Digital Commons Network^™

Effects Of Brain-Derived Neurotrophic Factor And Its Signaling Pathway On Sensory Neuronal Activation During Colitis, Fiza Hashmi

Theses and Dissertations

Visceral hypersensitivity is the heightened response to sensory stimuli. Visceral sensations are transmitted through primary afferent neurons in the dorsal root ganglion (DRG) and the sensitization of the neural pathway leads to modification in spinal ascending and descending neurons. The aim of this investigation is to determine the effects of brain-derived neurotrophic factor (BDNF) and its signaling pathway on sensory neuronal activation during colitis. In order to evaluate this, levels of calcitonin-gene related peptide (CGRP), a neuropeptide marker for nociceptive transmission, and phosphorylated cAMP-response element binding protein (pCREB), a molecular switch in neuronal plasticity, were studied in response to BDNF …

Effects Of Hiv-1 Viral Protein Tat On The Viability And Function Of Oligodendroglial Cells, Shiping Zou

Theses and Dissertations

Myelin pallor is frequently reported in HIV patients, and can occur in the CNS prior to other evidence of disease process. Our exploratory studies showed that oligodendrocytes (OLs) are direct targets of HIV-1 Tat (transactivator of transcription). Tat induces a dose-dependent increase of intracellular Ca²⁺ level ([Ca²⁺]_i) in cultured murine OLs, which can be attenuated by ionotropic glutamate receptor (iGluR) antagonists MK801 and CNQX. The Tat-induced [Ca²⁺]_i increase leads to increased death in immature (O4⁺, MBP^-), but not mature (O4⁺, MBP⁺) OLs, over 96 …

Psychoactive Synthetic Cathinones (Or 'Bath Salts'): Investigation Of Mechanisms Of Action, Farhana Sakloth

Theses and Dissertations

Synthetic cathinones represent threatening and high abuse-potential designer drugs. These are analogs of cathinone (the b-keto analog of amphetamine (AMPH)) a naturally occurring stimulant found in the plant Catha Edulis. Methcathinone (MCAT) was the first synthetic analog of cathinone to be identified in 1987 by Glennon and co-workers and it exerted its action primarily through the dopamine transporter (DAT). Most central stimulants exert their action via monomaine transporters by causing either the release (e.g. cathinone analogs such as MCAT) or by preventing the reuptake (e.g. cocaine) of the neurotransmitter dopamine (DA) thus increasing the extracellular synaptosomal concentration of this …

Interaction Between Atm Kinase And P53 In Determining Glioma Radiosensitivity, Syed F. Ahmad

Theses and Dissertations

Glioblastoma multiforme (GBM) is the most common primary brain tumor. Studies have shown that targeting the DNA damage response can sensitize cancer cells to DNA damaging agents. Ataxia telangiectasia mutated (ATM) is involved in signaling DNA double strand breaks. Our group has previously shown that ATM inhibitors (ATMi) sensitize GBM cells and tumors to ionizing radiation. This effect is greater when the tumor suppressor p53 is mutated.

The goals of this work include validation of a new ATM inhibitor, AZ32, and elucidation of how ATMi and p53 status interact to promote cell death after radiation. We propose that ATMi and …

Conduction States Of The Human Dopamine Transporter, Krasnodara Cameron

Theses and Dissertations

Dysregulation of dopaminergic homeostasis has been established as the primary source of numerous neurological disorders including Parkinson’s and drug addiction. A tonic increase of dopamine (DA) in the nucleus accumbens is required for associating everyday events and behaviors with rewards. Yet many addictive exogenous compounds such as amphetamine (AMPH) and cocaine (COC) produce a much greater augmentation of synaptic DA levels that are linked to euphoria and a shift in behavior towards drug seeking. The protein responsible for maintaining extracellular levels of DA is the dopamine transporter (DAT). It is primarily located in the perisynaptic area at terminals of pre-synaptic …

