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 …

Stress Increases Peripheral Axon Growth And Regeneration Through Glucocorticoid Receptor-Dependent Transcriptional Programs, Jessica K. Lerch, Jessica K. Alexander, Kathryn M. Madalena, Dario Motti, Tam Quach, Akhil Dhamija, Alicia Zha, John C. Gensel, Jeanette Webster Marketon, Vance P. Lemmon, John L. Bixby, Phillip G. Popovich

Physiology Faculty Publications

Stress and glucocorticoid (GC) release are common behavioral and hormonal responses to injury or disease. In the brain, stress/GCs can alter neuron structure and function leading to cognitive impairment. Stress and GCs also exacerbate pain, but whether a corresponding change occurs in structural plasticity of sensory neurons is unknown. Here, we show that in female mice (Mus musculus) basal GC receptor (Nr3c1, also known as GR) expression in dorsal root ganglion (DRG) sensory neurons is 15-fold higher than in neurons in canonical stress-responsive brain regions (M. musculus). In response to stress or GCs, adult …

Induced Aberrant Organisms With Novel Ability To Protect Intestinal Integrity From Inflammation In An Animal Model, Helieh S. Oz

Physiology Faculty Publications

Abstract: Robust and balanced gut microbiota are required to support health and growth. Overgrowth of gut microbial or pathogens can change ecosystem balance, and compromise gut integrity to initiate gastrointestinal (GI) complications. There is no safe and effective modality against coccidiosis. Antibiotic additives routinely fed to food animals to protect against infection, are entered into the food chain, contaminate food products and pass to the consumers. Hypothesis: induced aberrant organisms possess distinct ultrastructure and are tolerated by immunodeficient-animals yet are non-pathogenic, but immunogenic in various strains of chicks to act as a preventive (vaccine) and eliminating the needs for antibiotic …

Body Size Predicts Cardiac And Vascular Resistance Effects On Men's And Women's Blood Pressure, Joyce M. Evans, Siqi Wang, Christopher Greb, Vladimir Kostas, Charles F. Knapp, Qingguang Zhang, Eric S. Roemmele, Michael B. Stenger, David C. Randall

Biomedical Engineering Faculty Publications

Key Points Summary

• We report how blood pressure, cardiac output and vascular resistance are related to height, weight, body surface area (BSA), and body mass index (BMI) in healthy young adults at supine rest and standing.
• Much inter-subject variability in young adult's blood pressure, currently attributed to health status, may actually result from inter-individual body size differences.
• Each cardiovascular variable is linearly related to height, weight and/or BSA (more than to BMI).
• When supine, cardiac output is positively related, while vascular resistance is negatively related, to body size. Upon standing, the change in vascular resistance is positively related to size. …

Carbonyl Reduction By Ymfi Completes The Modification Of Ef-P In Bacillus Subtilis To Prevent Accumulation Of An Inhibitory Modification State, Katherine R. Hummels, Anne Witzky, Andrei Rajkovic, Rodney Tollerson Ii, Lisa A. Jones, Michael Ibba, Daniel B. Kearns

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Translation elongation factor P (EF‐P) in Bacillus subtilis is required for a form of surface migration called swarming motility. Furthermore, B. subtilis EF‐P is post‐translationally modified with a 5‐aminopentanol group but the pathway necessary for the synthesis and ligation of the modification is unknown. Here we determine that the protein YmfI catalyzes the reduction of EF‐P‐5 aminopentanone to EF‐P‐5 aminopentanol. In the absence of YmfI, accumulation of 5‐aminopentanonated EF‐P is inhibitory to swarming motility. Suppressor mutations that enhanced swarming in the absence of YmfI were found at two positions on EF‐P, including one that changed the conserved modification site (Lys …

