Digital Commons Network^™

Characterization Of Chemical Uptake And Aryl Hydrocarbon Receptor Mutations In Zebrafish, Jaclyn Paige Souder

All ETDs from UAB

In a society driven by technology and industry, we must be increasingly aware of how changes to our environment impact our health. This is especially true concerning embryonic development, which is easily influenced by extra-embryonic factors, including environmental contaminants. Determining how exogenous compounds are absorbed, which receptors they act through, and how these receptors act endogenously is important to fully understand to what extent developmental exposures impact fetal and adult health. I have used the zebrafish model system to address these questions for two classes of environmentally-relevant chemicals—estrogens and dioxins. First, I developed an assay to measure the uptake of …

Dysregulation In The Central Nervous System Upon Mcmv Infection In Newborn Mice, Cathy Yea Won Sung

All ETDs from UAB

Human cytomegalovirus (HCMV) infection is a major cause of morbidity in infants and children throughout the world. Between 0.2-1.2% of all live births is infected with HCMV in the United States. Approximately 5-15% of these newborn babies will develop long-term neurological damage resulting in motor disorders, mental retardation, and sensorineural hearing loss. Although the neurological sequelae associated with congenital HCMV infections are well characterized, little is known about the pathogenesis of the damage to the central nervous system (CNS). To study the pathogenesis of congenital HCMV infection, we have developed a mouse model in which newborn mice are infected intraperitoneally …

Therapeutic Mechanisms In Sickle Cell Nephropathy, Crystal Taylor

All ETDs from UAB

Sickle cell disease (SCD) is a commonly inherited genetic blood disorder that causes hypoxia-induced polymerization of mutant hemoglobin resulting in erythrocyte sickling, transient microvascular occlusion, ischemic injury, and end-organ damage. Systemic endothelial dysfunction and vaso-occlusive episodes observed in SCD are particularly deleterious to the kidney, where the hypoxic, hyperosmotic environment of the medulla makes it particularly susceptible to ischemic injury. Over recent decades, chronic kidney disease has emerged as a significant contributor to mortality and morbidity in SCD patients. Despite a growing interest in the importance of sickle cell nephropathy (SCN), therapeutic options are limited and much remains undiscovered regarding …

Acetylcholine Signaling In Glioblastoma Invasion And Peritumoral Hyperexcitability, Emily Grace Thompson

All ETDs from UAB

Glioblastomas are the most common and deadly form of primary brain cancer in adults. Current treatment strategies are aggressive, including a combination of surgical resection, radiotherapy, and chemotherapy. However, median patient survival has remained stagnant at 12 to 15 months for the last several decades. This dismal patient outcome has prompted efforts to understand the unique characteristics of these tumors, since traditional therapeutics have not been efficacious. Extensive invasion is a salient feature of glioblastomas that significantly diminishes the effectiveness of current treatment strategies and is ultimately the cause of tumor recurrence within 2 years in approximately 80% of patients. …

Novel Biomarkers For Parkinson Disease, Shijie Wang

All ETDs from UAB

Parkinson disease (PD) is the second most common neurodegenerative disorder with no reliable biochemical biomarkers for disease prediction or progression, nor disease-modifying treatments to slow the relentless progression. Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are known to increase LRRK2 kinase activity and increase the risk for late-onset PD. In this thesis, I discovered that LRRK2 is secreted into exosomes in urine and CSF, where LRRK2 kinase activity, reflected by autophosphorylation at pS1292 site, is preserved and reflective of cytosolic LRRK2 levels. In a cohort of biosamples from LRRK2 mutation carriers and matched controls, with and without PD, …

The Anti-Tumor Effects Of Hur Inhibition In Glioblastoma, Jiping Wang

All ETDs from UAB

Glioblastomas (GBMs) are the most malignant primary brain tumor. GBMs represent 14.7% of total primary CNS tumors and 47.7% of malignant CNS tumors. The median survival of GBM is 18-20 months, while five-year survival rate is only 5.6%. GBMs are maintained by glioma stem cells (GSCs), and poor treatment outcomes are linked to the high resistance of GSCs to radiation and chemotherapy, and the immunosuppressive tumor microenvironment. The mRNA binding protein HuR is a key regulator of tumor growth and development based upon the fact that HuR targets mRNAs that are broadly involved in tumorigenesis. We have previously shown that …

