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Full-Text Articles in Physiology

Re-Engineering Cardio-Oncology Testing Using Biomimetic Heart Slice Cultures., Jessica Miller Dec 2022

Re-Engineering Cardio-Oncology Testing Using Biomimetic Heart Slice Cultures., Jessica Miller

Electronic Theses and Dissertations

28% of drug withdrawal from the market are due to unforeseen disruptions in cardiomyocyte contractility and electrophysiology. The most commonly used platforms for drug testing are in vivo animal models and in vitro cell culture models. While both have been of paramount importance for the discovery and detection of many cardiotoxicities and mechanisms of action, they lack the ability to model an intact human myocardium. This work aims to establish cardiac tissue slices, which are 300-micron thin tissue sections taken from the left ventricular myocardium, as an alternative platform for cardio-oncology studies, specifically cardiotoxicity testing. Additionally, this work aims to …


Establishing The Efficacy Of Non-Cellular Components Of Adipose-Derived Stromal Vascular Fraction In Promoting Angiogenesis., Daniel Benson Dec 2022

Establishing The Efficacy Of Non-Cellular Components Of Adipose-Derived Stromal Vascular Fraction In Promoting Angiogenesis., Daniel Benson

Electronic Theses and Dissertations

Microvascular disease is hallmarked by pathophysiological conditions such as endothelial senescence, intimal thickening which impairs vasodilation, and regression of the capillary beds causing tissue ischemia in the myocardium or in peripheral vascular networks. Adipose-derived stromal vascular fraction (SVF) has previously demonstrated the ability to revascularize tissue. Increasing evidence shows that regenerative cells elicit their therapeutic benefit by paracrine mechanisms, leaving open extracellular vesicles (EVs) as a potential crux of the cell therapy paradigm. To test this idea, three types of gelatin methacrylate hydrogels were employed: SVF gels, EV gels derived from SVF, and blank control gels, which were used in-vitro …


Integrative Physiology-Coupled Pilot-Centered Flight Simulation, Shawn C. Harrison Dec 2022

Integrative Physiology-Coupled Pilot-Centered Flight Simulation, Shawn C. Harrison

Electrical & Computer Engineering Theses & Dissertations

Maintaining the pilot’s physiological performance envelope within the limits of human capabilities may be crucial for avoiding hazardous physiological episodes in fighter aircraft that compromise safety. The main physiological episode of interest is impaired pilot respiration, better known as hypoxia caused by a high fraction of inspired oxygen (FiO2) at high altitudes and variation in accelerative gravitational forces (g-forces). Integrated into fighter aircraft is an Onboard Oxygen Generating System (OBOGS) developed to mitigate the necessity of gaseous and liquid oxygen cannisters [1]. OBOGS act as a life support in hypoxic environments by providing oxygen-rich air, thereby oxygenating the …


Frontiers In The Self-Assembly Of Charged Macromolecules, Khatcher O. Margossian Oct 2022

Frontiers In The Self-Assembly Of Charged Macromolecules, Khatcher O. Margossian

Doctoral Dissertations

The self-assembly of charged macromolecules forms the basis of all life on earth. From the synthesis and replication of nucleic acids, to the association of DNA to chromatin, to the targeting of RNA to various cellular compartments, to the astonishingly consistent folding of proteins, all life depends on the physics of the organization and dynamics of charged polymers. In this dissertation, I address several of the newest challenges in the assembly of these types of materials. First, I describe the exciting new physics of the complexation between polyzwitterions and polyelectrolytes. These materials open new questions and possibilities within the context …


Functionality Of The Gracilis Collateral Is Impaired Following Arteriogenesis And Cell Transplantation, Ada A. Tadeo Oct 2022

Functionality Of The Gracilis Collateral Is Impaired Following Arteriogenesis And Cell Transplantation, Ada A. Tadeo

Biomedical Engineering

Peripheral Arterial Disease involves narrowed arteries, reducing blood flow to limbs. Increasing blood flow to those extremities is possible by redirecting the blood to flow through natural bypasses (i.e. collateral arteries), which can enlarge via arteriogenesis to maintain blood supply once the prominent arteries have become occluded. This study aims to investigate how arteriogenesis affects collateral function, if myoblast transplantation can stimulate collateral growth, and how that in turn may affect collateral function. Femoral artery ligation was performed to mimic the blockage that occurs in patients with ischemic diseases on lean mice and mice with diet induced obesity (DIO). A …