The Interommatidial Bristle Variability Of Diptera, Kimberly Palmer

Honors College Theses

Insects of the order Diptera are a popular biological model for understanding morphological trait evolution. One area of particular interest is the development of the compound eyes. While the development of ommatidia and photoreceptors has been thoroughly studied in this case, little attention has been paid to the interommatidial bristles (IOBs) present on the eyes of some dipteran families. A preliminary survey suggested that these bristles exhibit high variability among IOB families on multiple taxonomic levels and are not uniformly present or absent in any suborder of the Diptera. To confirm this observation, I conducted a literature search to …

Co-Modulation Masking Release Begins In The Auditory Periphery, Kareem R. Hussein, Agudemu Borjigan, Mark Sayles

The Summer Undergraduate Research Fellowship (SURF) Symposium

Understanding speech in noisy environments can be difficult, especially for people with hearing loss. The background noise can cover up the sounds of interest. Normally, the auditory system works to alleviate this problem by tagging and then cancelling the noise. Our experiments are aimed at understanding the mechanism of this noise cancellation process. We hypothesize that non-linear signal processing in the mammalian cochlea (the most peripheral part of the auditory system) is the basis of noise cancellation. To test this hypothesis, we measured the responses of auditory-nerve fibers (ANFs) to sounds embedded in background noise with different statistical properties. ANFs …

Designing An Authentic Behavioral Research Experience In The Classroom Using Siamese Fighting Fish, Betta Splendens, Gianne Souza, Ronald M. Coleman

STAR Program Research Presentations

Recently there have been major shifts in biology education towards emphasizing the teaching of the scientific process to more closely reflect actual scientific practices. Authentic research experiences require the development of many higher order cognitive skills. Creating an authentic research experience that appropriately scaffolds the development of these complex skills while engaging individual student motivation remains challenging in classroom settings. Some common challenges include limited time available for working with large numbers of students, cramped working areas, and limited funding and materials resources. Using the Siamese Fighting Fish, Betta splendens, we have created an economically viable authentic animal behavioral …

Molecular Mechanisms Of Dna Replication Initiation In Hpvs With Genetic Variations Leading To Cellular Carcinogenesis, Gulden Yilmaz

Graduate School of Biomedical Sciences Theses and Dissertations

Human papillomaviruses are a vast family of double-stranded DNA viruses containing non-carcinogenic and carcinogenic types, whose crucial differences remain unknown, except for the difference in the frequency of DNA replication. The human papillomavirus (HPV) E2 protein regulates the initiation of viral DNA replication and transcription. Its recognition and binding to four 12 bp palindromic sequences in the viral origin is essential for its function. Little is known about the DNA binding mechanism of the E2 protein found in HPV types that have low risk for oncogenicity (low-risk) as well as the roles of various elements of the individual binding sites. …

Chaperoning Ef Hands That Shape Calcium Response: Ncald, Hpca And S100b, Jingyi Zhang

Graduate School of Biomedical Sciences Theses and Dissertations

All organisms have an internal clock with a defined period between repetitions of activities. The period for circadian clock in human is 24.5 hours, while in mouse and rat, it is 23.5 hours. However, all organisms are forced to be in synchronization with their environment. A major environmental force that resets the internal clock to 24 hours is light. This phenomenon is defined as “light entrainment” or “phase-setting”. It is unclear how this entrainment process occurs. Studies from this laboratory indicate a role for two neuronal calcium sensor proteins: Neurocalcin  (NCALD) and S100B. For these two genes, mRNA as …

Elongation Factor P Interactions With The Ribosome Are Independent Of Pausing, Rodney Tollerson Ii, Anne Witzky, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Bacterial elongation factor P (EF-P) plays a pivotal role in the translation of polyproline motifs. To stimulate peptide bond formation, EF-P must enter the ribosome via an empty E-site. Using fluorescence-based single-molecule tracking, Mohapatra et al. (S. Mohapatra, H. Choi, X. Ge, S. Sanyal, and J. C. Weisshaar, mBio 8:e00300-17, 2017, https://doi.org/10.1128/mBio.00300-17 ) monitored the cellular distribution of EF-P and quantified the frequency of association between EF-P and the ribosome under various conditions. Findings from the study showed that EF-P has a localization pattern that is strikingly similar to that of ribosomes. Intriguingly, EF-P was seen to bind ribosomes more …

