Medical Physiology Commons^™

Effects Of Maternal Protein Restriction On The Pulmonary Surfactant System During The Early Life And Adulthood, Reza Khazaee

Electronic Thesis and Dissertation Repository

Fetal growth restriction (FGR) is defined by low birth weight and contributes to a variety of adult-onset diseases with different severities between males and females. However, the effects of FGR on the pulmonary surfactant are not fully elucidated. In this thesis, first, we investigated the FGR effects on the lung function and the surfactant system at the early postnatal life. It was hypothesized that FGR contributes to alterations of lung mechanics and the surfactant system during the neonatal period. Second, we assessed the FGR effects on the surfactant system in response to sepsis in adulthood. It was hypothesized that FGR …

Myocyte [Na+]I Dysregulation In Heart Failure And Diabetic Cardiomyopathy, Sanda Despa

Pharmacology and Nutritional Sciences Faculty Publications

By controlling the function of various sarcolemmal and mitochondrial ion transporters, intracellular Na⁺ concentration ([Na⁺]_i) regulates Ca²⁺ cycling, electrical activity, the matching of energy supply and demand, and oxidative stress in cardiac myocytes. Thus, maintenance of myocyte Na⁺ homeostasis is vital for preserving the electrical and contractile activity of the heart. [Na⁺]_i is set by the balance between the passive Na⁺ entry through numerous pathways and the pumping of Na⁺ out of the cell by the Na⁺/K⁺-ATPase. This equilibrium is perturbed in heart failure, …

Spinal Control Of Locomotion: Individual Neurons, Their Circuits And Functions, Marie-Pascale Côté, Lynda M. Murray, Maria Knikou

Publications and Research

Systematic research on the physiological and anatomical characteristics of spinal cord interneurons along with their functional output has evolved for more than one century. Despite significant progress in our understanding of these networks and their role in generating and modulating movement, it has remained a challenge to elucidate the properties of the locomotor rhythm across species. Neurophysiological experimental evidence indicates similarities in the function of interneurons mediating afferent information regarding muscle stretch and loading, being affected by motor axon collaterals and those mediating presynaptic inhibition in animals and humans when their function is assessed at rest. However, significantly different muscle …

Systematic Pan-Cancer Analysis Of Somatic Allele Frequency., Liam Spurr, Muzi Li, Nawaf Alomran, Qianqian Zhang, Paula Restrepo, Mercedeh Movassagh, Chris Trenkov, Nerissa Tunnessen, Tatiyana Apanasovich, Keith A Crandall, Nathan Edwards, Anelia Horvath

Pharmacology and Physiology Faculty Publications

Imbalanced expression of somatic alleles in cancer can suggest functional and selective features, and can therefore indicate possible driving potential of the underlying genetic variants. To explore the correlation between allele frequency of somatic variants and total gene expression of their harboring gene, we used the unique data set of matched tumor and normal RNA and DNA sequencing data of 5523 distinct single nucleotide variants in 381 individuals across 10 cancer types obtained from The Cancer Genome Atlas (TCGA). We analyzed the allele frequency in the context of the variant and gene functional features and linked it with changes in …

Effect Of Exercise And Hypoxia On Plasma Telomerase, Charli D. Aguilar

UNLV Theses, Dissertations, Professional Papers, and Capstones

Introduction: Telomerase reverse transcriptase (TERT) is the enzyme that adds telomeric sequences to the end of linear chromosomes. Exercise has shown to upregulate acutely leukocyte TERT after just 30 minutes of running on a treadmill at 80% of VO2max (Denham et al., 2016). Hypoxia inducible factor 1 (HIF-1) is also a mediator of TERT in in vitro (Nishi et al., 2004). Moderate acute exposure to hypoxia was associated with substantial increases in plasma TERT in a recent study on rats (Wang et al., 2014). The specific aim of the current study was to identify if acute hypoxia upregulates plasma TERT …

Disruption Of Neonatal Cardiomyocyte Physiology Following Exposure To Bisphenol-A., Manelle Ramadan, Meredith Sherman, Rafael Jaimes, Ashika Chaluvadi, Luther Swift, Nikki Gillum Posnack

Pharmacology and Physiology Faculty Publications

Bisphenol chemicals are commonly used in the manufacturing of polycarbonate plastics, polyvinyl chloride plastics, resins, and thermal printing applications. Humans are inadvertently exposed to bisphenols through contact with consumer products and/or medical devices. Recent reports have shown a link between bisphenol-a (BPA) exposure and adverse cardiovascular outcomes; although these studies have been limited to adult subjects and models. Since cardiac physiology differs significantly between the developing and adult heart, we aimed to assess the impact of BPA exposure on cardiac function, using a neonatal cardiomyocyte model. Neonatal rat ventricular myocytes were monitored to assess cell viability, spontaneous beating rate, beat …

