bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oaks to arteries: The Physiology Core Concept of flow down gradients supports transfer of student reasoning
Authors: Doherty Jennifer , McFarland Jenny , Wenderoth Mary Pat 
Published: May 2023

The Physiology Core Concept of flow down gradients is a major concept in physiology as pressure gradients are the key driving force for the bulk flow of fluids in biology. However, students struggle to understand this principle is foundational to the mechanism governing bulk flow across diverse physiological systems (e.g., blood flow, phloem sap flow). In this study, we explore if bulk flow items that differ in context (i.e., taxa, amount of scientific terminology, living or non-living system) or which aspect of the pressure gradient is kept constant (i.e., starting pressure or pressure gradient) influences undergraduate students’ reasoning. We found item context did not impact the type of reasoning students used. However, students were more likely to use the Physiology Core Concept of “flow down [pressure] gradients” when the pressure gradient was kept constant and less likely to use this concept when the starting pressure was kept constant. We also investigated if item context or which aspect of the pressure gradient is kept constant impacted how consistent students were in the type of reasoning they used across two bulk flow items on the same homework. We found most students were consistent across item contexts (76%) and aspects of the pressure gradient kept constant (70%). Students who reasoned using “flow down gradients” on the first item were the most consistent (86, 89%) while students using “pressures indicate (but don’t cause) flow” were the least consistent (43, 34%). Students who are less consistent know pressure is somehow involved or indicative of fluid flow but do not have a firm grasp of the concept of a pressure gradient as the driving force for fluid flow. These findings are the first empirical evidence to support the claim that using Physiology Core Concept reasoning supports transfer of knowledge across different physiological systems. National Science Foundation award DUE 1661263 This is the full abstract presented at the American Physiology Summit 2023 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.
In adults who had a concussion, cardiac autonomic function is not impaired beyond three months from injury
Authors: Garza Nicole , Young Benjamin , Skow Rachel , Nandadeva Damsara , Stephens Brandi , Lockette Warren , Fadel Paul 
Published: May 2023

Introduction: Concussion is a form of traumatic brain injury (TBI) which temporarily disrupts normal brain function. It is well established that cardiac autonomic function is impaired immediately following concussion. However, studies investigating cardiac autonomic function as measures of spontaneous cardiac baroreflex sensitivity (BRS) and heart rate variability (HRV) beyond three months from the event are limited, and the results are inconsistent. Therefore, the purpose of this study was to investigate the lasting impact of concussion on cardiac BRS and HRV in participants who are beyond 3 months from their last concussion. We hypothesized that cardiac BRS and HRV would be impaired in adults who previously had a concussion compared to healthy controls with no known history of concussion. Methods: Five adults (3 females, 27 ± 6 years; mean ± standard error) with a diagnosed concussion prior to assessment (6.2 ± 0.5 months) and six controls (3 females, 27 ± 5 years) without a known history of concussion were studied. Heart rate (HR; ECG) and beat-to-beat blood pressure (BP; finger photoplethysmography) were recorded continuously during a five-minute supine rest period. Spontaneous cardiac BRS was estimated using the Sequence Method for overall BRS gains, then separately for up gains (increase systolic BP: increase R-R interval) and down gains (decrease systolic BP: decrease R-R interval). HRV was measured in the time-domain using the root mean square of successive differences between normal heartbeats (RMSSD), and in the frequency-domain using normalized low frequency (LF) and high frequency (HF) power, and as the LF/HF ratio. Results: There were no differences in resting BP or HR between groups (P > 0.050 for both). Overall cardiac BRS gains was also not different between controls (20.3 ± 4.3 ms/mmHg) and participants with TBI (28.6 ± 9.3 ms/mmHg, P = 0.4116). Likewise, we found no group differences for up and down gains (P > 0.050 for both). For HRV measures, no differences between groups were observed for RMSSD (control: 63 ± 20 ms; TBI: 63 ± 21 ms, P = 0.890), LF power (control: 40 ± 9 n.u.; TBI: 40 ± 14 n.u.; P > 0.999), HF power (control: 56 ± 9 n.u.; TBI: 57 ± 14 n.u.; P = 0.940), or the LF/HF ratio (control: 1.08 ± 0.50; TBI: 1.49 ± 0.85; P = 0.792). Conclusion: These preliminary findings suggest that, in contrast to our hypothesis, adults at six months post-concussion do not demonstrate impairments in any indices of cardiac autonomic function. This project was supported by the Henry M. Jackson Foundation HU0001-18-2-0016. This is the full abstract presented at the American Physiology Summit 2023 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.
XX Sex Chromosome Complement in Female Mice is Obligatory for Vascular Function
Authors: Sakamuri Anil , Visniauskas Bruna , Kilanowski-Doroh Isabella , McNally Alexandra , Imulinde-Sugi Ariane , Lindsey Sarah , Ogola Benard 
Published: May 2023

