Medicine and Health Sciences Commons^™

The Effects Of Synthetic And Dietary Therapeutics On Learning, Memory, Motor Coordination, And Seizure In An Angelman Syndrome Mouse Model, Stephanie Lynn Ciarlone

USF Tampa Graduate Theses and Dissertations

Angelman syndrome (AS) is a rare genetic and neurological disorder presenting with severe developmental delay, ataxia, epilepsy, and lack of speech. AS is associated with a neuron-specific loss of function of the maternal UBE3A allele, a gene encoding an E3 ubiquitin ligase. Currently, no cure exists for this disorder; however, recent research using an AS mouse model suggests that pharmacological intervention is plausible, and can alleviate some of the detrimental phenotypes reported in AS patients.

Although there is no curative treatment for AS, seizure medication and behavioral therapies are most commonly prescribed in order to minimize symptoms. However, these options …

Hypercapnic Hyperoxia Increases Free Radical Production And Cellular Excitability In Rat Caudal Solitary Complex Brain Slice Neurons, Geoffrey Edward Ciarlone

USF Tampa Graduate Theses and Dissertations

The caudal solitary complex (cSC) is a cardiorespiratory integrative center in the dorsal medulla oblongata that plays a vital role in the central CO₂-chemoreceptive network. Neurons in this area respond to hypercapnic acidosis (HA) by a depolarization of the membrane potential and increase in firing rate, however a definitive mechanism for this response remains unknown. Likewise, CO₂-chemoreceptive neurons in the cSC respond to hyperoxia in a similar fashion, but via a free radical mediated mechanism. It remains unknown if the response to increased pO₂ is merely an increase in redox signaling, or if it’s the …

Regulation Of Palmitoylation Enzymes And Substrates By Intrinsically Disordered Regions, Krishna D. Reddy

USF Tampa Graduate Theses and Dissertations

Protein palmitoylation refers to the process of adding a 16-carbon saturated fatty acid to the cysteine of a substrate protein, and this can in turn affect the substrate’s localization, stability, folding, and several other processes. This process is catalyzed by a family of 23 mammalian protein acyltransferases (PATs), a family of transmembrane enzymes that modify an estimated 10% of the proteome. At this point in time, no structure of a protein in this family has been solved, and therefore there is poor understanding about the regulation of the enzymes and their substrates. Most proteins, including palmitoylation enzymes and substrates, have …

Hormone Replacement Therapy (Hrt) Modulates Peripheral And Central Auditory System Processing With Aging, Tanika Williamson

USF Tampa Graduate Theses and Dissertations

After the findings were reported for the Women’s Health Initiative (WHI) study in the past decade, there has been a significant decline in the overall use of hormone replacement therapy (HRT) among women. However, there are still millions of middle-aged, menopausal women in the U.S. who are currently undergoing hormone therapy. Their reasons for continuing treatment include relief of severe menopausal symptoms, aid in the management of osteoporosis and reduction in the risk of colon cancer (Ness et al., 2005). The purpose of the following investigation was to evaluate the impact of HRT on the central and peripheral auditory systems …

Intraocular Pressure Sensing And Control For Glaucoma Research, Simon Antonio Bello

USF Tampa Graduate Theses and Dissertations

Animal models of ocular hypertension are important for glaucoma research but come with experimental costs. Available methods of intraocular pressure (IOP) elevation are not always successful, the amplitude and time course of IOP changes are unpredictable and irreversible, and IOP measurement by tonometry is laborious. This dissertation focuses on the development and implementation of two novel systems for monitoring and controlling IOP without these limitations. The first device consists of a cannula implanted in the anterior chamber of the eye, a pressure sensor that continually measures IOP, and a bidirectional pump driven by control circuitry that can infuse or withdraw …

Designing The Haptic Interface For Morse Code, Michael Walker

USF Tampa Graduate Theses and Dissertations

Two siblings have a muscular degenerative condition that has rendered them mostly blind, deaf and paraplegic. Currently, the siblings receive communication by close range sign language several feet in front of their vision. Due to the degenerative nature of their condition, it is believed that the siblings will eventually become completely blind and unable to communicate in this fashion. There are no augmented communication devices on the market that allow communication reception for individuals who cannot see, hear or possess hand dexterity (such as braille reading). To help the siblings communicate, the proposed communication device will transmit Morse code information …

