Medicine and Health Sciences Commons^™

Mutations In The 5’ Ntr And The Non-Structural Protein 3a Of The Coxsackievirus B3 Selectively Attenuate Myocarditogenicity, Chandirasegaran Massilamany, Arunakumar Gangaplara, Rakesh H. Basavalingappa, Rajkumar A. Rajasekaran, Hiep Vu, Jean-Jack Riethoven, David Steffen, Asit K. Pattnaik, Jay Reddy

School of Veterinary and Biomedical Sciences: Faculty Publications

The 5’ non-translated region (NTR) is an important molecular determinant that controls replication and virulence of coxsackievirus B (CVB)3. Previous studies have reported many nucleotide (nt) sequence differences in the Nancy strain of the virus, including changes in the 5’ NTR with varying degrees of disease severity. In our studies of CVB3-induced myocarditis, we sought to generate an infectious clone of the virus for routine in vivo experimentation. By determining the viral nt sequence, we identified three new nt substitutions in the clone that differed from the parental virus strain: C97U in the 5’ NTR; a silent mutation, A4327G, in …

Confocal Fluorescence Microscopy: An Ultra-Sensitive Tool Used To Evaluate Intracellular Antiretroviral Nano-Drug Delivery In Hela Cells, Subhra Mandal, You Zhou, Annemarie Shibata, Christopher J. Destache

School of Veterinary and Biomedical Sciences: Faculty Publications

In the last decade, confocal fluorescence microscopy has emerged as an ultra-sensitive tool for real-time study of nanoparticles (NPs) fate at the cellular-level. According to WHO 2007 report, Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome (HIV/AIDS) is still one of the world’s major health threats by claiming approximately 7,000 new infections daily worldwide. Although combination antiretroviral drugs (cARV) therapy has improved the life-expectancy of HIV-infected patients, routine use of high doses of cARVhas serious health consequences and requires complete adherence to the regimen for success. Thus, our research goal is to fabricate long-acting novel cARV loaded poly(lactide-co-glycolic acid) (PLGA) nanoparticles (cARV-NPs) as …

Association Of Autophagy In The Cell Death Mediated By Dihydrotestosterone In Autoreactive T Cells Independent Of Antigenic Stimulation, Ting Jia, Annandurai Anandhan, Chandirasegaran Massilamany, Rajkumar A. Rajasekaran, Rodrigo Franco, Jay Reddy

School of Veterinary and Biomedical Sciences: Faculty Publications

Gender disparity is well documented in the mouse model of experimental autoimmune encephalomyelitis (EAE) induced with proteolipid protein (PLP) 139–151, in which female, but not male, SJL mice show a chronic relapsing-remitting paralysis. Furthermore, dihydrotestosterone (DHT) has been shown to ameliorate the severity of EAE, but the underlying mechanisms of its protective effects are unclear. Using major histocompatibility complex (MHC) class II dextramers for PLP 139-151, we tested the hypothesis that DHT selectively modulates the expansion and functionalities of antigen-specific T cells. Unexpectedly, we noted that DHT induced cell death in antigen-specific, autoreactive T cells, but the effects were not …

Evaluation Of An Interactive Workshop Designed To Teach Practical Welfare Techniques To Beef Cattle Caretakers And Decision Makers, Reneé Dewell, Christy Hanthorn, Jared Danielson, Rebecca Burzette, Johann Coetzee, D. Dee Griffin, Alejandro Ramirez, Grant Dewell

School of Veterinary and Biomedical Sciences: Faculty Publications

The purpose of the project was to evaluate the use of an interactive workshop designed to teach novel practical welfare techniques to beef cattle caretakers and decision makers. Following training, respondents reported being more likely to use or recommend use of local anesthesia for dehorning and castration and were more inclined to use meloxicam for pain management. Respondents also reported improvement in performing all skills taught in the workshop. These results suggest instructional techniques used to teach practical concepts/techniques relevant to beef cattle welfare led to improvements in both perceived competency and estimated likelihood that the material will be used. …

