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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 …

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, …

Gene Expression And Alzheimer's Disease: Evaluation Of Gene Expression Patterns In Brain And Blood For An Alzheimer's Disease Mouse Model, Amanda Hazy

Senior Honors Theses

Previous studies have established a causative role for altered gene expression in development of Alzheimer’s disease (AD). These changes can be affected by methylation and miRNA regulation. In this study, expression of miRNA known to change methylation status in AD was assessed by qPCR. Genome-wide expression changes were determined by RNA-sequencing of mRNA from hippocampus and blood of control and AD mice. The qPCR data showed significantly increased expression of Mir 17 in AD, and sequencing data revealed 230 genes in hippocampus, 58 genes in blood, and 8 overlapping genes showing significant differential expression (p value ≤ 0.05). Expression data …

Esophageal Replacement By Hydroxylated Bacterial Cellulose Patch In A Rabbit Model, Changlai Zhu, Fang Liu, Wenbo Qian, Yingjie Wang, Qingsheng You, Tianyi Zhang, Feng Li

Turkish Journal of Medical Sciences

Background/aim: To repair esophageal defects by hydroxylated and kombucha -synthesized bacterial cellulose (HKBC) patch in a rabbit model. Materials and methods: Semicircular esophageal defects 1 cm in length of the cervical esophagus were initially created in 18 Japanese big-ear rabbits and then repaired with HKBC patch grafts. The clinical outcomes including survival rate, weight change, food intake, and hematological and radiologic evaluation were observed. After X-ray evaluation, the rabbits were sacrificed sequentially at 1, 3, and 6 months for histopathologic analysis with light microscopy and scanning electron microscopy. Results: Survival rate during the first month was 88.9% (n = 16). …

Alzheimer Disease And Anesthesia, Gözde İnan, Zerri̇n Özköse Şatirlar

Turkish Journal of Medical Sciences

Alzheimer disease (AD) is one of the most common neurodegenerative diseases and the most prevalent form of dementia. Some factors in the development of AD, age being the best-known one, have been suggested; however, no causes have been found yet. The pathophysiology of the disease is highly complex, current therapies are palliative, and a cure is still lacking. Adverse effects of anesthetics in the elderly have been reported since the 1950s; however, awareness of this old problem has recently gained importance again. Whether exposure to surgery and general anesthesia (GA) is associated with the development of AD has been questioned. …

Immunogenicity Of Conserved Cork And Ss-Barrel Domains Of Baumannii Acinetobactin Utilization Protein In An Animal Model, Yaqub Hajiaghatabar Sangroodi, Iraj Rasooli, Shahram Nazarian, Walead Ebrahimizadeh, Fatemeh Sefid

Turkish Journal of Medical Sciences

Background/aim: The uptake of the ferric-acinetobactin complex into the periplasmic space relies on the baumannii acinetobactin utilization (BauA) protein. BauA is composed of cork and the β-barrel domains. We constructed a recombinant protein from conserved antigenic domains of cork and the β-barrel of BauA to evaluate their immunogenic role in an animal model. Materials and methods: The selected bauA domains were amplified from a purified genome of Acinetobacter baumannii ATCC 19606. The domains were then cloned into pET28a and the proteins expressed in E. coli BL21 (DE3) were purified using nickel nitrilotriacetic acid chromatography. Mice and rabbits were immunized with …

Ebola Viral Disease: What Should Be Done To Combat The Epidemic In 2014?, Ali̇ye Baştuğ, Hürrem Bodur

Turkish Journal of Medical Sciences

Ebola virus disease (EVD) was defined first in 1976. Since then, more than 24 epidemics have been reported from Africa, predominantly with the Zaire species. On 21 March 2014, the current West Africa outbreak was reported by the World Health Organization, the largest one ever recorded. The Congo epidemic was reported in July 2014. It was considered that the two epidemics had unrelated origins with 96.8% identical genomic sequence of the virus. EVD outbreaks occurred in areas with limited resources but it has a potentially global effect due to the possibility of imported infection and the potential misuse of the …

Gastrointestinal System Lesions In Children Due To The Ingestion Of Alkali And Acid Corrosive Substances, Kaan Demi̇rören, Hali̇l Kocamaz, Yaşar Doğan

