Digital Commons Network^™

Endocannabinoid Involvement In Impulsivity And Decision-Making, Christopher P. Norris

Theses and Dissertations (Comprehensive)

Problem gambling is a widespread phenomenon with a prevalence estimate of 2.3% globally (Williams, Volberg, & Stevens, 2012). Although little is known about the neurochemistry underlying this pathological behaviour, evidence suggests that dysregulation of the brain’s endocannabinoid (eCB) system may be implicated in impulsivity and decision-making. For example, chronic cannabis users exhibit impulsive behaviour and impaired decision-making on the Iowa Gambling Task (IGT). The present study sought to further examine the role of the eCB system in problem gambling-related decision-making in laboratory rats using the five-choice serial reaction time task (5-CSRTT), and a recently-developed rodent analogue of the IGT called …

Detecting Knowledge Of Incidentally Acquired, Real-World Memories Using A P300-Based Concealed-Information Test, John B. Meixner Jr., J. Peter Rosenfeld

Scholarly Works

Autobiographical memory for events experienced during normal daily life has been studied at the group level, but no studies have yet examined the ability to detect recognition of incidentally acquired memories among individual subjects. We present the first such study here, which employed a concealed-information test in which subjects were shown words associated with activities they had experienced the previous day. Subjects wore a video-recording device for 4 hr on Day 1 and then returned to the laboratory on Day 2, where they were shown words relating to events recorded with the camera (probe items) and words of the same …

Proteomic Analysis Of Rosenthal Fibers And The Development Of Software For Proteomics, Michael Raymond Heaven

All ETDs from UAB

The first aim of my thesis was to identify the protein composition of the protein aggregates, called Rosenthal fibers, which are the defining feature of Alexander disease (AxD). AxD is a rare neurodegenerative disease caused by mutations in the astrocyte specific protein, glial fibrillary acidic protein (GFAP). GFAP is a type III intermediate filament protein that is overexpressed in AxD. A guiding hypothesis of this project was that sequestration of vital cell proteins in the aggregates contributed to disease. The results of my research do not support this hypothesis, but do provide an in depth characterization of the protein composition …

The Role Of Gene Fragmentation And Loss In Poxvirus Evolution, Eneida Hatcher

All ETDs from UAB

temperatures were near pivotal. The second chapter addresses the effects of fluctuating

Using Neuroimaging To Predict Treatment Response In Patients With Schizophrenia, Nathan Lyle Hutcheson

All ETDs from UAB

Schizophrenia is a severe debilitating mental illness that affects approximately 1% of people worldwide. Compared to healthy controls (HC), patients with schizophrenia (SZ) have memory deficits, specifically prominent disruptions in their episodic memory. These memory disruptions are thought to be caused by altered structure and function of areas within the memory network, specifically the prefrontal and temporal lobe including the hippocampus. Recently, identifying biomarkers of treatment response by using neuroimaging has become a prominent area of interest in schizophrenia. Biomarkers in schizophrenia could help by allowing for more efficient treatment using current method and also the development of novel treatments. …

Expression Of The Influenza Protein M2 During Viral Infection Inhibits Cftr Activity, James David Londino

All ETDs from UAB

The purpose of these dissertation studies was to 1) determine whether influenza infection alters CFTR activity in polarized epithelium; 2) measure CFTR expression and activity in cells co-expressing influenza M2 protein; and 3) examine the role of M2 on the alteration of CFTR during viral infection. We determined that infection of polarized primary epithelial cells with influenza decreases CFTR expression and activity. In addition, individual cells infected with influenza had decreased CFTR conductance as measured by whole-cell patch clamp. We also found that the influenza ion channel, matrix protein 2 (M2), alone reduced CFTR expression and activity. M2 is expressed …

Altered Dna Methylation Contributes To Temporal Lobe Epilepsy And Associated Memory Deficits, Robert Ryley Parrish

