Digital Commons Network^™

Testosterone Treatment Fails To Accelerate Disease In A Transgenic Mouse Model Of Spinal And Bulbar Muscular Atrophy., Erica S Chevalier-Larsen, Diane E Merry

Department of Biochemistry and Molecular Biology Faculty Papers

Evidence from multiple animal models demonstrates that testosterone plays a crucial role in the progression of symptoms in spinal and bulbar muscular atrophy (SBMA), a condition that results in neurodegeneration and muscle atrophy in affected men. Mice bearing a transgene encoding a human androgen receptor (AR) that contains a stretch of 112 glutamines (expanded polyglutamine tract; AR112Q mice) reproduce several aspects of the human disease. We treated transgenic male AR112Q mice with testosterone for 6 months. Surprisingly, testosterone treatment of AR112Q males did not exacerbate the disease. Although transgenic AR112Q males exhibited functional deficits when compared with non-transgenics, long-term testosterone …

Synergetic Effect Of Recoverin And Calmodulin On Regulation Of Rhodopsin Kinase., Ilya I Grigoriev, Ivan I Senin, Natalya K Tikhomirova, Konstantin E Komolov, Sergei E Permyakov, Evgeni Yu Zernii, Karl-Wilhelm Koch, Pavel P Philippov

Department of Biochemistry and Molecular Biology Faculty Papers

Phosphorylation of photoactivated rhodopsin by rhodopsin kinase (RK or GRK1), a first step of the phototransduction cascade turnoff, is under the control of Ca(2+)/recoverin. Here, we demonstrate that calmodulin, a ubiquitous Ca(2+)-sensor, can inhibit RK, though less effectively than recoverin does. We have utilized the surface plasmon resonance technology to map the calmodulin binding site in the RK molecule. Calmodulin does not interact with the recoverin-binding site within amino acid residues M1-S25 of the enzyme. Instead, the high affinity calmodulin binding site is localized within a stretch of amino acid residues V150-K175 in the N-terminal regulatory region of RK. Moreover, …

Efficient And Robust Rna-Seq Process For Cultured Bacteria And Complex Community Transcriptomes, Georgia Giannoukos, Dawn M. Ciulla, Katherine Huang, Brian J. Haas, Jacques Izard, Joshua Z. Levin, Jonathan Livny, Ashlee M. Earl, Dirk Gevers, Doyle V. Ward, Chad Nusbaum, Bruce W. Birren, Andreas Gnirke

Department of Food Science and Technology: Faculty Publications

We have developed a process for transcriptome analysis of bacterial communities that accommodates both intact and fragmented starting RNA and combines efficient rRNA removal with strand-specific RNA-seq. We applied this approach to an RNA mixture derived from three diverse cultured bacterial species and to RNA isolated from clinical stool samples. The resulting expression profiles were highly reproducible, enriched up to 40-fold for non-rRNA transcripts, and correlated well with profiles representing undepleted total RNA.

Effects Of Arterial Strain And Stress In The Prediction Of Restenosis Risk: Computer Modeling Of Stent Trials, Shijia Zhao, Linxia Gu, Stacey R. Froemming

Department of Mechanical and Materials Engineering: Faculty Publications

Purpose — In-stenting restenosis is one of the major complications after stenting. Clinical trials of various stent designs have reported different restenosis rates. However, quantitative correlation between stent features and restenosis statistics is scant. In this work, it is hypothesized that stress concentrations on arterial wall caused artery injury, which initiates restenosis. The goal is to assess the correlation between stent-induced arterial stress and strain and the documented restenosis rates.

