Biology Commons^™

An Evolving Epigenome That Determines Tissue And Cell Specificity, Renee Louise Sears

Arts & Sciences Electronic Theses and Dissertations

Understanding the mechanisms driving phenotypic variation is a major goal of biology that unifies classical genetics with the emerging fields of genomics and epigenomics. Human and mouse share over 90% of genes and global tissue-specific patterns of expression are maintained between the species. Thus, it is hypothesized that gene expression is influenced through distinctive regulation among species in order to account for the unmistakable phenotypic divergence. DNA methylation, histone modifications, open chromatin patterns, transcription factor binding, and other epigenetic factors are all associated with shaping, maintaining, and repressing regulatory regions which in turn coordinate gene expression. It is vital to …

Restructuring Of The Axon Initial Segment In Mouse Models Of Neurodevelopmental Disorders, Rachel Ali Rodriguez

UNLV Theses, Dissertations, Professional Papers, and Capstones

Neurodevelopmental disorders (NDDs) affect more than 36% of children in countries with low- and middle- incomes (Boivin, 2015; McCoy, 2016). Interestingly, these heterogeneous disorders share a high incidence of epileptic seizures, suggesting a shared pathology. Seizures result when neuronal firing activity becomes disturbed and neurons fire excessively or in unregulated patterns. A key site in the control of neuronal firing patterns is the axon initial segment (AIS), where the local density of proteins and the morphology of the AIS in part determine the firing of neurons. We hypothesized that a disruption in the morphology and/or composition of the AIS can …

Investigating The Relationship Between Hormone Receptors Dax-1 And Estrogen Receptor Within Prostate Cancer Cell Lines, Meghana G. Vijayraghavan

Master's Theses

Prostate cancer (PCa) is estimated to be the second leading cause of cancer-related deaths among men in the United States in 2019. While most prostate tumors rely on androgens for growth signaling, there are subsets of tumors that become androgen-resistant, therefore resisting conventional androgen-depravation therapy. Consequently, research has focused on targeting different hormone receptors for novel therapeutics. One such receptor is Dosage-sensitive sex reversal, adrenal hypoplasia critical region, on chromosome X, gene 1 (DAX-1). DAX-1 is known to interact with other hormone receptors, such as androgen receptor (AR) and estrogen receptors (ERs) to suppress the proliferative effects …