All ETDs from UAB

Status epilepticus (SE) triggers molecular mechanisms that underlie the cellular and network changes that occur during the development of temporal lobe epilepsy (TLE). Additionally, gene expression alterations occur during epileptogenesis and in the epileptic brain that contribute to the persistence of the phenotype. However, the underlying epigenetic mechanisms responsible for aberrant gene expression that occur with epilepsy require further investigation. This dissertation investigates how DNA methylation in the hippocampus affects epilepsy and contributes to the memory impairments associated with the disorder. We found that DNA methylation was altered in a hippocampal subregion specific manner in the epileptic brain, displaying altered …

Epithelial Sodium Channel Purification And X-Ray Crystallographic Studies, Bharat G. Reddy

All ETDs from UAB

Epithelial sodium channels (ENaC) play a critical role in maintaining Na+ homeostasis in various tissues throughout our body. Understanding of ENaC structure is mediated from studies of the homologous acid sensing ion channel 1 (ASIC1). However, ENaC has sev-eral notable functional differences compared to ASIC1, thereby providing justification for determination of its three-dimensional structure. Unfortunately, this goal remains elu-sive due to several experimental challenges. Of the subunits that comprise a physiological hetero-trimeric ENaC (α, ß, and γ), the α-subunit alone is of significant interest. αENaC is unique in that it is capable of forming a homo-trimeric structure capable of conducting …

Copper Homeostasis In Mycobacteria, Jennifer L. Rowland

All ETDs from UAB

Mycobacterium tuberculosis, the causative agent on tuberculosis in humans, is a globally important pathogen. In 2013, nearly 1.2 million people died from tuberculosis. Drug treatments and effective vaccines are lacking for this pathogen. A better understanding of the basic physiology of M. tuberculosis is required to improve disease outcomes. Upon inhalation into the lungs, M. tuberculosis is taken up by macrophages, in a process called phagocytosis, which normally destroys invading bacteria. As the phagosome inside the macrophage matures, bactericidal mechanisms are activated including: lowering pH, and introducing reactive oxygen and nitrogen species and hydrolytic enzymes to degrade bacterial cell walls. …

Transmitted/Founder Siv In The Rhesus Macaque Model Of Hiv-1 Infection, Mike Lopker

All ETDs from UAB

Vitally important to HIV-1 vaccine and prevention studies is a well-characterized animal model that recapitulates the salient features of HIV infection in humans. SIVmac and SIVsmm infection of rhesus macaques share key virological and pathological parallels with HIV-1 infection of humans including target cell entry via CD4 and CCR5 (Edinger et al., 1997), progressive T cell loss (Swanstrom & Coffin, 2012), generalized immune activation and preferential loss of mucosal Th17 cells (Brenchley et al., 2008; Klatt & Brenchley, 2010), and a vigorous but ultimately ineffective adaptive immune response. Though commonly used as a vaccine challenge strain in the macaque model, …

The Role Of Primary Cilia In Mammary Gland And Skeletal Development, Elizabeth Mitchell

All ETDs from UAB

and satiation of predators. Additionally, the arribada significantly affected sex ratios and

Heterogeneous Immunological Landscapes And Medieval Plague : An Invitation To A New Dialogue Between Historians And Immunologists., Fabian Crespo, Matthew B. Lawrenz

Faculty and Staff Scholarship

Efforts to understand the differential mortality caused by plague must account for many factors, including human immune responses. In this essay we are particularly interested in those people who were exposed to the Yersinia pestis pathogen during the Black Death, but who had differing fates—survival or death—that could depend on which individuals (once infected) were able to mount an appropriate immune response as a result of biological, environmental, and social factors. The proposed model suggests that historians of the medieval world could make a significant contribution to the study of human health, and especially the role of human immunology in …

Assessing The Active Kinome Of Influenza Virus Infected A549 Cells, Colm Atkins

All ETDs from UAB

Influenza A Virus is a respiratory pathogen of the family Orthomyxoviridae and causes significant worldwide morbidity and mortality during seasonal epidemics and periodic pandemics. As with all viruses, influenza's limited coding capacity requires the use of host proteins and processes in its replication and release cycle. Phosphorylation, mediated by cellular kinases and phosphatases, represents a significant mechanism of post-translational modification of cellular products, and is responsible for regulating the activi-ty, lifespan and localization of many lipids and proteins in host-cells. Several cellular kinases have been associated with various steps of the Influenza lifecycle, including PKC-ßII (viral entry), PKR (host defense), …