Using Peptide Mimetics To Probe Protein-Protein Interactions Significant In Cancers, Robert H. Whitaker

All ETDs from UAB

Protein-protein interactions are critical for cell life. One aspect of cellular regulation where such protein-protein interactions occur is in the highly regulated process of programmed cell death (or apoptosis). Apoptosis is critical for normal tissue homeostasis, differentiation, and if dysregulated is a driver of disease including cancers. At the center of apoptotic regulation is the BCL2 protein family whose intra-familial protein-protein interactions balance cell stress signaling either allowing the cell to survive or inducing mitochondrial cell death. These BCL2 protein interactions are accomplished through the BH3 motif. While unique to the BCL2 family, a similar motif, the reverse BH3, has …

O-Glcnac Regulation Of Inhibitory Circuits, Kavitha Abiraman

All ETDs from UAB

Post translational modification of proteins plays a crucial role in regulating their function, and the role of one such modification, termed O-GlcNAcylation, is understudied. O-GlcNAcylation involves the dynamic cycle of adding and removing an O-linked N-acetylglucosamine (O-GlcNAc) by the enzymes O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), which are highly expressed in the hippocampus. Enzymes that catalyze O-GlcNAcylation are found at both presynaptic and postsynaptic sites, and O-GlcNAcylated proteins localize to synaptosomes. We have shown that acute and selective increase in O-GlcNAcylation of AMPAR GluA2 subunits underlies expression of a novel form of LTD at CA3-CA1 synapses (O-GlcNAc LTD), as well …

Identification Of Two Spop-Mediated Pathways In Prostate Cancer Progression, Joshua Fried

All ETDs from UAB

Prostate cancer is one of the most common malignancies and causes of cancer related death in men. Morbidity is primarily attributed to late-stage and metastatic disease. Re-cent genomic screening studies have revealed that the Speckle type Poz Protein (SPOP) is the most frequently altered gene by missense mutations in prostate cancer. Interestingly, all of the identified mutations were located in the substrate binding domain of SPOP. Here, two pathways highlighting the impact of SPOP mutation on prostate cancer are pre-sented. First, evidence showing that one of the naturally occurring SPOP mutations, ser-ine 119 to asparagine (S119N), induces radiosensitivity and an …

Baf Chromatin Landscaping During Bone Formation And Maintenance, Tanner Cole Godfrey

All ETDs from UAB

Bone loss is a worldwide problem resulting in increased risk of fracture. Osteoblasts are responsible for bone synthesis; therefore, treatments promoting osteoblast differentiation and/or activity would result in increased bone formation. The regulation of DNA accessibility is a key mechanism controlling gene expression and cellular differentiation. BAF (BRG1 Associated Factor) mediated chromatin remodeling increases DNA accessibility by sliding or ejecting nucleosomes. This process can occur in a cell type specific manner based on the composition of BAF. In many tissue types, a unique combination of BAF subunits has been identified to be responsible for the maintenance or differentiation of that …

Pannexin 1 Channel Inhibition To Prevent Triggered Arrhythmia, Grace Elizabeth Salzer

All ETDs from UAB

The mechanism of triggered arrhythmia generation involves inappropriate diastolic calcium (Ca2+) releases from the sarcoplasmic reticulum that promote membrane depolarization when the released Ca2+ is transported out of the cardiomyocyte via the sodium Ca2+ exchanger (NCX). If membrane depolarization is large enough, these events can trigger an ectopic action potential. However, it is not fully understood what physiological factors facilitate triggered events at the tissue level. Pannexin 1 (Px1), a large transmembrane conductance channel, can be activated by various stimuli including increases in intracellular Ca2+. We predict that during diastolic Ca2+ releases, Px1 becomes activated and together with the NCX, …

