Biochemistry, Biophysics, and Structural Biology Commons^™

Regulation Of The Transmembrane Mucin Muc4 By Wnt/Β-Catenin In Gastrointestinal Cancers, Priya Pai

Theses & Dissertations

The transmembrane mucin MUC4 is a high molecular weight glycoprotein that is expressed de novo in pancreatic ductal adenocarcinoma (PDAC). MUC4 has been shown to play a tumor-promoting role in malignancies such as PDAC, ovarian cancer and breast cancer. Unlike the normal pancreas, MUC4 is ordinarily expressed by goblet and absorptive cells in the normal colonic epithelium. However, its expression/role in colorectal cancer (CRC) is not well studied.

In this dissertation, the goal was to identify factor(s) that may differentially regulate MUC4 in these two disparate malignancies. Furthermore, in light of its pro-tumorigenic role in other malignancies, we analyzed the …

Amyloid Proteins Structure, Dynamics, Interactions And Early Stages Of Self-Assembly, Yuliang Zhang

Theses & Dissertations

The self-assembly and aggregation of amyloid protein are associated with several neurodegenerative diseases. The evidence indicates that the oligomeric intermediates, formed prior to the final fibrillary product, are the primary culprits of neurotoxicity. Although tremendous efforts have been dedicated for the characterization of structures, dynamics and toxic-related hallmarks of the oligomers, to date, yet the mechanism of such assembly from disordered monomers and their structure remain elusive.

In this dissertation, I focused on understanding the dimerization process of amyloid proteins and peptides of different sizes and I combined experimental studies with high-power computer simulations. The AFM force spectroscopy experiments showed …

A Novel Transcription Factor In Arabidopsis Thaliana Abiotic Stress Response, Achira S. Weerathunga Arachchilage

LSU New Orleans Theses and Dissertations

Plants respond to environmental stress by altering their gene expression. Under stress conditions some genes are activated and some genes are repressed. Even though a lot of work has been done to understand mechanisms of gene activation under abiotic stress very little information is available on how stress responsive genes are kept repressed under normal growth conditions. Recent work has revealed that plants use transcriptional repression as common mechanism of gene repression. Transcriptional repression is achieved by recruitment co-repressor complexes to the target genes. Recent studies have revealed that the co-repressor LUH complexes with SLK1 and SLK2 to silence Arabidopsis …

Control Of The Basal Recycling And Surface Expression Of Epidermal Growth Factor Receptor By The Endocytic Recycling Regulator Ehd1 Utilizing A Pathway Shared By Rusc2, Eric Tom

Theses & Dissertations

The epidermal growth factor receptor (EGFR) is a prototype receptor tyrosine kinase (RTK) and oncogene aberrantly expressed or mutated in solid tumors. Its surface expression is dynamically regulated. Display of an activation-competent pool is essential for response to ligands. Internalization and degradation of EGFR following stimulation has received the most attention, fewer studies have characterized the recycling arm of EGFR transit, basal traffic and surface display are poorly understood. Thus, we evaluated the endocytic recycling of EGFR for its therapeutic potential in EGFR driven cancers. The C-Terminal Eps15 homology (EH) domain-containing proteins have emerged as regulators of surface receptor recycling …

Ubiquitin Goes Green, Zhihua Hua, Richard D. Vierstra

Biology Faculty Research

Chloroplasts depend on the nucleus for much of their proteome. Consequently, strong transcriptional coordination exists between the genomes, which is attuned to the developmental and physiological needs of the organelle. Recent studies highlight that the post-translational modifier ubiquitin adds another layer to plastid homeostasis and even helps eliminate damaged chloroplasts.