Recognition Of Hiv-1 Cryptic Epitopes During Infection And Following Vaccination, Anne Bet

All ETDs from UAB

Cryptic epitopes (CE) are a unique set of human leukocyte antigen class I (HLA-I)-restricted peptides that are encoded by alternative reading frames (ARFs) of genes. During human immunodeficiency virus-1 (HIV-1) infection, CE translated from either sense or antisense transcripts elicit epitope-specific CD8 T cell responses. Previous studies using simian immunodeficiency virus (SIV)-vaccinated animals have shown that an increased breadth of CD8 T cell responses is correlated with controlling viral replication, therefore stressing the potential clinical benefit of vaccine-induced T cell responses to a diverse set of viral epitopes. Yet, the genetic profiles and immunological significance of CE remain poorly understood. …

The Multifaceted Role Of Neutrophils In Hiv-1-Infection, Nathan Bowers

All ETDs from UAB

In recent years, a new appreciation of the role of neutrophils in regulating the immune system has emerged. Neutrophils are the most abundant leukocyte population and are traditionally recognized as essential effector cells of the innate immune system in the host defense against invading organisms. Neutrophils play a critical role in controlling bacterial and fungal infections by multiple mechanisms including phagocytosis, degranulation, and formation of neutrophil extracellular traps (NETs). Neutrophils have been shown to play important roles in viral pathogenesis, a knowledge gap exists in our understanding of the function of neutrophils in individuals infected with human immunodeficiency virus-1 (HIV-1). …

Targeting Reactive Oxygen Species Production To Prevent Left Ventricle Remodeling In Volume Overload, Danielle Marie Yancey

All ETDs from UAB

Mechanisms of left ventricular dysfunction in cardiac volume overload (VO) are not well understood and currently, no medical therapy exists to treat this condition. Cardiac VO is marked by eccentric remodeling and contractile dysfunction ultimately resulting in cardiac failure. Oxidative stress is implicated in the pathophysiology of heart failure and recent evidence suggests mitochondrially- produced reactive oxygen species play a role in VO. To study VO, we used a rat model of aortocaval fistula (ACF). ACF results in early diastolic stress on the left ventricle (LV) and recapitulates the progressive nature of heart failure with contractile function being initially maintained …

Multiple Human Itgam Variants Alter Mac-1, Fcgamma Receptor And Tlr Functions On Neutrophils, Yebin Zhou

All ETDs from UAB

Multiple studies have demonstrated that single-nucleotide polymorphisms (SNPs) in the ITGAM locus (including the non-synonymous SNPs rs1143679, rs1143678 and rs1143683) are associated with SLE. ITGAM encodes the protein CD11b, a subunit of the ß2 integrin Mac-1. The purpose of this work was to determine the effects of ITGAM genetic variation on the biological functions of neutrophil Mac-1. Neutrophils from ITGAM genotyped and sequenced healthy donors were isolated for functional studies. The phagocytic capacity of neutrophil ITGAM variants was probed with complement coated erythrocytes, serum treated zymosan, heat treated zymosan and IgG coated erythrocytes. The adhesion capacity of ITGAM variants, in …

Development Of A Patient-Derived Xenograft Model Of Ovarian Cancer To Characterize The Chemotherapy Resistant Population, Zachary Christopher Dobbin

All ETDs from UAB

Ovarian cancer while the second most common gynecologic malignancy is the most commons cause of death due to a gynecologic malignancy and the fifth most common cause of death to cancer in women. In 2014, there will be an expected 21,980 cases and 14,270 deaths. Unfortunately, the five-year survival for ovarian cancer is only 40% and this has barely increased over the past 30 years. New approaches need to be developed in order to study ovarian cancer and identify methods of overcoming chemotherapy resistance. This dissertation presents the work conducted in the development of a patient-derived xenograft model of ovarian …

Characterization Of Glycosylation-Associated Protein, Gap2, Required For The Biogenesis Of Streptococcus Parasanguinis Fimbriae-Associated Protein, Fap1, Haley Echlin

