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Annotation Of The Nuclear Receptors In An Estuarine Fish Species, Fundulus Heteroclitus, William S. Baldwin

Publications

The nuclear receptors (NRs) are ligand-dependent transcription factors that respond to various internal as well as external cues such as nutrients, pheromones, and steroid hormones that play crucial roles in regulation and maintenance of homeostasis and orchestrating the physiological and stress responses of an organism. We annotated the Fundulus heteroclitus (mummichog; Atlantic killifish) nuclear receptors. Mummichog are a non-migratory, estuarine fish with a limited home range often used in environmental research as a field model for studying ecological and evolutionary responses to variable environmental conditions such as salinity, oxygen, temperature, pH, and toxic compounds because of their hardiness. F. heteroclitus …

Birc6 Mediates Imatinib Resistance Independently Of Mcl-1, Denis O. Okumu, Michael P. East, Merlin Levine, Laura E. Herring, Raymond Zhang, Thomas S.K. Gilbert, David Litchfield, Yanping Zhang, Lee M. Graves

Biochemistry Publications

© 2017 Okumu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Baculoviral IAP repeat containing 6 (BIRC6) is a member of the inhibitors of apoptosis proteins (IAPs), a family of functionally and structurally related proteins that inhibit apoptosis. BIRC6 has been implicated in drug resistance in several different human cancers, however mechanisms regulating BIRC6 have not been extensively explored. Our phosphoproteomic analysis of an imatinib-resistant chronic myelogenous leukemia (CML) cell line (MYL-R) …

A Review Of The Signal Transduction Pathways Involved In Epithelial Mesenchymal Transition Induced In Breast Cancer Metastasis And Their Cross-Talks, Kasey Cervantes '17

Independent Study

Epithelial-Mesenchymal Transition (EMT) is a biological process utilized by epithelial cells to transform into motile mesenchymal cells, initiating metastasis in cancer. EMT is also utilized during development and wound healing [10]. This process allows for cancerous cells to detach themselves from their primary tumor and invade normal tissue in preferred organ sites, forming secondary tumors called metastases. Metastasis is very important in the progression of cancer in patients as it the process responsible for the mortality of patients through the collection of metastases that effect vital organs like the brain, lung, or immune system. The most common metastases for malignant …

Lymphoid Hematopoiesis And The Role Of B-Cells In Transgenic Mouse Model Of Sickle Cell Disease, Christina Cotte

University Scholar Projects

Sickle cell disease (SCD) has been shown to be associated with decreased baseline immunity and thus increased susceptibility to infection. I sought to discern possible causes of this by looking into the correlations between SCD and hematopoiesis, the immune system and the neuroendocrine system, and ultimately by conducting experiments surrounding the impaired immune system of SCD. These experiments focused on the potential causes and effects of the diminution of B-1a cells in the SCD spleen. Adoptive transfers, infections with Streptococcus pneumoniae, and histologic imaging were conducted to establish if the diminution of the B-1a cells in the SCD spleen …

Determination Of The Substrate Specificity Of Citrus Paradisi Flavonol Specific 3-O-Glucosyltransferase Mutant D344p, Nathan R. Spaulding

Undergraduate Honors Theses

Plants produce a vast array of secondary metabolites. A group of phenolic compounds, the flavonoids, are metabolites ubiquitous among plants and are known to aid in processes such as plant reproduction, UV defense, pigmentation and development. In relation to human health, flavonoids have been found to possess anti-inflammatory, anti-cancer, and antioxidant properties. Flavonoid’s ability to participate in so many interactions is due in part to their subclass variation and further chemical modification. One such modification is glucosylation, where a glucose molecule is added to the flavonoid substrate. The enzymes that catalyze these reactions are known as glucosyltransferases (GT). Citrus paradisi …

Perspectives And Expectations In Structural Bioinformatics Of Metalloproteins, Sen Yao, Robert M. Flight, Eric C. Rouchka, Hunter N. B. Moseley

Molecular and Cellular Biochemistry Faculty Publications

Recent papers highlight the presence of large numbers of compressed angles in metal ion coordination geometries for metalloprotein entries in the worldwide Protein Data Bank, due mainly to multidentate coordination. The prevalence of these compressed angles has raised the controversial idea that significantly populated aberrant or even novel coordination geometries may exist. Some of these papers have undergone severe criticism, apparently due to views held that only canonical coordination geometries exist in significant numbers. While criticism of controversial ideas is warranted and to be expected, we believe that a line was crossed where unfair criticism was put forth to discredit …