Gmr36a08, Anuradha Venkatakrishnan Chimata, Oorvashi Roy Puli, Amit Singh

DVE Enhancer Sequences Utilized in GMR Line

dve enhancer 49927

• ID - GMR36A08
• Location - 2R: 18120673, 18124576
• Base pairs - 3903

Gmr40e08, Anuradha Venkatakrishnan Chimata, Oorvashi Roy Puli, Amit Singh

DVE Enhancer Sequences Utilized in GMR Line

dve enhancer 41238

• ID - GMR40E08
• Location - 2R: 18162090, 18165058
• Base pairs - 2968

Gmr42a07, Anuradha Venkatakrishnan Chimata, Oorvashi Roy Puli, Amit Singh

DVE Enhancer Sequences Utilized in GMR Line

dve enhancer 45284

• ID - GMR42A07
• Location - 2R: 18146520, 18150306
• Base pairs - 3786

Gmr36a10, Anuradha Venkatakrishnan Chimata, Oorvashi Roy Puli, Amit Singh

DVE Enhancer Sequences Utilized in GMR Line

dve enhancer 49373

• ID - GMR36A10
• Location - 2R: 18116788, 18120701
• Base pairs - 3913

Gmr40c09, Anuradha Venkatakrishnan Chimata, Oorvashi Roy Puli, Amit Singh

DVE Enhancer Sequences Utilized in GMR Line

dve enhancer

• ID - GMR40C09
• Location - 2R: 18132203, 18134987
• Base pairs - 2784

Gmr41f05, Anuradha Venkatakrishnan Chimata, Oorvashi Roy Puli, Amit Singh

DVE Enhancer Sequences Utilized in GMR Line

dve enhancer 50133

• ID - GMR41F05
• Location - 2R: 18139042, 18142672
• Base pairs - 3630

Gmr35a04, Anuradha Venkatakrishnan Chimata, Oorvashi Roy Puli, Amit Singh

DVE Enhancer Sequences Utilized in GMR Line

dve enhancer

• ID - GMR35A04
• Location - 2R: 18125755, 18128365
• Base pairs - 2610

Gmr39h01, Anuradha Venkatakrishnan Chimata, Oorvashi Roy Puli, Amit Singh

DVE Enhancer Sequences Utilized in GMR Line

dve enhancer 50066

• ID - GMR39H01
• Location - 2R: 18153797, 18156108
• Base pairs - 2311

Gmr42e10, Anuradha Venkatakrishnan Chimata, Oorvashi Roy Puli, Amit Singh

DVE Enhancer Sequences Utilized in GMR Line

dve enhancer

• ID - GMR42E10
• Location - 2R: 18133506, 18137474
• Base pairs - 3968

Gmr41c04, Anuradha Venkatakrishnan Chimata, Oorvashi Roy Puli, Amit Singh

DVE Enhancer Sequences Utilized in GMR Line

dve enhancer

• ID - GMR41C04
• Location -2R: 18143594, 18147064
• Base pairs - 3470

Gmr40c05, Anuradha Venkatakrishnan Chimata, Oorvashi Roy Puli, Amit Singh

DVE Enhancer Sequences Utilized in GMR Line

dve enhancer 45682

• ID - GMR40C05
• Location - 2R: 18141630, 18144381
• Base pairs - 2751

Gmr41h07, Anuradha Venkatakrishnan Chimata, Oorvashi Roy Puli, Amit Singh

DVE Enhancer Sequences Utilized in GMR Line

dve enhancer 46241

• ID - GMR41H07
• Location - 2R: 18150920, 18154671
• Base pairs - 3751

Gmr42h01, Anuradha Venkatakrishnan Chimata, Oorvashi Roy Puli, Amit Singh

DVE Enhancer Sequences Utilized in GMR Line

dve enhancer 48150

• ID - GMR42H01
• Location - 2R: 18158419, 18162751
• Base pairs - 4332

Recruitment Of Polycomb-Group Proteins At Giant In Drosophila Embryos, Elnaz Ghotbi Ravandi

Biological Sciences Theses and Dissertations

Polycomb Group (PcG) proteins are evolutionarily conserved epigenetic transcriptional regulators that maintain the transcriptional repression of silenced genes. PcG mediated silencing is divided into two phases: initiation and maintenance. During the initiation phase, PcG proteins initially recognize and bind to their target genes. Once PcG proteins are recruited to their target genes, they can maintain transcriptional repression through an unlimited number of cell cycles. Most studies on PcG proteins have been focused on the maintenance phase of PcG silencing, and the molecular mechanisms by which PcG proteins are initially recruited to their target genes remained unknown. Two models have been …

Toward Understanding The Mechanism Of Protein Targeting In The Chloroplast Signal Recognition Particle Pathway, Mercede Furr

Graduate Theses and Dissertations

Protein targeting is a vital cellular function. The signal recognition particle (SRP) pathway is a universally conserved targeting system present in the cytosol and used to co-translationally target many proteins to the inner membrane of prokaryotes and the endoplasmic reticulum of eukaryotes. The chloroplast has a homologous SRP system which post-translationally targets light harvesting chlorophyll binding proteins (LHCPs) to the thylakoid membrane for integration. The chloroplast SRP (cpSRP) is a heterodimer with a 54 kDa subunit equivalent to SRP54 in the canonical pathway. In addition, cpSRP contains a novel 43 kDa subunit which is a unique and irreplaceable component. cpSRP43 …

Uncovering The Zeb1 Interactome To Identify Novel Regulators Of Metastatic Non-Small Cell Lung Cancer, Roxsan Manshouri

Dissertations & Theses (Open Access)

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death in the United States, due in part to the robust affinity of lung cancer cells to metastasize. Understanding the processes that contribute to metastasis provides promise for the discovery of novel therapeutic targets. Epithelial-tomesenchymal transition (EMT) is a proposed model for the initiation of metastasis. During EMT cell adhesion and polarity is reduced, allowing epithelial cancer cells to dissociate from the primary tumor and invade distant organs. The transcription factor zinc finger E-box-binding homeobox 1 (ZEB1) has been reported to uniquely correlate with NSCLC disease progression and to …

The Role Of Membrane Domains In Protein And Lipid Sorting During Endocytic Traffic, Blanca B. Diaz-Rohrer

Dissertations & Theses (Open Access)

The lipid and protein composition of the plasma membrane (PM) must be tightly controlled to maintain cellular functionality, despite constant, rapid endocytosis. Because de novo synthesis of proteins and lipids is energetically costly, the cell depends on active recycling to return endocytosed membrane components back to the PM. For most proteins, the mechanisms and pathways of their PM retention remain unknown. The work presented here shows that association with ordered membrane microdomains is fully sufficient for PM recycling and that abrogation of raft partitioning leads to their degradation in lysosomes. These findings support a model wherein ordered membrane domains mediate …

