Genetics and Genomics Commons^™

Elucidating The Impact Of Sos-Response Timing In On Escherichia Coli Survival Following Treatment With Fluoroquinolone Topoisomerase Inhibitors, Stephanie Schofield

Honors Scholar Theses

Antibiotic treatment failure is a public health crisis, with a 2019 report stating that roughly 35,000 deaths occur in the United States yearly due to bacterial infections that are unresponsive to antibiotics (1). One complication in the treatment of bacterial infection is antibiotic persistence which further compromises our battle to effectively treat infection. Bacterial persisters can exist in clonal bacterial cultures and can tolerate antibiotic treatment by undergoing reversible phenotypic changes. They can survive drug concentrations that their genetically identical kin cannot. Some persisters remain in a slow growing state and are difficult to target with current antibiotics. A specific …

Creation Of Tatde Rlnps For The Excision Of Integrated Hiv-1 Proviral Dna, Mahmudul Hasan

Theses & Dissertations

The persistence of integrated human immunodeficiency virus type 1 (HIV-1) proviral DNA despite combination antiretroviral therapy (ART) is the principal challenge to eliminating HIV-1 infection. This is made ever more complex based on the high viral mutation rates, diversity and resistance profiles. Taken together, these factors present principal obstacles towards any means to eliminate the virus from its infective human host. To address these factors, we have developed and validated a TatDE rLNP RNA delivery system. The system utilizes Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR) guide RNAs (gRNAs) to target multiple exons of an integrated proviral HIV-1 (tat_{1-2 …}

The Ethics Of Governance Of Data Analytics In Healthcare, Andrew Harrington

Electronic Theses and Dissertations

Recent literature and studies on data governance usually focus on data ethics and governance from a specific country or industry, which has been mostly business, without considering the larger global impact that is affected. Data is a worldwide asset; thus, its implications and considerations should be viewed as such. Hence, this dissertation attempts to incorporate this view by weaving together topics in healthcare, such as the blending of finance and delivery, data governance at the micro and macro levels, data analytics in healthcare, ethics of AI and information management, and technology’s impact on end-of-life practices. Through highlighting these areas of …

Appearance Of Choline Metabolites In Plasma And Milk When Choline Is Infused Into The Abomasum With Or Without Methionine, C. J.R. Jenkins, Paul J. Kononoff

Department of Animal Science: Faculty Publications

Four lactating, ruminally cannulated Jersey cows, (mean ± standard deviation) 264 ± 54.2 d in milk and 484 ± 24.1 kg of body weight, were arranged in a 4 × 4 Latin square design to measure the effects of abomasal infusion of choline chloride with or without dl-Met on milk and plasma choline metabolites and plasma AA in cows fed a Met-deficient diet. Cows were randomly assigned to 1 of 4 experimental treatments: (1) control; no supplemental Met or choline (CON), (2) 13 g/d of choline ion delivered via abomasal infusion (CHO), (3) 13 g/d of Met delivered via abomasal …

Comparative Analysis Of The Effects Of Actual Versus Assumed Opioid Experience On The Regulation Of Ventral Striatal Opioid Receptor Gene Expression, Indu Mithra Madhuranthakam, Martin Job

Rowan-Virtua Research Day

Rationale: We conducted experiments to assess the effect of prior opioid experience on gene expression changes. We compared the current experimenter-imposed short versus extended-access conditions of opioid self-administration and developed a new quantitative method to determine their effectiveness in identifying the role of opioid experience in regulating opioid receptor expression levels in the ventral striatum (VS) using an oxycodone self-administration/abstinence model.

Methods: In this study, male Sprague-Dawley rats (n=36) were trained for 20 days to self-administer oxycodone at 0.1 mg/kg/infusion under short access (n=15, or saline as controls n=3, for 3h/day) or extended access (n=15, or saline as controls n=3, …

Orthologs Of The C. Elegans Heterochronic Genes Have Divergent Functions In C. Briggsae, Maria Ivanova, Eric G. Moss

Rowan-Virtua Research Day

The heterochronic genes of C. elegans comprise the best-studied pathway controlling the timing of tissue and organ formation in an animal. To begin to understand the evolution of this pathway, the significance of each factor, and the relationships among the components, we characterized 11 C. briggsae orthologs of C. elegans heterochronic genes. Using CRISPR/Cas9, we made a variety of alleles and found that several mutant phenotypes differ in significant ways from those of C. elegans. Although most orthologs displayed defects in developmental timing, those phenotypes could differ in which stages they controlled, the penetrance and expressivity of the phenotypes, or …