Methods — Six commercially available stents, including balloon-expandable stents and self-expanding stents, were virtually implanted into the arteries through finite element method. The resulted peak Von Mises stress, principal stress, …

Rhodotorula Minuta Fungemia In A Ewe Lamb, C G. Chitko-Mckown, K A. Leymaster, M. P. Heaton, D D. Griffin, J K. Veatch, S A. Jones, M. L. Clawson

School of Veterinary and Biomedical Sciences: Faculty Publications

An 8-month-old crossbred ewe, normal upon physical examination, was humanely euthanized for tissue collection. After approximately 3 weeks in tissue culture, fungi began budding out of cells obtained from the choroid plexus. After an additional 3 weeks, budding was observed in kidney cell cultures and eventually in monocyte cultures as well. Serum from the lamb was submitted to the Veterinary Diagnostic Laboratory at Colorado State University for fungal diagnosis and was found negative for Aspergillus, Blastomyces, Coccidioidomycosis and Histoplasmosis. DNA was isolated from fungi collected from tissue culture supernatants and used in a set of pan-fungal PCR assays with DNA …

Posttranslational Modification Of Vesicular Stomatitis Virus Glycoprotein, But Not Jnk Inhibition, Is The Antiviral Mechanism Of Sp600125, Sabrina Marozin, Jennifer Altomonte, Sibylle Apfel, Phat X. Dinh, Enrico De Toni, Antonia Rizzani, Andreas Nüssler, Nobuyuki Kato, Roland M. Schmid, Asit K. Pattnaik, Oliver Eberta

School of Veterinary and Biomedical Sciences: Faculty Publications

Vesicular stomatitis virus (VSV), a negative-sense single-stranded-RNA rhabdovirus, is an extremely promising oncolytic agent for cancer treatment. Since oncolytic virotherapy is moving closer to clinical application, potentially synergistic combinations of oncolytic viruses and molecularly targeted antitumor agents are becoming a meaningful strategy for cancer treatment. Mitogenactivated protein kinase (MAPK) inhibitors have been shown to impair liver cell proliferation and tumor development, suggesting their potential use as therapeutic agents for hepatocellular carcinoma (HCC). In this work, we show that the impairment of MAPK in vitro did not interfere with the oncolytic properties of VSV in HCC cell lines. Moreover, the administration …

Identification Of Amino Acid Residues Important For Anti-Ifn Activity Of Porcine Reproductive And Respiratory Syndrome Virus Non-Structural Protein 1, Lalit Beura, Sakthivel Subramaniam, Hiep Vu, Byungjoon Kwon, Asit K. Pattnaik, Fernando A. Osorio

School of Veterinary and Biomedical Sciences: Faculty Publications

The non-structural protein 1 (nsp1) of porcine reproductive and respiratory syndrome virus is partly responsible for inhibition of type I interferon (IFN) response by the infected host. By performing alanine-scanning mutagenesis, we have identified amino acid residues in nsp1α and nsp1β~ (the proteolytic products of nsp1) that when substituted with alanine(s) exhibited significant relief of IFNsuppression. A mutant virus (16-SA, in which residues 16-20 of nsp1β were substituted with alanines) encoding mutant nsp1β recovered from infectious cDNA clone was shown to be attenuated for growth in vitro and induced significantly higher amount of type I IFN transcripts in infected macrophages. …

A Single Amino Acid Change Resulting In Loss Of Fluorescence Of Egfp In A Viral Fusion Protein Confers Fitness And Growth Advantage To The Recombinant Vesicular Stomatitis Virus, Phat X. Dinh, Debasis Panda, Phani B. Das, Subash C. Das, Anshuman Das, Asit K. Pattnaik

School of Veterinary and Biomedical Sciences: Faculty Publications

Using a recombinant vesicular stomatitis virus encoding eGFP fused in-frame with an essential viral replication protein, the phosphoprotein P, we show that during passage in culture, the virus mutates the nucleotide C289 within eGFP of the fusion protein PeGFP to A or T, resulting in R97S/C amino acid substitution and loss of fluorescence. The resultant non-fluorescent virus exhibits increased fitness and growth advantage over its fluorescent counterpart. The growth advantage of the non-fluorescent virus appears to be due to increased transcription and replication activities of the PeGFP protein carrying the R97S/C substitution. Further, our results show that the R97S/C mutation …