Spiral Ganglion Degeneration And Hearing Loss As A Consequence Of Satellite Cell Death In Saposin B-Deficient Mice, Omar Akil, Ying Sun, Sarath Vijayakumar, Wujuan Zhang, Tiffany Ku, Chi-Kyou Lee, Sherri Jones, Gregory A. Grabowski, Lawrence R. Lustig

School of Veterinary and Biomedical Sciences: Faculty Publications

Saposin B (Sap B) is an essential activator protein for arylsulfatase A in the hydrolysis of sulfatide, a lipid component of myelin. To study Sap B’s role in hearing and balance, a Sap B-deficient (B^-/-) mouse was evaluated. At both light and electron microscopy (EM) levels, inclusion body accumulation was seen in satellite cells surrounding spiral ganglion (SG) neurons from postnatal month 1 onward, progressing into large vacuoles preceding satellite cell degeneration, and followed by SG degeneration. EM also revealed reduced or absent myelin sheaths in SG neurons from postnatal month 8 onwards. Hearing loss was initially seen …

Pseudorabies Virus Fast Axonal Transport Occurs By A Pus9- Independent Mechanism, Gina R. Daniel, Patricia J. Sollars, Gary E. Pickard, Gregory A. Smith

School of Veterinary and Biomedical Sciences: Faculty Publications

Reactivation from latency results in transmission of neurotropic herpesviruses from the nervous system to body surfaces, referred to as anterograde axonal trafficking. The virus-encoded protein pUS9 promotes axonal dissemination by sorting virus particles into axons, but whether it is also an effector of fast axonal transport within axons is unknown. To determine the role of pUS9 in anterograde trafficking, we analyzed the axonal transport of pseudorabies virus in the presence and absence of pUS9.

Haemorrhagic Colitis Associated With Enterohaemorrhagic Escherichia Coli O165:H25 Infection In A Yearling Feedlot Heifer, Rodney A. Moxley, Zachary R. Stromberg, Gentry L. Lewis, John D. Loy, Bruce W. Brodersen, Isha R. Patel, Jayanthi Gangiredla

School of Veterinary and Biomedical Sciences: Faculty Publications

Introduction: Enterohaemorrhagic Escherichia coli (EHEC) cause haemorrhagic colitis and haemolytic uraemic syndrome in humans. Although EHEC infection typically results in haemorrhagic colitis in all ages of human patients, in cattle it is usually limited to 1- to 5-week-old nursing calves.

Case Presentation: A 1-year-old feedlot beef heifer was moribund with neurological signs and bloody diarrhoea. At necropsy, the colonic mucosa contained multiple grossly visible haemorrhagic erosions, each measuring <1 mm in diameter. Histologically, foci corresponding to the gross erosions had E. coli O165 antigen-positive bacterial rods adherent to the apical surfaces of degenerate and necrotic colonic mucosal epithelial cells in association with attaching and effacing lesions, and also within cytoplasmic vacuoles in …

Characterization Of Newly Revealed Sequences In The Infectious Myonecrosis Virus Genome In Litopenaeus Vannamei, Duan S. Loy, Sijun Liu, Mark A. Mogler, J. Dustin Loy, Bradley J. Blitvich, Lyric C. Bartholomay

School of Veterinary and Biomedical Sciences: Faculty Publications

Infectious myonecrosis virus (IMNV) causes significant economic losses in farmed shrimp, where associated mortality in ponds can reach 70%. To explore host/pathogen interactions, a next-generation sequencing approach using lymphoid organ tissue from IMNV-infected Litopenaeus vannamei shrimp was conducted. Preliminary sequence assembly of just the virus showed that there were at least an additional 639 bp at the 5′ terminus and 23 nt at the 3′ terminus as compared with the original description of the IMNV genome (7561 nt). Northern blot and reverse transcription-PCR analysis confirmed the presence of novel sequence at both ends of the genome. Using 5′ RACE, an …

Mri-Compatible Bioreactors And Methods Of Using, Shadi Othman, Huihui Xu, Karin Wartella, Vahid Khalilzad-Sharghi, Ian Bargar

School of Veterinary and Biomedical Sciences: Faculty Publications

This disclosure describes a MRI-compatible bioreactor that allows a biological sample to be imaged in culture without disrupting or compromising the culture.