Production Of A Gonadotropin-Releasing Hormone 2 Receptor Knockdown (Gnrhr2 Kd) Swine Line., Amy T. Desaulniers, Rebecca Middleton, Ginger A. Mills, Clay A. Lents, Brett R. White

Department of Animal Science: Faculty Publications

Swine are the only livestock species that produce both the second mammalian isoform of gonadotropin-releasing hormone (GNRH2) and its receptor (GNRHR2). Previously, we reported that GNRH2 and GNRHR2 mediate LH-independent testosterone secretion from porcine testes. To further explore this ligand-receptor complex, a pig model with reduced GNRHR2 expression was developed. Small hairpin RNA sequences targeting porcine GNRHR2 were subcloned into a lentiviral-based vector, lentiviral particles were generated and microinjected into the perivitelline space of zygotes, and embryos were transferred into a recipient. One GNRHR2 knockdown (KD) female was born that subsequently produced 80 piglets from 6 litters with 46 hemizygous …

Mitochondrial Transcription Factor A'S Role In Heart Failure., George H. Kunkel

Electronic Theses and Dissertations

Background: An essential mitochondrial component, Mitochondrial Transcription Factor A (TFAM) is reduced within the failing heart. TFAM maintains regulatory functions of cardiomyocyte physiology and stability. Mitochondrial Transcription Factor A forms a mitochondrial nucleoid anti-oxidant structure and reduces pathophysiological abnormalities to structural and contractile proteins. Overall, this functions to physically stabilize mtDNA. Significant molecular changes such as a loss of TFAM drive pathophysiological concentrations of cytoplasmic Ca2+ and reactive oxygen species. Both of these factors induce proteolytic enzymes to degrade the physiological cardiomyocyte. In TFAMs absence, heart function deteriorates and hypertrophic expansion ensues: thereby changing the physiological myocardium to a pathological …

Optimization Of Mitochondrial Isolation Techniques For Intraspinal Transplantation Procedures, Jenna L. Gollihue, Samir P. Patel, Charles B. Mashburn, Khalid C. Eldahan, Patrick G. Sullivan, Alexander G. Rabchevsky

Physiology Faculty Publications

Background—Proper mitochondrial function is essential to maintain normal cellular bioenergetics and ionic homeostasis. In instances of severe tissue damage, such as traumatic brain and spinal cord injury, mitochondria become damaged and unregulated leading to cell death. The relatively unexplored field of mitochondrial transplantation following neurotrauma is based on the theory that replacing damaged mitochondria with exogenous respiratory-competent mitochondria can restore overall tissue bioenergetics.

New Method—We optimized techniques in vitro to prepare suspensions of isolated mitochondria for transplantation in vivo. Mitochondria isolated from cell culture were genetically labeled with turbo-green fluorescent protein (tGFP) for imaging and tracking purposes …

Role Of Tlrs, Hippo-Yap1 Signaling, And Micrornas In Cardiac Repair And Regeneration Of Damaged Myocardium During Ischemic Injury, Xiaohui Wang

Electronic Theses and Dissertations

Cardiovascular disease is a leading cause of death in the United States. Toll-like receptor (TLR)-mediated pathways have been demonstrated to play a role in myocardial ischemia/reperfusion (I/R) injury. We and others have shown that PI3K/Akt signaling is involved in regulating cellular survival and protecting the myocardium from I/R induced injury. In this dissertation, we provide compelling evidence that miR-125b serves to “fine tune” TLR mediated NF-kB responses by repressing TNF-a and TRAF6 expression. We constructed lentiviral expressing miR-125b, delivered it into the myocardium. The data showed that delivery of lentivirus expressing miR-125b significantly reduces myocardial infarct size and improves cardiac …