Improving Cardiac Cell Therapy: Role Of Hdac1 In Directing Cmc Cell Fate Decisions And Therapeutic Efficacy., John Zhao

Electronic Theses and Dissertations

Cardiac mesenchymal stromal cell (CMC) administration has improved cardiac function in pre-clinical animal models of heart failure. Specifically, both transdifferentiation and secretion of paracrine signaling molecules are potential mechanisms by which transplanted cells exert their cardiac reparative effects. The inhibition of histone deacetylases (HDACs) has been shown to enhance the cardiogenic differentiation capacity of various progenitor cell types. In the current study the consequences of HDAC1 inhibition on CMC in vitro differentiation, in vivo cardiac reparative capabilities, and in vitro cytokine secretion were investigated using either genetic depletion of HDAC1 or pharmacological inhibition with entinostat. CMCs depleted of HDAC1 exhibit …

Evaluation Of Different Probiotic Strains Supplemented In Commercial Broiler Rations And Their Influences On Performance, Yield, And Intestinal Microbiota., Justin M. Glasscock

Electronic Theses and Dissertations

The objective of this study was to evaluate Bacillus megaterium, Bacillus licheniformis, and Bacillus subtilis, as probiotic strains compared to Bacitracin Methylene Disalicylate (BMD) 50 as the antibiotic growth promotor, supplemented in commercial broiler rations and their influences on performance, yield, and intestinal microbiota. This trial was completed as a randomized-block design with 4,800 birds split into 96, 5’x10’ pens, and randomly assigned to one of eight treatment groups. The birds were placed at a stocking density of 1.00 ft²/bird, (50 birds/pen), and reared on used pine shaving for 55 days. Throughout the study, bird …

Ubr-5, A Conserved Hect-Type E3 Ubiquitin Ligase, Negatively Regulates Notch-Type Signaling In Caenorhabditis Elegans, Anniya Gu

Renée Crown University Honors Thesis Projects - All

Germline stem cell proliferation in C. elegans is regulated by the distal tip cell (DTC) located at the distal end of each gonad arm. The DTC signals germ cells, through a Notch-type signaling pathway, to proliferate. As germ cells move farther away from the DTC, they transition into meiosis and produce gametes. There are two Notch-type receptors in C. elegans, GLP-1 and LIN-12, which play a role in regulating cell fate decisions. Whenever GLP-1 function is lost, all the germ cells exit mitosis and enter meiosis. If this happens early in development, then the animal is sterile because it does …

Elucidating The Interplay Between Sodium Selenite On The Tick Amblyomma Maculatum Selenoprotein Gene Expression, Afnan M. Beauti

Honors Theses

Selenium (Se) is an element recognized as an essential micronutrient in eukaryote organisms. Selenoproteins contain selenium as selenocysteine, the 21st amino acid. Selenium plays a role in cell growth and functioning. At low concentrations, it can induce growth and at high concentrations, it can cause a cell to stop growing and potentially have toxic effects on the cell and organism. When selenium levels are high, oxidative stress results by the production of reactive oxidative species. Selenoproteins, however, can aid the antioxidant response in the cell. Ticks are arthropods of interest, as they are one of few that contain many selenogenes, …

Generation Of Mutant Snap-23 To Arrest Mast Cell Degranulation At Trans-Snare Complex Formation, Suzette Wafford-Turner

Honors Theses

Regulated secretion of pro-inflammatory molecules (e.g, histamines, proteases) from mast cells plays critical roles in immunity, allergic reactions, cardiovascular disease and cancer. These molecules are stored in secretory granules inside the cell and are rapidly released into the extracellular environment when mast cells are activated. It is known that mast cell degranulation depends upon membrane anchored SNAREs (soluble N-ethylmaleidimide-sensitive factor attachment protein receptors) and accessory proteins that form the trans-SNARE complex, a 4 helical bundle central to exocytic fusion. There are three SNARE proteins that contribute to the 4-helical bundle during exocytosis; Syntaxin and VAMP proteins each provide one helix …

Characterization Of P43lgrn-3, Kelly G. Hill

Honors Theses

Alzheimer’s Disease (AD) is a progressive neurodegenerative disorder characterized by extensive memory loss and cognitive deficits, which occur due to severe neuronal loss. Two hallmark lesions, intracellular neurofibrillary tangles composed of hyperphosphorylated tau and extracellular neuritic plaques formed by the aggregation of amyloid-β (Aβ), are responsible for the progressive neuronal loss seen in AD brains. Neurotoxic Aβ aggregates are also known to cause inflammation within the brain. It has recently come to light that severe and acute inflammation, such as seen in traumatic brain injury (TBI), may also lead to AD-type dementia. This has raised the question whether some of …

The Preparation Of Synthetic Myod Mrna For Cellular Differentiation And Innate Immune Response Downstream Application, James D. Grenn

Honors Theses

The development of therapeutic immune responses from the manipulation of embryonic stem cells (ESCs) via induction of synthetic RNA with 5’ capped and 3’ poly(A)tailed ends would lead to development of stem cell therapy. A necessary step in attaining such a goal is to first produce an mRNA transcript from a plasmid containing the open reading frame (ORF) for a transcription factor for cellular activation.