Influence Of Planning Resources On Gait Control In Parkinson’S Disease, Frederico P. Faria

Theses and Dissertations (Comprehensive)

Movement disturbances in individuals with Parkinson’s disease (PD) have been associated with difficulties to plan complex actions. Performance of simple and complex actions overloads resources for individuals with Parkinson’s disease (PD). However, it is unclear if central resources required to plan gait adjustments while walking exacerbate gait disturbances of patients with PD. More specifically, it is unclear how gait impairments, sensory processing, and the dopaminergic system influence the load on processing resources (e.g. cognitive load) during the planning of step modifications. In order to investigate the relative influence of these factors on cognitive load and its impact on gait control, …

High-Definition Tdcs Of Noun And Verb Retrieval In Naming And Lexical Decision, Svetlana Malyutina, Dirk B. Den Ouden

Communication Sciences and Disorders Faculty Articles and Research

High-definition transcranial direct current stimulation (HD-tDCS) is a novel brain stimulation method that has high potential for use in language therapy for speakers with aphasia, due to its safety and focality. This study aimed to obtain foundational data on using HD-tDCS to modulate language processing in healthy speakers. Participants received stimulation either of left Broca’s area or of angular gyrus (20 minutes of anodal, cathodal and sham stimulation on separate days), followed by naming and lexical decision tasks with single-word verb and noun stimuli. We found that cathodal stimulation over both Broca’s area and left angular gyrus increased naming speed …

Amla Enhances Autophagy And Modulates Beta Amyloid Metabolism In An In Vitro Model Of Alzheimer’S Disease, Elham Teimouri, Prashant Bharadwaj, Stephanie R. Rainey-Smith, Paul Fraser, Giuseppe Verdile, Ralph N. Martins

ECU Posters

Alzheimer’s disease (AD) is a progressive, fatal neurodegenerative disease characterized by extensive neuronal loss associated with increased accumulation of the beta amyloid (Aβ) protein. Reducing production, preventing aggregation and improving clearance of Aβare areas of active research in the development of therapeutic agents to ameliorate neurodegeneration in AD. The Indian plant amla (Emblicaofficinalis), commonly known as Indian gooseberry, has widely been utilized in traditional Ayurvedic medicine preparations in the treatment of a variety of disease conditions including cardiovascular disease and diabetes: accumulating evidence also suggests that amla may be beneficial in AD. Amla exhibits antioxidant, anti-inflammatory, and anti-apoptotic mechanisms and …

Development Of Cytotoxic Natural Killer Cells For Ovarian Cancer Treatment, Veethika Pandey

Electronic Theses and Dissertations

Ovarian cancer is a leading cause of gynecological malignancy. Cytoreductive surgery and frontline platinum/taxane-based chemotherapy provides good initial efficacy in the treatment, but poor long-term patient survival. This is mainly caused by tumor relapse due to intraperitoneal spreading and ineffective alternate therapies to treat these resistant tumors. The challenge in the field is to develop strategies that would prove effective in these patients and extend overall survival. Over the years, various treatments have been developed for the treatment of cancer amongst which, adoptive cell immunotherapy has shown promising results. But despite the efficacy seen in the clinic, there are concerns …

The Role Of A Highly Conserved Eubacterial Ribosomal Protein In Translation Quality Control, Anusha Naganathan

Electronic Theses and Dissertations

The process of decoding is the most crucial determinant of the quality of protein synthesis. Ribosomal protein L9 was first implicated in decoding fidelity when a mutant version of L9 was found to increase the translation of a T4 phage gene. Later studies confirmed that the absence of L9 leads to increased translational bypassing, frameshifting, and stop codon readthrough. L9 is part of the large subunit of the prokaryotic ribosome and is located more than 90 Å from the site of decoding, making it difficult to envision how it might affect decoding and reading frame maintenance. Twenty years after the …

Proteomic Analysis Delineates The Signaling Networks Of Plasmodium Falciparum, Brittany Pease