Microsolvation Of Anions By Molecules Forming Ch∙∙X- Hydrogen Bonds, Steve Scheiner, Binod Nepal

Chemistry and Biochemistry Faculty Publications

Various anions were surrounded by n molecules of CF₃H, which was used as a prototype CH donor solvent, and the structures and energies studied by M06-2X calculations with a 6-31+G∗∗ basis set. Anions considered included the halides F^-, Cl^-, Br^- and I^-, as well as those with multiple proton acceptor sites: CN^-, NO₃ ^-, HCOO^-, CH₃COO^-, HSO₄ ^-, H₂PO₄ ^-, and anions with higher charges SO₄ ^2-, HPO₄ ^2- and PO_{4 …}

Aggregation Characterization Of Wild-Type P53 And Six Common P53 Mutants, Taylor A. Arhar

Honors Thesis

P53 is a tumor suppressor protein, which functions in maintaining the cell cycle. When p53 loses its function, cells may multiply at an uncontrolled rate and form tumors. This loss of function is linked to over fifty percent of human cancers. This investigation aims to explore the possible link between p53 aggregation and tumorigenesis. There is a possibility that p53, especially in mutant form, will aggregate beyond its normal tetrameric conformation and lose its function, leading to tumor formation. Wild-type p53 and six mutants, R175H, R175C, R248Q, R248W, R273C, and R273H (six of the most common mutations found in human …

Population Density Of The Florida Scrub Lizard (Sceloporus Woodi) In Managed Sand Pine Scrub And Longleaf Pine Sandhill Habitats, Matthew D. Kaunert, Lance D. Mcbrayer

Biology: Faculty Publications

Studies investigating managed landscapes are of increasing importance, as fragmentation is a known cause of biodiversity loss. From June to September 2012, we sampled populations of the rare, endemic Florida Scrub Lizard (Sceloporus woodi) across the Ocala National Forest (ONF) to compare lizard density across two managed habitat types. Florida Scrub habitat in the ONF is clearcut and roller-chopped, whereas Longleaf Pine habitat is managed via prescribed burning. We sampled 10 stands of Florida Scrub (2–3 y post disturbance) and 10 stands of Longleaf Pine (1 y post-disturbance) for lizards. We compared lizard density between the interior of …

Chemo-Enzymatic Synthesis Of Site-Specific Isotopically Labeled Nucleotides For Use In Nmr Resonance Assignment, Dynamics And Structural Characterizations, Andrew P. Longhini, Regan M. Leblanc, Owen Becette, Carolina Salguero, Christoph H. Wunderlich, Bruce A. Johnson, Victoria M. D'Souza, Christoph Kreutz, T. Kwaku Dayle

Advanced Science Research Center

Stable isotope labeling is central to NMR studies of nucleic acids. Development of methods that incorporate labels at specific atomic positions within each nucleotide promises to expand the size range of RNAs that can be studied by NMR. Using recombinantly expressed enzymes and chemically synthesized ribose and nucleobase, we have developed an inexpensive, rapid chemo-enzymatic method to label ATP and GTP site specifically and in high yields of up to 90%.We incorporated these nucleotides into RNAs with sizes ranging from 27 to 59 nucleotides using in vitro transcription: A-Site (27 nt), the iron responsive elements (29 nt), a fluoride riboswitch …

Linker Histone H1 And H3k56 Acetylation Are Antagonistic Regulators Of Nucleosome Dynamics, Morgan Bernier, Yi Luo, Kingsley C. Nwokelo, Michelle Goodwin, Sarah J. Dreher, Pei Zhang, Mark R. Parthun, Yvonne N. Fondufe-Mittendorf, Jennifer J. Ottesen, Michael G. Poirier

Molecular and Cellular Biochemistry Faculty Publications

H1 linker histones are highly abundant proteins that compact nucleosomes and chromatin to regulate DNA accessibility and transcription. However, the mechanisms that target H1 regulation to specific regions of eukaryotic genomes are unknown. Here we report fluorescence measurements of human H1 regulation of nucleosome dynamics and transcription factor (TF) binding within nucleosomes. H1 does not block TF binding, instead it suppresses nucleosome unwrapping to reduce DNA accessibility within H1-bound nucleosomes. We then investigated H1 regulation by H3K56 and H3K122 acetylation, two transcriptional activating histone post translational modifications (PTMs). Only H3K56 acetylation, which increases nucleosome unwrapping, abolishes H1.0 reduction of TF …

