Digital Commons Network^™

Functional Determinants Of The Porin Mspa And Its Role In Permeabilizing Mycobacterial Outer Membranes, Jason Huff

All ETDs from UAB

Mycobacterium tuberculosis (Mtb) infects one third of the global population and causes approximately 2,000,000 Tuberculosis-related deaths annually. Mycobacteria are Gram positive organisms but contain a unique outer membrane (OM) which is functionally similar but structurally different from those of Gram negative bacteria. The mycobacterial OM presents an efficient permeability barrier towards hydrophilic solutes. Slow permeation kinetics of hydrophilic molecules through membranes and several discoveries of cell wall channel-forming proteins indicate that mycobacterial OMs are functionalized by proteins. MspA is the primary porin of M. smegmatis and mediates diffusion of small, hydrophilic nutrients and antibiotics across the OM. Unlike porins of …

Role Of The Human Cytomegalovirus Tegument Protein Pp150 In The Trafficking And Assembly Of Infectious Virions, Sabarish Vellatheri Indran

All ETDs from UAB

Human cytomegalovirus, a ubiquitous human pathogen, establishes a persistent infection in the infected host. HCMV assembly takes place in the nucleus and cytoplasm of infected cells by a complex and incompletely defined process. The viral DNA is enclosed by the capsid, which is surrounded by a proteinaceous tegument, which is covered by a cell-derived envelope studded with viral glycoproteins. The assembly pathway and protein interactions required for formation of the tegument layer and the function of most of the proteins in the tegument remain poorly understood. In this study, we investigated the functions of an essential abundant tegument protein, pp150, …

In Vitro Elucidation Of The Role And Mechanism Of Rankl In Tnf-And Il-1-Mediated Osteoclast Formation And Function, Joel Jules

All ETDs from UAB

The receptor activator of NF-қB (RANK) ligand (RANKL) and its receptor RANK play a critical role in osteoclast biology. RANK has three tumor necrosis factor receptor associated factor (TRAF)-binding motifs [PFQEP369-373 (Motif 1), PVQEET559-564 (Motif 2), and PVQEQG604-609 (Motif 3)] that regulate osteoclast formation and function. RANK also contains a TRAF-independent motif (IVVY535-538) that commits bone marrow macrophages (BMMs), which are osteoclast precursors, to the osteoclast lineage for osteoclastogenesis. Notably, tumor necrosis factor-α (TNF) and interlukin-1 (IL-1) utilize TRAFs to initiate most of the signaling pathways known to be activated by RANKL but fail to form osteoclasts unless attended by …

Role Of Epithelial Sodium Channel And Acid Sensing Ion Channel In Glioblastoma Multiforme, Niren Kapoor

All ETDs from UAB

Glioblastoma Multifrome is the most common and aggressive of the primary brain tumors. These tumors express multiple members of the Epithelial Sodium Channel (ENaC)/Degenerin (Deg) family, associated with a basally active amiloride sensitive cation current. We hypothesize that this glioma current is mediated by a hybrid channel composed of a mixture of Epithelial Sodium Channel (ENaC) and Acid Sensing Ion Channel (ASIC) subunits. To test this hypothesis we made dominant negative cDNAs for ASIC1, αENaC, and γENaC. D54-MG glioma cells transfected with the dominant negative constructs for ASIC1, αENaC, or γENaC showed reduced protein expression for each of the specific …

Transcriptional Regulation Of The Human Heme Oxygenase-1 Via Chromatin Looping In Renal Cells, Junghyun Kim

All ETDs from UAB

Heme oxygenase-1 (HO-1) is a critical enzyme catalyzing the degradation of heme and generating carbon monoxide, iron, and biliverdin. In addition to heme degradation, HO-1 expression is known to protect against various cellular insults and disease states including acute kidney injury, atherosclerosis, vascular restenosis, and others. Human HO-1 gene expression is tightly regulated at the level of transcription. The main goal of this study is to explore the transcriptional regulation of the human HO-1 gene in renal epithelial cells. Chromosome Conformation Capture (3C) demonstrates that multiple regulatory regions within the HO-1 promoter and enhancer regions are physically interacting with each …