Effects Of Hiv-1 Tat On The Enteric Nervous, Joy Ngwainmbi

Theses and Dissertations

More than 1.2 million people are estimated to be currently living with the human immunodeficiency virus (HIV) in the United States of America. The gastrointestinal (GI) tract is both a major target and an important component of HIV pathogenesis. The GI processes that are dysregulated during HIV infection are controlled by the enteric nervous system (ENS). Indeed, both clinical and experimental studies have implicated the ENS in HIV and simian immunodeficiency virus (SIV) pathogenesis. In addition to direct viral effects, the HIV virus also indirectly affects the GI tract via cellular and/or viral toxins released by infected cells. Trans-activator of …

Dual Pi3k/Mtor Inhibition With Bez235 Augments The Therapeutic Efficacy Of Doxorubicin In Cancer Without Influencing Cardiac Function, David E. Durrant

Theses and Dissertations

Cancer continues to be a leading cause death in the United States despite improved treatments. Cancerous lesions form after acquiring oncogenic driver mutations or losing tumor suppressor function in normal cells. Traditional therapies have included use of genotoxic substances that take advantage of the increased growth rate and loss of tumor suppressor function to cause cell death. One such drug is the anthracycline antibiotic doxorubicin (DOX). DOX interchelates into DNA and disrupts transcriptional machinery while also poisoning topoisomerase II. This results in single and double stranded DNA breaks, which if severe enough leads to either necrotic or apoptotic cell death. …

Investigating The Role Of Bptf In Immunoediting In Breast Cancer And Melanoma, Kristen N. Peterson

Theses and Dissertations

In this study, we explore the effects of NURF depletion on the growth of tumors in immune-competent mice. NURF depletion in tumors results in reduced tumor growth in immune-competent mice, suggesting enhanced anti-tumor immunity. Analysis of the tumor microenvironment by flow cytometry revealed a significantly elevated CD8 and progressively elevated activated CD8 phenotype in Bptf KD tumors, possibly contributing to the increase in cell death and decrease in tumor weight observed. Examination of antigen presentation was evaluated using the OT-1 and Pmel-17 models, though no significant difference in cytotoxicity was observed as measured by LDH and/or IFNγ assays. This indicates …

Inhibition Of Mtor Signaling Protects Against Myocardial Reperfusion Injury, Acute Myocardial Infarction, Scott M. Filippone

Theses and Dissertations

Acute myocardial infarction (AMI) is the leading cause of death worldwide. Currently, the best method of treating cardiac ischemia is early reperfusion which, itself, induces myocardial damage. The mTOR complex is a key regulator of cardioprotection against cell stressors. We hypothesized that reperfusion therapy with Rapamycin, a potent mTOR inhibitor, would reduce infarct size in adult mouse hearts. Rapamycin was administered at the onset of reperfusion following 30 min in situ LAD ligation. After 24 hours of reperfusion, myocardial infarct size and apoptosis were significantly reduced in rapamycin-treated mice compared to control. Rapamycin inhibited pro-apoptotic protein Bax and phosphorylation of …

Hypolipidemic Effects Of Nimesulide And Celecoxib In Experimentally Induced Hypercholesterolemia In Rabbits, Sagheer Ahmed, Saima Gul, Muhammad Zia-Ul-Haq, Muhammad Riaz

Turkish Journal of Medical Sciences

Hypercholesterolemia plays an important role in the development of atherosclerotic disease, which is one of the leading causes of mortality in the world. Previous studies showed that cyclooxygenase (COX) inhibitors could be used in treating hypercholesterolemia. The present study was designed to test whether COX-2 inhibition can improve lipid profiles in hypercholesterolemia. Materials and methods: Rabbits were fed a high-cholesterol diet to produce hypercholesterolemia. The role of COX-2 was evaluated using celecoxib and nimesulide. Rabbits were divided into 4 groups: the first with normal healthy rabbits, second with high-cholesterol diet and pretreatment with saline, third with high-cholesterol diet and pretreatment …

The Effects Of Prenatal Long-Duration Exposure To 900-Mhz Electromagnetic Field On The 21-Day-Old Newborn Male Rat Liver, Zehra Topal, Hati̇ce Hanci, Tolga Mercantepe, Hüseyi̇n Serkan Erol, Osman Nuri̇ Keleş, Haydar Kaya, Sevdegül Mungan, Ersan Odaci