In this research, the DNA plasmid pMD4 encoding MyoD was transcribed into synthetic mRNA. The plasmid was first amplified using Polymerase Chain Reaction (PCR), and analyzed using gel electrophoresis. The amplified template was purified via …

Altering The Structure Of Carboxysomal Carbonic Anhydrase Csosca To Determine The Necessity Of The N-Terminal Domain In Csosca Function, Dana L. Dillistone

Honors Theses

In this project, a DNA construct was designed and developed to remove the first fifty amino acids of the CsoSCA protein in the chemolithotrophic bacterium Halothiobacillus neapolitanus. The csoS3 gene codes for a carbonic anhydrase enzyme (CsoSCA) that is unique to a structure called a carboxysome. Carboxysomes are polyhedral microcompartments where carbon fixation is housed. The carbonic anhydrase is a shell-associated protein that improves the catalytic efficiency of ribulose-bisphosphate carboxylase/oxygenase (RuBisCO), the enzyme that catalyzes the fixation of carbon. By deleting the first fifty amino acids of the carbonic anhydrase, the necessity of the amino acids in carboxysome function was …

Influence Of Histidine Residues, Ph And Charge Interactions On Membrane-Spanning Peptides, Ashley N. Henderson

Graduate Theses and Dissertations

Designed transmembrane peptides were employed for investigations of histidine residues within the hydrophobic environment of the lipid bilayer by means of oriented solid-state deuterium NMR spectroscopy. Using the model peptide GWALP23 sequence (GGALW(LA)6LWLAGA) as a host framework, the effects of single and double histidine mutations were explored. Replacement of leucine residue 12 to polar neutral histidine had little influence on the peptide average orientation, however under strongly acidic pH conditions in DOPC bilayers, the histidine becomes positively charged (pKa 2.5) and the GWALP23-H12 peptide exits the membrane and adopts a surface-bound orientation. Conversely, mutation of leucine 14 to neutral histidine …

Identification Of Molecular Signatures Of Environmental And Nutritional Stress Responses In Poultry, Phuong Hieu Nguyen

Graduate Theses and Dissertations

Poultry production plays an important role in the food supply and security for billions of people. Poultry meat is considered the most efficient, nutritious source of protein, without religious taboos, and is relatively inexpensive. However, the poultry industry is facing substantial challenges. The global environmental temperature has experienced dramatic changes in the last few years. Modern broilers are not well adapted to environmental challenges (heat and cold stress), which have resulted in heavy economic loss in the poultry industry worldwide. In addition, the use of feed restriction regimens in management of breeders as well as the transportation of young chicks …

Role Of Mir-29b-1 And Mir-29a In Endocrine-Resistant Breast Cancer., Penn Muluhngwi

Electronic Theses and Dissertations

Therapies targeting estrogen receptor α (ERα) including selective estrogen receptor modulators (SERMs), e.g., tamoxifen (TAM); selective estrogen receptor downregulators (SERDs), e.g., fulvestrant (ICI 182,780); and aromatase inhibitors (AI), e.g., letrozole, are successfully used in treating breast cancer patients whose initial tumor expresses ERα. Unfortunately, the effectiveness of endocrine therapies is limited as ~ 40% of breast cancer patients will eventually acquire resistance to them. The role of miRNAs in the progression of endocrine-resistant breast cancer is of keen interest in developing biomarkers and therapies to counter metastatic disease. This dissertation begins with a review on miRNAs implicated …

Genetically Encoded Fluorescent Protein Biosensor For Nitric Oxide, Wenjia Zhai

Department of Chemistry: Dissertations, Theses, and Student Research

Nitric oxide (NO) is an important molecule in living cells for signaling, thus a specific sensor to detect its level in live cells is needed. Currently there are a few small molecule probes for the detection of NO. A common shortcoming of these probes is their unavoidable leakage from the target cells. In this project, I seek to develop a novel green fluorescent protein (GFP)-based biosensor to detect cellular NO. This GFP-based sensor is genetically encodable and can potentially avoid the possible false positive result due to the leakage. I synthesized an unnatural amino acid (unAA) and examined its incorporation …