Aniseed 2019: 4d Exploration Of Genetic Data For An Extended Range Of Tunicates, J. Dardaillon, D. Dauga, P. Simion, E. Faure, T. A. Onuma, M. B. Debiasse, A. Louis, K. R. Nitta, M. Naville, L. Besnardeau, W. Reeves, K. Wang, M. Fagotto, M. Guéroult-Bellone, S. Fujiwara, R. Dumollard, M. Veeman, J.-N. Volff, H. Roest Crollius, E. Douzery, J. F. Ryan, Bradley Justin Davidson , '91, H. Nishida, C. Dantec, P. Lemaire

Biology Faculty Works

ANISEED (https://www.aniseed.cnrs.fr) is the main model organism database for the worldwide community of scientists working on tunicates, the vertebrate sister-group. Information provided for each species includes functionally-annotated gene and transcript models with orthology relationships within tunicates, and with echinoderms, cephalochordates and vertebrates. Beyond genes the system describes other genetic elements, including repeated elements and cis-regulatory modules. Gene expression profiles for several thousand genes are formalized in both wild-type and experimentally-manipulated conditions, using formal anatomical ontologies. These data can be explored through three complementary types of browsers, each offering a different view-point. A developmental browser summarizes the information in a gene- …

Discovery Of An Egfr Inhibitor For The Treatment Of Lung And Other Cancers, Jodie Meng '20

Student Publications & Research

The Epidermal Growth Factor Receptor (EGFR), a transmembrane protein involved in the regulation of signaling pathways, is frequently overexpressed in epithelial tumors. First generation EGFR TKIs, such as erlotinib and gefitinib, traditionally improved outcomes for non-small-cell lung carcinoma and pancreatic cancer patients by attaching competitively and reversibly to the ATP binding domain of EGFR. Second-generation EGFR TKIs have been developed to combat resistance among patients, despite demonstrating toxic side effects. In the present study, 1400 selective inhibitors were designed based on the molecular scaffolds of first and second generation EGFR TKIs. Results were refined by parameters outlined in Lipinski’s rule. …

Cul3 Regulates Cyclin E1 Protein Abundance Via A Degron Located Within The N-Terminal Region Of Cyclin E, Brittney Marie Davidge, Katia De Oliveira Rebola, Larry N. Agbor, Curt D. Sigmund, Jeffrey D. Singer

Biology Faculty Publications and Presentations

mammalian cells. Increased levels of cyclin E are found in some cancers. Additionally, proteolytic removal of the cyclin E N-terminus occurs in some cancers and is associated with increased cyclin E–Cdk2 activity and poor clinical prognosis. Cyclin E levels are tightly regulated and controlled in part through ubiquitin-mediated degradation initiated by one of two E3 ligases, Cul1 and Cul3. Cul1 ubiquitylates phosphorylated cyclin E, but the mechanism through which Cul3 ubiquitylates cyclin E is poorly understood. In experiments to ascertain how Cul3 mediates cyclin E destruction, we identified a degron on cyclin E that Cul3 targets for ubiquitylation. Recognition of …

Updating Molecular Diagnostics For Detecting Methicillin- Susceptible And Methicillin-Resistant Staphylococcus Aureus Isolates In Blood Culture Bottles, Fred C. Tenover, Isabella A. Tickler, Victoria M. Le, Scott Dewell, Rodrigo E. Mendes, Richard V. Goering, Mrsa Consortium

Biology Faculty Publications

Molecular diagnostic tests can be used to provide rapid identification of staphylococcal species in blood culture bottles to help improve antimicrobial stewardship. However, alterations in the target nucleic acid sequences of the microorganisms or their antimicrobial resistance genes can lead to false-negative results. We determined the whole-genome sequences of 4 blood culture isolates of Staphylococcus aureus and 2 control organisms to understand the genetic basis of genotypephenotype discrepancies when using the Xpert MRSA/SA BC test (in vitro diagnostic medical device [IVD]). Three methicillin-resistant S. aureus (MRSA) isolates each had a different insertion of a genetic element in the staphylococcal cassette …

Equine Hoof Stratum Internum K14+Cd105+ Progenitor Cells: Culture, Characterization, And Model Of Epithelial To Mesenchymal Transition, Qingqiu Yang

LSU Doctoral Dissertations

For the potential benefit of progenitor cells to be realized in cell-based clinical therapies, it is vital to investigate the mechanism between progenitor cells and abnormal tissue formation. Laminitis is a fatal condition that is often presented by equine hoof inflammation and hoof tissue disarrangement. The persistence of abnormal tissue formation after the resolution of equine laminitis suggests there is progenitor cell compromise. So far, there is limited information about equine hoof progenitor cells and the effects of inflammation on hoof progenitor cells. To pursue a better understanding of both hoof progenitor cell and hoof growth as well as find …

