Medical Physiology Commons^™

Overexpressed Somatic Alleles Are Enriched In Functional Elements In Breast Cancer., Paula Restrepo, Mercedeh Movassagh, Nawaf Alomran, Christian Miller, Muzi Li, Chris Trenkov, Yulian Manchev, Sonali Bahl, Stephanie Warnken, Liam Spurr, Tatiyana Apanasovich, Keith Crandall, Nathan Edwards, Anelia Horvath

Pharmacology and Physiology Faculty Publications

Asymmetric allele content in the transcriptome can be indicative of functional and selective features of the underlying genetic variants. Yet, imbalanced alleles, especially from diploid genome regions, are poorly explored in cancer. Here we systematically quantify and integrate the variant allele fraction from corresponding RNA and DNA sequence data from patients with breast cancer acquired through The Cancer Genome Atlas (TCGA). We test for correlation between allele prevalence and functionality in known cancer-implicated genes from the Cancer Gene Census (CGC). We document significant allele-preferential expression of functional variants in CGC genes and across the entire dataset. Notably, we find frequent …

Carotid Body-Mediated Chemoreflex Drive In The Setting Of Low And High Output Heart Failure., Rodrigo Del Rio, David C. Andrade, Camilo Toledo, Hugo S. Diaz, Claudia Lucero, Alexis Arce-Alvarez, Noah J. Marcus, Harold D. Schultz

Journal Articles: Cellular & Integrative Physiology

Enhanced carotid body (CB) chemoreflex function is strongly related to cardiorespiratory disorders and disease progression in heart failure (HF). The mechanisms underlying CB sensitization during HF are not fully understood, however previous work indicates blood flow per se can affect CB function. Then, we hypothesized that the CB-mediated chemoreflex drive will be enhanced only in low output HF but not in high output HF. Myocardial infarcted rats and aorto-caval fistulated rats were used as a low output HF model (MI-CHF) and as a high output HF model (AV-CHF), respectively. Blood flow supply to the CB region was decreased only in …

Brain Microvascular Injury And White Matter Disease Provoked By Diabetes-Associated Hyperamylinemia, Han Ly, Nirmal Verma, Fengen Wu, Miao Liu, Kathryn E. Saatman, Peter T. Nelson, John T. Slevin, Larry B. Goldstein, Geert Jan Biessels, Florin Despa

Pharmacology and Nutritional Sciences Faculty Publications

OBJECTIVE: The brain blood vessels of patients with type 2 diabetes and dementia have deposition of amylin, an amyloidogenic hormone cosecreted with insulin. It is not known whether vascular amylin deposition is a consequence or a trigger of vascular injury. We tested the hypothesis that the vascular amylin deposits cause endothelial dysfunction and microvascular injury and are modulated by amylin transport in the brain via plasma apolipoproteins.

METHODS: Rats overexpressing amyloidogenic (human) amylin in the pancreas (HIP rats) and amylin knockout (AKO) rats intravenously infused with aggregated amylin were used for in vivo phenotyping. We also carried out biochemical analyses …

Strength-Based Physiological Profiles Of Ncaa Division I Womens Basketball And Gymnastics Athletes: Implications For Injury Risk Assessment, Curtis Cazier

All Graduate Plan B and other Reports, Spring 1920 to Spring 2023

The purpose of this study was to provide a comprehensive strength-based physiological profile of women’s collegiate basketball and gymnastic athletes; and to make sport-specific comparisons for various isokinetic and maximal and rapid isometric strength characteristics of the knee flexor and extensor muscles. A focus on antagonist muscle balance (hamstrings to quadriceps ratios, H:Q) will help elucidate particular vulnerabilities in these at-risk female athletes. Fourteen Division I collegiate level women’s basketball and 13 women’s gymnastics athletes performed isokinetic and isometric strength testing of the knee extensors and flexors. Outcome measures included absolute and body mass normalized (relative) isokinetic and isometric peak …

Enduring Chronic Kidney Disease: An Investigation Of Psychosocial Factors And Life Satisfaction In Older Adults Receiving Dialysis Treatment, Bailee Sobotka

Honors Program: Senior Projects (Public)

