possible, it could improve the survival of DMD patients. This project was supported by RMM091621DS008, NIH155993, and NIH160665. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Is the Serpin-Enzyme Complex Receptor an Orphan G-Protein Coupled Receptor?
Authors: Mahmood Ammar , Cortner Loki , Rahimi Nastaran , Samson Willis , Yosten Gina 
Published: May 2024

Alpha-1 antitrypsin (α1-AT) is a member of serine proteinase inhibitors, collectively known as serpins, that inactivate their target enzymes by forming a stabilized serpin-enzyme complex. α1-AT molecules interact with elastase, forming biologically active complexes. It was suggested that the formation of α1-AT-elastase complex would expose a domain from α1-AT molecule that is recognized by a specific cell receptor. Thus, a synthetic peptide, called 105Y, was made based on the sequence of the exposed domain. The peptide binds specifically to human hepatoma HepG2 cells, human monocytes, human neutrophils, and rat pheochromocytoma cells (PC12). This binding is blocked by α1-AT-elastase complex and other serpin-enzyme complexes, suggesting an existence of a specific cell surface receptor, termed SEC receptor, that recognizes serpin enzyme complexes. However, the identity of SEC receptor is still unknown. Thus, we decided to use the Deductive Reasoning Strategy approach to investigate if the SEC receptor belongs to G-protein-coupled receptor (GPCR) family. We measured responsiveness of HepG2 cells as well as human neuroblastoma SHSY5Y cells to 105Y peptide by quantifying their expression of an early response gene c-Fos using real time quantitative polymerase chain reaction (qPCR) and measured their expression of orphan GPCRs using polymerase chain reaction (PCR) followed by gel electrophoresis. Our results indicate that the cells were responding to 105Y peptide and express certain orphan GPCRs. Our goal is to evaluate the necessity of these oGPCRs in 105Y peptide signaling in order to determine the best candidate(s) for the 105Y receptor. These results would shed light on the identity of the SEC receptor for better understanding of the molecular biology and physiology of the serpin-enzyme complexes and their receptors. National Institute of Health. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Identification of Spinal Afferent Innervation in the Rat Heart: Atria and Ventricles: Anterograde Tracing
Authors: Ma Jichao , Bizanti Ariege , Barton Kayla , Kwiat Andrew M. , Nguyen Duyen , Bendowski Kohlton T. , Madas Jazune 
Published: May 2024

The spinal afferent innervation of the heart regulates cardiac functions by sending sensory information from the dorsal root ganglia (DRG) to the brain. However, the distribution and morphology of spinal afferents in the whole heart are not well characterized. The challenges here are: 1) diffculty in surgically accessing the upper thoracic DRG to label only cardiac spinal afferents. 2) handling flat-mounts of whole atria and ventricles (thickness ~850 μm) without using sections or partial tissues that could disrupt the continuity of axonal structures. To overcome these challenges, we injected anterograde tracer dextran biotin (DB) into the left DRG (C8-T3) of male SD rats (3-5 months) and allowed them to recover for 14 days for tracer transportation. Flat-mounts of the left and right atria and ventricles were prepared, and DAB (3,3′-Diaminobenzidine) stained, followed by imaging, tracing, and digitization using the Neurolucida system. Our findings are: In the atria, the DB-labeled axons entered the atria potentially through the left precaval vein (LPCV), with predominant innervation of the left side of the atrial wall and extended their projection towards the auricles, middle region of the atrium, and pulmonary veins. Most of the spinal afferent axons were present in the myocardial layer. Varicose DB-labeled axons were also observed on cardiac targets at different regions, and distinct morphological structures were found. In the cardiac muscle, DB-labeled axons ran mainly in the direction of muscle fibers. Also, varicose axons ran along the small vasculature on the atria. Spinal afferents formed varicose contacts with individual principal neurons within some intrinsic cardiac ganglia (ICG). In the ventricles, DB-labeled axons were present in the left and right ventricles, which ramified and expressed spherical-like varicosities on the cardiac muscle. In both the atria and ventricles, spinal afferent axons formed simple, branching, and complex terminal structures. Thus, our work, for the first time, successfully labeled, traced, and digitized the spinal cardiac afferents in the flat-mounts of whole atria and ventricles, which will provide a foundation for specific labeling of cardiac spinal afferent fibers. In addition, it will lead to the future study of topographical cardiac spinal afferent innervation, functional studies, and their remodeling in pathological conditions. This study was supported by NIH HEAL/SPARC U01 NS113867-01, NIH R15 R15HL137143-01A1, and UCF dissertation completion Fellowships. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
E-Cigarette Aerosol Inhibition of Compositionally Different Surfactants
Authors: Graham Emma , Gehani Sabrine , Veldhuizen Ruud 
Published: May 2024

