Cell and Developmental Biology Commons^™

Functional Investigation Of Shaggy, An Inhibitor Of Canonical Wnt Signaling, In The Tardigrade Hypsibius Exemplaris, Raul A. Chavarria

UNF Graduate Theses and Dissertations

Tardigrades have a highly simplified anteroposterior (AP) axis. The mechanisms that regulate the development of this secondarily simplified AP axis are not known. In many animals, the canonical Wnt (cWnt) signaling pathway regulates primary axis establishment through antagonistic interactions with inhibitors of cWnt signaling. This study investigated the roles of shaggy, an inhibitor of cWnt signaling, in regulating development in the tardigrade Hypsibius exemplaris. Gene expression patterns of shaggy and other components of the cWnt signaling pathway were analyzed alongside markers of anterior and posterior identity using Hybridization Chain Reaction in situ in H. exemplaris. RNA interference …

Consequences Of Spatial Structure In Soil–Geomorphic Data On The Results Of Machine Learning Models, Daehyun Kim, Insang Song, Lorrayne Miralha, Daniel R. Hirmas, Ryan W. Mcewan, Tom G. Mueller, Pavel Samonil

Biology Faculty Publications

In this paper, we examined the degree to which inherent spatial structure in soil properties influences the outcomes of machine learning (ML) approaches to predicting soil spatial variability. We compared the performances of four ML algorithms (support vector machine, artificial neural network, random forest, and random forest for spatial data) against two non-ML algorithms (ordinary least squares regression and spatial filtering regression). None of the ML algorithms produced residuals that had lower mean values or were less autocorrelated over space compared with the non-ML approaches. We recommend the use of random forest when a soil variable of interest is weakly …

Regulation Of Mrna And Circrna As A Cause And Consequence Of Aging In Caenorhabditis Elegans, Rebekah Napier-Jameson

Biological Sciences Theses and Dissertations

A role for RNA binding proteins in regulating lifespan has emerged. We identified a pair of neuronal RBPs, exc-7 and mbl-1, which display synthetic lifespan defects. Such a strong synthetic phenotype represented an opportunity to use transcriptomics to search for potential causative targets that are synthetically regulated. We identified a small handful of genes synthetically dysregulated in double mutants and systematically tested each candidate gene for functional contribution to the exc-7; mbl-1 lifespan phenotype. We identified one such gene, the ion transporter nhx-6, which is highly upregulated in double mutants. Overexpression of nhx-6 causes reduced lifespan, and deletion …

Characterization Of Trafficking And Metabolic Functions Of The Endocytic Regulator Ehd1 In Ewing Sarcoma, Sukanya Chakraborty

Theses & Dissertations

Ewing sarcoma (EWS) is the second most common bone malignancy in children and adolescents. Despite improvement in survival due to advances in multimodality treatment strategies, patients with metastatic or recurrent disease have very poor outcomes. Overexpression of the EPS15 Homology Domain containing 1 (EHD1) protein has been linked to tumorigenesis but whether its core function as a regulator of intracellular traffic of cell surface receptors plays a role in oncogenesis remains unknown.

Studies presented in this dissertation establish that EHD1 overexpression is a feature of nearly 90% EWS patient tumors with high EHD1 expression specifying shorter patient survival. ShRNA-knockdown and …

Pathogenicity Of Acinetobacter Calcoaceticus, Kaitlan A. Sullivan

MUSC Theses and Dissertations

Acinetobacter is a genus of gram-negative bacteria that have been appearing frequently in hospitals contributing to infections in the blood, lungs, urinary tract, and other parts of the body. It infects patients with weakened immune systems that are placed on ventilators, after the use of catheters, or have any other open wounds produced by prolonged hospital stays. This genus of bacteria is problematic due to its high probability of becoming resistant to multiple classes of antibiotics. Thus, we are determining the pathogenicity of clinical isolates of Acinetobacter calcoaceticus using the organism Caenorhabditis elegans as a model.