Turkish Journal of Medical Sciences

Background/aim: To determine what effect a 900-MHz electromagnetic field (EMF) applied in the prenatal period would have on the liver in the postnatal period. Materials and methods: At the start of the study, adult pregnant rats were divided into two groups, control and experimental. The experimental group was exposed to a 900-MHz EMF for 1 h daily during days 13?21 of pregnancy. After birth, no procedure was performed on either mothers or pups. Male rat pups (n = 6) from the control group mothers (CGMR) and male rat pups (n = 6) from the experimental group mothers (EGMR) were sacrificed …

Sigma Receptor Activation Mitigates Toxicity Evoked By The Convergence Of Ischemia, Acidosis And Amyloid-Beta, Adam Alexander Behensky

USF Tampa Graduate Theses and Dissertations

Stroke is the fifth leading cause of death in the United States and a major cause of long-term disability in industrialized countries. The core region of an ischemic stroke dies within minutes due to activation of necrotic pathways. Outside of this core region is the penumbral zone, where some perfusion is maintained via collateral arteries. Delayed cell death occurs in this area due to the triggering of apoptotic mechanisms, which expands the ischemic injury over time. The cellular and molecular events that produce the expansion of the ischemic core continue to be poorly understood. The increases in the amyloid precursor …

Neuroinflammatory Alterations Via Cd-36 In Traumatic Brain Injury, Diana G. Hernandez-Ontiveros

USF Tampa Graduate Theses and Dissertations

Traumatic brain injury (TBI) has become an increasingly unmet clinical need due to intense military conflicts worldwide. Directly impacted brain cells suffer massive death, with neighboring cells succumbing to progressive neurodegeneration accompanied by inflammatory and other secondary cell death events. Subsequent neurodegenerative events may extend to normal areas beyond the core of injury, thereby exacerbating the central nervous system’s inflammatory response to TBI. Recently CD-36 (cluster of differentiation 36/fatty acid translocase (FAT), a class B scavenger receptor of modified low-density lipoproteins (mLDLs) in macrophages, has been implicated in lipid metabolism, atherosclerosis, oxidative stress, and tissue injury in cerebral ischemia, and …

Preparing The Periphery For A Subsequent Behavior: Motor Neuronal Activity During Biting Generates Little Force But Prepares A Retractor Muscle To Generate Larger Forces During Swallowing In Aplysia, Hui Lu, Jeffrey M. Mcmanus, Miranda J. Cullins, Hillel J. Chiel

Faculty Scholarship

Some behaviors occur in obligatory sequence, such as reaching before grasping an object. Can the earlier behavior serve to prepare the musculature for the later behavior? If it does, what is the underlying neural mechanism of the preparation? To address this question, we examined two feeding behaviors in the marine mollusk Aplysia californica, one of which must precede the second: biting and swallowing. Biting is an attempt to grasp food. When that attempt is successful, the animal immediately switches to swallowing to ingest food. The main muscle responsible for pulling food into the buccal cavity during swallowing is the I3 …

Liver Perilipin 5 Expression Worsens Hepatosteatosis But Not Insulin Resistance In High Fat-Fed Mice, Michelle B. Trevino, David Mazur-Hart, Yui Machida, Timothy King, Joseph Nadler, Elena V. Galkina, Arjun Poddar, Sucharita Dutta, Yumi Imai

Mathematics & Statistics Faculty Publications

Perilipin 5 (PLIN5) is a lipid droplet (LD) protein highly expressed in oxidative tissues, including the fasted liver. However, its expression also increases in nonalcoholic fatty liver. To determine whether PLIN5 regulates metabolic phenotypes of hepatosteatosis under nutritional excess, liver targeted overexpression of PLIN5 was achieved using adenoviral vector (Ad-PLIN5) in male C57BL/6J mice fed high-fat diet. Mice treated with adenovirus expressing green fluorescent protein (GFP) (Ad-GFP) served as control. Ad-PLIN5 livers increased LD in the liver section, and liquid chromatography with tandem mass spectrometry revealed increases in lipid classes associated with LD, including triacylglycerol, cholesterol ester, and phospholipid classes, …