Biological sex plays an important role in cardiovascular disease (CVD) predisposition and incidence. Arterial stiffening assessed by pulse wave velocity is an independent marker for CVD and contributes to early vascular aging. Men have stiffer arteries than women, a sex difference that is diminished with aging. Sex hormones are indicated to play a role in stiffening arteries but the role for sex chromosomes is unknown. To assess the role for sex hormones, sex chromosomes or their interaction we used four core genotype (FCG) mice (N=5-8/group). 2-Way ANOVA and Sidak’s multiple comparison test was used for statistical analysis and P<0.05 was considered significant. In this mouse model, males (M) with testes and female (F) with ovaries have either XX or XY sex chromosome complement. Mice were either left gonadal intact or gonadectomized at 8 weeks followed by PWV assessment, blood pressure, and pressure myography at 16 weeks. In gonadal intact mice, males were significantly stiffer than females (P=0.002) with XYM (3.5 m/s) having greater PWV than XXM (3 m/s), XXF (2.8 m/s), and XYF (2.8 m/s), respectively without significant difference in blood pressure (BP). Gonadectomy increased PWV in all groups removing the sex difference in XYM (4.6 m/s), XXM (4.3 m/s), XXF (4.6 m/s), XYF (4.4 m/s) while BP remained unchanged. Pressure diameter relationship was greater in XYM than XXM (P<0.001) in both gonadal intact and gonadectomized mice. Aortic distensibility was greater in XXF than XYF (P=0.008) and XYM than XXM (P=<0.001). Stress-strain curves indicated significant leftward shift (P<0.05) XYM, XXM, and XYF mice after gonadectomy. Masson’s trichrome staining was increased (P<0.05) in mice with XX than XY sex chromosome complement after gonadectomy. In conclusion, we found that decline in sex hormones increases arterial stiffening, removes sex differences in distensibility, and shifts elastic modulus to the left in all groups but XXF mice. R00HL155841 and R25HL105400 This is the full abstract presented at the American Physiology Summit 2023 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 length-tension characteristics of small coronary arteries vary with transmural origin
Authors: Essajee Sal , Warne Cooper , Tucker Selina , Tune Johnathan , Dick Gregory 
Published: May 2023

There are transmural differences in the structure of arteries across the left ventricular wall. For example, for arteries of the same size, wall thickness is greater in arteries of the epicardium than those from the endocardium. This observation suggests that there could be differences in their passive and active length-tension relationships, as different amounts of connective tissue or smooth muscle would be expected to alter these characteristics. We tested this hypothesis by studying similarly sized porcine coronary arteries from opposite transmural locations. Endocardial arteries had a diameter of 389 ± 33 μm (n = 8), while epicardial arteries measured 388 ± 50 μm (n = 6). A wire myograph was used to study the mechanical properties of these arteries under isometric conditions in Krebs-Henseleit buffer at 37 °C. Arteries were cut into rings with an axial length of 2 mm. Rings were repetitively stimulated to contract at increasing lengths with the addition of high extracellular K+ (80 mM). Coronary arteries developed active tension to a plateau level over approximately 3-5 min and K+-induced contractions readily washed out. Arteries from the epicardium were stiffer, as the passive-length tension curve of these vessels was elevated over arteries from the endocardium. Passive tensions at optimal length were 3.2 ± 0.4 vs. 5.6 ± 1.5 mN/mm (p < 0.05). The active tension developed in response to K+ depolarization was greater in epicardial arteries. Active tensions at optimal length were 3.4 ± 1.1 vs. 2.4 ± 0.3 mN/mm (p < 0.05). Our results represent the first comparison of transmural differences in coronary arteries under isometric tension. Our findings support the hypothesis that differences exist in the passive and active length-tension relationships of epicardial and endocardial arteries that correlate with wall thickness. R01HL158723 This is the full abstract presented at the American Physiology Summit 2023 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.
T3 Transection as a Mouse Model of Bowel Dysfunction after Spinal Cord Injury
Authors: Wireman Olivia , Hammers Gabrielle , Sams Ellie , Marino Felicia , Bailey William , Patel Samir , Gensel John 
Published: May 2023

