Digital Commons Network^™

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 …

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 …

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 …

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 …

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 …

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 …

Anatomy And Physiology I & Ii Labs (Uga), Deloris Hesse, Deanna Cozart, Brett Szymik, Rob Nichols

Biological Sciences Grants Collections

This Grants Collection for Anatomy and Physiology I & II Labs was created under a Round Four ALG Textbook Transformation Grant.

Affordable Learning Georgia Grants Collections are intended to provide faculty with the frameworks to quickly implement or revise the same materials as a Textbook Transformation Grants team, along with the aims and lessons learned from project teams during the implementation process.

Documents are in .pdf format, with a separate .docx (Word) version available for download. Each collection contains the following materials:

• Linked Syllabus
• Initial Proposal
• Final Report

Temperature As A Circadian Marker In Older Human Subjects: Relationship To Metabolic Syndrome And Diabetes, Brianna D. Harfmann, Elizabeth A. Schroder, Jonathan H. England, Natalie J. Senn, Philip M. Westgate, Karyn A. Esser, Philip A. Kern

Internal Medicine Faculty Publications

Background: Circadian rhythms are characterized by approximate 24-hour oscillations in physiological and behavioral processes. Disruptions in these endogenous rhythms, most commonly associated with shift work and/or lifestyle, are recognized to be detrimental to health. Several studies have demonstrated a high correlation between disrupted circadian rhythms and metabolic disease. The aim of this study was to determine which metabolic parameters correlate with physiological measures of circadian temperature amplitude (TempAmp) and stability (TempStab).

Methods: Wrist skin temperature was measured in 34 subjects (ages 50 to 70, including lean, obese, and diabetic subjects) every 10 minutes for 7 consecutive days. Anthropometric measures and …

The Chondrocyte Channelome: A Novel Ion Channel Candidate In The Pathogenesis Of Pectus Deformities, Anthony J. Asmar

Biological Sciences Theses & Dissertations

Costal cartilage is a type of rod-like hyaline cartilage connecting the ribs to the sternum. The chest wall deformities pectus excavatum (PE) and pectus carinatum (PC) involve displacement of the sternum causing a depression or protrusion of the chest. There is little knowledge about costal cartilage and pectus deformities with much of its understanding based on assumptions from articular cartilage. Chondrocytes are subjected to a constantly changing environment with fluctuations in pH and osmolarity. Ion channels detect these changes and in turn regulate proliferation, differentiation, and extracellular matrix production. Using ion channel qPCR arrays, we produced expression profiles for normal, …

Modulation Of Synaptic Plasticity: Endocannabinoids And Novel G-Protein Coupled Receptors Expression And Translational Effects In Interneurons, Katrina M. Hurst

Theses and Dissertations

Learning and memory are important processes that occur in the brain. The brain is comprised of neurons that make connections with each other known as synapses. Synaptic plasticity is widely believed to be the physiologic mechanism by which learning and memory occur. Synapses can either be strengthened through a process known as long-term potentiation (LTP) or weakened through long-term depression (LTD). The area of the brain that is most studied for its role in learning and memory is the hippocampus, which has been shown to be involved in memory consolidation. The detection of endocannabinoids and their receptors has opened a …

Uga Anatomy And Physiology 1 Lab Manual, 3rd Edition, Deloris Hesse, Deanna Cozart, Brett Szymik, Rob Nichols

Biological Sciences Open Textbooks

This lab manual was created for Anatomy and Physiology I at the University of Georgia under a Textbook Transformation Grant and revised through a Scaling Up OER Pilot Grant.

The manual contains the following labs:

1. Introduction to Anatomy & Physiology
2. Cells
3. Histology – Epithelial & Connective Tissues
4. Histology – Muscle & Nervous Tissues
5. The Integumentary System
6. Introduction to the Skeletal System
7. Introduction Joints
8. The Lower Limb – Bones
9. The Lower Limb – Muscles
10. The Lower Limb – Joints
11. The Lower Limb – Nerves
12. The Lower Limb – Movement
13. The Upper Limb – Bones
14. The Upper Limb – Muscles
15. The …

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 …

Mechanism Of Action For Rtms: A Working Hypothesis Based On Animal Studies, Thangavelu Soundara Rajan, Maria Felice Ghilardi, Hoau-Yan Wang, Emanuela Mazzon, Placido Bramanti, Domenico Restivo, Angelo Quartarone

Publications and Research

Experiments in rodents have elucidated some of the molecular mechanisms underlying repetitive transcranial magnetic stimulation (rTMS). These studies may be useful in a translational perspective so that future TMS studies in rodents can closely match human TMS protocols designed for therapeutic purposes. In the present work we will review the effects of rTMS on glutamate neurotransmission which in turn induce persistent changes in synaptic activity. In particular, we will focus on the role of NMDA and non-NMDA transmission and on the permissive role of BDNF-TrKB interaction in the rTMS induced after-effects.

Cib2 Interacts With Tmc1 And Tmc2 And Is Essential For Mechanotransduction In Auditory Hair Cells, Arnaud P. J. Giese, Yi-Quan Tang, Ghanshyam P. Sinha, Michael R. Bowl, Adam C. Goldring, Andrew Parker, Mary J. Freeman, Steve D. M. Brown, Saima Riazuddin, Robert Fettiplace, William R. Schafer, Gregory I. Frolenkov, Zubair M. Ahmed

Physiology Faculty Publications

Inner ear hair cells detect sound through deflection of stereocilia, the microvilli-like projections that are arranged in rows of graded heights. Calcium and integrin-binding protein 2 is essential for hearing and localizes to stereocilia, but its exact function is unknown. Here, we have characterized two mutant mouse lines, one lacking calcium and integrin-binding protein 2 and one carrying a human deafness-related Cib2 mutation, and show that both are deaf and exhibit no mechanotransduction in auditory hair cells, despite the presence of tip links that gate the mechanotransducer channels. In addition, mechanotransducing shorter row stereocilia overgrow in hair cell bundles of …

The Validity Of Submaximal Exercise Testing In Obese Women, Gabrielle Ringenberg

Mahurin Honors College Capstone Experience/Thesis Projects

Background: Submaximal exercise tests use heart rate responses to low-to-moderate intensity activity in order to predict cardiorespiratory fitness (VO_2max). Currently used tests may be inappropriate for obese populations as obese women have altered heart rate responses to exercise. The purpose of this project is to test the validity of the Modified Bruce Protocol submaximal treadmill test in obese women. Methods: Normal-weight (NWG) and obese women (OBG) completed the Modified Bruce submaximal treadmill test (to predict VO_2max using previously validated equations) and a maximal graded exercise test on a treadmill using the Standard Bruce Protocol (to obtain an …

Tempo And Mode Of Performance Evolution Across Multiple Independent Origins Of Adhesive Toe Pads In Lizards, Travis J. Hagey, Josef C. Uyeda, Kristen E. Crandell, Jorn A. Cheney, Kellar Autumn, Luke J. Harmon

Biology

Understanding macroevolutionary dynamics of trait evolution is an important endeavor in evolutionary biology. Ecological opportunity can liberate a trait as it diversifies through trait space, while genetic and selective constraints can limit diversification. While many studies have examined the dynamics of morphological traits, diverse morphological traits may yield the same or similar performance and as performance is often more proximately the target of selection, examining only morphology may give an incomplete understanding of evolutionary dynamics. Here, we ask whether convergent evolution of pad-bearing lizards has followed similar evolutionary dynamics, or whether independent origins are accompanied by unique constraints and selective …