We are testing …

Breaking Virulent: The Coincidental Evolution Of Virulence Factors In Bacteria., Rhiannon Emmanuelle Cecil

Electronic Theses and Dissertations

Understanding how innocuous organisms can evolve to be pathogenic to humans is of increasing global concern. Further, understanding how existing pathogens may evolved to be more virulent is also vital to our ability to provide healthcare to people afflicted with diseases that promote chronic bacterial infections, such as cystic fibrosis. With the rise of antibiotic resistance in both bacteria and fungi it is paramount that new therapeutics are identified. Understanding what mutations occur that result in increased virulence in microbes can potentially provide new targets for antimicrobial drugs to combat antibiotic resistance. The Coincidental Evolution Hypothesis is a fundamental hypothesis …

Repositioning Propranolol To Block Mitogenic Signaling In Breast Cancer, Alexa Noel Montoya

Open Access Theses & Dissertations

Breast cancer is the second most diagnosed cancer among women and is about 30% of all new cases of female cancers each year. It is projected that 1 in 8 every U.S. woman (about 13%) develop invasive breast cancer over the course of her lifetime. While advances in cancer research have made it possible to elucidate several breast cancer genomic subtypes, and develop new novel therapies, many of these agents are associated with significant toxicity, as well as high costs. A retrospective cross-sectional study of 404 breast cancer patients was performed to determine the effect of β-blocker usage on tumor …

Oncolytic Tanapoxvirus Recombinants Expressing Mil-2, Flagellin-C, And Mccl2 Regress Human Cancer Xenografts In Immune Deficient Nude Mice And Immune Cell Reconstituted Balb/C Nude Mice., Michael Leonard Monaco

Dissertations

Tanapoxvirus (TPV) is a double stranded DNA virus from the genus Yatapoxvirus which has been engineered for the purpose of potentially treating a number of human cancers. Previous studies have shown TPV recombinants are capable of inducing tumor inhibition and even regression in athymic nude mice bearing human cancer xenografts of colorectal, melanoma and triple negative breast cancer (TNBC). However, TPV is host-restricted to humans and monkeys, including cancerous cells, which has provided a unique obstacle in its development as an oncolytic virus (OV). Namely, standard syngeneic mouse models cannot be used as test systems to evaluate TPV’s efficacy against …

Induced Pluripotent Stem Cells Derived From Patients Carrying Mitochondrial Mutations Exhibit Altered Bioenergetics And Aberrant Differentiation Potential, Fibi Meshrkey, Kelly M. Scheulin, Christopher M. Littlejohn, Joshua Stabach, Bibhuti Saikia, Vedant Thorat, Yimin Huang, Thomas Laframboise, Edward J. Lesnefsky, Raj R. Rao, Franklin D. West, Shilpa Iyer

Biological Sciences Faculty Publications and Presentations

Background

Human mitochondrial DNA mutations are associated with common to rare mitochondrial disorders, which are multisystemic with complex clinical pathologies. The pathologies of these diseases are poorly understood and have no FDA-approved treatments leading to symptom management. Leigh syndrome (LS) is a pediatric mitochondrial disorder that affects the central nervous system during early development and causes death in infancy. Since there are no adequate models for understanding the rapid fatality associated with LS, human-induced pluripotent stem cell (hiPSC) technology has been recognized as a useful approach to generate patient-specific stem cells for disease modeling and understanding the origins of the …

Effects Of Growth Rate On Peptidoglycan Crosslink Density Of E. Coli Using Fluorescent Labeling, Morgan Olszewski

Harrisburg University Research Symposium: Highlighting Research, Innovation, & Creativity

Peptidoglycan (PG) is a polymer composed of polysaccharides and crosslinked peptide chains found in bacterial cell walls. It helps to protect the cell from environmental stress and maintain cell morphology throughout its life cycle and further generations. The PG is made up of two sugars, N-acetyl muramic acid (NAM) and N-acetyl glucosamine (NAG). NAM and NAG are connected by glycosidic linkages to form repeated chains. The chains are formed in layers, which are interconnected via a polypeptide stem linked by a peptide bridge. During cell growth, continuous turnover of existing PG occurs by severing existing crosslinks, inserting new PG into …

