bluuebunny/crossref_metadata_2025_split huggingface dataset:
Disruption of the surfactant protein A receptor isoform SP-R210L in alveolar macrophages alters airway, vascular, and immune homeostasis in the lung
Authors: Chroneos Zissis , Umstead Todd 
Published: May 2023

Surfactant protein A modulates alveolar macrophage activation and pathogen clearance through the receptor SP-R210, which consists of a homeostatic SP-R210L and an inflammatory SP-R210S isoform in alveolar macrophages (AMs). Both isoforms are encoded from alternatively spliced mRNAs of the Myo18α/MYO18Aα gene in mice and humans. The objective of this study is to elucidate the functions of SP-R210 isoforms in AM function in vivo. We hypothesized that disruption of SP-R210L in AMs would alter the local microenvironment. To address this hypothesis in vivo, we generated conditional transgenic mice by targeting exon 1 encoding the unique amino-terminal KE/PDZ domain of SP-R210L. This strategy enabled selective deletion of SP-R210L in AMs via ITGAXCre-mediated inversion recombination. The impact of AM selective deletion of SP-R210L was studied by histological, biochemical, flow cytometric, and respiratory mechanics measurements in young and aged mice. Airway hyperresponsiveness was measured during exposure to escalating doses of methacholine. These studies show that conditional disruption of SP-R210L results in pulmonary disease consisting of hemosiderin deposition in AMs, decline in long-term maintenance of AMs and lung immune cells, obstructive-restrictive pulmonary mechanics, increased airway hyper-responsiveness, alteration in small solute permeability, arterial smooth muscle hyperplasia and inflammation. Our findings support the novel idea that SP-R210L modulates paracrine functions of AMs in maintenance of alveolar- and airway-capillary homeostasis in the lung. SP-R210L dysfunction may increase the risk for development of pulmonary hypertension. Department of Pediatrics, Penn State College of Medicine, The Children's Miracle Network, NIH HL128746 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.
Gamification, reasoning, application and situated learning approach in Physiology - GRASP the concepts
Authors: Taranikanti Madhuri , John Nitin Ashok , M Kalpana , Kamble Prafull , Singhal Anish , Ganji Vidya , U Madhusudhan , Gaur T Archana , Ansari Afna 
Published: May 2023

Background: Deep learning happens through comprehension of various mechanisms particularly in concept oriented disciplines like Physiology. Hypothesis: Students when exposed to real life situations especially in a collaborative learning environment become more active and immersed in learning. Gamification models can sustain the attention of learners for longer periods and instill interest and motivate them to explore the concepts further. These models can enhance knowledge retention and make learning more enjoyable transforming them into self directed learners. Objectives: To design multifaceted gamification models using situated learning approaches to enhance learning, knowledge retention, application and performance in Physiology. Methodology: Students of first year medical course of both sexes were divided into teams and exposed to the gamification models. Individual and team based performances were assessed. Nine stations with time bound team based gaming activities were designed through focused group discussions. A total of 100 marks were allotted for all activities together. Activities had elements to understand the significance of team work, critical thinking, situated learning using gaming modules. Faculty moderators at each station scored the team performance based on correctness of the activity. Performance as a team was also given scores by observing various attributes and extent of involvement of each team member in the activity. Students, as a team, were given an opportunity to instantly rate each gaming activity. Pretest to assess initial knowledge followed by activities by rotation through stations and post test to assess individual performance were given. Results / Observations: Pretest, Post test scores, faculty assessment of activity, performance as a team and feedback rating by students were tabulated and analyzed. The class average score was 70% (out of total 100 marks) which is considered good. The post test score was significantly higher than the pre test mean scores (p<0.0001) using the situated learning approach model with gamification. There was a significant improvement in the performance in the Formative Assessment (p<0.05) conducted after the GRASP activity. Conclusion: Situated learning approach using near real life situations is an effective learning strategy and can be a useful formative assessment tool. Multifaceted gaming modules enabled actual visualization and critical thinking rather than mere imagination. Team based performance helped exchange of thoughts for higher order thinking and projected significance of teamwork in healthcare setup. 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.
Reduced venous oxygen depletion in response to at-sea acoustic disturbance in diving northern elephant seals
Authors: Williams Cassondra , McDonald Birgitte , Horning Markus , Klinck Holger , Ponganis Paul , Costa Daniel , Hindle Allyson 
Published: May 2023