Chronic kidney disease is a condition during which the kidneys begin to shut down and no longer filter blood efficiently. Once the disease has progressed far enough, dialysis treatments are mandatory to sustain life. To further understand how older adults receiving dialysis treatments cope with their disease, psychosocial factors were evaluated to investigate possible correlations with life satisfaction using a Life Satisfaction Index Z (LSI-Z). Expected correlations with life satisfaction were sociability, financial satisfaction, importance of spirituality, and activities of daily living scores. Interviews were conducted with 30 dialysis patients and results were analyzed using various statistical measures. Significant correlations …

Local Anesthesia Toxicity, Nicole Mccleery

Nursing Student Class Projects (Formerly MSN)

Local anesthesia (LA) provides a way to relieve temporary pain in a small part of the body and has been used for over 100 years (Fencl, 2015). LA also prevents the passage of surgical stimuli into the central nervous system (CNS) making a surgical procedure less painful for the patient (Noble, 2015). According to Noble, “altering the passage of stimuli from smaller diameter neurons in a confined area with lower drug dosages is called LA, such as the injection of LA around a surgical incision” (Noble, 2015, p.325). LA can be used in a variety of settings, such as in …

Changes In The Gut Microbial Communities Following Addition Of Walnuts To The Diet, Lauri O. Byerley, Derrick Samuelson, Eugene Blanchard, Meng Luo, Brittany N. Lorenzen, Shelia Banks, Monica A. Ponder, David A. Welsh, Christopher M. Taylor

School of Graduate Studies Faculty Publications

Walnuts are rich in omega-3 fatty acids, phytochemicals and antioxidants making them unique compared to other foods. Consuming walnuts has been associated with health benefits including a reduced risk of heart disease and cancer. Dysbiosis of the gut microbiome has been linked to several chronic diseases. One potential mechanism by which walnuts may exert their health benefit is through modifying the gut microbiome. This study identified the changes in the gut microbial communities that occur following the inclusion of walnuts in the diet. Male Fischer 344 rats (n=20) were randomly assigned to one of two diets for as long as …

Maternal Nicotine Exposure Leads To Decreased Cardiac Protein Disulfide Isomerase And Impaired Mitochondrial Function In Male Rat Offspring., Nicole G Barra, Maria Lisyansky, Taylor A Vanduzer, Sandeep Raha, Alison C Holloway, Daniel B Hardy

Physiology and Pharmacology Publications

Smoking throughout pregnancy can lead to complications during gestation, parturition and neonatal development. Thus, nicotine replacement therapies are a popular alternative thought to be safer than cigarettes. However, recent studies in rodents suggest that fetal and neonatal nicotine exposure alone results in cardiac dysfunction and high blood pressure. While it is well known that perinatal nicotine exposure causes increased congenital abnormalities, the mechanisms underlying longer-term deficits in cardiac function are not completely understood. Recently, our laboratory demonstrated that nicotine impairs placental protein disulfide isomerase (PDI) triggering an increase in endoplasmic reticulum stress, leading us to hypothesize that this may also …

Increased Incidence Of Non-Alcoholic Fatty Liver Disease In Male Rat Offspring Exposed To Fluoxetine During Fetal And Neonatal Life Involves The Nlrp3 Inflammasome And Augmented De Novo Hepatic Lipogenesis., Nicole E De Long, Daniel B Hardy, Noelle Ma, Alison C Holloway

Physiology and Pharmacology Publications

Up to 10% of women take selective serotonin reuptake inhibitors (SSRI) during pregnancy. Children exposed to SSRIs in utero have an increased risk of being overweight suggesting that fetal exposure to SSRIs can cause permanent metabolic changes. We have previously shown in rats that fetal and neonatal exposure to the SSRI antidepressant fluoxetine results in metabolic perturbations including increased hepatic triglyceride content; a hallmark of non-alcoholic fatty liver disease (NAFLD). Therefore, the aim of this study was to identify the mechanism(s) underlying the fluoxetine-induced increase in intrahepatic triglyceride content. Female nulliparous Wistar rats were given vehicle or fluoxetine (10 mg/kg/day) …

Maternal Undernutrition And Long-Term Effects On Hepatic Function, Daniel B. Hardy

Physiology and Pharmacology Publications

Undernutrition in utero, regardless of the source, can impair proper liver development leading to long-term metabolic dysfunction. Understanding the molecular mechanisms underlying how nutritional deficits during perinatal life lead to permanent alterations in hepatic gene expression will provide better therapeutic strategies to alleviate the undernourished liver in postnatal life. This chapter addresses the different experimental models of undernutrition in utero, and highlights the direct and indirect mechanisms involved leading to metabolic diseases in the liver. These include hypoxia, oxidative stress, epigenetic alterations, and endoplasmic reticulum (ER) stress. In addition, promising perinatal nutritional and pharmaceutical interventions are highlighted which …