The Influence Of O-Glcnacylation On Dna 5-Hydroxymethylation In The Epileptic Hippocampus, Richard Gilbert Sánchez

All ETDs from UAB

Epilepsy is a neurological disorder that affects roughly 3 million Americans and 65 million individuals worldwide. Although there are several known causes of epilepsy, little is understood about the development of epilepsy or epileptogenesis. What has been observed through multiple studies of epilepsy is an alteration of the proteomic profile, along with a distinct change in post-translational modifications (PTM). Studies have focused on phosphorylation and a variety of kinases that are upregulated during epilepsy with little clinical translation. This dissertation investigates O-GlcNAcylation, a PTM that is highly intertwined with the cellular metabolism, and its epigenetic effects on gene expression via …

Novel Approaches To Enhance Translational Readthrough Efficacy For Cystic Fibrosis Nonsense Mutations, Jyoti Sharma

All ETDs from UAB

Cystic fibrosis (CF) is a monogenic autosomal recessive disease caused by over 1,900 naturally occurring variants in the CF transmembrane conductance regulator (CFTR). CFTR is an epithelial anion channel which regulates the movement of chloride and bicarbonate ions. Mutations in the CFTR causes diminished CFTR protein and/or reduced CFTR function that lead to clinical manifestations. These include severe epithelial dysfunction of multiple tissues, including the lungs, intestine, pancreas, and reproductive organs. Premature termination codons (PTC), or nonsense mutations, are among the most severe CFTR variants and occur in ~11% of the CF population. PTCs are caused by the presence of …

Differences In The M1 And M2 Macrophage Subtypes Between The Sexes Determine Susceptibility To Francisella Tularensis Infection, Michelle Arlene Sanchez

Open Access Theses & Dissertations

Francisella tularensis is the causative agent of the human disease tularemia. It is highly infectious with as few as 10 microorganisms via inhalation causing a lethal infection. F. tularensis infects a variety of cell types, including macrophages and neutrophils, since it needs to enter, survive and proliferate in order to cause pathogenicity. Disease is the result of over activating the host's own inflammatory response initiated by the macrophage's response to infection.

Known differences exist in the intensity of the inflammatory response between the sexes which leads to differences in sensitivity to autoimmune and infectious disease. Males tend to be more …

Axon Initial Segment Integrity In Aging And Traumatic Brain Injury, Mazen M. Gouda

Theses and Dissertations

According to the Center for Disease Control’s (CDC) report to the Congress, there are 2.2 million emergency department visits; 80,000 hospitalizations; and 50,000 deaths each year due to traumatic brain injury. Adults 65 years and older account substantially for the majority of the hospitalization and deaths. Over 70% of the traumatic brain injuries of the older adults are classified as mild to moderate; however, even with these milder injuries, older adults present with a significantly higher morbidity and mortality compared to all other age groups (LeBlanc et al., 2006). With that in mind, it seems essential to develop a deeper …

The Effect Of Isotretinoin On Insulin Resistance And Adipocytokine Levels In Acne Vulgaris Patients, Gonca Soyuduru, Esra Özsoy Adişen, İlkay Özer, Ahmet Burhan Aksakal

Turkish Journal of Medical Sciences

Recent data draw attention to the effect of body composition, insulin resistance, and adipocytokines to acne vulgaris (AV) development. The aim of this study was to assess the association of AV with insulin resistance and adipocytokine levels and to evaluate the effect of isotretinoin on insulin resistance and adipocytokine levels. Materials and methods: In 29 AV patients and 29 healthy volunteers, body mass index (BMI) and body fat mass (BFM), lipid, adiponectin, leptin, resistin, retinol binding protein-4 (RBP4), and insulin levels were measured and insulin resistance was assessed by HOMA-IR index in serum samples taken twice from patients before and …

Iron Supplementation Should Be Given In Breath-Holding Spells Regardless Of Anemia, Gürkan Gürbüz, Peren Perk Yücel, Turgay Çokyaman, Özge Berfu Gürbüz