Marine mammals face increased human activities in the ocean, including shipping, recreation, and seismic exploration. Such disturbances may alter short-term behavior and long-term life history patterns; however, many of the mechanistic details of responses remain unknown. Because marine mammals survival depends on their diving abilities, physiological specializations to diving will likely define the scope of underwater responses to a disturbance. Prior research in aquatic animals has demonstrated an increased bradycardia in response to underwater stressors. We examined cardiovascular physiological responses to disturbances at sea in freely diving juvenile northern elephant seals ( Mirounga angustirostris). We predicted that, after an acoustic disturbance at sea, seals would intensify the dive response, resulting in reduced whole-body oxygen (O2) consumption and slower venous O2 depletion. To test this hypothesis, we recorded venous PO2 and diving behavior in translocated juvenile northern elephant seals that were exposed to experimental acoustic disturbances while freely diving at sea. Venous PO2 was measured in the extradural vein using a Clark polarographic electrode attached to a biologger. After being exposed to an acoustic noise during the ascent phase of deep dives, seals typically exhibited an immediate inversion of the dive, descending to deeper depths. Dives with acoustic disturbances were significantly longer than dives prior to the acoustic disturbance (24.8 ± 6.2 mins vs 19.1 ± 2.9 mins). Although the magnitude of PO2 depletion was not significantly different between pre-disturbance dives and disturbed dives (52.6 ± 21.6 mmHg vs 53.5 ± 20.8 mmHg, n= 27 paired dives), the depletion rate was slower in disturbed dives. In dives prior to the disturbance, PO2 depletion was 3.2 ± 1.5 mmHg min-1, but in dives with a disturbance, PO2 depletion was 2.5 ± 1.3 mmHg min-1. This reduction in venous PO2 depletion rate suggests O2 consumption during disturbed dives may be similar to the amount consumed during non-disturbed dives. This reduction may be a result of altered perfusion, including reduced muscle blood flow. In particular, reduced perfusion to working muscle would likely reduce O2 extraction, and may be a key factor in fine-tuning the dive response after a disturbance to conserve O2 for the brain and heart. National Science Foundation 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 CXCR4 in vascular endothelial cells in ischemic heart diseases
Authors: Wang Yang , Gadd James , Enrick Molly , Ogunmiluyi Blessing , Dong SARAH , Zhang Lily , Zhang Laura , Yin Liya 
Published: May 2023

CXCR4 and CXCL12 signaling pathways are essential in cardiovascular development, ischemia heart diseases, and cardiovascular regeneration. Coronary collaterals are nature bypass of ischemic heart diseases. Recently reports showed that CXCR4 and CXCL12 signaling is involved in coronary collateral growth (CCG) in a mouse model of myocardial infarction. Our study showed that endothelial cell (EC) sprouting is essential to coronary collateral formation in a mouse model of CCG induced by repetitive ischemia (RI). It is unknown the role of CXCR4 in EC in CCG. In this study, we used genetically modified mice (CXCR4 EC-specific knockout) to study the role of CXCR4 in ECs in myocardial ischemia. First, we generated EC-specific CXCR4 knockout (CXCR4 flox/flox-tie-2-cre). Surprisingly we found spontaneous aortic stenosis in these EC-specific CXCR4 knockout mice. To exclude the effect of CXCR4 in ECs during embryonic development, we generated an inducible CXCR4 EC-specific knockout (CXCR4 flox/flox-VE-cadherin-cre). Our preliminary data showed no aortic stenosis in these mice after being induced by tamoxifen at six weeks old, suggesting that CXCR4 signaling in EC affects cardiovascular development. We compared the phenotypes of two mouse lines of CXCR4 endothelial knockouts by echocardiography and histology. Furthermore, these CXCR4 EC-specific knockout mice and their littermate controls underwent myocardial infarction (MI) and RI surgery. We measured the cardiac function, vessel density, and coronary blood flow in the mice with RI. We measured the cardiac function, vessel density and infarction size, and fibrosis in the mice with MI. Our preliminary data showed that the CXCR4 and CXCL12 signaling in vascular EC is essential to cardiovascular regeneration during myocardial ischemia, suggesting that CXCR4/CXCL12 signaling pathway could be a potential target for treating ischemic heart diseases and preventing heart attack. 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.
Cardioprotection from Acute Myocardial Infarction with RRx-001, an NLRP3 Inflammasome Inhibitor, in Phase 3 for the Treatment of Cancer
Authors: Cabrales Pedro , Reid Tony , Caroen Scott , Oronsky Bryan 
Published: May 2023