Bowel dysfunction, in the form of constipation and/or incontinence, is one of the most prevalent and life-impacting co-morbidities associated with spinal cord injury (SCI) with no long- term treatment available. The extent to which SCI-induced changes in the colon (e.g. inflammation, fibrosis, and reduced enteric neuron density) cause progressive dysfunction is understudied. There remains a significant unmet need to develop strategies to prevent or reverse bowel dysfunction after SCI. This need remains, in part, due to the lack of a mouse model which recapitulates the human condition. We hypothesized that a T3 spinal transection in mice would trigger bowel dysfunction alongside early colonic inflammation and downstream remodeling of the colon musculature as seen in both humans and rats after SCI. Bowel dysfunction was defined as increased number of fecal pellets within the colon, smaller pellet size, and decreased water content in the stool. The number of fecal pellets within the colon increased significantly in animals receiving SCI compared to sham (laminectomy only) injuries by 4 days post injury (dpi) and persisted to 21dpi. Furthermore, fecal pellet size was significantly decreased in the SCI animals at 21dpi and trended toward decreased water content. Together, these functional measurements are indicative of chronic bowel dysfunction after T3 transection. We next molecularly interrogated whole colon tissue for inflammatory cytokine levels and found increased levels of IFN-γ at 4 dpi but not at 21dpi and found increased collagen deposition in the colonic musculature at both 4 and 21 dpi in the SCI versus sham animals. The acute spike in INF-γ and deposition of collagen after injury are consistent with our hypothesis that T3 transection causes acute inflammation followed by remodeling of the colon wall. Establishing this mouse model will enable further interrogation of cell-type specific responses and signaling pathways using transgenic models. T32 Fellowship in Physiology (GM118292) and T32 Fellowship Neurobiology of CNS Injury & Repair (5T32 NS077889) This is the full abstract presented at the American Physiology Summit 2023 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 role of Glycoprotein Nonmetastatic Melanoma Protein B in vascular inflammation during infectious challenge
Authors: Lamb Celia , Nguyen Hong-Ngan , Stark Ryan 
Published: May 2023

Glycoprotein nonmetastatic melanoma protein B (GPNMB) is a transmembrane glycoprotein that has been shown to play an important role in inflammation. GPNMB levels are increased in association with pro-inflammatory conditions, such as lipopolysaccharide exposure. Further, GPNMB is increased in aged endothelial cells, and reduction of GPNMB in mice has been shown to reduce aging and increase lifespan. Thus, we sought to test the hypothesis that reduction in GPNMB would provide a protective phenotype to endothelial cells undergoing bacterial challenge. In order to test this, GPNMB was knocked down in either immortalized or primary human dermal microvascular endothelial cells (HMVECs) using siRNA. The cells were then treated with heat-killed Escherichia coli (HKEC, 3x108 cells/ml), one of the most common pathogens encountered in severe, systemic infections. With immortalized (i)HMVECs, siRNA-treated GPNMB knockdown produced cells appearing more compact and organized when exposed to HKEC as compared to siRNA controls. GPNMB knockdown iHMVECs also showed decreased IL-6 cytokine production after HKEC exposure (93.8 ± 8.1 pg/ml in siRNA controls versus 4.3 ± 0.03 pg/ml in siGPNMB, p < 0.005). Under similar conditions, primary (p)HMVECs exposure to siGPNMB showed no specific morphologic changes. Because GPNMB is also expressed by other cells, we also tested whether exogenous, secreted GPNMB from a non-endothelial source could impact HMVECs during infection. Interestingly, exogenous GPNMB exposure also significantly reduced pHMVEC IL-6 secretion (1372 ± 89 in control cells treated with HKEC versus 672 ± 36 in GPNMB treated cells followed by HKEC, p < 0.0001) during exposure to HKEC. Thus, our data suggests that endogenous GPNMB may be detrimental to endothelial cells depending on their age. Alternatively, exogenous GPNMB may offer protection to endothelial cells under certain conditions. Overall, the role of GPNMB in vascular health appears both age and source specific. Understanding the dynamic role of GPNMB may provide an opportunity to intervene in a GPNMB-specific manner to provide protection to endothelial cells during acute infectious challenge. Grant: R35 GM138191 This is the full abstract presented at the American Physiology Summit 2023 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.
Fibroblast growth factor-21 attenuates olanzapine induced hyperglycemia
Authors: Jeromson Stewart , Medak Kyle , Bellucci Annalaura , Arbeau Meagan , Wright David 
Published: May 2023