Meiosis In Budding Yeast, G. Valentin Borner, Andreas Hochwagen, Amy J. Macqueen

Biological, Geological, and Environmental Faculty Publications

Meiosis is a specialized cell division program that is essential for sexual reproduction. The two meiotic divisions reduce chromosome number by half, typically generating haploid genomes that are packaged into gametes. To achieve this ploidy reduction, meiosis relies on highly unusual chromosomal processes including the pairing of homologous chromosomes, assembly of the synaptonemal complex, programmed formation of DNA breaks followed by their processing into crossovers, and the segregation of homologous chromosomes during the first meiotic division. These processes are embedded in a carefully orchestrated cell differentiation program with multiple interdependencies between DNA metabolism, chromosome morphogenesis, and waves of gene expression …

Dynamics And Inhibition Of Abc And Rnd Transporters Associated With Multidrug Resistances In Cancer And Pathogenic Bacteria, Hang Zhao

Biological Sciences Theses and Dissertations

The overexpression of efflux transporters is deemed to be one of the important mechanisms that contribute to Multidrug Resistance (MDR). In this dissertation, three transporters of significance were studied, the Breast Cancer Resistance Protein (BCRP/ABCG2) in a variety of cancer cells, the mtrCDE transporter from Neisseria gonorrhoeae, and the acrAB-tolC transporter from Escherichia coli. It is well known that the overexpression of BCRP in cancer cells results in these cells being resistant to the effects of many chemotherapeutics. This results in multidrug resistance for this cancer because of the fact that BCRP can transport many different types of …

College Of Natural Sciences Newsletter, September - October 2023, College Of Natural Sciences

College of Natural Sciences Newsletters and Reports

Page 1 Dean's Message
Page 2 New Faculty an Staff for the Fall 2023 Semester
Page 3 Awards
Page 4 Student Ambassadors in CNS
Page 5 Meet our Jacks
Page 6-8 Events
Page 9-11 Media Coverage of CNS
Page 12-13 Spring 2023 Dean's List
Page 14 Open PRAIRIE Data

Understanding An Inflammatory Pathway In Diabetic Retinopathy, Reanna R. Rodriguez

Research Symposium

Diabetic Retinopathy (DR) is the leading cause of blindness in the U.S. However, not much is known of its molecular pathway and how it attributes to increases in inflammatory response in the eye. One avenue we will investigate is the transforming growth factor beta (TGFB) signaling pathway and its effect of vascular endothelial growth factor (VEGF) secretion and cell viability. VEGF is the hallmark that exacerbates DR progression in prolonged diabetes. Some major concern that have arisen are the underlying effects of oxidants and antioxidants in elevating VEGF secretion in diabetes. In attempt to learn more, we evaluated how an …

Trimeric Complex Interactions Of Antp-Tbp With Tfiieb And Exd Are Involved In The Genetic Control Of Drosophila Melanogaster, Gustavo Jiménez Mejía, Ruben De Jesus Montalvo Mendez, Claudia Dalila Altamirano Torres, Diana Reséndez Pérez

Research Symposium

Background: Homeoproteins are transcriptional factors (TFs) that shape animal body axes during development. These TFs are highly conserved and represent one of the most fascinating groups of regulatory molecules. Reports shown the multiplicity of interactions in hox proteins, as complexes trimeric involved to transcriptional activity. The study of trimeric complexes in Hox interactome will allow the better understanding of Hox genetic regulation during embryonic development.

Methodology: Using a new combination BiFCFRET approach performed in HEK293, the quantification was performed by FRETTY of ImageJ. Fly crosses were incubated at 25ºC on standard yeast-agar-cornmeal medium. Embryo cuticle preparations were carried out according …

International Conference On Cancer Health Disparities, Juhi Rais, Asif Jafri, Neelam Shivnath, Habiba Khan, Md Arshad

Research Symposium

Background: Biochanin A, an isoflavone that is mainly present in red clover, has potent chemopreventive properties against many cancers. Ovarian carcinoma is fifth most common and deadliest gynaecological malignancy that causes the highest mortality in females worldwide. Hence a substantial need for new therapies for combating this gynaecological malignancy arises.