Role Of 14-3-3&Tau In Autophagy And Role Of Edd In P53 Regulation, Shiyun Ling

All ETDs from UAB

Unrestricted cell proliferation and suppression of cell death are two essential events for tumor development. My dissertation research involves two proteins, 14-3-3 &tau and EDD which are involved in diverse pathways related to these two fields in recent studies. Previous study demonstrates that 14-3-3ô regulates p21 degradation. Up-regulation of 14-3-3ô is seen in breast cancer and is correlated with the down-regulation of p21 in breast cancer. Amplification or overexpression of EDD was observed in breast cancer and ovarian cancers. Illustrating the new roles of these two proteins in proliferation and cell death will advance our knowledge in tumorigenesis and help …

A Nucleolar Specificity Factor For E2f1 Induced Cell Death, Jason Chang Paik

All ETDs from UAB

The E2F family of transcription factors are important regulators of cell proliferation, and are often dysregulated in cancers. One member of the E2F family, E2F1, also has the ability to induce apoptosis; therefore, uncovering how E2F1-induced apoptosis is controlled is of interest in understanding tumorigenesis. To this end, we identified RRP1B as a novel target specifically induced by E2F1. RRP1B expression is specifically upregulated by E2F1 overexpression, but not other E2F family members. RRP1B expression is correlated with E2F1 expression during the cell cycle, and is significantly induced after DNA damage. The minimal RRP1B promoter region responsive to E2F1 was …

Differential Genome-Wide Array–Based Methylation Profiles In Prognostic Subsets Of Chronic Lymphocytic Leukemia, Meena Kanduri, Nicola Cahill, Hanna Göransson, Camilla Enström, Fergus Ryan, Anders Isaksson, Richard Rosenquist

Articles

Global hypomethylation and regional hypermethylation are well-known epigenetic features of cancer; however, in chronic lymphocytic leukemia (CLL), studies on genome-wide epigenetic modifications are limited. Here, we analyzed the global methylation profiles in CLL, by applying high-resolution methylation microarrays (27 578 CpG sites) to 23 CLL samples, belonging to the immunoglobulin heavy-chain variable (IGHV) mutated (favorable) and IGHV unmutated/IGHV3-21 (poor-prognostic) subsets. Overall, results demonstrated significant differences in methylation patterns between these subgroups. Specifically, in IGHV unmutated CLL, we identified methylation of 7 known or candidate tumor suppressor genes (eg, VHL, ABI3, and IGSF4) as well as 8 unmethylated genes involved in …

Translocation And Function Of Akt In The Mitochondria, Keri A. Mans

All ETDs from UAB

The ubiquitously expressed kinase Akt is a known survival protein, and is involved in multiple cell signaling cascades, notably the phosphatidylinositol 3-kinase (PI3K) pathway. Active Akt translocates from the plasma membrane to different subcellular compartments, including mitochondria, where it phosphorylates compartment-specific substrates. The mechanism of this translocation and the specific function of Akt within the mitochondria remains a mystery. The goals of this study were to elucidate the mechanism by which Akt enters the mitochondria and examine the role of Akt in mitochondrial function. Finally, the possibilities of using post-mortem human brain tissue to study mitochondrial function in normal and …

Translation Initiation Signaling Components Altered By Mechanical Load Dictate Skeletal Muscle Hypertrophy, David Lawrence Mayhew

All ETDs from UAB

The regulation of protein synthesis (i.e., mRNA translation) is an energetically costly and extensively regulated process, which is primarily regulated at the initiation step. Mechanical load is a potent stimulus of translation in skeletal muscle, and thus this tissue provides an excellent model system to study the plasticity of the translational apparatus. We investigated the effects of alterations in translation initiation cell signaling pathways in skeletal muscle using a variety of in vitro and in vivo mouse and human model systems. Collectively, our results suggest that, although many proteins in translational signaling pathways are responsive to mechanical load, the response …

Canonical Wnt Signaling By The Proteolytic Processing Of Lrp6, Brandon Richard Beagle

All ETDs from UAB

Low density Lipoprotein receptor Related 6 (LRP6) functions as an essential co-receptor for Wnt/Beat;-catenin signaling as pathway activation, reflected by cytosolic Beta-catenin stabilization and TCF/LEF-1 transactivation, requires Glycogen Synthase Kinase 3Beta(GSK3Beta)-mediated phosphorylation of multiple PPP(S/T)P motifs within the membrane anchored LRP6 intracellular domain. Additionally, LRP6 undergoes a proteolytic cleavage event resulting in the formation of a soluble LRP6 intracellular domain (LRP6-ICD). LRP6-ICD can function within the Wnt/Beta-catenin pathway by interacting with GSK3Beta and attenuating the phosphorylation of GSK3Beta substrates such as cytosolic Beta-catenin as well as stimulate TCF/LEF-1 activity. However, LRP6-ICD's role(s) within the Wnt/Beta-catenin pathway and the mechanism(s) that …