All ETDs from UAB

Streptococcal species possess a multitude of adhesins that facilitate adherence to a wide range of substrates; this is the first step necessary for the development of disease. Streptococcus parasanguinis is a primary colonizer of the oral cavity and adheres to the tooth surface using long fimbriae, which are composed of Fap1, a serine-rich repeat glycoprotein (SRRP). SRRPs are conserved in many Gram-positive bacteria and play a role in bacterial adhesion, fimbrial formation, biofilm formation, and bacterial pathogenesis. Although SRRPs play such an important role, the exact mechanism of their biogenesis remains a mystery. For Fap1, an eleven gene cluster is …

Elucidating The Role Of Gsk3 In Synaptic And Cognitive Deficits In Fragile X Syndrome, Aimee Vinson Franklin

All ETDs from UAB

Fragile X Syndrome (FX) is the most common inherited form of mental retarda-tion. Prominent characteristics of FX are mimicked in a mouse model with deleted fmr1 including hyperactivity, anxiety, developmental delay and social deficits. Additionally, FX mice display deficits in n-methyl-d-aspartate receptor (NMDAR) dependent long-term potentiation (LTP) at medial perforant path synapses onto dentate granule cells (MPP-DGC synapses). Because LTP is a cellular correlate of learning and memory, defi-cits in LTP at this synapse are thought to underlie impairments in pattern separation, a form of learning and memory dependent on proper DG function. Identifying the patho-logical mechanisms that cause impaired …

Targeting Tau-Mediated Nmdar Hypofunction Reverses Deficits In A Mouse Model Of Frontotemporal Dementia, Brian Andrew Warmus

All ETDs from UAB

Frontotemporal dementia (FTD) is a rapidly progressive and lethal disease, with no disease-modifying treatments. It is known that tau mutations cause FTD, but the underlying neurobiology is undefined. We sought to identify how tau affects the neurobiology in order to find potential treatment targets. Here, we address this question using a new mouse model expressing human tau with an FTD-associated mutation. We studied behavior, physiology, biochemistry, and neuropathology in several cohorts of mice at different ages. These mutant tau mice had abnormal repetitive behavior characteristic of FTD and synaptic deficits selectively in regions associated with FTD (ventral striatum and insula). …

Multifunctional Gold Nanocarriers For Cancer Theranostics - From Bench To Bedside And Back Again?, Joao Conde, Furong Tian, Pedro V. Baptista, Jesús M. De La Fuente

Books / book chapters

No abstract provided.

Modulating The Cxcl12/Cxcr4 Axis In The Pulmonary Vasculature By Adenoviral Vector-Mediated Delivery Of Soluble Cxcr4 (Scxcr4): A Prophylactic Approach To The Prevention Of Cancer Metastasis To The Lung, Anand Chandrasekaran Annan

All ETDs from UAB

The results also indicate that in situ nests were cooler than egg corral nests but still

Mitochondrial Dysfunction In Response To Neurotoxins And The Role Of Mitophagy, Samantha Giordano

All ETDs from UAB

Parkinson's disease (PD) is the second most common neurodegenerative disorder. Two major factors in both familial and sporadic PD are mitochondrial dysfunction and insufficient autophagy. My thesis research focuses on the interplay between these activities in PD. To investigate the common and differential effects of PD-inducing neurotoxins on mitochondrial bioenergetics and their relationships to cell survival, we used an in vitro culture system, differentiated dopaminergic SH-SY5Y neuroblastoma cells. We found that the neurotoxins rotenone, 1-methyl-4- phenylyridinium (MPP+) and 6-hydroxydopamine (6-OHDA), decreased mitochondrial respiration and induced cell death in these cells. The extent and characteristics of mitochondrial dysfunction in response to …

Contribution Of Kv4.2 To Neuronal Hyperexcitability In A Mouse Model Of Alzheimer's Disease, Alicia Marie Hall

All ETDs from UAB

may be advantageous for increasing seasonal and yearly variability in sex ratios.