The Concerted Regulation Of Intracellular Signaling By Amyloid Precursor Protein And Aβ Peptide, Lisa Kirouac

USF Tampa Graduate Theses and Dissertations

It is widely accepted that A-beta (Aβ) generated from amyloid precursor protein (APP) oligomerizes and fibrillizes to form neuritic plaques in the Alzheimer’s disease (AD) brain, yet little is known about the contribution of APP preceding AD pathogenesis. Our data presented here suggest that APP has a functional role in cell cycle regulation and proliferation. First, we demonstrat that APP is pathologically phosphorylated at Thr₆₆₈ and that P-APP localizes to the centrosomes. Furthermore, P-APP is proteolytically processed in a cell cycle -dependent manner to generate its pathogenic metabolites. Using Stable Isotope Labeling by Amino Acids in Culture (SILAC) and …

Static And Dynamic Spectral Acuity In Cochlear Implant Listeners For Simple And Speech-Like Stimuli, Benjamin Anderson Russell

USF Tampa Graduate Theses and Dissertations

For cochlear implant (CI) listeners, poorer than normal speech recognition abilities are typically attributed to degraded spectral acuity. However, estimates of spectral acuity have most often been obtained using simple (tonal) stimuli, presented directly to the implanted electrodes, rather than through the speech processor as occurs in everyday listening. Further, little is known about spectral acuity for dynamic stimuli, as compared to static stimuli, even though the perception of dynamic spectral cues is important for speech perception.

The primary goal of the current study was to examine spectral acuity in CI listeners, and a comparison group of normal hearing (NH) …

The Influence Of Motivational Salience On Attention Selection: An Erp Investigation, Constanza De Dios

USF Tampa Graduate Theses and Dissertations

The current study used event-related potentials (ERPs) to investigate how motivational salience in the form of expectation violation influences spatial attention. The medial frontal negativity (MFN) ERP indexes expected value, being negative to unexpected punishments and positive to unexpected rewards. The P1 and N1 ERPs index spatial attention, being larger to stimuli in attended locations. This design attached motivational value to locations by making one visual hemifield economically rewarding (greater probability of a rewarding outcome) and the other punishing (greater probability of a punishing outcome). Keypresses to a dot probe following a reward-signifying stimulus were awarded money if correct, and …

Inhibiting The Interaction Between Grp94 And Myocilin To Treat Primary Open-Angle Glaucoma, Andrew Stothert

USF Tampa Graduate Theses and Dissertations

Glaucoma is a neurodegenerative protein misfolding disorder classified by increases in IOP, damage to retinal ganglion cells (RGCs), optic nerve (ON) head damage, and progressive irreversible blindness. Primary open-angle glaucoma (POAG) is the most common form of glaucoma, constituting over 90% of clinical cases. POAG is observed in patients where normal outflow channels, mainly the trabecular meshwork (TM), are exposed at the angle formed by the iris and cornea. However, due to TM cellular dysfunction, aqueous outflow resistance is increased preventing normal circulation of aqueous humor. Recent studies have shown that in 2-4% of POAG cases, increased intracellular levels of …

The Effects Of Cognitive Training Among Individuals With Neurodegenerative Diseases, Elise Gabriela Valdes

USF Tampa Graduate Theses and Dissertations

With the growing older adult population, neurodegenerative diseases common in old age such as mild cognitive impairment (MCI) or Parkinson’s disease (PD) are becoming increasingly germane areas of research. Pharmacological treatments have thus far been unsuccessful in treating cognitive decline associated with these neurodegenerative disorders. Alternative interventions, such as cognitive training programs, have shown promise. The current dissertation contains three papers examining cognitive interventions in neurodegenerative diseases. The first paper examined the longitudinal effects of cognitive speed of processing training (SPT) among those with PD. Results showed that training gains seen at initial post-test were maintained three months later. The …

Targeting Tau Degradation By Small Molecule Inhibitors For Treatment Of Tauopathies, Mackenzie Martin