Role Of Heme Oxygenase-1 In Acute Kidney Injury, Subhashini Bolisetty

All ETDs from UAB

Acute kidney injury (AKI), defined as the rapid loss of kidney function, is often seen in the setting of multiple organ failure in critically ill patients. Lack of established therapeutic approaches to overcome AKI has lead to unacceptably high incidence of morbidity and mortality in these patients. The molecular mechanisms that lead to AKI often have oxidative stress as a common pathogenic event. The kidney responds by prompt induction of its own anti-oxidant machinery including the highly inducible, anti-inflammatory and anti-apoptotic gene-heme oxygenase-1 (HO-1). This microsomal enzyme degrades pro-oxidant heme, which is released from heme proteins. The cytoprotective properties of …

Cross-Talk Between Marginal Zone B Cells And Marginal Zone Macrophages, Yuying You

All ETDs from UAB

the test of group differences and the test of covariate. When we force the predictors in the

The Role Of Usp14 In Regulating Synaptic Development And Function Of The Neuromuscular Junctions, Ping-Chung Chen

All ETDs from UAB

The ubiquitin proteasome system (UPS) plays critical roles in regulating multiple cellular functions, including protein abundance, trafficking, and cell signaling. In the nervous system, the UPS has been implicated in controlling a wide diversity of cellular process such as synaptic transmission, axon outgrowth, axon targeting, and synapse development. Although impairment of the UPS is observed in both neurodegenerative and developmental diseases, the mechanisms underlying how UPS dysregulation contributes to disease pathogenesis are not known. The proteasome, an approximate 2.5 megadaltons protein complex composed of 19S and 20S assemblies, is the site of ubiquitin-dependent protein degradation. Recent studies have demonstrated dysfunction …

The Effects Of Environmental Ozone Exposure On Vascular Function, Oxidative Stress, And Atherosclerosis, Gin Chuang

All ETDs from UAB

Exposure to air pollutants are known to induce airway inflammation, decrease lung function, and worsen existing pulmonary conditions such as asthma. Additionally, air pollutant exposure has also been shown to impact cardiovascular health. Although these pollutant-induced cardiovascular effects were considered to be mediated by the direct action of pollutants upon the cardiovascular tissue and/or the indirect release of pro-inflammatory factors into the circulation, the relative contribution of the two pathways remained equivocal. Recently, several epidemiology studies associated ozone exposure with cardiovascular mortalities. However, relatively few studies to date have examined ozone in this context. In order to address our hypothesis …

Evolution And Genetic Diversity In Streptococcus Pneumoniae, Diana Lee Dupraw

All ETDs from UAB

The relative contributions of point mutations and intergenomic recombination via lateral gene transfer (LGT) determine the population structure and evolutionary style for a given bacterial species. Streptococcus pneumoniae has a weakly clonal population structure; adaptive clonal complexes can be detected; however, these can also be rapidly lost due to the high rate of recombination. To characterize the diversity of pneumococcal isolates in clonal complex, and to elucidate possible mechanisms for the long-term stability of such complexes, 35 serotype 6B strains belonging to a previously identified clonal complex, CC14, were assayed by Comparative Genome Hybridization (CGH) and Multi Locus Sequence Typing …

Mechanisms Of Major Outer Membrane Protein (Momp)-Vaccine Induced Protective Immunity Against Chlamydia Muridarum Genital Infection, Christina M. Farris

All ETDs from UAB

Urogenital infection with Chlamydia trachomatis is the most common bacterial sexually transmit-ted disease with an estimated 90 million new infections occurring each year worldwide. In women infection with C. trachomatis can result in serious complications including ectopic pregnancy, pelvic inflammatory disease and tubal factor infertility. Despite very effective antimicrobial chemotherapy, control of the infection will likely require an effective vaccine. We have assessed the protective effect of an outer membrane based vaccine using a murine model of chlamydial genital tract infection. Female mice were vaccinated with C. muridarum major outer membrane protein (MOMP) plus the immunostimulatory adjuvants CpG-1826 and Montanide …

Regulation Of Mucosal Innate And Adaptive Immune Responses To Commensal Microbiota, Ting Feng

All ETDs from UAB

and Davidson and MacKinnon’s HC3 perform reasonably well in terms of Type I error