Burkholderia Cenocepacia J2315-Mediated Destruction Of Staphylococcus Aureus Nrs77 Biofilms., Rachel Thompson

College of Arts & Sciences Senior Theses

Cystic fibrosis (CF) is an inherited disorder that affects over 30,000 people in the US and more than 70,000 people worldwide. Recurring bacterial infections in CF patients result in tissue damage that dramatically lowers respiratory function and are ultimately fatal. The formation of bacterial biofilms in the mucus and on lung epithelial tissue allows pathogens to be protected from antibiotics and the host immune system, making treatment of infection difficult. The interactions between CF pathogens in co-culture biofilms are not well understood and were examined in this study. Staphylococcus aureus and Burkholderia cenocepacia, two common CF pathogens, were used …

Oxidative Quenching Of Photoexcited Ru(Ii)-Bipyridine Complexes By Oxygen, Danielle Rebecca Latham

Undergraduate Honors Theses

An experimental approach was taken in determining the quantum yield of Ruthenium(II) with Oxygen using two different Ru complexes. This reaction results in Ruthenium(III) and O2-. The Coulombic interactions caused by a carboxylate functional was found to increase the yield of charge separation. This was done using a diode to measure the intensity of the completed reaction over a certain time frame. The intensities were turned into concentrations. The concentration over time was used to determine the quantum yield. This information is useful in creating more efficient light emitting diodes.

Uncovering The Identity And Metabolism Of Bacterial Coa-Rna, Joseph R. Spangler

Dissertations

Coenzyme A is an indispensable molecule in all known life with roles in metabolism, gene regulation, and macromolecule synthesis. As CoA is derived from RNA itself, it’s incorporation into RNA by in vitro methods has proven useful in research probing the origin of life based on the RNA World theory. The discovery in contemporary bacteria of RNA modified with CoA, however, provided an unexpected twist to previously well-characterized bacterial systems. The identity of sequences associated with CoA-RNA has been elusive since their discovery in 2009 based on the difficulties in isolation while maintaining RNA quality. The aim of this study …

Phopsphorylation And Ubiquitin Modification At Dna Damage Sites In Response To Double-Strand Breaks, Atanu Paul

Dissertations and Theses (Open Access)

Genomes of all organisms are continuously damaged by numerous exogenous and endogenous sources leading to different kinds of DNA lesions, which if not repaired efficiently may trigger wide-scale genomic instability, a hallmark of cancer development. To overcome this, cells have evolved a sophisticated sensory network called the DNA damage response (DDR) comprised of a large number of distinct protein complexes categorized as sensor, mediator, transducer and effector proteins that amplify the DNA damage signal and activate cell cycle checkpoint to initiate DNA repair or trigger apoptosis where the defect is beyond repair. This intricate signaling pathway is tightly regulated by …

Thylakoid Protein Targeting/Insertion By A Signal Recognition Particle In Chloroplasts, Priyanka Sharma

Graduate Theses and Dissertations

Protein targeting is a fundamental cellular process that directs proteins from their site of synthesis to the site where they function. The signal recognition particle (SRP) dependent targeting pathway is conserved in both eukaryotes and prokaryotes where it co-translationally targets polypeptide chains emerging from ribosomes to the endoplasmic reticulum (eukaryotes) or cytoplasmic membrane (prokaryotes). A structurally unique form of SRP is found in chloroplasts where it functions to post-translationally bind and target a subset of integral thylakoid membrane proteins, the light harvesting chlorophyll binding proteins (LHCPs). Mature LHCPs bind chlorophyll a/b and function in photosynthetic light capture. Like many other …

Disorder In Cysteine-Rich Granulin-3 And Its Implication In Alzheimer Disease, Gaurav Ghag

Dissertations

Granulins (GRNs) are a family of small, cysteine-rich proteins that are generated upon proteolytic cleavage of their precursor, progranulin (PGRN) during inflammation. All seven GRNs (1 – 7 or A – G) contain twelve conserved cysteines that form six intramolecular disulfide bonds, rendering this family of proteins unique. GRNs play multiple roles and are involved in a myriad of physiological as well as pathological processes. They are known to a play role in growth and embryonic development, wound healing, and signaling cascades as well as in tumorigenesis. They are also implicated in neurodegenerative diseases like frontotemporal dementia (FTD), Alzheimer disease …

Role And Regulation Of Sphingosine 1-Phosphate In Erythrocyte, Kaiqi Sun

Dissertations and Theses (Open Access)