Introduction: Pulmonary surfactant lines the alveolar surface where it reduces surface tension (ST) thereby facilitating breathing with minimal effort. As such, impairment of surfactant’s surface tension reducing function can contribute to lung injury. Isolated surfactant from the lung consists of up of 85-90% by weight saturated and unsaturated phospholipids, 5-10% neutral lipids, mainly cholesterol, and 10% surfactant proteins, designated SP-A, SP-B, and SP-C. However, studies examining surfactant function and dysfunction have often utilized surfactants with simpler compositions. One recent area of interest is the impact of e-cigarette (EC) generated aerosols on surfactant. EC use remains a popular habit despite reports of vaping associated acute lung injury. Upon inhalation, EC aerosol comes into direct contact with pulmonary surfactant and previous studies have demonstrated that EC aerosol exposure can impair surfactant function using either bovine lipid-extracted surfactant (BLES) or simple lipid mixtures. Comparing inhibition by EC aerosol of a more diverse set of surfactant preparations can further elucidate which components of surfactant are most affected by EC aerosol. We hypothesized that EC aerosol would cause varying degrees of functional inhibition in compositionally different surfactants. Methods: The following surfactant preparations were tested: BLES, BLES + SP-A, natural bovine, SP-A deficient bovine, and synthetic surfactants composed of saturated lipids + cholesterol + SP-C, and saturated + unsaturated lipids + cholesterol + SP-C. To test the exposure to EC aerosol, 2ml of surfactant was placed in a syringe (30ml) attached to an EC. The generated aerosol was drawn into the syringe for 30 sec and then expelled, this was repeated 30 times. The functional impact was then tested on a constrained sessile drop surfactometer to analyse changes in ST reduction. Results: Upon exposure to EC aerosol, natural bovine surfactant had significantly higher minimum ST compared to non-exposed and BLES. This difference did not appear to be mediated by SP-A. Synthetic lipid mixtures containing only saturated phospholipids (DPPC) were not significantly inhibited by EC aerosol, but the addition of unsaturated lipids resulted in increased minimum ST. Conclusion: Functional impairment of pulmonary surfactant due to EC aerosol is dependent on aerosol interaction with unsaturated lipids. This effect is more pronounced in natural complete surfactants. Western, NSERC, OGS. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Compound 48/80 causes overactive bladder without altering urothelial permeability in mice
Authors: Flood Emma , Jones Brothely , Jackson William , Tykocki Nathan 
Published: May 2024

The urothelium, a transitional epithelium lining the urinary bladder, is essential for preventing leakage of urine into the underlying tissue. Disruption of this barrier by noxious stimuli or inflammatory mediators increases bladder wall permeability and causes bladder dysfunction. Compound 48/80 is a pro-inflammatory basic secretagogue that causes urothelium-dependent increases in urinary bladder contractility, as well as bladder overactivity in mice. We hypothesized that Compound 48/80 causes bladder dysfunction by increasing urothelial permeability. Intact bladders from male C57BL/6 mice (N=4) were cannulated, filled with HEPES-buffered physiological salt solution containing FITC-labeled-dextran (70 kDa), and pressurized to 25 mmHg. Z-stacks of baseline fluorescence were captured across the bladder wall using 2-photon laser microscopy. Compound 48/80 (50 μg/mL) was then instilled intravesically for 10 minutes before the bladder wall was imaged again. Average FITC intensity plots wall showed no consistent increase in fluorescence with or without Compound 48/80 from the lumen into the bladder wall. There was also no statistical difference in the area under the curve of these line graphs (p=0.5898). Our findings suggest that Compound 48/80 causes overactive bladder without affecting urothelial permeability. Future studies will investigate other secretagogues and lower molecular weight dextrans to clarify the mechanisms by which secretagogues cause a loss of urothelial barrier function. This research is supported by NIH P20-DK127554 (NRT), NIH R01-DK119615 (NRT). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Effects of Aging and Fatigue on Human Skeletal Muscle Cellular Contractile Function
Authors: Ricci Austin , Privett Grace , Callahan Damien 
Published: May 2024