Electronic Theses and Dissertations

Malaria is a life-threatening disease caused by Plasmodium parasites that are spread through the bites of infected mosquito vectors. It is a worldwide pandemic that threatens 3.4 billion people annually. Currently, there are only a few validated Plasmodium drug targets, while drug resistance continues to rise. This marks the urgency for the development of novel parasite-specific therapeutics. Plasmodium falciparum diverges from the paradigm of the eukaryotic cell cycle by undergoing multiple rounds of DNA replication and nuclear division without cytokinesis. A better understanding of the molecular switches that coordinate the progression of the parasite through the intraerythrocytic developmental stages will …

Timp-1 Activates A Unique Cardiac Stem Cell Population, Cd63+Ve/C-Kit+Ve, Thereby Enhancing Cardiac Differentiation, And Protects The Heart From Adverse Cardiac Remodeling Following Myocardial Infarction, Latifa Abdelli

Electronic Theses and Dissertations

We previously demonstrated that embryonic stem (ES) cells over-expressing tissue inhibitor of metalloproteinase-1 (TIMP-1) have increased potential to engraft and differentiate into cardiac myocytes following transplantation into the infarcted heart. However, the ability of TIMP-1 to activate endogenous stem cells and enhance their differentiation into cardiac regenerative cell types is still unknown. We postulate that TIMP-1 may additionally activate a stem cell population that enhances cardiac cell type differentiation in the infarcted myocardium. To prove this hypothesis, we isolated c-kit+ve cells from four weeks old C57BL/6 mice and cultured them in vitro in presence of ES conditioned media (ESCM), ES-TIMP-1-CM …

Decreased Pain Severity And Differential Gene Expression Following Calmare Therapy, Jeffrey Petraco, Angela R. Starkweather, Amy Heineman

UROP Posters

We present the results of a double-blinded randomized sham-controlled research study of a non-pharmacologic low back pain intervention. Calmare therapy is an neurocutanous electrical stimulation approach for pain management. The intervention group received Calmare therapy and the other received sham. Differences in pain severity and interference scores, pain sensitivity measures and gene expression profiles are reported. Patterns of downregulated gene expression suggest that Calmare may alter proteins involved in pain transduction may have implications for the treatment of other chronic pain conditions.

Feasibility Of Integrating Tripterygium Wilfordii Into Modern Cancer Therapy For Increased Efficacy And Minimal Toxicity, Ngoc T. Vo

UROP Posters

Cancer is the second leading cause of death in the U.S. and millions of novel cancer cases are being diagnosed each year. While chemotherapy and ionizing radiation are effective treatments against these malignant tumors, the adverse effects that accompany such treatments are devastating. In order to find alternative treatment methods with less side effects, we turn to Eastern herbal medicine. Recent scientific research has found that Tripterygium wilfordii, an herbal medicine traditionally used to treat inflammation in China, contains compounds (triptolide and celastrol) that prevent the growth of solid tumors, induce apoptosis, and prevent metastasis of developed tumors. Investigations …

Regulation Of System XC- By Pharmacological Manipulation Of Cellular Thiols, Rebecca Albano, Nicholas J. Raddatz, Julie Hjelmhaug, David A. Baker, Doug Lobner

Biomedical Sciences Faculty Research and Publications

The cystine/glutamate exchanger (system x_c^-) mediates the transport of cystine into the cell in exchange for glutamate. By releasing glutamate, system x_c^- can potentially cause excitotoxicity. However, through providing cystine to the cell, it regulates the levels of cellular glutathione (GSH), the main endogenous intracellular antioxidant, and may protect cells against oxidative stress. We tested two different compounds that deplete primary cortical cultures containing both neurons and astrocytes of intracellular GSH, L-buthionine-sulfoximine (L-BSO), and diethyl maleate (DEM). Both compounds caused significant concentration and time dependent decreases in intracellular GSH levels. However; DEM caused an increase …

Patterns Of Barbell Acceleration During The Snatch In Weightlifting Competition, Kristof Kipp, Chad Harris