Impaired glucose and lipid metabolism are known side effects of the anti-psychotic drug olanzapine. A single bolus of olanzapine induces a rapid rise in blood glucose, circulating fatty acids, and ketones. Strategies to offset these impairments in metabolism are of great interest. Our lab has demonstrated that interventions such as exercise, fasting, and ketogenic diets are effective at reducing olanzapine induced hyperglycemia. Fibroblast growth factor 21 (FGF-21) is a secreted protein that is induced by these interventions. We hypothesized that increased FGF-21 may be a common protective factor in reducing the hyperglycemic response to olanzapine. Our aim was to test if altered FGF-21 concentrations impacted the glycemic response to olanzapine. To increase FGF-21, male mice were fed a low-fat diet (10% Kcal) supplemented with Fenofibrate (0.2% w/w) or a matched control diet for 7 days prior to injection of Olanzapine or vehicle control. The fenofibrate diet significantly increased circulating FGF-21 concentrations (LFD: 744±404pg/ml, Fen: 3187±1050pg/ml, p=0.001, N=14). Olanzapine increased glycemia and circulating fatty acids but mice on the fenofibrate diet had an attenuated glycemic response to olanzapine and reduced circulating fatty acids compared to mice fed the control diet (Area under curve LFD: 1321±354 AU, Fen:1783±70 AU, P=0.0014, N=7). We also investigated if the loss of FGF-21 would lead to an increased glycemic response to olanzapine. In FGF-21 knockout mice, olanzapine induced a larger hyperglycemic response compared to olanzapine treated controls (Area under curve FGF-21 KO: 1788±280 AU, Con:1413±373 AU, p=0.00072, N=12). FGF-21 knockout, however, did not reduce the effect of olanzapine on serum non-esterified fatty acids or beta-hydroxybutyrate. These data show that FGF-21 may determine the extent of the hyperglycemic response to olanzapine and increasing FGF-21 may also offset the impairments in lipid metabolism. This is the full abstract presented at the American Physiology Summit 2023 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.
Beta-arrestin-biased protease-activated receptor-2 antagonists preferentially limit allergen-induced responses in vivo.
Authors: Schiff Hillary , Gillman Samuel , Pederson William , Dussor Gregory , Price Theodore , Vagner Josef , DeFea Kathryn , Boitano Scott 
Published: May 2023

Biased signaling in G protein-coupled receptors (GPCRs) has emerged as a target for drug development. Protease-activated receptor-2 (PAR2) is a GPCR present in the airway epithelium with biased signaling that has been shown to trigger both detrimental effects [airway hyperresponsiveness (AHR), inflammation, mucus overproduction] and beneficial effects (bronchorelaxation) associated with allergen-induced asthma. These dual effects have been shown to be dictated by the two primary signaling pathways downstream of PAR2 activation: Gαq/Ca 2+ signaling is associated with bronchorelaxation, and β-arrestin/MAPK signaling is associated with AHR, inflammation and mucus overproduction. We have developed full (C391 which antagonizes Gαq/Ca 2+ and β-arrestin/MAPK signaling) and biased (C781 which antagonizes β-arrestin/MAPK signaling) antagonists of PAR2 and tested their efficacy in acute allergen-induced asthma mouse models. Both full and β-arrestin/MAPK signaling compounds attenuated AHR and inflammation in mouse models, and to a lesser extent, mucus overproduction. In a human bronchial model, the full PAR2 antagonist C391 prevented PAR2- dependent bronchial relaxation while the biased PAR2 antagonist C781 did not. Antagonism by C781 and other biased PAR2 antagonists can fine tune and effectively improve safety profiles for drug development in asthma treatment. Grants from the National Institute of Health (NS098826, AI140257, HL16024, HL152942) This is the full abstract presented at the American Physiology Summit 2023 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.
Understanding the role of ZO-1 in cell phenotype and gene expression through myosin inhibition
Authors: Turbow Benjamin , Doran John , Uwaezuoke Brittany , Wilkinson Nancy , Peng Lindsey , Cheng Kwan , King Jonathan 
Published: May 2023

Zonula occludens-1 (ZO-1) is a tight junction protein contributing to junctional formation as well as mediating interactions with junctional proteins and the actomyosin cytoskeleton. To investigate the role of ZO-1, Madin-Darby canine kidney (MDCK) II knockout cells lacking ZO-1 were created utilizing a CRISPR gene editing platform. These ZO-1 KO cells display characteristic phenotypic changes including actin accumulation and junction linearization. We evaluated membrane tension and found ZO-1 loss leads to increased membrane tension and nuclear density. We hypothesized that due changes in cytoskeletal organization and membrane tension the ZO-1 KO cells would spread less following plating. It is suspected that phenotypic changes related to actin accumulation may be the result of myosin dysregulation in the absence of ZO-1. ZO-1 KO cells that are exposed to blebbistatin, a myosin II inhibitor, resemble wild type cells in cell height and junction linearization. RNAseq and qRT-PCR were used to investigate gene expression changes related to ZO-1 loss to further interrogate ZO-1’s role in regulating membrane tension. This study highlights and expands our understanding of how ZO-1 regulates the mechanical properties of epithelial cells. Trinity University, Mach Research Fellowship This is the full abstract presented at the American Physiology Summit 2023 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.