The Role Of The Planar Cell Polarity Pathway In The Second Heart Field During Outflow Tract Morphogenesis, Tanvi Sinha

All ETDs from UAB

Outflow Tract (OFT) malformations underlie a majority of congenital heart defects (CHD) in humans and are a leading cause of childhood mortality. The OFT, which gives rise to the aorta and pulmonary artery of the heart, relies on the contribution of the Second Heart Field (SHF) progenitors in the pharyngeal and the splanchnic mesoderm, outside of the initial heart. OFT morphogenesis requires highly regulated SHF development involving the proliferation, differentiation and deployment of the SHF progenitors to the heart. Extensive studies elegantly demonstrate how transcriptional networks integrating signaling input from multiple pathways finely balance the proliferation and differentiation of SHF …

Effects Of Cpla-2 On The Migration And Proliferation Of Human Vascular Smooth Muscle Cells And The 2-D Migratory Patterns Of Tropomyosin In Femoral And Abdominal Aorta Tissue, Jaimeson Thomas Powell

Theses and Dissertations

Abstract 1: Platelet derived growth factor BB (PDGF BB) has an important influence on smooth muscle cell proliferation in restenosis and atherosclerosis. Our understanding of different signal transduction pathways involved in the response of smooth muscle cells to PDGF BB is potentially significant for understanding and manipulating these processes. Prior studies have demonstrated a crucial activation of cytosolic phospholipase A2 (cPLA2) in smooth muscle cells to PDGF BB with the production of arachidonic acid and prostaglandin E2. In these studies we investigated the role for another PLA2, calcium-independent PLA2 (iPLA2) in comparison to cPLA2 on smooth muscle cell migration and …

Self-Medication With Antibiotics Among Non-Medical University Students Of Karachi: A Cross-Sectional Study, Syed Jawad Shah, Hamna Ahmad, Rija Binte Rehan, Sidra Najeeb, Mirrah Mumtaz, Muhammad Hashim Jilani, Muhammad Sharoz Rabbani, Muhammad Zakariya Alam, Saba Farooq, M Masood Kadir

Community Health Sciences

Background: The prevalence of self -medication with antibiotics is quite high in developing countries as opposed to developed countries. Antibiotics are often taken erroneously for certain ailments, without having the appropriate knowledge of their use. This carries potential risks for the individual as well as the community, in form of several side effects such as antibiotic resistance. Therefore the prevalence of self-medicated antibiotics in developing countries needs to be studied.Methods: A descriptive cross-sectional study was carried out at six different non-medical universities of Karachi. 431 students were included in the study. Data was collected using self-administered questionnaires and analyzed using …

Does The Preparticipation Examination Aid In Identifying Future Risk Of Concussion?, Kassandra E. Johns

College of Graduate Studies: Theses & Dissertations

Context: A pre-participation examination (PPE) has become standard practice among the athletic community. This examination commonly includes a multifaceted baseline concussion assessment and an injury history survey. Recent evidence suggests that neuropsychological testing can aid in predicting individuals at an increased risk of lower extremity injury. However, no known previous study has investigated the relationship between neuropsychological function and potential risk of sustaining a concussion.

Objective: This study sought to identify a relationship between components of a standard PPE and an elevated risk of concussion.

Design: All data was extracted from the institution concussion database.

Setting: A large university in …

A Comparison Of The Effects Of Hyperbaric And Isobaric Bupivacaine Spinal Anesthesia On Hemodynamics And Heart Rate Variability, Mehmet Toptaş, Si̇nan Uzman, İlke İşi̇temi̇z, Tümay Uludağ Yanaral, İbrahi̇m Akkoç, Gülşen Bi̇can

Turkish Journal of Medical Sciences

To compare the effects of hyperbaric and isobaric bupivacaine spinal anesthesia on hemodynamics and heart rate variability (HRV) in nonobstetric surgery. Materials and methods: Sixty patients were randomly allocated to 2 groups. Group I (n = 30) received 15 mg (3 mL) of hyperbaric bupivacaine and Group II (n = 30) received 15 mg (3 mL) of isobaric bupivacaine for spinal anesthesia. Hemodynamic parameters were recorded before and after spinal anesthesia over 30 min. Analyses of HRV were performed on the day of surgery, after volume loading, and 20 min after spinal injection. Low frequency (LF) values, high frequency (HF) …