Acute myocardial infarction (MI) is a major cause of morbidity and mortality. Massive cell death leads to inflammation, a necessary evil for wound healing, but also “evil” or harmful due to infarct expansion and adverse remodeling. Also, studies in experimental models have demonstrated the potential cytoprotective effects of nitric oxide (NO) supplemented at the time of reperfusion. In these experiments, we investigated whether RRx-001, a NO donor only under hypoxia and an NLRP3 inflammasome inhibitor, in a Phase 3 trial (REPLATINUM; NCT03699956) for the treatment of cancer was protective after MI. Methods: Male Sprague-Dawley rats (n=8/group) subjected to coronary ligation and reperfusion were randomized to receive either no treatment (sham), vehicle control, or 5mg/kg intravenous RRx-001 at 1-hour post-infarction. We assessed structural and functional cardiac remodeling, infarct expansion, fibrosis, cardiomyocyte hypertrophy, and the expression of inflammatory genes. Results: Treatment with RRx-001 after reperfused MI decreased infarct expansion and scarring, increased left ventricular systolic function to levels approaching normal values, and reduced myocardial hypertrophy. No hypotensive effects were observed. Postinfarction was associated with the activation of NF-κB and NLRP3 inflammasome components and increased the protein and expression of IL-1β. Compared with vehicle, infarcted rats treated with RRx-001 significantly attenuated myocardial messenger RNA and protein levels of NF-κB, NLRP3 inflammasome, mature caspase-1, and IL-1β. Significance: This is the first report that RRx-001 reduces infarct size. It provides proof of principle for administering RRx-001 against ischemia/reperfusion injury. RRx-001 increases local NO levels under hypoxia without requiring the continuous intravenous infusion of NO donors and without altering systemic hemodynamics. It can potentially improve wound healing responses and pathological remodeling, thereby attenuating the development of ischemic heart failure. Commercial and private foundation grants. 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.
Importance of learning the connection between form and function together - redesigning anatomy and physiology for improved student learning outcomes
Authors: Bates Holly , West Sarah 
Published: May 2023