History Of Concussion And Current Functional Movement Screen Scores In A Collegiate Recreational Population, Jordan M. Dorrien

College of Graduate Studies: Theses & Dissertations

Introduction: 1.6-3.8 million concussions occur annually related to sport.¹ Although neurometabolic alterations in the brain last 7-10 days following a concussion, an increased Cortical Silent Period (CSP) has been found to persist after 19 months.^2,3 Further, movement impairments have been noted years after injury.⁴ The Functional Movement Screen (FMS) assesses mobility and stability in the body.⁵ The purpose of this study was to assess if FMS scores correlate to history of a concussion in healthy college club sport participants. Methods: Health history and FMS score were collected on 55 participants (38 male, …

A Quantum Theory Of Consciousness May Require A Paradigm Shift In Biology, Maurice Goodman

Articles

It is often assumed that the known physical laws form a closed system and are complete. It is also assumed that biological theories require no additional principles that are fundamental other than those we already know. Assumptions such as these are acting as a barrier to progress in biological theories and an understanding of consciousness. This paper examines the unexplained inconsistencies among fundamental particles and forces and the fundamental gaps in our knowledge of biology and the cell in particular that may impact on such progress. Also, the laws of quantum mechanics are examined and found to be grossly incomplete. …

Functional Conservation Of An Ancestral Pellino Protein In Helminth Species, Christopher Cluxton, Brian Caffrey, Gemma Kinsella, Paul Moynagh, Mario Fares, Padraic Fallon

Articles

The immune system of H. sapiens has innate signaling pathways that arose in ancestral species. This is exemplified by the discovery of the Toll-like receptor (TLR) pathway using free-living model organisms such as Drosophila melanogaster. The TLR pathway is ubiquitous and controls sensitivity to pathogen-associated molecular patterns (PAMPs) in eukaryotes. There is, however, a marked absence of this pathway from the plathyhelminthes, with the exception of the Pellino protein family, which is present in a number of species from this phylum. Helminth Pellino proteins are conserved having high similarity, both at the sequence and predicted structural protein level, with that …

An Investigation Of The Relationship Between Axonal Injury, Biomarker Expression And Mechanical Response In A Rodent Head Impact Acceleration Model, Yan Li

Wayne State University Dissertations

In the United States 1.4 million people sustain traumatic brain injury (TBI) each year, resulting in 235,000 hospitalizations and 50,000 fatalities annually. Traumatic axonal injury (TAI) is a serious outcome of TBI that accounts for 40-50% of hospitalizations due to head injury and one third of the mortality due to TBI, and it is difficult to diagnose and evaluate. The purpose of this dissertation is to determine mechanical injury predictors for TAI and identify potential biomarkers to evaluate TAI.

In this dissertation, a modified Marmarou impact acceleration injury model was developed to allow the monitoring of velocity of the impactor …

Neural Function, Injury, And Stroke Subtype Predict Treatment Gains After Stroke, Erin Burke Quinlan, Lucy Dodakian, Jill See, Alison Mackenzie, Vu Le, Mike Wojnowicz, Babak Shahbaba, Steven C. Cramer

Physical Therapy Faculty Articles and Research

Objective

This study was undertaken to better understand the high variability in response seen when treating human subjects with restorative therapies poststroke. Preclinical studies suggest that neural function, neural injury, and clinical status each influence treatment gains; therefore, the current study hypothesized that a multivariate approach incorporating these 3 measures would have the greatest predictive value.