Amino Acid Residues In The Non-Structural Protein 1 Of Porcine Reproductive And Respiratory Syndrome Virus Involved In Down-Regulation Of Tnf-Cx Expression In Vitro And Attenuation In Vivo, Sakthivel Subramaniam, Lalit Beura, Byungjoon Kwon, Asit K. Pattnaik, Fernando A. Osorio

School of Veterinary and Biomedical Sciences: Faculty Publications

Porcine reproductive and respiratory syndrome virus (PRRSV) suppresses tumor necrosis factor-alpha (TNF-α) production at both transcriptional and post-transcriptional levels by its non-structural proteins 1α and 1β (Nsp1α and Nsp1β). To identifY the amino acid residues responsible for this activity, we generated several alanine substitution mutants of Nsp1α and Nsp1β. Examination of the mutant proteins revealed that Nsp1α residues Gly90, Asn91 , Arg97, Argl 00 and Arg124 were necessary for TNF-α promoter suppression, whereas several amino acids spanning the entire Nsp1β ~ were found to be required for this activity. Two mutant viruses, with mutations at Nsp1α Gly90 or Nsp1β residues …

Staphylococcal Response To Oxidative Stress, Rosmarie Gaupp, Nagender Ledala, Greg A. Somerville

School of Veterinary and Biomedical Sciences: Faculty Publications

Staphylococci are a versatile genus of bacteria that are capable of causing acute and chronic infections in diverse host species. The success of staphylococci as pathogens is due in part to their ability to mitigate endogenous and exogenous oxidative and nitrosative stress. Endogenous oxidative stress is a consequence of life in an aerobic environment; whereas, exogenous osidative and nitrosative stress are often due to the bacteria's interaction with host immune systems. To overcome the deleterious effects of oxidative and nitrosative stress, staphylococci have evolved protection, detoxification, and repair mechanisms that are controlled by a network of regulators. In this review, …

Redefining Onyx Hd 500 In The Flow Diversion Era., Richard Tyler Dalyai, Ciro Randazzo, George Ghobrial, L Fernando Gonzalez, Stavropoula I Tjoumakaris, Aaron S Dumont, Robert H Rosenwasser, Pascal Jabbour

Department of Neurosurgery Faculty Papers

We report the largest US case series results using Onyx HD-500 (EV3), a new liquid embolic agent, in the successful treatment of 21 patients with wide-neck intracranial aneurysms (mean size 4.5 mm), which are at increased risk of incomplete occlusion or recanalization with standard endovascular intervention utilizing detachable platinum coils. All aneurysms were located in the anterior circulation, and three aneurysms presented as acute subarachnoid hemorrhages. Complete aneurysm occlusion was present in 19 of 21 patients (90%). On six-month followup, one patient with an initially small residual neck progressed to total occlusion. Aneurysm recanalization was not detected in any patients …

Investigating The Role Of Α6 And Α4 Containing Neuronal Nicotinic Acetylcholine Receptors In Nicotine And Cocaine Conditioned Place Preference Tests In Mice., Sarah Sanjakdar

Theses and Dissertations

Neuronal nicotinic acetylcholine receptors modulate both cholinergic and non-cholinergic synaptic transmission. Our research concerns α6 and α4 neuronal nicotinic subunits because they often co-assemble with the β2 subunit, which has abundant expression in the CNS and previous work has demonstrated that β2* nAChRs are involved in nicotine and cocaine reward. α6β2* and α4β2* nAChRs are highly expressed in midbrain, which is known to be critical for the incentive salience associated with natural and artificial (drug) reward. Our goal was to assess the role of α6β2* and α4β2* nAChRs in nicotine and cocaine reward using an unbiased conditioned place preference (CPP) …

The Role Of High Affinity Nicotinic Acetylcholine Receptors On Anxiety-Like Behavior: A Study In Female Mice, Jessicka Hall

