Biochemistry Commons^™

Support Needs Of Young Ovarian Cancer Survivors: A Pilot Study, Aurelie Chuong

Open Access Theses

Purpose. Young ovarian cancer survivor (18 years old or older but diagnosed before the age of 34 years old) support needs (i.e., physical and daily living, psychological, sexual, patient care and support, health system and information) were examined to guide the design and implementation of future young adult and adolescent cancer support groups and interventions. Method. This cross-sectional pilot study included 11 young ovarian cancer survivors. The Supportive Care Needs Survey Short Form 34 (SCNS-SF34) was used and open-ended questions were added. Results. The calculated standardized scores for the SCNS-SF34 survey results showed that sexuality needs were ranked highest (41.7 …

Developmentally Regulated Sumoylation In The Ciliate Tetrahymena Thermophila, Amjad M. Nasir

Open Access Dissertations

The Small Ubiquitin-like MOdifier (SUMO) protein regulates numerous nuclear events such as transcription, mitosis and meiosis and DNA repair. These processes are critical to the programmed nuclear events of conjugation in ciliates and provide the potential to investigate developmentally regulated SUMOylation. We predicted a developmental increase in SUMOylation during late conjugation based on the extensive genome remodeling in the developing macronucleus (anlagen) ofTetrahymena thermophila. Immunoblotting of cell lysates from vegetative and mating cells using anti-SUMO antibodies revealed distinct developmental differences and an increased signal correlated with formation of the anlagen. Immunofluorescence of mating Tetrahymena cells with the same antibody …

“Analyze, Acquire, Apply, And Write” As A New Learning Model In Science, Jeong Choe

Faculty Publications & Research

I have developed a new teaching and learning model called AAAW, which stand for Analyze, Acquire, Apply and Write. This model grows from action research and unique experience in teaching a biochemistry course to high school students who are talented in math and science. In this model, students first "Analyze" lab data to generate questions that lead them to "Acquire" background knowledge. Students then go back to the data and "Apply" their new knowledge to better understand the data. Finally, students "Write" about the connections they make from their reading, data analysis, and application of the data. The rationale behind …

Structural Analysis Of The 14-3-3Ζ/Chibby Interaction Involved In Wnt/Β-Catenin Signaling, Ryan C Killoran, Jingsong Fan, Daiwen Yang, Brian H Shilton, Wing-Yiu Choy

Biochemistry Publications

The partially disordered Chibby (Cby) is a conserved nuclear protein that antagonizes the Wnt/β-catenin signaling pathway. By competing with the Tcf/Lef family proteins for binding to β-catenin, Cby abrogates the β-catenin-mediated transcription of Wnt signaling genes. Additionally, upon phosphorylation on S20 by the kinase Akt, Cby forms a complex with 14-3-3 to facilitate the nuclear export of β-catenin, which represents another crucial mechanism for the regulation of Wnt signaling. To obtain a mechanistic understanding of the 14-3-3/Cby interaction, we have extensively characterized the complex using X-ray crystallography, nuclear magnetic resonance (NMR) spectroscopy, and isothermal titration calorimetry (ITC). The crystal structure …

Molecular Effects Of Cancer-Associated Somatic Mutations On The Structural And Target Recognition Properties Of Keap1., Halema Khan, Ryan C Killoran, Anne Brickenden, Jingsong Fan, Daiwen Yang, Wing-Yiu Choy

Biochemistry Publications

Kelch-like ECH-associated protein 1 (Keap1) plays an important regulatory role in the nuclear factor erythroid 2-related factor 2 (Nrf2)-dependent oxidative stress response pathway. It functions as a repressor of Nrf2, a key transcription factor that initiates the expression of cytoprotective enzymes during oxidative stress to protect cells from damage caused by reactive oxygen species. Recent studies show that mutations of Keap1 can lead to aberrant activation of the antioxidant pathway, which is associated with different types of cancers. To gain a mechanistic understanding of the links between Keap1 mutations and cancer pathogenesis, we have investigated the molecular effects of a …

Role Of Syk In The Regulation Of Cytoskeleton And Stress Granules In Breast Cancer, Mariya Krisenko