Methods

Patients 3 to 6 months poststroke underwent a battery of assessments before receiving 3 weeks of standardized upper extremity robotic therapy. Candidate predictors included measures of brain injury (including to gray and white matter), neural function (cortical function and cortical connectivity), and clinical …

Amyloid-Related Memory Decline In Preclinical Alzheimer's Disease In Dependent On Apoe Ε4 And Is Detectable Over 18-Months, Christine Thai, Yen Ying Lim, Victor L. Villemagne, Simon Laws, David Ames, Kathryn A. Ellis, Stephanie Rainey-Smith, Ralph Martins, Colin L. Masters, Christopher C. Rowe, Paul Maruff, Australian Imaging, Biomarkers And Lifestyle (Aibl) Research Group

Research outputs 2014 to 2021

High levels of β-amyloid (Aβ) in the brain and carriage of the APOE ε4 allele have each been linked to cognitive impairment in cognitively normal (CN) older adults. The aim of this study was to investigate the relationship between cerebral Aβ level, APOE ε4 carrier status, and cognitive decline over 18 monthes, in 317 cognitively healthy (CN) older adults (47% males, 52.4% females) aged between 60 and 89 years (Mean = 69.9, SC = 6.8). Cognition was assessed using the Cogstate Brief Battery (CBB) and the California Verbal Learning Test, Second Edition (CVLT-II). Planned comparisons indicated that CN older adults …

Butyrylated Starch Intake Can Prevent Red Meat-Induced O6-Methyl-2-Deoxyguanosine Adducts In Human Rectal Tissue: A Randomised Clinical Trial, Richard K. Le Leu, Jean M. Winter, Claus T. Christophersen, Graeme P. Young, Karen J. Humphreys, Ying Hu, Silvia W. Gratz, Rosalind B. Miller, David L. Topping, Anthony R. Bird, Michael A. Conlon

Research outputs 2014 to 2021

Epidemiological studies have identified increased colorectal cancer (CRC) risk with high red meat (HRM) intakes, whereas dietary fibre intake appears to be protective. In the present study, we examined whether a HRM diet increased rectal O⁶-methyl-2-deoxyguanosine (O⁶MeG) adduct levels in healthy human subjects, and whether butyrylated high-amylose maize starch (HAMSB) was protective. A group of twenty-three individuals consumed 300 g/d of cooked red meat without (HRM diet) or with 40 g/d of HAMSB (HRM+HAMSB diet) over 4-week periods separated by a 4-week washout in a randomised cross-over design. Stool and rectal biopsy samples were collected for …

Inflamation And Oxidative Stress : The Molecular Connectivity Between Insulin Resistance, Obesity And Alzheimer's Disease, Guiseppe Verdile, Kevin N. Keane, Vinicius F. Cruzat, Sandra Medic, Miheer Sabale, Joanne Rowles, Nadeeja Wijesekara, Ralph Martins, Paul E. Fraser, Philip Newsholme

Research outputs 2014 to 2021

Type 2 diabetes (T 2 DM), Alzheimer’s disease (AD), and insulin resistance are age-related conditions and increased prevalence is of public concern. Recent research has provided evidence that insulin resistance and impaired insulin signalling may be a contributory factor to the progression of diabetes, dementia, and other neurological disorders. Alzheimer’s disease (AD) is the most common subtype of dementia. Reduced release (for T 2 DM) and decreased action of insulin are central to the development and progression of both T 2 DM and AD. A literature search was conducted to identify molecular commonalities between obesity, diabetes, and AD. Insulin resistance …

Expression Of Enteropathogenic Escherichia Coli Map Is Significantly Different Than That Of Other Type Iii Secreted Effectors In Vivo., Mai Nguyen, Jason Rizvi, Gail Hecht

Department of Medicine Faculty Papers

The enteropathogenic Escherichia coli (EPEC) locus of enterocyte effacement (LEE)-encoded effectors EspF and Map are multifunctional and have an impact on the tight junction barrier while the non-LEE-encoded proteins NleH1 and NleH2 possess significant anti-inflammatory activity. In order to address the temporal expression of these important genes in vivo, their promoters were cloned upstream of the luxCDABE operon, and luciferase expression was measured in EPEC-infected mice by bioluminescence using an in vivo imaging system (IVIS). Bioluminescent images of living mice, of excised whole intestines, and of whole intestines longitudinally opened and washed were assessed. The majority of bioluminescent bacteria localized …

Strategies For Preventing Age And Neurodegenerative Disease-Associated Mitochondrial Dysfunction, Vedad Delic