Turkish Journal of Medical Sciences

To examine esophageal and gastric lesions in children due to the ingestion of alkali and acid corrosive substances and to emphasize all related complications. Materials and methods: The reports of 103 children who ingested or were suspected to have ingested corrosive substances and who then underwent upper gastrointestinal endoscopic inspections were evaluated retrospectively. Results: Of the patients, the mean age was 41 ± 3.6 months, and 57.3% were male. Vomiting was the most common symptom (44.7%). Eighteen different commercial products were defined as corrosive substances: 59.2% of them were alkali, 39.8% were acids, and 1% had a neutral pH. These …

Stat4 Regulates Multiple Pathogenic Mechanisms Of Cd4 T Cells In Experimental Autoimmune Encephalomyelitis, A Model Of Multiple Sclerosis, Ian Lee Mcwilliams

All ETDs from UAB

Multiple Sclerosis (MS) is an autoimmune disease whereby the host immune system fails to recognize self vs non-self and targets myelin of the central nervous system. Currently there is no permanent cure for MS and the efficacy of immune modulatory treatments often wane over time, therefore we seek to determine novel pathogenic mechanisms to target therapeutically. CD4 T cells have been found within inflammatory CNS lesions of MS patients and are believed to be important mediators of MS pathology. To study CD4 T cells in the context of MS, we use the well-defined MS mouse model experimental autoimmune encephalomyelitis (EAE). …

Innate Immunity Mechanisms In Parkinson Disease, Mark Moehle

All ETDs from UAB

Parkinson disease (PD) is a late onset, progressive neurodegenerative movement disorder with cardinal symptoms of tremor at rest, bradykinesia, postural instability, and rigidity. These motor symptoms of PD are caused by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). However, despite PDs first modern observation in 1817, little is understood about the causes and molecular mechanisms behind dopaminergic neuron loss. The relatively weak understanding of pathological mechanisms has hindered the development of treatments to slow or halt the progression of PD. However, recently, mounting evidence from post-mortem, imaging, and retrospective studies suggest an important role …

Tau-Sh3 Interactions: Implications For Alzheimer's Disease, Jesse Nicholas Cochran

All ETDs from UAB

Alzheimer’s disease (AD) is the most common neurodegenerative disease and with Americans’ increasing longevity it is becoming an epidemic. There are currently no effective treatments for this disorder. Abnormalities of tau track more closely with cognitive decline than the most studied therapeutic target in AD, amyloid-beta, but the optimal strategy for targeting tau has not yet been identified. Based on considerable preclinical data from AD models, we hypothesize that interactions between tau and SH3 domain–containing proteins are pathogenic in AD. Genetically reducing either tau or tau interactants has beneficial effects relevant to AD. Here, we describe a drug screen for …

Behavioral And Developmental Abnormalities In Sult4a1 Deficient Zebrafish, Francis Crittenden

All ETDs from UAB

Since its identification in 2000, sulfotransferase (SULT) 4A1 has presented an enigma to the field of cytosolic SULT biology. SULT4A1 is exclusively expressed in neural tissue, is highly conserved, and has been identified in every vertebrate studied to date. Despite this singular level of conservation, no substrate or function for SULT4A1 has been identified. Previous studies demonstrated that SULT4A1 does not bind the obligate sulfate donor, 3’-phosphoadenosine-5’-phosphosulfate (PAPS), yet SULT4A1 is classified as a SULT superfamily member based on sequence and structural similarities to the other SULTs. In this study, RNA-seq was used to search for alterations in gene ex-pression …

Hepatocyte Clock And Alcohol-Dependent Disruption In Glycogen Metabolism, Uduak Sunday Udoh

All ETDs from UAB

Chronic alcohol consumption has been shown to significantly decrease hepatic glycogen, an important storage form of energy for the body and liver. Emerging studies indicate a link between metabolism and the molecular circadian clock. Previously, we have shown that chronic alcohol consumption disrupts the liver molecular clock mechanism. However, it is not known how this alteration impacts hepatic energy (e.g., glycogen) metabolism and contributes to alcohol hepatotoxicity. This dissertation investigates the impact chronic alcohol consumption has on time-of-day-dependent oscillations of various aspects of liver glycogen metabolism, and the importance of the liver circadian clock in these metabolic alterations. Chapter 1: …