Methods: The present study aimed to investigate anti-cancerous potentials of biochanin A on cultured human ovarian carcinoma PA-1 cells through the cell viability assay, cellular apoptosis, disruption of mitochondrial membrane potential (MMP), involvement of ROS, cell cycle kinetics, and expression of apoptosis-related genes namely, p53, Bax, Bcl-2, Noxa and Puma. …

Trimeric Interaction Of Antp-Ubx With Tbp And Homeoprotein Exd In The Genetic Control Of Development In D. Melanogaster, Alely Cecilia Villarreal-Puente, Claudia Dalila Altamirano-Torres, Diana Resendez-Perez

Research Symposium

Homeoproteins specify body segments along the anteroposterior axis during embryo development; they bind DNA through the homeodomain (HD). Homeoproteins bind to similar and repetitive target sequences on DNA, raising the question of how they achieve functional specificity. Homeoproteins form complexes with proteins through the HDs or other regions. Antennapedia (Antp) and Ultrabithorax (Ubx) have an important role in conferring thorax identity; also they are involved in a repression transcriptional mechanism: Ubx binds to Antp promoter repressing its expression. We analyzed if Ubx and Antp perform protein-protein interaction as a regulation mechanism and if the complex Antp-Ubx are involved in trimeric …

Identification Of Tectorigenin As A Natural Pro-Hypoxia Compound: Implications In Modulation Of Cellular Differentiation And Senescence, Mallika Khurana, Renu Wadhwa, Sunil Kaul

Research Symposium

Background: Hypoxia, a suboptimal level of oxygen, evokes stress response in cells and activated hypoxia signaling has been largely established as a pro-metastasis and pro-angiogenic factor for tumor cells. On the other hand, age-related neurodegenerative disorders are characterized by hypoxic environment, accumulation of molecular garbage and induction of premature senescence. Several recent studies have reported anti-stress impact of the intermittent induction of hypoxia signaling in these cells.

Methods: Screening of a phytochemical library using Hypoxia Responsive Element (HRE) driven luciferase as a reporter was carried out to identify hypoxia-modulating phytochemicals. Activation of HIF-1a (master regulator of hypoxia signaling) was validated …

Identification Of The Functional Domain Of The Dense Core Vesicle Biogenesis Factor Hid-1, Blake H. Hummer, Theodore Carter, Breanna L. Sellers, Jenna D. Triplett, Cedric S. Asensio

Biological Sciences: Faculty Scholarship

Large dense core vesicles (LDCVs) mediate the regulated release of neuropeptides and peptide hormones. HID-1 is a trans-Golgi network (TGN) localized peripheral membrane protein contributing to LDCV formation. There is no information about HID-1 structure or domain architecture, and thus it remains unknown how HID-1 binds to the TGN and performs its function. We report that the N-terminus of HID-1 mediates membrane binding through a myristoyl group with a polybasic amino acid patch but lacks specificity for the TGN. In addition, we show that the C-terminus serves as the functional domain. Indeed, this isolated domain, when tethered to the TGN, …

Transcriptional Pausing Factor M1bp Regulates Cellular Homeostasis By Suppressing Autophagy And Apoptosis In Drosophila Eye, Anuradha Venkatakrishnan Chimata, Hannah Darnell, Akanksha Raj, Madhuri Kango-Singh

Biology Faculty Publications

During organogenesis cellular homeostasis plays a crucial role in patterning and growth. The role of promoter proximal pausing of RNA polymerase II, which regulates transcription of several developmental genes by GAGA factor or Motif 1 Binding Protein (M1BP), has not been fully understood in cellular homeostasis. Earlier, we reported that M1BP, a functional homolog of ZKSCAN3, regulates wingless (wg) and caspase-dependent cell death (apoptosis) in the Drosophila eye. Further, blocking apoptosis does not fully rescue the M1BP^RNAi phenotype of reduced eye. Therefore, we looked for other possible mechanism(s). In a forward genetic screen, members of the Jun-amino-terminal-(NH2)-Kinase (JNK) pathway …

Metabolic Control Of Proliferation And Differentiation In Oligodendrocytes, Sami Sauma