Open Access Dissertations

The Syk protein-tyrosine kinase, a well-characterized modulator of immune recognition receptor signaling, also plays important, but poorly characterized, roles in tumor progression, acting as an inhibitor of cellular motility and metastasis in highly invasive cancer cells. Multiharmonic atomic force microscopy (AFM) was used to map nanomechanical properties of live MDA-MB-231 breast cancer cells either lacking or expressing Syk. The expression of Syk dramatically altered the cellular topography, reduced cell height, increased elasticity, increased viscosity, and allowed visualization of a more substantial microtubule network. The microtubules of Syk-expressing cells were more stable to nocodazole-induced depolymerization and were more highly acetylated than …

Structural And Biophysical Analysis Of The Proteasomal Deubiquitinase, Uch37, Marie Elizabeth Morrow

Open Access Dissertations

Ubiquitin carboxyl-terminal hydrolase 37, or UCH37, is a deubiquitinating enzyme associated with the 26S proteasome, the primary protein degradation machinery in eukaryotic cells. UCH37 is responsible for the disassembly of polymeric ubiquitin chains, or polyubiquitin, which have been ligated onto proteins in order to target them for degradation. The 26S utilizes two associated deubiquitinating enzymes, UCH37 and USP14, and one intrinsic, Rpn11, to remove polyubiquitin chains from substrate proteins as they are unfolded and translocated into the proteolytic core of the proteasome, where proteins are cleaved into small peptides and then released for recycling by the cell. UCH37 associates with …

Paralogous Genes In Arabidopsis Thaliana Contribute To Diversified Phenylpropanoid Metabolism, Li Yi

Open Access Dissertations

Significant evidence supports the idea that gene duplication drives the evolution of new gene function. Besides being silenced, duplicated genes can either neofunctionalize or subfunctionalize under selective pressure or neutral drift. Understanding the trajectory of how each gene is fixed and presumably provides added fitness remains difficult. Plant specialized metabolism provides an attractive platform to study the fixation of genes post duplication and how this process leads to the chemical diversity seen today. Specialized metabolites by definition are thought to be dispensable under normal growth conditions. Thus deleterious mutations occurring in paralogous genes that otherwise would be selected against in …

Biochemical Investigation Of The Ubiquitin Carboxyl-Terminal Hydrolase Family, Joseph Rashon Chaney

Open Access Dissertations

The proteasome is the machinery in eukaryotic cells that degrades protein and recycles the amino acids. Protein degradation is a highly regulated process which starts by the attachment of chains of ubiquitin, which serves as a tag that marks a protein for degradation. This function involves the work of several proteins at the proteasome that work either as ubiquitin chaperones, ubiquitin binders or cleave ubiquitin from the protein that is to be degraded. As this is a highly regulated process, various irregularities can have deleterious effects including the onset of disease, including cardiovascular, cancer, and neurological. ^ The focus of …

Novel Methods For Manipulating Ion Types In The Solution And Gas Phases For The Structural Analysis Of Biomolecules Using Mass Spectrometry, Christine M Fisher

Open Access Dissertations

Mass Spectrometry has become a valuable tool for the analysis of a variety of molecules, making it applicable to many fields. The advent of nanoelectrospray ionization (nESI) as a soft/low energy ionization technique has enabled the analysis of large, intact biomolecules. Most mass spectrometry experiments consist of three main steps: ionization, probe step(s), and mass analysis. The present work focuses on a variety of methods for altering ion types at various stages of the mass spectrometry experiment to affect ion fragmentation. Ion types can be manipulated in the solution/droplet phases using novel nESI emitters, generated from borosilicate theta capillaries. These …

Identification Of Perilipin 5 Interaction Partners, Emily E. Burton

Undergraduate Honors Thesis Projects

Perilipin 5 is one of the more recently discovered in the PAT protein family. Several studies on this protein have shown that it resides in multiple intracellular locations such as the endoplasmic reticulum, the cytosol, the mitochondria, and most interestingly on lipid droplets. These lipid droplets have proven not to be just clumps of fat, but to be very complex intracellular organelles, with a core of lipids surrounded by a phospholipid monolayer coated by specific proteins, one of those being perilipin 5. Some proteomic studies have revealed these lipid droplets to be involved in intracellular trafficking, signaling, cytoskeletal organization and …

Aggregatibacter Actinomycetemcomitans Cytolethal Distending Toxin Activates The Nlrp3 Inflammasome In Human Macrophages Leading To The Release Of Pro-Inflammatory Cytokines, Bruce J. Shenker, David M. Ojcius, Lisa P. Walker, Ali Zekavat, Monika Damek Scuron, Kathleen Boesze-Battaglia