Reactive Oxygen Species Homeostasis And Proline Catabolism, Lu Zhang

Department of Biochemistry: Dissertations, Theses, and Student Research

The role of proline metabolism in regulating cellular redox status was first proposed three decades ago. Proline catabolism was then later found to induce programmed cell death and cell apoptosis by regulating ROS signaling. Proline oxidation was also found to promote cell survival under oxidative stress. Proline catabolism-mediated reactive oxygen species (ROS) were suggested to be involved in both cases by serving as a regulatory signal. In this work, the sources of proline oxidation-induced ROS production were explored in both bacteria and animal cells. Proline oxidation-induced ROS was found to be shared by bacteria (Escherichia coli) and animals …

Differential Impact Of Lpg-And Pg-Deficient Leishmania Major Mutants On The Immune Response Of Human Dendritic Cells, Michelle A. Favila, Nicholas S. Geraci, Asha Jayakumar, Suzanne Hickerson, Janet Mostrom, Salvatore J. Turco, Stephen M. Beverley, Mary Ann Mcdowell

Molecular and Cellular Biochemistry Faculty Publications

BACKGROUND: Leishmania major infection induces robust interleukin-12 (IL12) production in human dendritic cells (hDC), ultimately resulting in Th1-mediated immunity and clinical resolution. The surface of Leishmania parasites is covered in a dense glycocalyx consisting of primarily lipophosphoglycan (LPG) and other phosphoglycan-containing molecules (PGs), making these glycoconjugates the likely pathogen-associated molecular patterns (PAMPS) responsible for IL12 induction.

METHODOLOGY/PRINCIPAL FINDINGS: Here we explored the role of parasite glycoconjugates on the hDC IL12 response by generating L. major Friedlin V1 mutants defective in LPG alone, (FV1 lpg1-), or generally deficient for all PGs, (FV1 lpg2-). Infection with metacyclic, infective …

A New Method For Shear Wave Speed Estimation In Shear Wave Elastography, Aaron J. Engel, Gregory R. Bashford

Biomedical Imaging and Biosignal Analysis Laboratory

Visualization of mechanical properties of tissue can aid in noninvasive pathology diagnosis. Shear wave elastography (SWE) measures the elastic properties of soft tissues by estimation of local shear wave propagation speed. In this paper, a new robust method for estimation of shear wave speed is introduced which has the potential for simplifying continuous filtering and real-time elasticity processing. Shear waves were generated by external mechanical excitation and imaged at a high frame rate. Three homogeneous phantoms of varying elastic moduli and one inclusion phantom were imaged. Waves propagating in separate directions were filtered and shear wave speed was estimated by …

Investigation Of The Inherent Chemical, Structural, And Mechanical Attributes Of Bio-Engineered Composites Found In Nature: Alligator Gar’S Exoskeleton Fish Scales, Wayne Derald Hodo

Graduate Theses and Dissertations

The U.S. Army has determined a huge cost savings of up to 51% can be accomplished by reducing the gross vehicle weight, for their personnel carrier, by 33%. To cut cost, composite materials are needed. Man-made composites can have superior material properties (high-strength, high-fracture toughness, and lightweight), but they are prone to delamination at the glued-layered interface. In contrast, fish scale is a natural composite that has the same material properties and, additionally, tend not to delaminate.

The focus of this study was to learn how nature integrates hard and soft materials at each length scale to form a layered …

Glucose-Fructose Likely Improves Gastrointestinal Comfort And Endurance Running Performance Relative To Glucose-Only, P. B. Wilson, S. J, Ingraham

Athletic Performance Research

This study aimed to determine whether glucose-fructose (GF) ingestion, relative to glucose-only, would alter performance, metabolism, gastrointestinal (GI) symptoms, and psychological affect during prolonged running. On two occasions, 20 runners (14 men) completed a 120-min submaximal run followed by a 4-mile time trial (TT). Participants consumed glucose-only (G) or GF (1.2:1 ratio) beverages, which supplied ~1.3 g/min of carbohydrate. Substrate use, blood lactate, psychological affect [Feeling Scale (FS)], and GI distress were measured. Differences between conditions were assessed using magnitude-based inferential statistics. Participants completed the TT 1.9% (−1.9; −4.2, 0.4) faster with GF, representing a likely benefit. FS ratings were …