Dissertations, Theses, and Capstone Projects

Oligodendrocytes (OLs) are specialized cells whose membrane extension, called myelin, wraps the axons providing insulation, trophic and metabolic support, and is essential for proper functioning of the central nervous system. Inappropriate myelin formation, damage or dysfunction of oligodendrocytes has been identified in several neurological disorders and often precedes the loss of neuronal cells. OLs derive from proliferating oligodendrocyte progenitor cells (OPCs), which exit from the cell cycle and undergo a series of transcriptional and epigenetic events, including histone post-translational modifications, resulting in morphological and functional changes. Our lab previously identified elevated levels of histone acetylation in proliferating OPCs during the …

The Minimal Suf System Is Not Required For Fe–S Cluster Biogenesis In The Methanogenic Archaeon Methanosarcina Acetivorans, Jasleen Saini, Thomas M. Deere, Daniel J. Lessner

Biological Sciences Faculty Publications and Presentations

Iron–sulfur (Fe–S) proteins are essential for the ability of methanogens to carry out methanogenesis and biological nitrogen fixation (diazotrophy). Nonetheless, the factors involved in Fe–S cluster biogenesis in methanogens remain largely unknown. The minimal SUF Fe–S cluster biogenesis system (i.e., SufBC) is postulated to serve as the primary system in methanogens. Here, the role of SufBC in Methanosarcina acetivorans, which contains two sufCB gene clusters, was investigated. The CRISPRi-dCas9 and CRISPR-Cas9 systems were utilized to repress or delete sufC1B1 and sufC2B2, respectively. Neither the dual repression of sufC1B1 and sufC2B2 nor the deletion of both sufC1B1 and sufC2B2 …

The Co-Oncogenic Function Of Ecdysoneless Protein With Erbb2 In Mammary Epithelial Cells, Benjamin B. Kennedy

Theses & Dissertations

The Ecdysoneless (ECD) protein is highly evolutionarily conserved and ubiquitously expressed across human tissues. ECD has established roles in cell cycle regulation, embryogenesis, cell survival, and RNA biogenesis. ECD mRNA and protein are overexpressed in breast cancer, and its overexpression correlates with poor patient survival, especially in ErbB2/HER2-positive breast cancer. This thesis work investigates the co-oncogenic role of ECD in ErbB2-driven oncogenesis using immortalized mammary epithelial cells. Here, we show that ECD and ErbB2 overexpression in immortalized human mammary epithelial cells increases cancer traits, such as invasion, migration, and anchorage independent growth. Significantly, ECD+ErbB2 co-overexpression further enhanced all oncogenic traits. …

Nanoscale Modeling Of Membrane Systems Under Mechanical Deformation In Traumatic Brain Injury Using Molecular Dynamics, Anh Thi Ngoc Vo

Theses and Dissertations

Neuronal membrane disruption and mechanoporation are nanoscale damage mechanisms that critically affect brain cell viability during traumatic brain injury (TBI). These nanoscale cellular impairments are elusive in experiments and necessitate in silico approaches such as molecular dynamics (MD) simulations. Implementing MD, this research aims to investigate the effects of different key factors related to membrane deformation and damage, including force field resolutions, lipid compositions, and loading conditions.

To examine the impact of force field resolution, MD deformation simulations were conducted on 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine (POPC) lipid bilayer membranes, using all-atom (AA), united-atom (UA), and coarse-grained Martini (CG-M) force fields. The mechanical responses …

Analyzing Pseudomonas Aeruginosa With Bacteriophage Tags Using Photoacoustic Flow Cytometry, Jennifer C. Schinke

Electronic Theses and Dissertations

The number of daily bacterial infections is climbing and the CDC explains that this is due to the antibiotic-resistant threat in the United States. Finding a faster way of bacterial identification is necessary as it currently takes 1-4 days for a medical lab to culture and identify bacteria. Photoacoustic flow cytometry (PAFC) can be used as an alternative method resulting in swift identification within an hour (Edgar, 2019). Pseudomonas aeruginosa, cell line PA01, will be coated in up to a few hundred red dyed phages making it detectible by the photoacoustic flow cytometry system. Bacteriophages (phages) are viruses that …

Polar Body Membrane Breakdown Occurs Independent Of Macroautophagy In C. Elegans, Shruti Kolli