Preclinical Development Of Therapeutic Strategies Against Triple-Negative And Inflammatory Breast Cancer, Angie M. Torres-Adorno

Dissertations and Theses (Open Access)

Triple-negative (TNBC) and inflammatory (IBC) breast cancer are the most aggressive forms of breast cancer, accounting for 20% and 10% of cancer-related deaths, respectively. Among IBC cases, 30% are additionally classified with TNBC molecular pathology, a diagnosis that significantly worsens patient’s prognosis. The current lack of TNBC and IBC molecular understanding prevents the development of effective therapeutic strategies. To identify effective treatments, we explored aberrant apoptosis pathways and cell membrane fluidity as novel therapeutic targets.

We first identified an effective therapeutic strategy against TNBC and IBC by pro-apoptotic protein NOXA-mediated inhibition of the anti-apoptotic protein MCL1 following inhibition of histone …

Removal Of Endocrine Disrupting Compounds Using Membrane Bioreactor, Mohanad Ali Abdulsahib Kamaz

Graduate Theses and Dissertations

The presence of endocrine disrupting compounds (EDCs) and pharmaceutically active compounds (PhAC) such as pesticides, personal care products, antibiotics and pharmaceutical compounds, in sewage, industrial, and domestic waters has extensively become the major concern for health and environmental organizations. These compounds have the ability to interact with mammalian endocrine system and disrupting their functions. The traditional activated sludge processes are designed to degrade solids, organic carbon and nitrogen loading. Although several treatment steps in a wastewater treatment plant can contribute to partial removal of EDCs, effective removal has been a challenge due to their resistant chemical and biological degradation and …

Mri T2 Signal Changes Indicate Tau Pathophysiology In A Murine Alzheimer's Disease Model, Rajan Deep Adhikari

Theses and Dissertations

Pathogenesis, diagnosis and treatment, the essential domains in medical practice, seem helpless to address Alzheimer's disease (AD). With a huge mortality rate, it is looming and threatening the socioeconomic barrier. Despite many different studies, the pathogenesis of AD remains inconclusive. However, growing numbers of studies suggest oxidative stress to contribute to the initiation and progression of AD. We propose an iron hypothesis: iron mediated oxidative damage by reactive oxygen species (ROS), which induces protective roles of amyloid beta and hyper-phosphorylated tau (HP-tau) to sequester iron and limit the disease. We propose to study such mechanism using transgenic mice models for …

The Effect Of Blinded Hydration State On Thermoregulation And Performance In Male Cyclists, Jon David Adams

Graduate Theses and Dissertations

Purpose: The purpose of these studies was to observe the effect of dehydration on exercise performance while subjects were blinded to their hydration status. Methods: Study 1: Seven male cyclists (weight: 71±8 kg, body fat: 14±6%, VO2peak: 59.4±6 ml∙kg-1·min-1) exercised for 2 hours on a cycle ergometer at 55% VO2peak, in a hot-dry environment (35°C, 30% rh), with a nasogastric (NG) tube under euhydrated (EUH-NT) and hypohydrated (DEH-NT) conditions. In both trials, thirst was matched by drinking 25 mL every 5 min. In the EUH-NT trial sweat losses were fully replaced via the NG tube. Following the 2 hours of …

Noninvasive Measures Of Stress And Lameness In Broilers, Shawna L. Weimer

Graduate Theses and Dissertations

The concept of broiler chicken welfare has evolved from a component of animal husbandry to a label on a chicken product package. Recent attention from the public has led to the need for higher welfare standards for animal production. A primary concern of broiler production is low activity/locomotion attributed to fast growth rates leading to poor leg health. To collect the scientific data necessary to determine conditions providing the best welfare for the bird, multiple methods of assessment are required. Stress is influenced by external (temperature, humidity, lighting, stocking density) and internal (metabolism, thermoregulation, hormonal balance) factors. This series of …