Structural And Functional Study Of P58(Ipk), Jiahui Tao

All ETDs from UAB

P58(IPK) is an endoplasmic reticulum (ER)-resident protein which is upregulated during unfolded protein response (UPR). In stressed cells, P58(IPK) functions to restore protein folding equilibrium in ER by suppressing protein aggregation and promoting protein folding. P58(IPK) associates with the unfolded protein via its N-terminal TPR domain and presents it to BiP (binding immunoglobulin protein) for subsequent folding. P58(IPK) belongs to the Hsp40 family. Collectively, P58(IPK) is a stress-inducible ER-resident molecular chaperone. In this dissertation, we report the crystal structure of P58(IPK) TPR domain to 2.5 Å resolution. In the crystal structure, the 43-kDa TPR domain consists of nine tandemly linked …

The Role Of Socs Proteins In Hiv Immune Evasion, Lisa Nowoslawski Akhtar

All ETDs from UAB

Upon human immunodeficiency virus (HIV) infection the host mounts a robust and multifaceted immune response. To achieve successful replication, HIV must possess a powerful arsenal of immune evasion weapons. While a complex strategy for HIV immune evasion has been described in the periphery, little is known about the mechanism allowing HIV to overcome the simple interferon (IFN)-ß-mediated innate immune defenses of the central nervous system (CNS). In light of the devastating cognitive dysfunction that is caused by HIV replication within the CNS, a better understanding of this mechanism is critical. Recent studies have shown that viral pathogens can induce the …

The Mechanism Of Human Papillomavirus E7 Protein Mediated S-Phase Reentry In The Squamous Epithelium, Nicholas John Genovese

All ETDs from UAB

different heteroskedasticity consistent covariance matrix estimators (HCCM) under

Associative Learning In Larval Dosophila Melanogaster: The Role Of Heredity In Learning Speed And Persistence Of Leaning Into Adulthood, Jasmin Hicklen, Domonique Jones, Michelle Vieyra

Journal of the South Carolina Academy of Science

No abstract provided.

Mapping Haplotype-Haplotype Interactions With Adaptive Lasso, Ming Li, Roberto Romero, Wenjiang J. Fu, Yuehua Cui

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

The genetic etiology of complex diseases in human has been commonly viewed as a complex process involving both genetic and environmental factors functioning in a complicated manner. Quite often the interactions among genetic variants play major roles in determining the susceptibility of an individual to a particular disease. Statistical methods for modeling interactions underlying complex diseases between single genetic variants (e.g. single nucleotide polymorphisms or SNPs) have been extensively studied. Recently, haplotype-based analysis has gained its popularity among genetic association studies. When multiple sequence or haplotype interactions are involved in determining an individual's susceptibility to a disease, it …

The Role Of Synaptically Evoked Plateau Potentials In Retinogeniculate Development, Emily Dilger

Theses and Dissertations

We study the activity-dependent refinement of sensory systems by using the mouse retinogeniculate system as a model. Spontaneous retinal waves lead to robust excitatory post-synaptic activity in developing relay cells in the dorsal lateral geniculate nucleus (dLGN) of the thalamus and are reportedly needed to help guide the segregation of retinal inputs into eye-specific domains as well as for the pruning of extraneous retinal inputs onto single dLGN relay cells. The composition of retinally evoked post-synaptic activity activated by these retinal waves in dLGN is largely unknown, but based on our in vitro recordings, such activity seems well suited to …

Sustained Expression Of Tdp-43 And Fus In Motor Neurons In Rodent's Lifetime., Cao Huang, Pedro Yuxing Xia, Hongxia Zhou

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

TAR DNA-binding protein (TDP-43) and fused in sarcoma (FUS) are two highly conserved ribonucleoproteins. Pathogenic mutations of the TDP-43 or the FUS gene are all linked to amyotrophic lateral sclerosis (ALS) that is characterized by progressive degeneration of motor neurons. To better understand the correlation of ALS disease genes with the selectivity of chronic motor neuron degeneration, we examined the longitudinal expression of the TDP-43 and the FUS genes in C57BL6 mice and in Sprague-Dawley rats. TDP-43 and FUS were robustly and ubiquitously expressed in the postnatal mice and rats, but were markedly decreased in the adult rodents. In adulthood, …

Small-For-Gestational-Age Newborns Need A Special Fluid Therapy Strategy, Alparslan Tonbul, Cüneyt Tayman, Ahmet Karadağ, Hali̇se Akça, Nurdan Uras, Mustafa Mansur Tatli