All Dugoni School of Dentistry Faculty Articles

The cytolethal distending toxin (Cdt) is produced from a number of bacteria capable of causing infection and inflammatory disease. Our previous studies with Actinobacillus actinomycetemcomitans Cdt demonstrate not only that the active toxin subunit functions as a phosphatidylinositol-3,4,5-triphosphate (PIP3) phosphatase but also that macrophages exposed to the toxin were stimulated to produce proinflammatory cytokines. We now demonstrate that the Cdt-induced proinflammatory response involves the activation of the NLRP3 inflammasome. Specific inhibitors and short hairpin RNA (shRNA) were employed to demonstrate requirements for NLRP3 and ASC as well as caspase-1. Furthermore, Cdt-mediated inflammasome activation is dependent upon upstream signals, including reactive …

Functional Screening Of The Cronobacter Sakazakii Baa-894 Genome Reveals A Role For Prop (Esa_02131) In Carnitine Uptake, Audrey Feeney, Roy D. Sleator

Department of Biological Sciences Publications

Cronobacter sakazakii is a neonatal pathogen responsible for up to 80% of fatalities in infected infants. Low birth weight infants and neonates infected with C. sakazakii suffer necrotizing enterocolitis, bacteraemia and meningitis. The mode of transmission most often associated with infection is powdered infant formula (PIF) which, with an aw of ∼0.2, is too low to allow most microorganisms to persist. Survival of C. sakazakii in environments subject to extreme hyperosmotic stress has previously been attributed to the uptake of compatible solutes including proline and betaine. Herein, we report the construction and screening of a C. sakazakii genome bank and …

Exploring The Effect Of Climate Change On Biological Systems, Nardos Sori

Chemistry & Biochemistry Theses & Dissertations

The present and potential future effect of global warming on the ecosystem has brought climate change to the forefront of scientific inquiry and discussion. For our investigation, we selected two organisms, one from cyanobacteria and one from a cereal plant to determine how climate change may impact these biological systems. The study involved understanding the physiological and adaptive responses at both the genetic and protein function levels to counteract environmental stresses. An increase in atmospheric carbon dioxide is a key factor in global climate change and can lead to alterations in ocean chemistry. Cyanobacteria are important, ancient and ubiquitous organisms …

In Vivo Near Ir Fluorescent Imaging Of Hollow Polymeric Nanocapsules, Venkata Suresh Patthipati

Biological Sciences Theses & Dissertations

Medical Imaging has been an integral component in medical diagnosis and therapeutics. It is frequently used in conjunction with other treatment modalities and has been used for developing applications that range from cancer management to clinical practice. Nanotechnology and its applications are foreseen to have a profound impact on life sciences. Nanomaterial based imaging has a significant potential in addressing medical challenges such as tumor localization, targeted delivery of drugs and real time diagnosis and management of circulation pathology. In particular, polymer based nanoparticles are increasingly being developed as they can be customized according to the diagnostic and/or therapeutic requirements. …

Functional Genomic Analyses Of Switchgrass Developmental Processes, Nathan Palmer

Department of Biochemistry: Dissertations, Theses, and Student Research

Switchgrass (Panicum virgatum L.), a C_4-perennial grass species, is being developed as a bioenergy crop. Although much is known from a breeding perspective, there is limited information on the functional genomics of this crop, specifically regarding molecular mechanisms controlling aerial senescence, winter dormancy, and traits that confer winter hardiness. Using functional genomics to generate a transcriptional roadmap underpinning senescence and winter dormancy will provide researchers with a molecular understanding that can be applied to improve switchgrass germplasm.

In an initial study, a de novo assembly of the crown and rhizome transcriptome from an upland cultivar Summer was …

Immunoassays Of Potential Cancer Biomarkers In Microfluidic Devices, Jayson Virola Pagaduan

Theses and Dissertations

Laboratory test results are important in making decisions regarding a patient's diagnosis and response to treatment. These tests often measure the biomarkers found in biological fluids such blood, urine, and saliva. Immunoassay is one type of laboratory test used to measure the level of biomarkers using specific antibodies. Microfluidics offer several advantages such as speed, small sample volume requirement, portability, integration, and automation. These advantages are motivating to develop microfluidic platforms of conventional laboratory tests. I have fabricated polymer microfluidic devices and developed immunoassays on-chip for potential cancer markers. Silicon template devices were fabricated using standard photolithographic techniques. The template …