Sphingosine 1-phosphate (S1P) is a bioactive signaling sphingolipid produced in every mammalian cell. It plays a variety of important roles both in and outside of cells. S1P is highly enriched in mature erythrocytes because of the high enzymatic activity of the S1P-generating enzyme Sphingosine Kinase 1 (Sphk1) and the absence of S1P degrading enzymes. Erythrocytes are considered only a major reservoir for S1P because they supply S1P to the circulation for the regulation of various physiological processes which include but are not limited to immune cell trafficking, endothelial integrity and hematopoietic stem cell mobilization. However, if S1P plays a role …

Fret-Based Investigations Of The Structure-Function Relationships In The Nmda Receptor, Drew M. Dolino

Dissertations and Theses (Open Access)

The N-methyl-D-aspartate (NMDA) receptor is one member of a class of proteins known as the ionotropic glutamate receptors. Ionotropic glutamate receptors mediate the majority of excitatory neurotransmission in the central nervous system, with the NMDA receptor standing out among these receptors for its requirement of a co-agonist, its magnesium-block-based coincidence detection, its slow kinetics, its calcium permeability, its allosteric modulation, and its especially important functional roles in synaptic plasticity, excitotoxicity, and more. In recent years, a wealth of structural information has come about describing endpoint structures to high resolution, but such structures are unable to fully resolve the movements …

Non-Coding Rnas Identify The Intrinsic Molecular Subtypes Of Muscle-Invasive Bladder Cancer, Andrea E. Ochoa

Dissertations and Theses (Open Access)

NON-CODING RNAS IDENTIFY THE INTRINSIC MOLECULAR SUBTYPES OF MUSCLE-INVASIVE BLADDER CANCER

Andrea Elizabeth Ochoa, B.S.

Advisory Professors: David J. McConkey, Ph.D. and Joya Chandra, Ph.D.

There has been a recent explosion of genomics data in muscle-invasive bladder cancer (MIBC) to better understand the underlying biology of the disease that leads to the high amount of heterogeneity that is seen clinically. These studies have identified relatively stable intrinsic molecular subtypes of MIBC that show similarities to the basal and luminal subtypes of breast cancer. However, previous studies have primarily focused on protein-coding genes or DNA mutations/alterations.

There is emerging evidence implicating …

Analysis Of The Biochemical And Cellular Activities Of Substrate Binding By The Molecular Chaperone Hsp110/Sse1, Veronica M. Garcia

Dissertations and Theses (Open Access)

Molecular chaperones ensure protein quality during protein synthesis, delivery, damage repair, and degradation. The ubiquitous and highly conserved molecular chaperone 70-kDa heat-shock proteins (Hsp70s) are essential in maintaining protein homeostasis by cycling through high and low affinity binding of unfolded protein clients to facilitate folding. The Hsp110 class of chaperones are divergent relatives of Hsp70 that are extremely effective in preventing protein aggregation but lack the hallmark folding activity seen in Hsp70s. Hsp110s serve as Hsp70 nucleotide exchange factors (NEF) that facilitate the Hsp70 folding cycle by inducing release of protein substrate from Hsp70, thus recycling the chaperone for a …

The Role Of Adenosine Signaling In Mature Erythrocytes And Erythroid Progenitors, Hong Liu

Dissertations and Theses (Open Access)

Adenosine is a ubiquitous nucleoside in almost all the cells throughout our bodies. It is highly induced particularly under hypoxia or energy depletion conditions. Adenosine functions as a critical ligand, after binding to membrane-associated adenosine receptors, adenosine initiates a downstream signaling cascade and subsequently contributes to functions of nervous system, immune response, vascular function and even metabolism.

Hypoxia is a condition with limited O₂ availability in the whole body or a region of the body. It is a major consequence of many respiratory and cardiovascular diseases, as well as for people living and working at high altitudes or other …

Understanding The Mechanism Of Genomic Instability During Replicative Aging In Budding Yeast, Sangita Pal

Dissertations and Theses (Open Access)

Aging brings a gradual decline in molecular fidelity and biological functionality, resulting in age related phenotypes and diseases. Despite continued efforts to uncover the conserved aging pathways among eukaryotes, exact molecular causes of aging are still poorly understood. One of the most important hallmarks of aging is increased genomic instability. However, there remains much ambiguity as to the cause. I am studying the replicative life span (RLS) of the genetically tractable model organism Saccharomyces cerevisiae, or budding yeast using the innovative “mother enrichment program” as the method to isolate unparalleled numbers of aged yeast cells to investigate the molecular changes …