First-year undergraduate level human anatomy and physiology courses are required for numerous degrees and programs, including nursing, kinesiology, and biomedical sciences. These courses create an important foundation for students to build their continued learning. However, identifying the best way to offer these courses is still not fully clear. Some post-secondary institutions and/or programs offer integrated anatomy and physiology courses, while others, separate anatomy from physiology. As well, with the increased requirement and desire for online formats, additional consideration into course delivery is needed. Previously, we evaluated and reported student human physiology content retention 3-months following course completion at our institution that offers separate anatomy and physiology courses. We found that overall content retention was poor and exacerbated in the online format of course delivery. Given this, we identified that there may be a disconnect in the way these courses are delivered that is problematic to learning. Currently, the physiology course follows in the semester after the anatomy course. In both courses, a new body system is discussed each week in rapid succession. Out of necessity, the anatomy course includes some basic physiology to improve understanding and a review of anatomy occurs in the physiology course to fully understand function. Thus, there is significant overlap that takes away from time that can be spent reinforcing complex physiological topics. We hypothesize that redesign of these courses using a systems-based approach to combine the anatomy and physiology within one course will improve student retention of core physiological concepts, since students would learn both the form (anatomy) and function (physiology) together. We will discuss the considerations that we have evaluated with respect to the redesign of these courses and welcome discussion with respect to the strengths and weaknesses of separate versus combined anatomy and physiology curriculum delivery. Teaching Fellows Program, Trent University 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.
IGSF3 (immunoglobulin superfamily 3) and glycosphingolipids associated with lung cell proliferation during recovery from respiratory SARS-CoV-2 infection
Authors: Schweitzer Kelly , Egersdorf Nicholas , Rivera Tanner , DuBois Betty , Cornell Christina , Borowiec Alexander , Poczobutt Joanna , Matsuda Jennifer , Berdyshev Evgeny , Bowen Richard , Petrache Irina 
Published: May 2023

RATIONALE: IGSF3, a transmembrane tetraspanin interacting protein, is required for lung epithelial scratch wound repair and migration via inhibition of glucosyl ceramide synthase. However, as a result, a decrease in glycosphingolipids such as lactosylceramide may decrease cell proliferation and impair lung recovery from infections such as SARS-CoV-2 (CoV2). We hypothesized that recovery from CoV2 is associated with downregulation of lung IGSF3, increased glycosphingolipid synthesis, and enhanced lung cell proliferation. METHODS: Lung IGSF3, sphingolipid levels, and cell proliferation were measured in Golden Syrian hamsters harvested during the early recovery (at 7 days) following a single intranasal exposure to CoV2 (strain WA01; 10E4 pfu). Lung cell proliferation was measured in mice with constitutive deletion of IGSF3 (KO). Immunofluorescence (IF) was performed for cell-specific markers CD11b and CD11c, as well as CD31. Lipids were quantified using LC-MS/MS. RESULTS: CoV2 infection was associated with decreased Igsf3 [log2FC (fold change) -0.914; p<0.01] expression and immunostaining in the lung tissue and increased glucosylceramide (FC 11, p<0.001), lactosylceramide (FC 5, p<0.01), and lysophosphatidic acid (FC 6, p<0.001) in the BALF. Lung cell proliferation was increased, with high Proliferation Marker Protein Ki-67 expression (Ki-67; log2FC 2.17; p<0.0001). In mice, compared to control, IGSF3 KO mice exhibited increased lung Proliferating Cell Nuclear Antigen (PCNA; FC 2.44; p=0.03) and Ki-67 (FC 1.71; p=0.03) IF and enhanced EdU incorporation (in female mice only, FC 1.9; p=0.007), predominantly in the lung epithelium. Of the Ki-67+ cells in the IGSF3 KO lung parenchyma, the populations of cells that had higher proliferation rates than in control mice were alveolar epithelial (>70% of all proliferating cells) followed by recruited monocytes/macrophages, and vascular cells. CONCLUSIONS: Inhibition of IGSF3 may accelerate lung epithelial cell proliferation and lung repair during recovery from respiratory viral infections such as with CoV2 by a mechanism that may involve enhanced glycosphingolipid production. DOD W81XWH-21-PRMRP-IIRA, ALA ETRA736704 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.
Effect of adipose biopsy technique on adipocyte size and integrity
Authors: Brandt Anna , Lynch Colleen , Boyd Gerard , Vincenty Caroline , Skiles Chad , Robbins Ethan , Gouw Aaron , Kuszmaul Dillon , Naruse Masatoshi , Chambers Toby , Minchev Kiril , Belangee Alicia , Douglass Matthew , Trappe Todd , Trappe Scott 
Published: May 2023