Spinal Cord Trauma: An Overview Of Normal Structure And Function, Primary And Secondary Mechanisms Of Injury, And Emerging Treatment Modalities, Daniel Morin

Senior Honors Theses

The structures of the spinal cord and vertebral column are designed to provide flexibility, while still providing ample protection for the spinal cord deep within. While it does offer remarkable protection against most routine trauma, the spinal cord is still vulnerable to high-force etiologies of trauma and may become damaged as a result. These events are referred to as primary injury. Following the initial injury, the body’s own physiological responses cause a cascade of deleterious effects, known as secondary injury. Secondary injury is a major therapeutic target in mitigating the effects of spinal cord injury (SCI), and much research is …

Maternal Nicotine Exposure Leads To Augmented Expression Of The Antioxidant Adipose Tissue Triglyceride Lipase Long-Term In The White Adipose Of Female Rat Offspring., Nicole Barra, Taylor Vanduzer, Alison C. Holloway, Daniel B. Hardy

Physiology and Pharmacology Publications

Globally, approximately 10-25% of women smoke during pregnancy. Since nicotine is highly addictive, women may use nicotine containing products like nicotine replacement therapies for smoking cessation, but the long-term consequences of early life exposure to nicotine remain poorly defined. Our laboratory has previously demonstrated that maternal nicotine exposed (MNE) rat offspring exhibit hypertriglyceridemia due to increased hepatic de novo lipogenesis. Hypertriglyceridemia may also be attributed to impaired white adipose tissue (WAT) lipid storage; however, the effects of MNE on WAT are not completely understood. We hypothesize that nicotine-induced alterations in adipose function (e.g. lipid storage) underlie dyslipidemia in MNE adults. …

Developing Novel Therapeutics For Bacterial Lung Infections, Brandon J. Baer, Ruud Veldhuizen, Cory Yamashita

Western Research Forum

Background: Bacterial lung infections are leading causes of death worldwide. Unfortunately, increasing resistance to antibiotics and the inflammation often accompanying these infections are leading to poor outcomes despite antibiotic intervention. Complicating treatment further, the tree-like branching structure of the lung makes drug delivery to distal sites of infection difficult. Our research aims to address these challenges by developing new therapeutics and new tools to improve and assess drug delivery, bacterial killing and inflammation. Our therapy combines host defense peptides, which have been shown to kill antibiotic-resistant bacteria and down regulate inflammation, with a pulmonary vehicle, exogenous surfactant, that can improve …

Novel Antioxidant Properties Of Doxycycline, Dahn L. Clemens, Michael J. Duryee, Cleofes Sarmiento, Andrew Chiou, Jacob D. Mcgowan, Carlos D. Hunter, Sarah L. Schlichte, Jun Tian, Lynell W. Klassen, James R. O'Dell, Geoffrey M. Thiele, Ted R. Mikuls, Matthew C. Zimmerman, Daniel R. Anderson

Journal Articles: Cellular & Integrative Physiology

Doxycycline (DOX), a derivative of tetracycline, is a broad-spectrum antibiotic that exhibits a number of therapeutic activities in addition to its antibacterial properties. For example, DOX has been used in the management of a number of diseases characterized by chronic inflammation. One potential mechanism by which DOX inhibits the progression of these diseases is by reducing oxidative stress, thereby inhibiting subsequent lipid peroxidation and inflammatory responses. Herein, we tested the hypothesis that DOX directly scavenges reactive oxygen species (ROS) and inhibits the formation of redox-mediated malondialdehyde-acetaldehyde (MAA) protein adducts. Using a cell-free system, we demonstrated that DOX scavenged reactive oxygen …

Loss Of The Intellectual Disability And Autism Gene Cc2d1a And Its Homolog Cc2d1b Differentially Affect Spatial Memory, Anxiety, And Hyperactivity, Marta Zamarbide, Adam Oaks, Heather Pond, Julia Adelman, M. Chiara Manzini

Pharmacology and Physiology Faculty Publications

Hundreds of genes are mutated in non-syndromic intellectual disability (ID) and autism spectrum disorder (ASD), with each gene often involved in only a handful of cases. Such heterogeneity can be daunting, but rare recessive loss of function (LOF) mutations can be a good starting point to provide insight into the mechanisms of neurodevelopmental disease. Biallelic LOF mutations in the signaling scaffold CC2D1Acause a rare form of autosomal recessive ID, sometimes associated with ASD and seizures. In parallel, we recently reported that Cc2d1a-deficient mice present with cognitive and social deficits, hyperactivity and anxiety. In Drosophila, loss of the only …

Optimization Of Wavelength Selection For Multispectral Image Acquisition: A Case Study Of Atrial Ablation Lesions, Huda Asfour, S. Guan, Narine Muselimyan, Luther M. Swift, Murray Loew, Narine Sarvazyan