Variable Levels Of Drift In Tunicate Cardiopharyngeal Gene Regulatory Elements, W. Colgan, A. Leanza, A. Hwang, M. B. Debiasse, Isabel Llosa , '20, Daniel Rodrigues , '21, Hriju Adhikari , '20, Guillermo Barreto Corona , '19, Saskia Bock , '20, Amanda T. Carillo-Perez , '19, Meagan Currie , '20, S. Darkoa-Larbi, D. Dellal, Hanna Gutow , '20, P. Hokama, E. Kibby, N. Linhart, S. Moody, Allison Naganuma , '20, D. Nguyen, Ryan Stanton , '20, S. Stark, Cameron Tumey , '21, A. Velleca, J. F. Ryan, Bradley Justin Davidson , '91

Biology Faculty Works

Background: Mutations in gene regulatory networks often lead to genetic divergence without impacting gene expression or developmental patterning. The rules governing this process of developmental systems drift, including the variable impact of selective constraints on different nodes in a gene regulatory network, remain poorly delineated. Results: Here we examine developmental systems drift within the cardiopharyngeal gene regulatory networks of two tunicate species, Corella inflata and Ciona robusta. Cross-species analysis of regulatory elements suggests that trans-regulatory architecture is largely conserved between these highly divergent species. In contrast, cis-regulatory elements within this network exhibit distinct levels of conservation. In particular, while most …

Regulation Of The Microtubule Cytoskeleton And Cell Wall Development In Arabidopsis Thaliana, Christy J. Fornero

Theses and Dissertations

Regulation of the cortical microtubule cytoskeleton is critical for organized plant cell division. Arabidopsis ton1 and ton2 mutants display random cell division plane placement and lack the plant-specific cortical microtubule array that encircles the nucleus prior to mitosis. In wild type plants, this preprophase band (PPB) of cortical microtubules precisely marks the future division plane. The specific roles of TON1 and TON2 in PPB formation are not yet known. It is suspected that TON1 Recruiting Motif (TRM) proteins may be involved in TON1 and TON2 recruitment to the PPB. Here we describe results for the targeted disruption of a group …

Dormant Pathogenic Cd4(+) T Cells Are Prevalent In The Peripheral Repertoire Of Healthy Mice, Anna Cebula, Michal Kuczma, Edyta Szurek, Maciej Pietrzak, Natasha Savage, Wessam R. Elhefnawy, Grzegorz Rempala, Piotr Kraj, Leszek Ignatowicz

Computer Science Faculty Publications

Thymic central tolerance eliminates most immature T cells with autoreactive T cell receptors (TCR) that recognize self MHC/peptide complexes. Regardless, an unknown number of autoreactive CD4+Foxp3⁻ T cells escape negative selection and in the periphery require continuous suppression by CD4+Foxp3⁺ regulatory cells (Tregs). Here, we compare immune repertoires of Treg-deficient and Treg-sufficient mice to find Tregs continuously constraining one-third of mature CD4⁺Foxp3⁻ cells from converting to pathogenic effectors in healthy mice. These dormant pathogenic clones frequently express TCRs activatable by ubiquitous autoantigens presented by class II MHCs on conventional dendritic cells, including selfpeptides that select …

Structural Properties And Cellular Expression Of Afrlea6, A Group 6 Late Embryogenesis Abundant Protein From Embryos Of Artemia Franciscana, Blase M. Leblanc, Mike T. Le, Brett Janis, Michael Menze, Steven C. Hand

Faculty Scholarship

Late embryogenesis abundant (LEA) proteins are intrinsically disordered proteins (IDPs) commonly found in anhydrobiotic organisms and are frequently correlated with desiccation tolerance. Herein we report new findings on AfrLEA6, a novel Group 6 LEA protein from embryos of Artemia franciscana. Assessment of secondary structure in aqueous and dried states with circular dichroism (CD) reveals 89% random coil in the aqueous state, thus supporting classification of AfrLEA6 as an IDP. Removal of water from the protein by drying or exposure to trifluoroethanol (a chemical de-solvating agent) promotes a large gain in secondary structure of AfrLEA6, predominated by α-helix and exhibiting minimal …

5 Lipoxygenase's Role In Chondrogenesis Of The Atdc5 Cell Line, Tien My Tran

Seton Hall University Dissertations and Theses (ETDs)

5-Lipoxygenase metabolizes arachidonic acid (AA) to generate leukotrienes (LTs). Leukotrienes are very potent inflammatory mediators that can have negative effects on bone healing and cartilage tissue generation. Recent studies have shown that decreasing 5-lipoxygenase (5-LO) activity during fracture healing accelerates endochondral ossification and decreases healing time in animal fracture models, however, the roles of 5-LO in chondrogenesis is not fully investigated. In this study, we tested the hypothesis that 5-LO inhibition will increase the process of chondrogenesis. The ABT-761 is an N-hydroxyurea analog structurally similar to zileuton, which is a 5-LO enzyme inhibitor, The ATDC5 cell line which is derived …