Turkish Journal of Medical Sciences

The purpose of this retrospective study was to determine the effectiveness of oral iron therapy in breath-holding spells and evaluation of electrocardiographical changes.Materials and methods: Three hundred twelve children aged 1-48 months and diagnosed with breath-holding spells between January 2017 and April 2018 were included. Patients' laboratory findings were compared with 100 patients who had one simple febrile seizure.Results: Cyanotic breath-holding spells were diagnosed in 85.3% (n = 266) of patients, pallid spells in 5.1% (n = 16), and mixed-type spells in 9.6% (n = 30). Sleep electroencephalograms were applied for all patients, 98.2% (n = 306) of which were …

Faculty Publications 2018, Lsu Health Sciences Center New Orleans

Historical Faculty Publications

This Faculty bibliography contains 810 publications.

Mesenchymal Stromal Cell Therapeutic Delivery: Translational Challenges To Clinical Application, Henry Caplan, Scott D Olson, Akshita Kumar, Mitchell George, Karthik S Prabhakara, Pamela Wenzel, Supinder Bedi, Naama E Toledano-Furman, Fabio Triolo, Julian Kamhieh-Milz, Guido Moll, Charles S Cox

Faculty, Staff and Student Publications

For several decades, multipotent mesenchymal stromal cells (MSCs) have been extensively studied for their therapeutic potential across a wide range of diseases. In the preclinical setting, MSCs demonstrate consistent ability to promote tissue healing, down-regulate excessive inflammation and improve outcomes in animal models. Several proposed mechanisms of action have been posited and demonstrated across an array of in vitro models. However, translation into clinical practice has proven considerably more difficult. A number of prominent well-funded late-phase clinical trials have failed, thus calling out for new efforts to optimize product delivery in the clinical setting. In this review, we discuss novel …

Comparison Of Venous Repair Results Using Either Arterial Or Vein Grafts In A Crush-Avulsion Injury Model, Selami̇ Serhat Şi̇rvan, Işil Akgün Demi̇r, Fati̇h Irmak, Dağhan Dağdelen, Kamuran Zeynep Sevi̇m, Ayşe Ayşi̇m Özağari, Ayşi̇n Karasoy Yeşi̇lada

Turkish Journal of Medical Sciences

Background/aim: Venous insufficiency after replantation or revascularization is one of the most common causes of limb loss in either the short or the long term. The aim of this study was to evaluate the results of a new technique to overcome venous insufficiency.Materials and Methods: A crush-avulsion type of injury was formed in the femoral veins of rats of 3 separate groups. In the control group, primary repair was applied to the damaged veins and the remaining 2 groups were repaired with either an arterial graft or a vein graft. The success rates of anastomosis were then compared.Results: In the …

Review Of The Effect Of 3d Medical Printing And Virtual Reality On Urology Training With `Medtrain3dmodsim' Erasmus + European Union Project, İlkan Tatar, Emre Huri̇, İlker Selçuk, Young Lee Moon, Alberto Paoluzzi, Andreas Skolarikos

Turkish Journal of Medical Sciences

Background/aim: It is necessary to incorporate novel training modalities in medical education, especially in surgical fields, because of the limitations of cadaveric training. Traditional medical education has many drawbacks, such as residency working hour restrictions, patient safety conflicts with the learning needs, and the lack of hands-on workshops. The MedTRain3DModsim Project aimed to produce 3-dimensional (3D) medical printed models, simulations, and innovative applications for every level of medical training using novel worldwide technologies. It was aimed herein to improve the interdisciplinary and transnational approaches, and accumulate existing experience for medical education, postgraduate studies, and specialty training. Materials and methods: This …

Profiling Of 17 Y-Str Loci In Mazandaran And Gilan Provinces Of Iran, Minoo Sayyari, Ali Salehzadeh, Mohamad Amin Tabatabaiefar, Ali Abbasi

Turkish Journal of Medical Sciences

Background/aim: TheY-chromosome mainly consists of heterochromatin regions that have a father-to-son inheritance. Short tandem repeat polymorphic (STRP) markers distributed all over the chromosome provide the opportunity for investigations in forensic medicine and ancestral lineage studies. Due to the existence of wide varieties of geographical and ethnic groups in Iran, studying Y-STRP markers is necessary for further applications. Here we investigated the provinces of Mazandaran and Gilan for the first time. Materials and methods: Samples included 119 and 90 unrelated males from Mazandaran and Gilan, respectively. Using a PCR amplification kit, 17 Y-STRP markers were amplified and genotyping was conducted by …