Theses and Dissertations

Tobacco dependence is high in women who suffer from anxiety disorders yet little is known about the contributions of nicotinic acetylcholine receptors (nAChRs) on anxiety-like behavior. β2*nAChRs (*denotes assembly with other subunits) are the most abundantly expressed nAChRs in the brain yet little is known about the contributions of β2*nAChRs on anxiety-like behavior in female mice. In this study, antagonism and nicotine effects on anxiety-like behavior was investigated across the life span in 6, 12 and 24-month-old drug-naïve knockout (KO), heterozygous (HET) and a gain of function α6L9S mice and wild type (WT). HET mice showed increased sensitivity to di-hydrobeta-erythroidine …

Feasibility Study Of Trans-Cranial Direct Current Stimulation In Presence Of Brain Tumor, Abhilash Nair

Dissertations and Theses

Trans-cranial Direct Current Stimulation has been shown to modulate cortical neuronal activity. Weak constant current is applied to the scalp using electrodes, leading to sub-threshold changes in neuronal membrane potential. Before actual clinical stimulation is performed, such systems are validated by simulating the stimulation and the resulting current flow patterns using finite element solvers. However, the reliability of such models depends upon the accuracy with which the underlying anatomy has been modeled [1]. In earlier studies it has been shown that the current flow patterns within the brain are altered due to the presence of lesioned brain tissues[2]. Here we …

Severe Lamotrigine Neurotoxicity Treated With Intralipid Emulsion Therapy, Philip W. Moore Do, Megan C. Urquhart Do, Dale L. Mcmillion Do, Keith K. Burkhart Md, Louis R. Cantilena Jr, Md, J Ward Donovan Md

Department of Emergency Medicine

No abstract provided.

The Residency Cpc As A Means Of Faculty Development, Kathleen E. Kane Md, Kevin R. Weaver Do, Gavin C. Barr Jr. Md, Amy B. Smith Phd, Andrew C. Miller Do, Charles C. Worrilow Md, Terrence E. Goyke Do, Dawn M. Yenser, Bryan G. Kane Md

Department of Emergency Medicine

No abstract provided.

Determining Efficacy Of Breast Cancer Therapy By Pet Imaging Of Her2 Mrna, Bishnuhari Paudyal, Kaijun Zhang, Changpo Chen, Neil Mehta, Eric Wickstrom, Brian Gray, Jeffrey Mattis, Koon Pak, Mathew L Thakur

Department of Radiology Faculty Papers

No abstract provided.

Cell Cycle Arrest Associated With Anoxia-Induced Quiescence, Anoxic Preconditioning, And Embryonic Diapause In Embryos Of The Annual Killifish Austrofundulus Limnaeus, Camie Lynn Meller, Robert Meller, Roger P. Simon, Kristin M. Culpepper, Jason E. Podrabsky

Biology Faculty Publications and Presentations

Embryos of the annual killifish Austrofundulus limnaeus can enter into dormancy associated with diapause and anoxia-induced quiescence. Dormant embryos are composed primarily of cells arrested in the G1/G0 phase of the cell cycle based on flow cytometry analysis of DNA content. In fact, most cells in developing embryos contain only a diploid complement of DNA, with very few cells found in the S, G2, or M phases of the cell cycle. Diapause II embryos appear to be in a G0-like state with low levels of cyclin D1 and p53. However, the active form of pAKT is high during diapause II. …

C-C-Motif Chemokine Receptor/Ligand Gene Variants And Their Associations With Hiv-1 Transmission And Pathogenesis, Liangyuan Hu

All ETDs from UAB

Host factors including genes and their variants are important to HIV-1 acquisition, transmission and disease progression. In particular, chemokine (C-C motif) receptors 2 and 5 genes (CCR2 and CCR5) have multiple variants of interest. We first investigated the impact of CCR2-CCR5 haplotypes on several outcomes among 567 HIV-1 discordant Zambian couples. HHF*2 homozygosity was associated with significantly lower VL in seroconverters (mean beta=-0.58 log10 P=0.027) and the HHD/HHE diplotype was associated with significantly higher VL in the seroconverters (mean beta=0.54, log10 P=0.014) adjusted for age and gender in multivariable model. HHD/HHE was associated with more rapid acquisition of infection by …