Neurometabolic And Electrophysiological Changes During Cortical Spreading Depolarization: Multimodal Approach Based On A Lactate-Glucose Dual Microbiosensor Arrays, Cátia F. Lourenço, Ana Ledo, Greg A. Gerhardt, João Laranjinha, Rui M. Barbosa

Center for Microelectrode Technology Faculty Publications

Spreading depolarization (SD) is a slow propagating wave of strong depolarization of neural cells, implicated in several neuropathological conditions. The breakdown of brain homeostasis promotes significant hemodynamic and metabolic alterations, which impacts on neuronal function. In this work we aimed to develop an innovative multimodal approach, encompassing metabolic, electric and hemodynamic measurements, tailored but not limited to study SD. This was based on a novel dual-biosensor based on microelectrode arrays designed to simultaneously monitor lactate and glucose fluctuations and ongoing neuronal activity with high spatial and temporal resolution. In vitroevaluation of dual lactate-glucose microbiosensor revealed an extended linear range, …

Comparison Of Efficacy And Safety Between First And Second Generation Drug-Eluting Stents In Patients With Stable Coronary Artery Disease: A Single-Center Retrospective Study, Ru Liu, Fei Xiong, Yuan Wen, Yuan-Liang Ma, Yi Yao, Zhan Gao, Bo Xu, Yue-Jin Yang, Shu-Bin Qiao, Run-Lin Gao, Jin-Qing Yuan

Physiology Faculty Publications

Background: Lots of trials demonstrate that second-generation drug-eluting stents (G2-DES), with their improved properties, offer significantly superior efficacy and safety profiles compared to first generation DES (G1-DES) for patients with coronary artery disease (CAD) receiving percutaneous coronary intervention (PCI). This study aimed to verify the advantage of G2-DES over G1-DES in Chinese patients with stable CAD (SCAD).

Methods: For this retrospective observational analysis, 2709 SCAD patients with either G1-DES (n = 863) or G2-DES (n = 1846) were enrolled consecutively throughout 2013. Propensity score matching (PSM) was applied to control differing baseline factors. Two-year outcomes, including major adverse …

Alzheimer's Disease Genetics And Abca7 Splicing, Jared B. Vasquez, James F. Simpson, Ryan Harpole, Steven Estus

Physiology Faculty Publications

Both common and rare polymorphisms within ABCA7 have been associated with Alzheimer’s disease (AD). In particular, the rare AD associated polymorphism rs200538373 was associated with altered ABCA7 exon 41 splicing and an AD risk odds ratio of ∼1.9. To probe the role of this polymorphism in ABCA7 splicing, we used minigene studies and qPCR of human brain RNA. We report aberrant ABCA7 exon 41 splicing in the brain of a carrier of the rs200538373 minor C allele. Moreover, minigene studies show that rs200538373 acts as a robust functional variant in vitro. Lastly, although the ABCA7 isoform with an extended …

Increases In Variation Of Barbell Kinematics Are Observed With Increasing Intensity In A Graded Back Squat Test, Kevin M. Carroll, Kimitake Sato, Caleb D. Bazyler, N. Travis Triplett, Michael H. Stone

ETSU Faculty Works

The purpose of the current study was two-fold: (1) To examine the variation in velocity and power with increasing intensity in the back squat among subjects; and (2) To explore individual subject characteristics as possible explanations for variations of velocity in the back squat. Fourteen recreationally trained male subjects with experience in the back squat agreed to participate in the study (age = 25.0 ± 2.6 years, height = 178.9 ± 8.1 cm, body mass = 88.2 ± 15.8 kg). One-repetition maximums (1RM) were performed for each subject on force platforms with four linear position transducers attached to the barbell. …