Effects Of Phenytoin Injection On Vocal Cord Healing After Mechanical Trauma: An Experimental Study, Si̇bel Ali̇cura Tokgöz, Cem Saka, İstemi̇han Akin, Fatma Fulya Köybaşioğlu, Saffet Kiliçaslan, Murat Çalişkan, Ömer Beşalti, Emel Çadalli Tatar

Turkish Journal of Medical Sciences

Background/aim: Phenytoin is an anticonvulsant drug which causes fibroblast proliferation, collagen synthesis, and an increase in epidermal growth factor. Therefore, the aim of the present study is to evaluate the effect of phenytoin injection on the wound healing process in rats with vocal cord injury by histopathological methods. Materials and methods: The vocal cords of 10 albino Wistar rats were damaged bilaterally; the left vocal cord was kept as the control group. Phenytoin was injected in the right vocal cord. Ten rats were sacrificed. The thickness of the lamina propria and density of the fibroblast and collagen were evaluated histopathologically.Results: …

The Effects Of Eicosapentaenoic Acid (Epa) And Docosahexaenoic Acid (Dha) On Brown Adipogenesis In Stem Cell Culture, Darynne A. Dahlem, Yan Huang

Discovery, The Student Journal of Dale Bumpers College of Agricultural, Food and Life Sciences

Polyunsaturated fatty acids (PUFAs), especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are major maternal dietary supplements due to their positive benefits on neurological tissue growth during the first 12 weeks of gestation. Previous studies show that EPA and DHA inhibit muscle formation but promote adipogenesis. However, no research has addressed the question whether high intake of EPA and DHA affects brown fat development during gestation. The objective of this study was to measure the effect of EPA and DHA supplement on brown adipogenesis and potential pathways related to mitochondrial biosynthesis using fibroblasts as in vitro model. Using Oil-Red-O staining …

Development Of Improved Acellular Pertussis Vaccines Through Inclusion Of The Rtx Antigen Or Induction Of Mucosal Immunity, Dylan Tyler Boehm

Graduate Theses, Dissertations, and Problem Reports (ETD)

Pertussis is a human respiratory disease, primarily caused by the Gram-negative pathogen Bordetella pertussis. The infection is most severe and can be life-threatening in young children and infants where it manifests as a series of paroxysmal coughs. The disease is more commonly known as whooping cough, due to the whoop omitted during a massive inspiratory effort to bring air back into the lungs. Pertussis is a toxin-mediated disease that persists due to an early release of toxins that allow that bacteria to evade the cells of the innate immune response. The inhibition of the host response continues as toxin activity …

Role Of Sox9 In Cancer Stem Cell Regulation In Lung Cancer Chemoresistance And Particle-Induced Carcinogenesis, Maria Voronkova

Graduate Theses, Dissertations, and Problem Reports (ETD)

Lung cancer is a leading cause of cancer-related death worldwide. Every year it claims more lives than other common malignancies, breast, prostate, and colorectal cancers, combined. And despite recent improvements in disease diagnostics and treatment, drug resistance and tumor relapse remain major contributors to low patient survival. Both issues have been largely attributed to the existence of cancer stem-like cells (CSCs) or tumor initiating cells (TICs). CSCs are a small cell population within heterogeneous tumors that is inherently resistant to apoptosis, chemo- and radiation therapy. Thus, it is critical to elucidate CSC-specific signaling pathways and identify early biomarkers for therapeutic …

Viral Emergence In Marine Mammals In The North Pacific May Be Linked To Arctic Sea Ice Reduction, Elizabeth Vanwormer, J. A.K. Mazet, A. Hall, V. A. Gill, P. L. Boveng, J. M. London, T. Gelatt, B. S. Fadely, M. E. Lander, J. Sterling, V. N. Burkanov, R. R. Ream, P. M. Brock, L. D. Rea, B. R. Smith, A. Jeffers, M. Henstock, M. J. Rehberg, K. A. Burek-Huntington, S. L. Crosby, J. A, Hammond, T. Goldstein