Electronic Theses and Dissertations

Failure to digest cell corpses can lead to lupus-like autoimmune disorders in mammals. To better understand if LC3-associated phagocytosis (LAP) drives cell corpse breakdown in phagolysosomes, we studied the clearance of the C. elegans polar body during embryonic development. ATG16L1 has separable roles in regulating LC3 recruitment during macroautophagy and LAP. We demonstrated that the ATG16L1 C. elegans orthologs, ATG-16.1 and ATG-16.2, function redundantly to promote polar body membrane breakdown. We also discovered that truncating the LAP-specific WD40 domain of ATG-16.2 unexpectedly disrupts autophagy. Furthermore, we confirmed that polar body membrane breakdown occurs independent of macroautophagy. We also showed that …

Functional Analysis Of Two Campoletis Sonorensis Ichnovirus Vinnexins In Drosophila Melanogaster, Peng Zhang

All Dissertations

Campoletis sonorensis Ichnovirus (CsIV) is produced by the ichneumonid parasitoid Campoletis sonorensis (the primary host). Female parasitoid wasps restrictedly replicate viruses in their ovaries and inject them into a larval lepidopteran (secondary host) during oviposition. This symbiotic virus of C. sonorensis is essential for successful parasitization. CsIV is characterized by having a large, segmented double-stranded DNA genome with a large number of genes, many of which are associated with one of five multigene families. The CsIV vinnexin gene family is one of them and has four members, including CsIV-vnxD and CsIV-vnxG. Vinnexins are homologues of insect Innexins, which form gap …

Mob Family Proteins And Tricornered Kinase Are Required To Form Dorsal Appendages Of The Drosophila Eggshell, Keala H. D. Watson

UNLV Theses, Dissertations, Professional Papers, and Capstones

To understand how complex tissues are formed, we need to understand how cells communicate with other cells to build structures. In Drosophila melanogaster, epithelial cells form tubular structures to shape the dorsal appendages on the eggshells. One signaling pathway needed for this event is the Hippo-like kinase intracellular pathway. I focus on two key components in this pathway: the NDR kinase Tricornered (Trc) and Mob proteins. In eukaryotes, Mob proteins are known to interact with NDR kinases to promote their activation. The Hippo- like pathway involves the NDR kinase Trc; however, the specific Mob protein(s) that interact with Trc …

N-Acetyltransferase 9 Ameliorates Aβ42-Mediated Neurodegeneration In The Drosophila Eye, Prajakta Deshpande, Anuradha Venkatakrishnan Chimata, Emily E. Snider, Aditi Singh, Madhuri Kango-Singh, Amit Singh

Biology Faculty Publications

Alzheimer’s disease (AD), a progressive neurodegenerative disorder, manifests as accumulation of amyloid-beta-42 (Aβ42) plaques and intracellular accumulation of neurofibrillary tangles (NFTs) that results in microtubule destabilization. Targeted expression of human Aβ42 (GMR > Aβ42) in developing Drosophila eye retinal neurons results in Aβ42 plaque(s) and mimics AD-like extensive neurodegeneration. However, there remains a gap in our understanding of the underlying mechanism(s) for Aβ42-mediated neurodegeneration. To address this gap in information, we conducted a forward genetic screen, and identified N-acetyltransferase 9 (Mnat9) as a genetic modifier of GMR > Aβ42 neurodegenerative phenotype. Mnat9 is known to stabilize microtubules by inhibiting c-Jun-N- …

Early Stage Or Curable Cancer Diagnoses In Minorities: A Journey Of Survivors, Lora Asberry

Master of Science in Integrative Biology Theses

Patients diagnosed with early-staged or curable forms of cancer experience physical, as well as, mental challenges associated with disease progression and treatment. Previous studies have demonstrated that minorities and underrepresented communities did not receive the same level of care in comparison to their non-minority counterparts. Previous studies have also demonstrated that health disparities among minorities affected their cancer journey. This study addressed: how medical disparities varied between minorities and non-minorities, the overall effects of the cancer diagnoses in minorities compared to non-minorities, whether these perspectives differed in male vs. female participants, and whether there were any possible communication barriers between …