Retinoids And Abnormal Alveolar Development, Masheika L. James

All ETDs from UAB

Extremely preterm infants are at high risk for a form of chronic lung disease called bronchopulmonary dysplasia (BPD), which is characterized by impaired alveolar development. Exposure to hyperoxia and deficiency of vitamin A (VA) contribute to the development of BPD in preterm infants. Randomized controlled trials indicate VA supplementation decreases BPD and/or death. However, 25% of preterm infants continue to remain VA deficient despite supplementation, probably due to impairment in VA transport, VA is stored in the liver as retinyl esters which are transported to the lung and irreversibly metabolized into all-trans-retinoic acid (ATRA), the active metabolite. A combination of …

The Role Of C-Reactive Protein In Arthritic Disease, Nicholas Ryan Jones

All ETDs from UAB

C-reactive protein (CRP) is an acute phase protein that is commonly used to evaluate systemic inflammation level. Blood CRP level also correlates very well with rheumatoid arthritis (RA) disease severity. However, CRP has many biological actions that lead one to suspect that it may be playing a role in the development or pathology of the disease. We have directly addressed whether this is the case by the use of novel mouse models (CRP deficiency or transgenic overexpression). We have shown that CRP positively affects collagen-induced arthritis development and progression. In order to thoroughly address the question, we have also reported …

Mycobacterial Iron Acquisition Systems, Christopher M. Jones

All ETDs from UAB

Iron is an essential nutrient for the vast majority of organisms; yet, the availability of iron is limited to microorganisms due to the insolubility of ferric hydroxides and to pathogens by iron withholding strategies of their hosts. Many bacteria produce small, high-affinity iron chelators called siderophores to scavenge iron from the environment. In addition, many bacterial pathogens have evolved mechanisms to steal host iron contained in heme, hemoglobin, or transferrin. Mycobacteria are unique genera of bacteria represented by the notorious pathogens Mycobacterium tuberculosis and Mycobacterium leprae, the causative agents of tuberculosis (TB) and leprosy, respectively. Tuberculosis remains a global health …

A Study Of The Genetic Mechanisms Used To Regulate The Third Complementarity Determining Region Of The Immunoglobulin H Chain, Mohamed Khass

All ETDs from UAB

Developing B cells exhibit sequential changes in the representation of immunoglobulin (Ig) heavy (H) chain sequences with excess hydrophobic or charged amino acids in complementarity determining region 3 (CDR-H3). To begin to elucidate the mechanisms by which this process occurs, we used Bromodeoxy Uridine (BrdU) incorporation and Annexin V binding to quantify B cell turnover and cell cycle progression in developing B cell subsets in the bone marrow, spleen and peritoneal cavity of wild-type BALB/c mice. To magnify the effects of hydrophobicity and charge, we included in this analysis mice limited to the use of an IgH allele with a …

Is P53 A Target Of Hpv-18 E6 In The Viral Life Cycle?, Eun-Young Kho

All ETDs from UAB

The large family of human papillomaviruses (HPVs) infects the cutaneous or mucosal epithelia causing benign hyper proliferative diseases. Infections by the high-risk (HR) HPV genotypes in the anogenital tracts can progress to high grade lesions and cancers in men and women. Because the viral productive program requires squamous differentiation of epithelia, HPV encodes oncoproteins that recondition the differentiated cells that have withdrawn from the cell cycle to support viral DNA amplification. The HR HPV E6 and E7 oncogenes are selectively expressed in cervical carcinomas and are necessary to maintain the malignant state. In vitro, constitutive expression of the HR HPV …