School of Veterinary and Biomedical Sciences: Faculty Publications

Climate change-driven alterations in Arctic environments can influence habitat availability, species distributions and interactions, and the breeding, foraging, and health of marine mammals. Phocine distemper virus (PDV), which has caused extensive mortality in Atlantic seals, was confirmed in sea otters in the North Pacific Ocean in 2004, raising the question of whether reductions in sea ice could increase contact between Arctic and sub-Arctic marine mammals and lead to viral transmission across the Arctic Ocean. Using data on PDV exposure and infection and animal movement in sympatric seal, sea lion, and sea otter species sampled in the North Pacific Ocean from …

Ehdv-2 Infection Prevalence Varies In Culicoides Sonorensis After Feeding On Infected White-Tailed Deer Over The Course Of Viremia, Sandra Y. Mendiola, Mary K. Mills, Elin Maki, Barbara S. Drolet, William C. Wilson, Roy D. Berghaus, David E. Stallknecht, Jonathan Breitenbach, D. Scott Mcvey, Mark G. Ruder

School of Veterinary and Biomedical Sciences: Faculty Publications

Epizootic hemorrhagic disease viruses (EHDVs) are arboviral pathogens of white-tailed deer and other wild and domestic ruminants in North America. Transmitted by various species of Culicoides, EHDVs circulate wherever competent vectors and susceptible ruminant host populations co-exist. The impact of variation in the level and duration of EHDV viremia in white-tailed deer (Odocoileus virginianus) on Culicoides infection prevalence is not well characterized. Here we examined how infection prevalence in a confirmed North American vector of EHDV-2 (Culicoides sonorensis) varies in response to fluctuations in deer viremia. To accomplish this, five white-tailed deer were experimentally infected with EHDV-2 and colonized C. …

Near-Atomic Structure Of A Giant Virus, Qianglin Fang, Dongjie Zhu, Irina Agarkova, Jagat Adhikari, Thomas Klose, Yue Liu, Zhenguo Chen, Yingyuan Sun, Michael L. Gross, James L. Van Etten, Xinzheng Zhang, Michael G. Rossmann

Nebraska Center for Virology: Faculty Publications

Although the nucleocytoplasmic large DNA viruses (NCLDVs) are one of the largest group of viruses that infect many eukaryotic hosts, the near-atomic resolution structures of these viruses have remained unknown. Here we describe a 3.5 Å resolution icosahedrally averaged capsid structure of Paramecium bursaria chlorella virus 1 (PBCV-1). This structure consists of 5040 copies of the major capsid protein, 60 copies of the penton protein and 1800 minor capsid proteins of which there are 13 different types. The minor capsid proteins form a hexagonal network below the outer capsid shell, stabilizing the capsid by binding neighboring capsomers together. The size …

Persistent Viral Reservoirs In Lymphoid Tissues In Siv-Infected Rhesus Macaques Of Chinese-Origin On Suppressive Antiretroviral Therapy, Summer Siddiqui, Stefanie Perez, Yong Gao, Lara Doyle-Meyers, Brian T. Foley, Qingsheng Li, Binhua Ling

Nebraska Center for Virology: Faculty Publications

Understanding HIV latent reservoirs in tissues is essential for the development of new strategies targeting these sites for eradication. Here, we assessed the size of latent reservoirs and the source of residual viruses in multiple lymphoid tissues of SIV-infected and fully suppressed rhesus macaques of Chinese-origin (cRMs). Eight cRMs were infected with SIVmac251 and treated with tenofovir and emtricitabine daily for 24 weeks initiated 4 weeks post-infection. Four of the eight animals reached sustained full viral suppression with undetectable viremia. The levels of cell-associated SIV DNA varied in peripheral blood mononuclear cells (PBMCs) and multiple lymphoid tissues, but with higher …