A Novel Role For Usp14 In Regulating Non-Proteolytic Ubiquitin Signaling, Jada Hallengren Vaden

All ETDs from UAB

Loss of the deubiquitinating enzyme (DUB) USP14 in the ataxia (axJ) mice leads to altered neuromuscular junction (NMJ) structure, reduced synaptic transmission at the NMJ, and decreased mobility. However, the types of processes that USP14 regulates in the nervous system remain unclear. Because association with the proteasome stimulates USP14's ubiquitin hydrolase activity, it is thought to act primarily on proteasomal substrates. Therefore, one way for USP14 to support nervous system function is by modulating protein turnover. While a number of studies done in yeast and immortalized cell lines demonstrate that loss or inhibition of USP14 alters proteasome function, there is …

The Effects Of The Initially Transcribed Sequence On Reiterative Transcription In Escherichia Coli, Jeffery Michael Vahrenkamp

All ETDs from UAB

Transcription, the synthesis of a ribonucleic acid transcript using a nucleic acid template, is the first step in gene expression for all life. In most organisms, high fidelity transcription is achieved through the formation of an RNA:DNA hybrid which allows the RNA polymerase to maintain the correct register. Slippage, which would lead to improper base pairing, is prevented by the heterogeneous sequence of the DNA template. However, when homogenous tracts of bases are present in the template, slippage can occur, allowing a single base in the template to encode multiple bases in the transcript in a process called reiterative transcription. …

Characterizing The Nuclear Import And Functions Of Cystin, The Ciliary Protein Disrupted In The Cpk Mouse Model Of Recessive Polycystic Kidney Disease, Jacob Asher Watts

All ETDs from UAB

Autosomal recessive polycystic kidney disease (ARPKD; MIM 263200) is a ma-jor cause of pediatric morbidity and mortality. Typically, orthologous animal models are the mainstay for pathogenic studies of human diseases. However, gene-targeting of Pkhd1, the mouse ortholog of the ARPKD gene, results in mutants with little or no kidney disease. In contrast, disruption of the non-orthologous gene, Cys1, in the cpk mouse model closely phenocopies human ARPKD. We speculate that this phenotypic similarity suggests that the Pkhd1 and Cys1 genes encode proteins (FPC and cystin, respectively) that share, at least in part, common molecular pathways. Our laboratory, as well as …

The Mechanism Of Small Molecule Viral Fusion Inhibitors, Michael Joseph Rowse

All ETDs from UAB

All negative stranded RNA viruses (NSRV) have genomes encapsidated by oligomerized nucleoprotein (N). The N-RNA complex acts as the template for both transcription and replication. The crystal structure of the N protein from the model NSRV vesicular stomatitis virus (VSV) established the structural basis for the oligomerization of N-protein and the encapsidation of RNA. To determine how the structure of N protein changes in response to specific sequences of RNA, we developed a strategy to digest the random RNA encapsidated in the recombinant N-protein and reencapsidated specific RNA sequences. Poly-rA, poly-rC, poly-rU, and poly-rG sequences were encapsidated and co-crystallized with …

The Multifactorial Roles Of The Cytokines Il-21 And Il-22 In Mediating Host Defense Against Enteropathogenic Infection, Daniel James Silberger

All ETDs from UAB

Enteropathogenic strains of Escherichia coli are a major public health concern, causing diarrhea and mortality particularly among infants and children in developing countries. Citrobacter rodentium is a murine intestinal pathogen that models pathogenic E. coli infection. Both innate and adaptive immune cells contribute to the clearance of C. rodentium. In particular, B cells and CD4+ T cells but not CD8+ T cells are required for protection during a primary infection with C. rodentium. In addition, T cell-dependent antibody responses are required for clearance. Th17 cells are a major CD4+ T cell population that accumulates in the large intestine during C. …

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 …

Metabolic And Oxidative Regulation Of Neuronal Autophagy And Survival, Matthew Dodson