Examination Of The Impact Of Condensed Biofeedback Training On Acute Stress Responses, Meredith Carroll, Brent Winslow

Aeronautics Faculty Publications

The objective of this study was to measure the effects of a condensed 90 minute Biofeedback Training (BFT) method on stress response and decision making performance under stress. Forty one novice male participants received either BFT training, which incorporated diaphragmatic breathing with Stress Inoculation Training (SIT), or a control training task. Participants completed pre- and post-training assessments which incorporated a socio evaluative stress induction method followed immediately by performance of a simulation- based decision making under stress scenario. Stress was assessed using real-time physiological measures of the Autonomic Nervous System (ANS) response and cortisol measures of the Hypothalamic-Pituitary-Adrenal (HPA) axis …

Differential Requirement For Satellite Cells During Overload-Induced Muscle Hypertrophy In Growing Versus Mature Mice, Kevin A. Murach, Sarah H. White, Yuan Wen, Angel Ho, Esther E. Dupont-Versteegden, John J. Mccarthy, Charlotte A. Peterson

Physical Therapy Faculty Publications

Background: Pax7+ satellite cells are required for skeletal muscle fiber growth during post-natal development in mice. Satellite cell-mediated myonuclear accretion also appears to persist into early adulthood. Given the important role of satellite cells during muscle development, we hypothesized that the necessity of satellite cells for adaptation to an imposed hypertrophic stimulus depends on maturational age.

Methods: Pax7^CreER-R26R^DTA mice were treated for 5 days with vehicle (satellite cell-replete, SC+) or tamoxifen (satellite cell-depleted, SC-) at 2 months (young) and 4 months (mature) of age. Following a 2-week washout, mice were subjected to sham surgery or 10 day …

The Role Of Lkb1 In Obesity-Induced Skeletal Muscle Inflammation And Insulin Resistance, David Thomson

Journal of Undergraduate Research

The incidence of obesity and the health consequences that accompany it have increased rapidly over the past decade. Understanding the molecular pathways involved in its development will be crucial in developing novel treatment strategies for obesity and associated disorders. Low-grade inflammation likely plays a major role in many of the complications of obesity. We proposed to study the role of liver kinase B1 (LKB1) in the development of inflammation and insulin resistance in obese mice and saturated fatty acid-induced insulin-resistant cells.

Synaptic Modification Of Inhibitory Inputs To Gaba Neurons In The Ventral Tegmental Area: A Novel Potential Target Mediating Reward And Addiction In The Brain, Jeff Edwards

Journal of Undergraduate Research

The objectives of this award were met, especially in regard to the mentoring focus of the award. The students have been mentored and trained in an effective manner as outlined in my Mentoring Plan (abbreviated below). This includes mentoring students in research, writing, publishing, presenting at conferences, etc. Indeed, one measure of the success of mentoring is demonstrated by the fact that all the students graduating from my lab during this time were accepted to the professional school of their choice (see students listed below). Research, especially where the students are actually involved in all aspects of it including data …

Girk2 And Gababr1 Downregulate In Response To Ttx As Girk2, Gababr1, And Gababr2 Are Not Affected By Bc Treatment, Staci E. Hammer, Amanda Weiss, Hee Jung Chung

PRECS student projects

Homeostatic plasticity is the response neurons undergo to regulate changes in excitability levels and bring the cells back to homeostasis. Research on homeostatic plasticity at the molecular level can lead to improved treatments for neurological diseases such as epilepsy, Alzheimer's, and schizophrenia. The research featured in this poster looks at the response of GIRK (G protein-gated inwardly rectifying potassium) channels and GABAb (gamma-amniobutyric acid) receptors to neurotoxins, tetrodotoxin (TTX) or bicuculline (BC).

Prolonged activity blockade of 48 hour TTX treatment significantly reduced GABABR1 and GIRK2 expression. This supports the idea that because these two proteins inhibit action potentials, there will …