Adenovirus Entry From The Apical Surface Of Polarized Epithelia Is Facilitated By The Host Innate Immune Response, Poornima L.N. Kotha, Priyanka Sharma, Abimbola O. Kolawole, Ran Yan, Mahmoud Alghamri, Trisha L. Brockman, Julian Gomez-Cambronero, Julian Cambronero

Biological Sciences Faculty Publications

Prevention of viral-induced respiratory disease begins with an understanding of the factors that increase or decrease susceptibility to viral infection. The primary receptor for most adenoviruses is the coxsackievirus and adenovirus receptor (CAR), a cell-cell adhesion protein normally localized at the basolateral surface of polarized epithelia and involved in neutrophil transepithelial migration. Recently, an alternate isoform of CAR, CAREx8, has been identified at the apical surface of polarized airway epithelia and is implicated in viral infection from the apical surface. We hypothesized that the endogenous role of CAR^Ex8 may be to facilitate host innate immunity. We show that IL-8, …

Comparative Genomics Of Cluster O Mycobacteriophages, Steven G. Cresawn, Welkin H. Pope, Deborah Jacobs-Sera, Charles A. Bowman, Daniel A. Russell, Rebekah M. Dedrick, Tamarah Adair, Kirk R. Anders, Sarah Ball, David Bollivar, Caroline Breitenberger, Sandra H. Burnett, Kristen Butela, Deanna Byrnes, Sarah Carzo, Dr. Kathleen Cornely, Trevor Cross, Richard L. Daniels, David Dunbar, Ann M. Findley, Chris R. Gissendanner, Urszula P. Golebiewska, Grant A. Hartzog, J. Robert Hatherill, Lee E. Hughes, Chernoh S. Jalloh, Carla De Los Santos, Kevin Ekanem, Sphindile L. Khambule, Rodney A. King, Christina King-Smith, Karen Klyczek, Greg P. Krukonis, Christian Laing, Jonathan S. Lapin, A. Javier Lopez, Sipho M. Mkhwanazi, Sally D. Molloy, Deborah Moran, Vanisha Munsamy, Eddie Pacey, Ruth Plymale, Marianne Poxleitner, Nathan Reyna, Joel F. Schildbach, Joseph Stukey, Sarah E. Taylor, Vassie C. Ware, Amanda L. Wellmann, Daniel Westholm, Donna Wodarski, Michelle Zajko, Thabiso S. Zikalala, Roger W. Hendrix, Graham F. Hatfull

Chemistry & Biochemistry Faculty Publications

Mycobacteriophages – viruses of mycobacterial hosts – are genetically diverse but morphologically are all classified in the Caudovirales with double-stranded DNA and tails. We describe here a group of five closely related mycobacteriophages – Corndog, Catdawg, Dylan, Firecracker, and YungJamal – designated as Cluster O with long flexible tails but with unusual prolate capsids. Proteomic analysis of phage Corndog particles, Catdawg particles, and Corndog-infected cells confirms expression of half of the predicted gene products and indicates a non-canonical mechanism for translation of the Corndog tape measure protein. Bioinformatic analysis identifies 8–9 strongly predicted SigA promoters and all five Cluster O …

The Fragile Fiber1 Kinesin Contributes To Cortical Microtubule-Mediated Trafficking Of Cell Wall Components, Chuanmei Zhu, Anindya Ganguly, Tobias I. Baskin, Daniel D. Mcclosky, Charles T. Anderson, Cliff Foster, Kristoffer A. Meunier, Ruth Okamoto, Howard Berg, Ram Dixit

Biology Faculty Research

The cell wall consists of cellulose microfibrils embedded within a matrix of hemicellulose and pectin. Cellulose microfibrils are synthesized at the plasma membrane, whereas matrix polysaccharides are synthesized in the Golgi apparatus and secreted. The trafficking of vesicles containing cell wall components is thought to depend on actin-myosin. Here, we implicate microtubules in this process through studies of the kinesin-4 family member, Fragile Fiber1 (FRA1). In an fra1-5 knockout mutant, the expansion rate of the inflorescence stem is halved compared with the wild type along with the thickness of both primary and secondary cell walls. Nevertheless, cell walls in fra1-5 …