All ETDs from UAB

Neurodegenerative diseases, such as Parkinson's disease, Alzheimer's disease and Huntington's disease are all characterized by metabolic dysfunction, increased oxidative damage to proteins and organelles, formation of proteinaceous inclusions, decreased autophagic and proteasomal function, and eventual neuronal and glial cell death. While our understanding of the mechanisms that underlie many of these pathologies is constantly growing, their exact cause, onset, interplay and progression still remain unclear. The gap between the description of disease pathologies and understanding the fundamental mechanisms of disease pathogenesis, progression and potential therapeutics to mitigate disease progression is still large. Based on the observation that altered glucose utilization, …

The Characterization Of Human Cytosolic Sulfotransferase 1a1: Interactions With 17Α-Ethinylestradiol, Katie Jo Glowacki

All ETDs from UAB

Human cytosolic sulfotransferases (SULTs) are a family of Phase II conjugating enzymes that facilitate the transfer of a sulfonate moiety from 3’phosphoadenosine 5’phosphosulfate (PAPS) to hydroxyl or amine groups of acceptor substrates. SULT1A1, located in many tissues throughout the human body including the liver, is important in the metabolism of many endogenous, exogenous, xenobiotic, and drug compounds. The majority of substrates for SULT1A1 are small neutral phenols including 1-naphthol and acetaminophen; however, SULT1A1 sulfates larger compounds including 17β-estradiol (E2) and raloxifene. SULT1A1 conjugates E2 with a Km of 2.3 µM and the structure of E2 is almost identical to the …

Bioenergetics As A Biomarker Of Health And Disease, Philip Kramer

All ETDs from UAB

The increasing prevalence of metabolic syndrome, diabetes, atherosclerosis, and many other diseases only recently associated with aberrant metabolism, have led to a de-mand for clinical assays to determine a patient’s mitochondrial health. With the rapidly growing interest in personalized medicine, such an assay would ideally be able to capture the metabolic changes associated with oxidative stress, inflammation, and therapy of a patient in a swift and non-invasive manner. Short of tissue biopsies, this burgeoning field of Translational Bioenergetics has had minimal success in obtaining sufficient human cells and the means to assess them both accurately and swiftly. The purpose of …

The Alpha-Glucosidase Inhibitor Acarbose As A Calorie Restriction Mimetic To Modify Metabolic Outcomes In Mice, Rachel Ann Brewer

All ETDs from UAB

Age-related diseases continue to be a leading cause of death. One of the only replicable methods proven to decrease age-related morbidity and mortality in multiple species is calorie restriction (CR). CR is difficult for human populations to implement, and has a number of associated risks and side effects. A CR mimetic could provide the healthspan- and lifespan-extending benefits of CR without the limitations. Acarbose (ACA), an α-glucosidase and α-amylase inhibitor approved to treat type 2 diabetes in humans, was recently identified as able to extend lifespan in healthy mice. The purpose of this research was to determine the effects of …

The I507-Atc→Att Silent Codon Change Contributes To The Misfolding Of ∆F508 Cftr, Vedrana Bali

All ETDs from UAB

Synonymous codon changes (SCCs) do not alter the amino acid sequence of proteins, but may significantly change the phenotype. The frequency of synonymous codons is species- and gene-specific, described as codon usage bias (CUB). Over the past 50 years, research has shown that SCCs affect protein biogenesis, development of human disorders and the function of recombinant proteins developed for therapeutic applications. However, the molecular mechanisms by which SCCs alter the function of gene products are not completely understood. In Chapter 2 we summarize present knowledge in this field. The most common cause of cystic fibrosis (CF) is the deletion of …

The Mspa Nanopore As A Sensor For Dna Sequencing, Mikhail Pavlenok

All ETDs from UAB

Nanopore sequencing is a novel and promising DNA sequencing method. This single molecule technique is capable of long reads, retains epigenetic information, and is inexpensive and fast. In this method ionic current is measured while single-stranded DNA is electrophoretically translocated through a nanometer-scale pore. Each passing nucleotide blocks current with characteristic amplitude and duration which are used to identify DNA sequence. MspA is the primary porin of M. smegmatis and mediates the diffusion of small, hydrophilic nutrients across the outer membrane. MspA is an octameric, channel-forming protein and represents the founding member of a new class of mycobacterial outer membrane …