Co-Treatment With Conjugated Linoleic Acid And Nitrite Modulates Mitochondrial Respiration And Electron Transport Chain Activity In Vivo And Attenuates Mitochondrial Dysfunction During Cardiac Injury., Patrick Van Hoose

Electronic Theses and Dissertations

Cardiovascular disease and subsequent complications, such as myocardial infarction (MI), is the leading cause of death within the United States. Clinical intervention to reduce cardiac damage following myocardial ischemia is limited. Polyunsaturated fatty acids have been linked to an overall beneficial effect on cardiovascular health and function. Conjugated linoleic acid (cLA) is an 18:2 unsaturated fatty acid found within the diet in ruminant meat and dairy products. The cis-9 trans-11 isomer of cLA is the most prominent isomer within the diet and cLA has been linked to favorable outcomes in numerous disease states. The mechanism mediating the effects of cLA …

Effect Of Raised Body Fat On Vitamin D, Leptin And Bone Mass, Syeda Sadia Fatima, Saad Farooq, Maaida Asif Tauni, Omar Irfan, Faiza Alam

Department of Biological & Biomedical Sciences

Objective: To estimate leptin, vitamin D and bone mineral density levels in individuals with high fat mass, and to assess any correlation.Methods: The cross-sectional study was conducted at the Basic Medical Sciences Institute, Jinnah Post Graduate Medical Centre, Karachi, and Aga Khan University, Karachi, from August 2012 to July 2014, and comprised healthy male volunteers between the ages of 18-60 years. Body fat percentage was determined using bioelectrical impedance analysis and the participants were classified as: Group A (15-21.9); Group B (22-27.9); and Group C ( > 28). Bone mineral density was calculated by ultrasound bone densitometer (T-score between +1 and …

Fsh/Lh Ratio In Females And Intracytoplasmic Sperm Injection, Rehana Rehman, Hareem Syed, Najeeha Talat Iqbal, Sara Arif, Saeeda Sheharyar

Department of Biological & Biomedical Sciences

Objective: To observe the effect of follicle stimulating hormone-luteinizing hormone ratio on oocyte parameters, quality of embryo, implantation and clinical pregnancy rate after intracytoplasmic sperm injection.
Methods: The retrospective study was conducted at a fertility clinic in Islamabad, Pakistan, and comprised data of primary infertile females who underwent intracytoplasmic sperm injection from June 2011 to March 2013. All subjects had duration of infertility more than two years, and age range was 20-40 years. Follicle stimulating hormone and luteinizing hormone were estimated by enzyme-linked immunosorbent assay on day 3 of the cycle and the ratio was calculated. Groups were stratified on …

Expression Of Insulin Responsive Genes In Insulin Resistant Conditions, And The Effect Of Selenium On Gene Expression, David L. Ruff

Masters Theses

Chronically high blood glucose levels lead to many problems, such as insulin resistance, the hallmark of Type II diabetes. Increased flux through the hexosamine biosynthesis pathway is one mechanism by which high glucose as well as glucosamine has been shown to induce insulin resistance. This study tests the effects of glucosamine induced insulin resistance on insulin regulation of the metabolic genes glucose-6-phosphate dehydrogenase (G6PDH) and fatty acid synthase (FAS) as well as insulin responsive proteins tribbles homolog (TRIB3) and sterol regulatory element binding protein (SERBP-1c) 1c.

Selenium, a micronutrient has been shown to be an effective insulin mimetic in Type …

Blackberry Virosome: A Micro And Macro Approach, Archana Khadgi

Graduate Theses and Dissertations

Viruses pose a major concern for blackberry production around the world with more than 40 species known to infect the crop. Virus complexes have been identified recently as the major cause of plant decline with blackberry yellow vein disease (BYVD) being the most important disease of the crop in the Southern United States. The objective of this research was to study the blackberry virosome in both the macro and micro scale. The large scale approach involves identification of the major viruses known to be associated with BYVD in the Southern United States as well as the identification of other viruses …