Exercise Science Faculty Research and Publications

The purpose of this study was to determine the association between weightlifting performance and vertical barbell acceleration patterns. Barbell kinematic time-series data were tracked from 18 snatches from six weightlifters during a regional weightlifting competition. These data were used to calculate vertical barbell accelerations. Time-series data were normalised to 100% of lift phase, defined as the time interval between barbell lift-off and maximum height of the barbell during each snatch lift. The time-series data were then entered into a pattern recognition algorithm that extracted principal patterns and calculated principal pattern scores. Body mass-normalised lift weight, which was used to quantify …

Obesity Weighs Down Memory: Emerging Insights Into The Epigentic Basis Of Obesity-Induced Memory Impairment In Adult Mice, Frankie Darryn Heyward

All ETDs from UAB

A preponderance of evidence has established that obesity contributes to memory impairments in mid-age adults. Empirical evidence has revealed that diet-induced obesity contributes to memory impairments in adult rodents. Precisely how obesity disrupts memory remains an open question. Bourgeoning data indicate that molecular epigenetic mechanisms mediate the changes in gene transcription that are necessary for hippocampus-dependent memory consolidation. Epigenetic mechanisms, such as DNA methylation, stably regulate gene expression without affecting the DNA sequence. Moreover, DNA methylation of memory-related genes with in the hippocampus is indispensible for memory formation. There is recent evidence of obesity-induced aberrantions in DNA methylation both peripherally …

Caenorhabditis Elegans Sperm Chemotaxis, Hieu Dinh Hoang

All ETDs from UAB

Survival of animal species depends on fertilization, the union of an egg and a sperm. The sperm's ability to find an egg quickly allows it to pass on male genetic material. It is challenging to record sperm targeting or guidance efficiency and motility in utero. We use the Caenorhabditis elegans model organism to study sperm guidance, primarily because its epidermis is transparent, allowing the observation of live fluorescent sperm in the hermaphrodite uterus. Using genome-editing techniques, genetic analyses, fluorescent microscopy, and mass spectrometry, we aim to address the following two questions: how hermaphrodites regulate sperm motility in the uterus, and …

Mechanisms Of Heme Oxygenase-1-Mediated Protection Against Tissue Injury, Travis David Hull

All ETDs from UAB

Heme oxygenase-1 (HO-1) catalyzes the rate-limiting step in the catabolism of heme, which is released by necrotic cells in injured tissue. HO-1 expression is protective in cardiac and renal injury because it coordinates the degradation of pro-oxidant heme with the generation of equimolar quantities of iron (Fe2+) and the cytoprotective mole-cules carbon monoxide and biliverdin. While many studies have demonstrated that HO-1 expression is protective in numerous disease states, relatively few have examined the specific cellular compartment(s) through which HO-1 expression confers its protective effects. Our objective was to define the cellular compartments in which HO-1 expression is critical to …

Mechanisms Of Resistance To Oncolytic Herpes Simplex Viruses In Malignant Peripheral Nerve Sheath Tumors, Joshua Douglas Jackson

All ETDs from UAB

Malignant peripheral nerve sheath tumors (MPNSTs) are rare but highly aggressive cancer of the peripheral nervous tissue. Median patient survival is approximately two years following diagnosis due in part to the ineffective options for treatment. As an alternative therapeutic approach to conventional radio- and chemotherapy, oncolytic herpes simplex viruses type-1 (oHSVs) have been proposed to treat MPNSTs. These oHSVs have been shown safe in clinical trials with associated tumor regression. However, there is evidence that resistance to the therapy should be anticipated in a subset of patients. Therefore, the goal of this dissertation has been to identify the primary obstacles …

Zebrafish Wnt9b Patterns The First Pharyngeal Arch Into D-I-V Domains And Promotes Anterior-Medial Outgrowth, Henry Jackson

All ETDs from UAB

The secondary mouth and its associated face and jaws were an important evolutionary adaptation in the vertebrate lineage. The secondary mouth is formed from facial prominences including the fronto-nasal prominence and the 1st pharyngeal-arch derived maxillary and mandibular prominence. Cranial neural crest cells within these prominences give rise to the connective tissues of face and jaws, and strict spatio-temporal regulation of cranial neural crest cell fate patterning and subsequent prominence outgrowth is vital to normal facial development. Oral-facial clefting (OFC) is a common morbid human birth disorder characterized by disrupted oral and craniofacial morphogenesis. Our previous studies demonstrate that a …