Effects Of Protein Deficiency On Perinatal And Postnatal Health Outcomes, Shelby L. Oke, Daniel B. Hardy

Physiology and Pharmacology Publications

There are a variety of environmental insults that can occur during pregnancy which cause low birth weight and poor fetal health outcomes. One such insult is maternal malnutrition, which can be further narrowed down to a low protein diet during gestation. Studies show that perinatal protein deficiencies can impair proper organ growth and development, leading to long-term metabolic dysfunction. Understanding the molecular mechanisms that underlie how this deficiency leads to adverse developmental outcomes is essential for establishing better therapeuticstrategies that may alleviate or prevent diseases in later life. This chapter reviews how perinatal protein restriction in humans and animals leads …

Perinatal Malnutrition And Epigenetic Regulation Of Long-Term Metabolism In The Liver And Adipose Tissue, Daniel B. Hardy

Physiology and Pharmacology Publications

Maternal malnutrition in perinatal life can have long-lasting adverse effects on glucose and lipid homeostasis in the offspring, culminating in dyslipidemia, insulin resistance and obesity. Understanding the molecular mechanisms underlying how these nutritional deficits during perinatal life lead to permanent changes in hepatic and adipose function will provide efficacious therapeutic strategies to mitigate these metabolic defects short- and long-term. This chapter addresses how epigenetic mechanisms mediate alterations in hepatic and adipose gene expression identified from clinical studies and different experimental models of maternal malnutrition. These include DNA methylation, post-translational histone modifications, and microRNAs.

Neuromuscular Function In Women Postpartum, Rita Deering

Dissertations (1934 -)

Efficient abdominal muscle function is important for functional mobility in men and women, and dysfunction of these muscles has been associated with impaired function such as low back pain. This dissertation explored abdominal muscle function in healthy young men and young women who have never been pregnant (nulligravid). As pregnancy and child birth also impact the tissues of the abdominal wall, this dissertation will also explore abdominal muscle function in postpartum women. This dissertation involved three primary aims. Aim1 compared abdominal muscle function and experimental pain perception in males and nulligravid females. Maximal strength over a range of trunk angles, …

Alternative Splicing Promotes Tumour Aggressiveness And Drug Resistance In African American Prostate Cancer., Bi-Dar Wang, Kristin Ceniccola, Sujin Hwang, Ramez Andrawis, Anelia Horvath, Jennifer A Freedman, Jacqueline Olender, Stefan Knapp, Travers Ching, Lana Garmire, Vyomesh Patel, Mariano A Garcia-Blanco, Steven R Patierno, Norman H Lee

Pharmacology and Physiology Faculty Publications

linical challenges exist in reducing prostate cancer (PCa) disparities. The RNA splicing landscape of PCa across racial populations has not been fully explored as a potential molecular mechanism contributing to race-related tumour aggressiveness. Here, we identify novel genome-wide, race-specific RNA splicing events as critical drivers of PCa aggressiveness and therapeutic resistance in African American (AA) men. AA-enriched splice variants of PIK3CD, FGFR3, TSC2 and RASGRP2 contribute to greater oncogenic potential compared with corresponding European American (EA)-expressing variants. Ectopic overexpression of the newly cloned AA-enriched variant, PIK3CD-S, in EA PCa cell lines enhances AKT/mTOR signalling and increases proliferative …

H2s And Homocysteine Control A Novel Feedback Regulation Of Cystathionine Beta Synthase And Cystathionine Gamma Lyase In Cardiomyocytes., Shyam Sundar Nandi, Paras K. Mishra

Journal Articles: Cellular & Integrative Physiology

Hydrogen sulfide (H2S), a cardioprotective gas, is endogenously produced from homocysteine by cystathionine beta synthase (CBS) and cystathionine gamma lyase (CSE) enzymes. However, effect of H2S or homocysteine on CBS and CSE expression, and cross-talk between CBS and CSE are unclear. We hypothesize that homocysteine and H2S regulate CBS and CSE expressions in a dose dependent manner in cardiomyocytes, and CBS deficiency induces cardiac CSE expression. To test the hypothesis, we treated murine atrial HL1 cardiomyocytes with increasing doses of homocysteine or Na2S/GYY4137, a H2S donor, and measured the levels of CBS and CSE. We found that homocysteine upregulates CSE …