USF Tampa Graduate Theses and Dissertations

Tauopathies are neurodegenerative diseases that affect millions of people around the world. Tauopathies include more than 20 neurodegenerative diseases. Some of the most common tauopathies are Alzheimer’s disease (AD), frontotemporal dementia (FTD), chronic traumatic encephalopathy (CTE), Pick’s disease, corticobasal degeneration, progressive supranuclear palsy (PSP), agyrophillic grain disease, and amyotrophic lateral sclerosis (ALS). These diseases can cause significant memory loss, behavioral changes, motor deficits and speech impairments. Tauopathies stem from accumulation of the microtubule associated protein tau (MAPT). Tau stabilizes microtubules and helps with axonal transport. In a disease state tau becomes hyperphosphorylated and truncated leading to its aggregation. More recently …

Leukemia Inhibitory Factor As A Neuroprotective Agent Against Focal Cerebral Ischemia, Stephanie Davis

USF Tampa Graduate Theses and Dissertations

Previous publications from this laboratory demonstrated that administration of leukemia inhibitory factor (LIF) (125 µg/kg) to young, male Sprague-Dawley rats at 6, 24, and 48 h after middle cerebral artery occlusion (MCAO) reduced infract volume, improved sensimotor skills, and alleviated damage to white matter at 72 h after the injury. In vitro studies using cultured oligodendrocytes (OLs) showed that LIF (200 ng/ml) also protects against 24 h of oxygen-glucose deprivation through activation of Akt signaling and upregulation of the antioxidant enzymes peroxiredoxin IV and metallothionein III. Other groups have demonstrated that LIF reduces neurodegeneration in animal models of disease, but …

Cell Permeability Studies Of Aapeptides And Novel Molecular Probes For Ad, Ge Bai

USF Tampa Graduate Theses and Dissertations

Alzheimer's diseases(AD) has been discovered and under research for more than 70 years, However there is no cure for these progressive and devastating diseases. Based on the following hypothsis: Aß metabolite problem/over production result in the accumulation, and lead to aggregation is the cause of Alzheimer’s disease. AApeptide and Melatonin derivatives can bind to Aß and block the aggregation of β amyloid monomers, decrease the toxicity of Aß to neurons and slow the progressive of Alzheimer’s diseases. In addition, AApeptide which mimic transmembrane peptide Tat will have similar transmembrane function. We have set up our goals as follows: 1) Using …

Modulation Of Whole Cell Currents In Human Neuroblastoma Cells Via The Hormone Aldosterone: An In Vitro Study, Harish Kumar Chittam

USF Tampa Graduate Theses and Dissertations

Ion channels play a critical role in maintaining homeostasis by moving various ions in and out of cells. The Na⁺-K⁺-2Cl^- or NKCC1 ion channel is involved in the regulation of Na⁺, K⁺, and Cl^- across cell membranes, and plays a key role in many forms of cellular physiology. In the cochlea, NKCC1 is involved in endolymph production and maintenance of the endocochlear potential. Our hypothesis is that blocking NKCC1 channels should directly impact auditory sensitivity causing hearing loss. Our lab has also shown that the hormone aldosterone (ALD) can upregulate …

Cutaneous Human Papillomavirus Infection And Development Of Subsequent Squamous Cell Carcinoma Of The Skin, Shalaka S. Hampras, Rhianna A. Reed, Spencer Bezalel, Michael Cameron, Basil Cherpelis, Neil Fenske, Vernon K. Sondak, Jane Messina, Massimo Tommasino, Tarik Gheit, Dana E. Rollison

Pathology and Cell Biology Faculty Publications

The role of cutaneous human papillomavirus (HPV) infection in the development of subsequent cutaneous squamous cell carcinoma (SCC) is unknown. Pathologically confirmed cases of SCC () enrolled in a previously conducted case-control study were included in a retrospective cohort study to examine the association of cutaneous HPV at the time of SCC diagnosis with the risk of subsequent SCC development. Data on HPV seropositivity, HPV DNA in eyebrow hairs (EB) and SCC tumors were available from the parent study. Incidence of subsequent SCC was estimated using person-years of follow up. Cox Proportional Hazards ratios were estimated to evaluate the associations …