Changes In Gene Expression During Nitrogen Starvation Are Mediated By Targeted Degradation Of Translation And Mrna Decay Factors In Saccharomyces Cerevisiae, Shane Patrick Kelly

All ETDs from UAB

Autophagy is the cellular mechanism of recruitment and decay of cytoplasmic molecules, proteins, and organelles that are obsolete for a particular growth condition. Autophagic degradation is distinct from proteasomal degradation by the formation of a de-novo double membrane which engulfs its cargo to be delivered for degradation to the yeast vacuole. Once thought to be only a general phenomenon of bulk decay, several autophagic pathways have demonstrated selectivity. In the following work we show that during nitrogen starvation (a potent inducer of autophagy) in the yeast Saccharomyces cerevisiae, a subset of translation factors are degraded selectively and rapidly. We go …

Regulation Of Cks1 Protein Turnover In Cancer Cells, Vinayak Khattar

All ETDs from UAB

Cks1 is a crucial cell cycle regulator which plays pleiotropic roles in cancer cell growth and is highly expressed at both the protein, and mRNA levels, in cancer cells. In contrast, normal cells exhibit barely detectable levels of this protein, even though they express substantial Cks1 mRNA. One reason for high Cks1 protein in cancers appears to be its stabilization in these cells. Cks1 is known to be ubiquitinated and degraded by the proteasome. Coordinated ubiquitination dependent proteasomal degradation of cell cycle proteins is a major mechanism that regulates their activity. Therefore aberrant accumulation of Cks1, frequently observed in cancer, …

Impairment Of The Gliovascular Unit In Neurological Disease, Ian Kimbrough

All ETDs from UAB

Cerebral blood flow is regulated by vasoactive molecules released by astroglial cell processes that ensheath the entire cerebrovasculature. This regulation of blood flow in response to neuronal activity is a process known as functional hyperemia. Astrocytes, along with their associated neurons and microvessels, are organized into a functional system called the gliovascular unit (GVU). The astroglial component of the GVU is integral in both regulation of blood flow and maintenance of the blood-brain barrier (BBB). In disease, this system can be disrupted. We found that glioma cells displace astrocytic processes, called endfeet, and prevent their communication with associated vessels, leading …

An Nphp-4 Enhancer Mutagenesis Screen For Modifiers Of Cilia Phenotypes Reveals Novel Mks Alleles, Uncovers, A Specific Genetic Interaction Between Osm-3 And Nphp-4, And A Novel Ciliary Calcium Channel., Dawn Landis

All ETDs from UAB

Nephronophthisis (NPHP) is a ciliopathy with diverse clinical features likely caused by genetic modifiers. To identify NPHP modifiers, a screen was conducted on nphp-4(tm925) mutant C. elegans to reveal mutations that exacerbate the NPHP ciliary defects. Ten loci were generated, five of which have now been identified. Three are mutations in ciliopathy genes mks-1, mks-2, and mks-5. The fourth allele (yhw66) is a missense mutation (S316F) in OSM-3, a kinesin required for cilia distal segment assembly. As in osm-3 null mutants, nphp-4(tm925);osm-3(yhw66) mutants lack distal segments, are dye-filing defective (Dyf), and have osmotic avoidance defects (OSM). The osm-3(yhw66) mutant alone …

14-3-3 Proteins Regulate Mutant Lrrk2 Kinase Activity And Neurite Shortening, Nicholas Lavalley

All ETDs from UAB

Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common known cause of inherited Parkinson’s disease (PD), and LRRK2 is a risk factor for idiopathic PD. How LRRK2 function is regulated is not well understood. Recently, the highly-conserved 14-3-3 proteins, which play a key role in many cellular functions including cell death, have been shown to interact with LRRK2. In this study, we investigated whether 14-3-3s can regulate mutant LRRK2-induced neurite shortening and kinase activity. In the presence of 14-3-3θ overexpression, neurite length of primary neurons from BAC transgenic G2019S-LRRK2 mice returned back to wildtype levels. Similarly, 14-3-3θ overexpression …