Mixed-Mode Oscillations In Pyramidal Neurons Under Antiepileptic Drug Conditions, Babak V-Ghaffari, M. Kouhnavard, Sherif M. Elbasiouny

Neuroscience, Cell Biology, & Physiology Faculty Publications

Subthreshold oscillations in combination with large-amplitude oscillations generate mixedmode oscillations (MMOs), which mediate various spatial and temporal cognition and memory processes and behavioral motor tasks. Although many studies have shown that canard theory is a reliable method to investigate the properties underlying the MMOs phenomena, the relationship between the results obtained by applying canard theory and conductancebased models of neurons and their electrophysiological mechanisms are still not well understood. The goal of this study was to apply canard theory to the conductance-based model of pyramidal neurons in layer V of the Entorhinal Cortex to investigate the properties of MMOs under …

A Novel Micro Cold Atmospheric Plasma Device For Glioblastoma Both In Vitro And In Vivo., Zhitong Chen, Hayk Simonyan, Xiaoqian Cheng, Eda Gjika, Li Lin, Jerome Canady, Jonathan H Sherman, Colin Young, Michael Keidar

Pharmacology and Physiology Faculty Publications

: Cold atmospheric plasma (CAP) treatment is a rapidly expanding and emerging technology for cancer treatment. Direct CAP jet irradiation is limited to the skin and it can also be invoked as a supplement therapy during surgery as it only causes cell death in the upper three to five cell layers. However, the current cannulas from which the plasma emanates are too large for intracranial applications. To enhance efficiency and expand the applicability of the CAP method for brain tumors and reduce the gas flow rate and size of the plasma jet, a novel micro-sized CAP device (µCAP) was developed …

Thermal And Developmental Ecology Of Pupfish, Cyprinodon, Alexander Jones

UNLV Theses, Dissertations, Professional Papers, and Capstones

Pupfish from the genus Cyprinodon are among the most endangered groups of fishes on the planet, with nearly 40% of species being threatened with extinction. These pupfishes are often assumed to be the most temperature tolerant of all fish, coping with temperatures as low as 0 °C and as high as 44 °C. However, conflicting data exist and certain measures of thermal tolerance are not markedly higher in pupfish compared to common game fish. Pupfish egg production and growth has been known to be hampered at temperatures well below what they apparently experience in nature. I addressed why eggs fail …

Factors Influencing Induction Of Desiccation Tolerance In Bryophytes: Redefining Fundamental Aspects Of The Organism’S Relationship With The Environment In Xeric Habitats, Joshua Lee Greenwood

UNLV Theses, Dissertations, Professional Papers, and Capstones

If one wishes to understand the ecological role, range, habitat preferences, selective pressures, reproduction, response to climate change, and the potential for survival under climactic change, range expansion and range contraction for species and populations of bryophytes, an understanding of their survival of the desiccated state, is essential. In order to further our understanding of desiccation tolerance in mosses, three projects were undertaken. The first of these investigated the nature of desiccation tolerance in mosses, specifically if desiccation tolerance can be induced; thereby providing a desiccation tolerant phenotype in a moss species generally considered desiccation sensitive (Physcomitrella patens, the model …

G Protein-Coupled Kiss1 Receptor Is Overexpressed In Triple Negative Breast Cancer And Promotes Drug Resistance., Alexandra Blake, Magdalena Dragan, Rommel G Tirona, Daniel B Hardy, Muriel Brackstone, Alan B Tuck, Andy V Babwah, Moshmi Bhattacharya

Physiology and Pharmacology Publications

Triple-negative breast cancer (TNBC) lacks the expression of estrogen receptor α, progesterone receptor and human epidermal growth factor receptor 2 (HER2). TNBC patients lack targeted therapies, as they fail to respond to endocrine and anti-HER2 therapy. Prognosis for this aggressive cancer subtype is poor and survival is limited due to the development of resistance to available chemotherapies and resultant metastases. The mechanisms regulating tumor resistance are poorly understood. Here we demonstrate that the G protein-coupled kisspeptin receptor (KISS1R) promotes drug resistance in TNBC cells. KISS1R binds kisspeptins, peptide products of the KISS1 gene and in numerous cancers, this signaling pathway …