Turkish Journal of Medical Sciences

To determine the fluid requirement of small-for-gestational-age (SGA) newborns and to compare them with that of appropriate for gestational age (AGA) newborns in the first 5 days of life. Materials and methods: The present study was conducted from January 2007 to August 2007, including newborns with a gestation age of 32-40 weeks, with respiratory problems, feeding problems, and prematurity, and required intravenous fluid for at least 3 days. Two study groups were established: SGA (group 1) and AGA (group 2) according to the Lubchenco scale. All newborns were cared at an ambient humidity of 40% in an incubator and received …

Marital Adjustment And Emotional Symptoms In Infertile Couples: Gender Differences, Verda Tüzer, Altuğ Tuncel, Sema Göka, Süheyla Doğan Bulut, Fati̇h Volkan Yüksel, Ali̇ Atan, Erol Göka

Turkish Journal of Medical Sciences

To determine the psychosocial and demographic factors related to marital adjustment and emotional symptoms in infertile couples according to gender differences. Materials and methods: The study sample, consisting of 60 primary infertile couples, was assessed using the Beck Depression Inventory, State and Trait Anxiety Inventory, and Dyadic Adjustment Scale. The scores derived from men and women were compared according to infertility factor. Multiple regression analysis models were used to explore the linkages between emotional symptoms and marital adjustment. Results: Statistically significant gender differences were noted in affectional expression and sexual satisfaction domains of the Dyadic Adjustment Scale (P < 0.05). Our analyses showed that various aspects of marital adjustment have predictive power on anxiety and depressive symptoms of infertile men, especially when the infertility is due to male factor. Conclusion: Results of this study emphasize the importance of psychological and sexual counseling in the course of infertility treatment.

Serum Leptin, Lipoprotein Levels, And Glucose Homeostasis Between National Wrestlers And Sedentary Males, Faruk Yamaner, Taner Bayraktaroğlu, Hulusi̇ Atmaca, Mehmet Aki̇f Zi̇yagi̇l, Kemal Tamer

Turkish Journal of Medical Sciences

Leptin is an important controller of the size of fat stores by inhibiting appetite. In wrestling, fat metabolism is important not only for aerobic energy system, but also for weight control and weight loss before competition. The aim of this study was to measure and compare the serum leptin levels, glucose homeostasis, and serum lipoproteins between Turkish national wrestlers and sedentary males. Materials and methods: Forty-five Turkish national wrestlers at the end of Olympic training camp before Beijing 2008 Olympic Games and 43 sedentary students were selected as subjects. Post-exercise levels of serum leptin, HOMA (Homeostasis model assessment) values, triglycerides, …

N-Acetyltransferase 2 Gene Polymorphisms And Susceptibility To Prostate Cancer: A Pilot Study In The Turkish Population, Buket Kosova, Vi̇ldan Bozok Çeti̇ntaş, Ahmet Çağ Çal, Asli Teti̇k, Ruki̇ye Özel, Çağdaş Aktan, Cumhur Gündüz, Nejat Topçuoğlu, İbrahi̇m Kadri̇ Cürekli̇batir, Fatma Zuhal Eroğlu

Turkish Journal of Medical Sciences

To investigate the association between the 3 most frequently observed single nucleotide polymorphisms of the NAT2 gene and the risk of developing prostate cancer in the Turkish population. Materials and methods: A total of 110 unrelated patients with prostate cancer were included in this case-control association study and constituted the study group. The control group also consisted of 150 unrelated but healthy men. Genomic DNA was isolated from peripheral blood leukocytes of all patients and analyzed with a sensitive real-time PCR method. After melting curve analysis genotypes were identified for the NAT2*5A, NAT2*6A, and NAT2*7A/B polymorphisms. Results: Prostate cancer patients …

Chronic Pain And Depression: A Descriptive Survey Among Adult Primary Health Care Centre Patients, Nüket Paksoy Erbaydar, Nesri̇n Çi̇li̇ngi̇roğlu

Turkish Journal of Medical Sciences

Knowledge of chronic pain and its relationship to depression among primary health care patients in Turkey is inadequate. The aim of this study was to evaluate the frequency of chronic pain and its relationship to depression. Materials and methods: In this descriptive study, data was collected with a questionnaire based on sociodemographic and pain-related characteristics, which was administered to a study population (n = 259) of primary care patients, 18-64 years old. The Visual Analogue Scale (VAS) (min-max = 0-10) and Beck Depression Inventory (BDI) (min-max = 0-63) were used for the assessment of pain severity and depression. Results: Of …