Cellular Bioenergetics: Experimental Evidence For Alcohol-Induced Adaptations, Liz Simon, Patricia E. Molina Aug 2022

Cellular Bioenergetics: Experimental Evidence For Alcohol-Induced Adaptations, Liz Simon, Patricia E. Molina

School of Medicine Faculty Publications

At-risk alcohol use is associated with multisystemic effects and end-organ injury, and significantly contributes to global health burden. Several alcohol-mediated mechanisms have been identified, with bioenergetic maladaptation gaining credence as an underlying pathophysiological mechanism contributing to cellular injury. This evidence-based review focuses on the current knowledge of alcohol-induced bioenergetic adaptations in metabolically active tissues: liver, cardiac and skeletal muscle, pancreas, and brain. Alcohol metabolism itself significantly interferes with bioenergetic pathways in tissues, particularly the liver. Alcohol decreases states of respiration in the electron transport chain, and activity and expression of respiratory complexes, with a net effect to decrease ATP content. …


Engineering Of Ideal Systems For The Study And Direction Of Stem Cell Asymmetrical Division And Fate Determination, Martina Zamponi Aug 2022

Engineering Of Ideal Systems For The Study And Direction Of Stem Cell Asymmetrical Division And Fate Determination, Martina Zamponi

Biomedical Engineering Theses & Dissertations

The cellular microenvironment varies significantly across tissues, and it is constituted by both resident cells and the macromolecules they are exposed to. Cues that the cells receive from the microenvironment, as well as the signaling transmitted to it, affect their physiology and behavior. This notion is valid in the context of stem cells, which are susceptible to biochemical and biomechanical signaling exchanged with the microenvironment, and which plays a fundamental role in establishing fate determination and cell differentiation events. The definition of the molecular mechanisms that drive stem cell asymmetrical division, and how these are modulated by microenvironmental signaling, is …


Positive Rate-Dependent Action Potential Prolongation By Modulating Potassium Ion Channels, Candido Cabo Jun 2022

Positive Rate-Dependent Action Potential Prolongation By Modulating Potassium Ion Channels, Candido Cabo

Publications and Research

Pharmacological agents that prolong action potential duration (APD) to a larger extent at slow rates than at the fast excitation rates typical of ventricular tachycardia exhibit reverse rate dependence. Reverse rate dependence has been linked to the lack of efficacy of class III agents at preventing arrhythmias because the doses required to have an anti-arrhythmic effect at fast rates may have pro-arrhythmic effects at slow rates due to an excessive APD prolongation. In this report we show that, in computer models of the ventricular action potential, APD prolongation by accelerating phase 2 repolarization (by increasing IKs) and decelerating …


Bms 202: Human Anatomy And Physiology Laboratory Oer Curation, Chealsye Bowley Apr 2022

Bms 202: Human Anatomy And Physiology Laboratory Oer Curation, Chealsye Bowley

Curated OER Collections

This OER curation is an annotated bibliography of prospective OER for the GVSU course BMS 202: Human Anatomy and Physiology Laboratory, assembled by request from the instructor.


Hsp90 Inhibitors Modulate Sars-Cov-2 Spike Protein Subunit 1-Induced Human Pulmonary Microvascular Endothelial Activation And Barrier Dysfunction, Ruben Manuel Luciano Colunga Biancatelli, Pavel Solopov, Betsy W. Gregory, Yara Khodour, John D. Catravas Mar 2022

Hsp90 Inhibitors Modulate Sars-Cov-2 Spike Protein Subunit 1-Induced Human Pulmonary Microvascular Endothelial Activation And Barrier Dysfunction, Ruben Manuel Luciano Colunga Biancatelli, Pavel Solopov, Betsy W. Gregory, Yara Khodour, John D. Catravas

Bioelectrics Publications

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused more than 5 million deaths worldwide. Multiple reports indicate that the endothelium is involved during SARS-Cov-2-related disease (COVID-19). Indeed, COVID-19 patients display increased thrombophilia with arterial and venous embolism and lung microcapillary thrombotic disease as major determinants of deaths. The pathophysiology of endothelial dysfunction in COVID-19 is not completely understood. We have investigated the role of subunit 1 of the SARS-CoV-2 spike protein (S1SP) in eliciting endothelial barrier dysfunction, characterized dose and time relationships, and tested the hypothesis that heat shock protein 90 (HSP90) inhibitors would prevent and repair such injury. S1SP …