Pharmacology and Physiology Faculty Publications

In vivo autofluorescence hyperspectral imaging of moving objects can be challenging due to motion artifacts and to the limited amount of acquired photons. To address both limitations, we selectively reduced the number of spectral bands while maintaining accurate target identification. Several downsampling approaches were applied to data obtained from the atrial tissue of adult pigs with sites of radiofrequency ablation lesions. Standard image qualifiers such as the mean square error, the peak signal-to-noise ratio, the structural similarity index map, and an accuracy index of lesion component images were used to quantify the effects of spectral binning, an increased spectral distance …

Rhythm: An Open Source Imaging Toolkit For Cardiac Panoramic Optical Mapping, Christopher Gloschat, Kedar Aras, Shubnam Gupta, N. Rokhana Faye, Hanyu Zhang, Matthew W. Kay, Igor R Efimov, +Several Additional Authors

Pharmacology and Physiology Faculty Publications

Fluorescence optical imaging techniques have revolutionized the field of cardiac electrophysiology and advanced our understanding of complex electrical activities such as arrhythmias. However, traditional monocular optical mapping systems, despite having high spatial resolution, are restricted to a two-dimensional (2D) field of view. Consequently, tracking complex three-dimensional (3D) electrical waves such as during ventricular fibrillation is challenging as the waves rapidly move in and out of the field of view. This problem has been solved by panoramic imaging which uses multiple cameras to measure the electrical activity from the entire epicardial surface. However, the diverse engineering skill set and substantial resource …

S-Nitrosation Of Protein Phosphatase 1 Mediates Alcohol-Induced Ciliary Dysfunction, Michael E. Price, Adam J. Case, Jacqueline A. Pavlik, Jane M. Devasure, Todd A. Wyatt, Matthew C. Zimmerman, Joseph H. Sisson

Journal Articles: Cellular & Integrative Physiology

Alcohol use disorder (AUD) is a strong risk factor for development and mortality of pneumonia. Mucociliary clearance, a key innate defense against pneumonia, is perturbed by alcohol use. Specifically, ciliated airway cells lose the ability to increase ciliary beat frequency (CBF) to β-agonist stimulation after prolonged alcohol exposure. We previously found that alcohol activates protein phosphatase 1 (PP1) through a redox mechanism to cause ciliary dysfunction. Therefore, we hypothesized that PP1 activity is enhanced by alcohol exposure through an S-nitrosothiol-dependent mechanism resulting in desensitization of CBF stimulation. Bronchoalveolar S-nitrosothiol (SNO) content and tracheal PP1 activity was increased in wild-type (WT) …

Sympatho-Excitatory Response To Pulmonary Chemosensitive Spinal Afferent Activation In Anesthetized, Vagotomized Rats, Julia A. Shanks, Zhiqiu Xia, Steven J. Lisco, George J. Rozanski, Harold D. Schultz, Irving H. Zucker, Han-Jun Wang

Journal Articles: Cellular & Integrative Physiology

The sensory innervation of the lung is well known to be innervated by nerve fibers of both vagal and sympathetic origin. Although the vagal afferent innervation of the lung has been well characterized, less is known about physiological effects mediated by spinal sympathetic afferent fibers. We hypothesized that activation of sympathetic spinal afferent nerve fibers of the lung would result in an excitatory pressor reflex, similar to that previously characterized in the heart. In this study, we evaluated changes in renal sympathetic nerve activity (RSNA) and hemodynamics in response to activation of TRPV1-sensitive pulmonary spinal sensory fibers by agonist application …

Direct Conversion Of Mouse Astrocytes Into Neural Progenitor Cells And Specific Lineages Of Neurons, Kangmu Ma, Xiaobei Deng, Xiaohuan Xia, Zhaohuan Fan, Xinrui Qi, Yongxiang Wang, Yuju Li, Yizhao Ma, Qiang Chen, Hui Peng, Jianqing Ding, Chunhong Li, Yunlong Huang, Changhai Tian, Jialin C. Zheng

Journal Articles: Cellular & Integrative Physiology

Background: Cell replacement therapy has been envisioned as a promising treatment for neurodegenerative diseases. Due to the ethical concerns of ESCs-derived neural progenitor cells (NPCs) and tumorigenic potential of iPSCs, reprogramming of somatic cells directly into multipotent NPCs has emerged as a preferred approach for cell transplantation.

Methods: Mouse astrocytes were reprogrammed into NPCs by the overexpression of transcription factors (TFs) Foxg1, Sox2, and Brn2. The generation of subtypes of neurons was directed by the force expression of cell-type specific TFs Lhx8 or Foxa2/Lmx1a.

Results: Astrocyte-derived induced NPCs (AiNPCs) share high similarities, including the expression of NPC-specific genes, DNA methylation …