Objectives: The purpose of this study was to compare adipocyte size and integrity in adipose tissue between Mercedes and Bergström biopsy techniques in healthy, recreationally active adults. Hypothesis: There would be no difference in adipocyte size between the Mercedes and Bergström techniques. Mercedes biopsy samples would have a smaller area of intact adipocytes compared to Bergström biopsy samples. Methods: Baseline abdominal subcutaneous adipose tissue was obtained from 10 (7M, 3F; 28±4 y; 87±9 kg; Body Fat 30±8%; VO2max 3.4±0.8 L/min) healthy, recreationally active adults (i.e., regular aerobic and/or resistance exercise 3-5 days/wk) on contralateral sides via the Mercedes and Bergström biopsy techniques. Samples were cryopreserved until downstream processing and analysis. Adipocyte quality [i.e. intact cells and cross-sectional area (CSA)] was analyzed and compared between biopsy techniques. Results: Average tissue yield for the Mercedes biopsy was greater than the Bergström biopsy (1171±545 mg vs. 318±58 mg, respectively; P<0.05). The Mercedes and Bergström techniques had a range of yields (393-1940 mg vs. 215-380 mg, respectively) with the Mercedes technique obtaining more than 3.5x the amount of adipose tissue compared to the Bergström biopsy. Mean CSA did not differ between Mercedes and Bergström biopsy techniques (6517±952 μm2 vs. 6116±1652 μm2, respectively; P>0.05). The percent distribution for CSA clustering followed the same trend for both techniques. Intact area was similar between Mercedes (61±16%) and Bergström (63±11%) (P>0.05) techniques. Conclusions: Adipocyte size and integrity did not differ between Mercedes and Bergström biopsies suggesting that the two sampling techniques provide comparable quality of tissue for analysis. However, research questions may impact the technique chosen as the Mercedes biopsy obtains larger tissue yields whereas the Bergström technique may allow for an increased number of biopsies due to the abdominal area utilized. This research was supported by the Human Bioenergetics program at Ball State University. 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.
Zanamivir infusion improves endothelial function and reduces arterial stiffness in diabetic mice
Authors: Morales-Quinones Mariana , Foote Christopher , Ramirez-Perez Francisco , Jurrissen Thomas , Power Gavin , Betancourt-Cortes Edgar , Lazo-Fernandez Yoskaly , Augenreich Marc , Manrique-Acevedo Camila , Padilla Jaume , Martinez-Lemus Luis 
Published: May 2023

Endothelial dysfunction and arterial stiffening are consistently manifested in type 2 diabetes (T2D) and contribute to the development of cardiovascular disease. Consequently, there is an urgent need to identify novel therapies that improve endothelial function and reduce arterial stiffness in T2D. Endothelial dysfunction is characterized by a reduced capacity of the endothelium to induce vasodilation. Physiologically, this is evident as an impairment in flow-mediated dilation, a process in which the endothelial glycocalyx participates in the mechanosensation and mechanotransduction of shear that leads to the production of the vasodilator nitric oxide. Nitric oxide, in turn, has also been shown to be a potent regulator of vascular wall homeostasis, including arterial stiffness. In T2D, circulating neuraminidase activity is increased and implicated in glycocalyx degradation and endothelial dysfunction. Accordingly, we hypothesized that inhibition of neuraminidase activity would enhance endothelial function and reduce arterial stiffness in T2D. We tested this hypothesis in diabetic db/db mice infused with zanamivir (n=10) or vehicle control (n=10) for 4 weeks via subcutaneously implanted osmotic mini pumps. We chose to use the FDA approved neuraminidase inhibitor zanamivir to increase the translatability of our study. Treatment with zanamivir did not affect body weight or blood pressure. Nonetheless, it improved flow-mediated dilation in isolated mesenteric arteries assessed using pressure myography, with no associated changes in endothelium-independent vasodilation. Zanamivir also reduced stiffness in isolated mesenteric and femoral arteries, as well as aortic stiffness as assessed in vivo via pulse wave velocity and ex vivo via atomic force microscopy. These results indicate that zanamivir is a potential therapeutic to ameliorate vascular dysfunction in T2D. National Institutes of Health grant: R01HL153264 to LM-L and JP 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.