USF Tampa Graduate Theses and Dissertations

Mitochondrial dysfunction plays a pivotal role in the development of aging phenotypes and aging-associated neurodegenerative disorders, such as Alzheimer’s disease (AD), Parkinson’s disease (PD) and Amyotrophic lateral sclerosis (ALS). Strategies that restore mitochondrial dysfunction may rescue the deficits of central metabolism in these disorders and improve cell survival. For example, we found that modulating the mTOR signaling pathway in a tissue culture model of aging-induced mitochondrial DNA mutation enhanced mitochondrial function as evidenced by increased oxygen consumption. Our previous melatonin studies also led us to hypothesize that caloric restriction and the hormone melatonin would reverse brain mitochondrial dysfunction in animal …

Minocycline Treatment And The Necessity To Develop A Novel Outcome Measure For Children With Angelman Syndrome, Joseph Christopher Grieco

USF Tampa Graduate Theses and Dissertations

Angelman syndrome (AS) is a rare genetic disorder affecting 1/10,000 to 1/20,000 births. This disorder arises through the genetic disruption of the maternal UBE3A allele, which when coupled with epigenetic silencing of the paternal allele UBE3A allele, gives rise to an absence of UBE3A protein in the central nervous system. Clinical manifestations of the syndrome vary in severity and include poor motor function, deficits in language and severe intellectual impairments. Previous research in the Angelman syndrome mouse model revealed abnormalities in dendritic spine density and morphology of hippocampal pyramidal cells. As seen in humans with AS, mice show abnormal behavioral …

Effects Of Nicotine Withdrawal On Motivation, Reward Sensitivity And Reward-Learning, Jason A. Oliver

USF Tampa Graduate Theses and Dissertations

Research on addictive behavior has traditionally emphasized the role that primary reinforcing effects of drugs of abuse plays in the development and maintenance of dependence. However, contemporary behavioral economic theory and animal models of nicotine dependence suggest the need for greater attention to the impact that response to alternative rewards may have on smoking behavior. The present study sought to investigate the impact of nicotine withdrawal on self-report, behavioral and neural indices of motivation, immediate response to rewards and the capacity to learn and modify behavior in response to positive and negative feedback. Heavy smokers (n = 48) completed two …

Mechanisms, Potential Therapies, And The Role Of Tgf-Β In The Formation Of Scars, Isaac Traube

The Science Journal of the Lander College of Arts and Sciences

Scarring is the inevitable outcome of wound healing. This review looks at some of the underlying mechanisms of this complex process with the aim of identifying targets for therapeutic manipulation that could result in reduced scarring or even scarless wound repair. Fetal wounds are shown to heal without scars primarily due to low levels of TGF-β1 and TGF-β2 and high levels of TGF-β3 as compared to adult wounds which heal with scars. Abnormal excessive scarring in keloid and hypertrophic scars are also attributed to TGF-β. Clinical manipulation of TGF-β ratios showed promise as a therapeutic means of controlling scar formation. …

Transposon Based Gene Therapy As A Treatment For Cancer, Jacob Stauber

The Science Journal of the Lander College of Arts and Sciences

Gene therapy is the use of genes to treat or prevent diseases. Diseases such as cancer, which are difficult to treat using conventional methods, can be treated using gene therapy. The transport of the therapeutic transgene can be accomplished using viral or non-viral methods. However, widespread use of viral vectors is limited due to its high cost of manufacture and safety concern. Non-viral vectors are limited in their effectiveness. The use of transposons such as the Sleeping Beauty transposon system can effectively deliver the transgene with less concern than viral vectors. This review discusses the various vectors and treatment strategies …

Influence Of Environmental Exposure On Human Epigenetic Regulation, C. J. Marsit

Dartmouth Scholarship

Environmental toxicants can alter epigenetic regulatory features such as DNA methylation and microRNA expression. As the sensitivity of epigenomic regulatory features may be greatest during the in utero period, when critical windows are narrow, and when epigenomic profiles are being set, this review will highlight research focused on that period. I will focus on work in human populations, where the impact of environmental toxicants in utero, including cigarette smoke and toxic trace metals such as arsenic, mercury and manganese, on genome-wide, gene-specific DNA methylation has been assessed. In particular, arsenic is highlighted, as this metalloid has been the focus …