Mechanism Of Nfi-C Functionin During Tooth Root Formation, Ejvis Lamani

All ETDs from UAB

Currently, very little is known regarding tissue-specific gene regulation during the later stages of tooth development, especially those associated with root formation. Re-cent studies have identified nuclear factor I-C (NFI-C) as a critical factor for root for-mation in mammals. NFI-C functions as a cellular transcription factor and adenovirus DNA replication factor. Its role in root formation first became evident when Nfi-c null mice were shown to lack molar roots. A similar phenotype of incomplete or absent root formation is observed in patients with the autosomal dominant disease Radicular Dentin Dysplasia (RDD; MIM125400) also known as Rootless Teeth or Dentin Dysplasia …

Development Of An Adenoviral Vector Platform For Selective Gene Delivery To Neurons, Travis Benjamin Lewis

All ETDs from UAB

Parkinson disease (PD) is a devastating movement disorder affecting between 500,000 and 1,000,000 individuals in the United States alone, and for which there is currently no cure. Therapies such as dopamine replacement help initially, but with disease progression these lose efficacy and do not alter the underlying degenerative process. Gene therapy is the delivery of exogenous genetic material to correct an underlying disorder. A major advantage of this approach is the ability to distribute potent therapies to specific targets over an extended duration, properties necessary for the treatment of progressive degenerative diseases such as PD. A number of clinical trials …

Regulation Of P27kip1 By Trip6 And Its Implications In Cancer Progression, Victor T G Lin

All ETDs from UAB

TRIP6 is a focal adhesion molecule that functions as an adaptor protein to mediate diverse cellular functions, including motility and antiapoptotic signaling, through a wide variety of protein-protein interactions. We were able to characterize a novel interaction between TRIP6 and p27KIP1, a CDK inhibitor which can both suppress and promote tumorigenesis, depending on its regulation. TRIP6 expression specifically promotes the AKT-mediated phosphorylation of p27KIP1 at T157, which leads to its cytosolic retention, and accelerates the protein turnover rate of p27KIP1. We also found that phosphorylation of T157 by itself promotes cell motility and can be linked to the formation of …

Using Mouse Models To Investigate Ciliopathies, Raymond Carl Pasek

All ETDs from UAB

Cilia and flagella are microtubule based organelles found on nearly every cell type in the mammalian body. Flagella have an essential role in sperm locomotion and reproduction, while motile cilia have a known role in fluid movement in the brain, lungs, and portions of the female reproductive tract. While the role of most primary cilia remained unknown for decades, they are now recognized as being essential to mammalian development, renal homeostasis, and satiety, just to name a few. Because of their widespread presence and importance, dysfunction of cilia and flagella can lead to a variety of human diseases, collectively referred …

Development Of Electrospun Bone-Mimetic Matrices For Bone Regenerative Applications, Matthew Christopher Phipps

All ETDs from UAB

Although bone has a dramatic capacity for regeneration, certain injuries and procedures present defects that are unable to heal properly, requiring surgical intervention to induce and support osteoregeneration. Our research group has hypothesized that the development of a biodegradable material that mimics the natural composition and architecture of bone extracellular matrix has the potential to provide therapeutic benefit to these patients. Utilizing a process known as electrospinning, our lab has developed a bone-mimetic matrix (BMM) consisting of composite nanofibers of the mechanically sta-ble polymer polycaprolactone (PCL), and the natural bone matrix molecules type-I colla-gen and hydroxyapatite nanocrystals (HA). We herein …

Targeting Mitochondrial Function In Diabetic Nephropathy, Colin Reily

All ETDs from UAB

TARGETING MITOCHONDRIAL FUNCTION IN DIABETIC NEPHROPATHY The incidence of diabetes has increased to epidemic proportions over the last 50 years, due to a complex interaction of lifestyle and dietary factors. Changes in physical activity, caloric intake, and the composition of foods consumed over the last century are thought to interact with metabolic syndrome prone subpopulations leading ultimately to diabetes. It is widely accepted that chronic hyperglycemia in the blood characterizes the diabetic condition. Since the discovery of insulin therapy in the first half of the 20th century, diabetics have extended their lifespan considerably, but at the cost of increased morbitity …