Aging is associated with a reduction in skeletal muscle mass and function, known as sarcopenia. While reductions in contractile force are typically explained by loss in muscle cellular cross sectional area (CSA) loss of contractile power during high velocity contractions exceed reductions in force and cannot be solely explained by loss of muscle size and are observed at the single fiber within the same myosin heavy chain isoform (MHC). These phenomenon may be explained by myosin binding protein C (MyBP-C), which is known to modulate contractile force and velocity in a phosphorylation-dependent manner in both cardiac and skeletal muscle. Few studies have investigated the inherent contractile performance of single fibers between old and young adults, and none have explored the effects of altered MyBP-C phosphorylation on single fiber function. Therefore, the PURPOSE of this study was to investigate the effects of age and fatigue-induced MyBP-C phosphorylation on single fiber contractile performance. We HYPOTHESIZED that isometric tension will be enhanced in older adults but velocity and power will be reduced, and fatigue will enhance velocity and power in single fibers. To test this hypothesis, we recruited 4 young (18-35) and 3 older (65-80) adult males to perform a single bout of unilateral knee extensions at 30% maximal voluntary isometric contraction (MVIC) until task failure. Immediately following, a bilateral biopsy of the vastus lateralis (VL) muscle was performed on the fatigued and non-fatigued control limbs. Tissue was either flash frozen for western blot or prepared for mechanical analysis of single fiber tension (Tmax), velocity (Vmax), and power (Pmax) under optimal intracellular metabolic conditions. Our analyses were limited to MHC IIA due to differences in fiber type distribution between the groups. Our RESULTS showed that neither age nor fatigue had an effect on contractile performance in MHC IIA fibers. However, independent analysis of fatigue within age groups suggest trends towards an increase in velocity (p=0.055) in young (MHC IIA) and reduction in tension (p=0.085) in old (MHC I) adult fibers. We CONCLUDE that fatigue may modulate contractile function in the single fiber in an age- and fiber-type dependent manner. Future studies will be aimed at collecting multiple fiber types and investigating the role of biological sex. Wu Tsai Human Performance Alliance. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
The Integrated Stress Response Regulates Diurnal Rhythms in Liver Metabolism
Authors: Levy Jordan , Mirek Emily , Cao Ruifeng , Anthony Tracy 
Published: May 2024

Disruptions in biological rhythms are associated with the development of metabolic diseases. General control nonderepressible 2 (GCN2), a primary sensor of amino acid insuffciency and activator of the integrated stress response (ISR), plays an integral role in liver metabolism. The objective of this work was to examine the impact of feeding a low protein quality (LPQ) diet on diurnal rhythms in liver metabolism. We hypothesized that activation of the ISR by GCN2 maintains metabolic rhythms within the liver during LPQ feeding. To address our objective, wild type (WT) and whole body Gcn2 knockout (GCN2KO) mice were housed in total darkness and provided free access to either a Control or a LPQ diet (devoid of leucine) for 8-days and then killed at 2 circadian time (CT) points 12-hours apart (CT3, CT15). WT mice fed a Control diet showed oscillations in hepatic ISR activation that were lost in the livers of GCN2KO mice. Diurnal patterns in the liver transcriptome including genes regulating triglyceride metabolism were also dampened in GCN2KO mice. WT mice fed LPQ showed increased hepatic ISR activation and greater abundance of ISR target genes relative to Control only at CT15 (p<0.05 by two factor ANOVA). GCN2KO mice fed LPQ failed to show oscillations in ISR activation and instead displayed reductions in liver intracellular amino acids alongside significant upregulation of genes encoding gluconeogenesis and amino acid catabolism at CT15 (q<0.05, Log2FC>1). In conclusion, GCN2 is required for diurnal ISR activation and execution in the liver. LPQ feeding increases hepatic ISR activation in a time dependent manner. Sensing of LPQ by GCN2 is necessary for the maintenance of rhythms in liver macronutrient metabolism. NIH DK109714, Pilot award from the NJ IFNH Center for Human Nutrition, Exercise, and Metabolism (NExT). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.