Bi-Allelic Variants In Ints11 Are Associated With A Complex Neurological Disorder, Burak Tepe, Erica L Macke, Marcello Niceta, Monika Weisz Hubshman, Oguz Kanca, Laura Schultz-Rogers, Yuri A Zarate, G Bradley Schaefer, Jorge Luis Granadillo De Luque, Daniel J Wegner, Benjamin Cogne, Brigitte Gilbert-Dussardier, Xavier Le Guillou, Eric J Wagner, Lynn S Pais, Jennifer E Neil, Ganeshwaran H Mochida, Christopher A Walsh, Nurit Magal, Valerie Drasinover, Mordechai Shohat, Tanya Schwab, Chris Schmitz, Karl Clark, Anthony Fine, Brendan Lanpher, Ralitza Gavrilova, Pierre Blanc, Lydie Burglen, Alexandra Afenjar, Dora Steel, Manju A Kurian, Prab Prabhakar, Sophie Gößwein, Nataliya Di Donato, Enrico S Bertini, Undiagnosed Diseases Network, Michael F Wangler, Shinya Yamamoto, Marco Tartaglia, Eric W Klee, Hugo J Bellen

Faculty, Staff and Students Publications

The Integrator complex is a multi-subunit protein complex that regulates the processing of nascent RNAs transcribed by RNA polymerase II (RNAPII), including small nuclear RNAs, enhancer RNAs, telomeric RNAs, viral RNAs, and protein-coding mRNAs. Integrator subunit 11 (INTS11) is the catalytic subunit that cleaves nascent RNAs, but, to date, mutations in this subunit have not been linked to human disease. Here, we describe 15 individuals from 10 unrelated families with bi-allelic variants in INTS11 who present with global developmental and language delay, intellectual disability, impaired motor development, and brain atrophy. Consistent with human observations, we find that the fly ortholog …

An Overview Of Viruses And The Infamous Sars-Cov-2, Jake Sun

The Confluence

Background information on viruses is first presented which include topics like evolution, ecology, history, identification, structure, and application. The novel SARS-CoV-2, which causes COVID-19, pandemic originated in Wuhan, China in December 2019. Millions of people were infected with the virus in a short time period causing urgent concern worldwide. The purpose of this review is to provide a brief and general understanding of the SARS-CoV-2 to increase awareness and actions toward preventive measures. COVID-19 is a (+) ssRNA spherical enveloped virion that causes primarily respiratory illnesses. The S protein interacts with ACE-2 receptors on the host cell to gain entry …

Single Nucleotide Polymorphisms In Plasmodium Falciparum Genes: Their Roles In Antimalarial Drugs Resistance And Recent Detection Strategies, Raihanny Andrea Zahra, Ananda Maulana Fanshur, Aurelia Maria Prajna Saraswati, Nurul Inayah Rahmani

Indonesian Journal of Medical Chemistry and Bioinformatics

Introduction: Malaria is a serious tropical disease with Plasmodium falciparum as its most well-known causative parasite for producing higher levels of late stage parasites that leads to sequestration in vital organs which could lead to death. There is a growing trend of antimalarial drugs resistance against Plasmodium falciparum. Molecular assessment using polymerase chain reaction could trace the presence of mutation and also determine single-nucleotide polymorphism (SNP) in Plasmodium falciparum genes. This SNP can determine the particular population’s response to antimalarial drugs. Objectives: This study aims to examine the relationship between SNP in Plasmodium falciparum genes and antimalarial drugs resistance. …

Reverse Genetics: Downregulating Chk-1 And Fasn-1 In The Gonads Of C. Elegans, Sam Thompson

Undergraduate Theses

Despite its widespread use in research, the model organism C. elegans has several biological processes like gonadal development with potentially unexplored genetic regulators. Previous transcriptome analysis has identified several genes that are upregulated in a specific tissue or sex during the development of the somatic gonad in C. elegans (Kroetz et al. 2015) that have not been previously connected to this process. Of these genes, this research is concerned with chk-1 and fasn-1. Abrogating the expression of these genes in gonadal tissue during gonadogenesis could cause a change in phenotype for affected C. elegans that would aid in understanding these …

Association Of Mitochondrial Dna Copy Number With Brain Mri Markers And Cognitive Function: A Meta-Analysis Of Community-Based Cohorts, Yuankai Zhang, Xue Liu, Kerri L Wiggins, Nuzulul Kurniansyah, Xiuqing Guo, Amanda L Rodrigue, Wei Zhao, Lisa R Yanek, Scott M Ratliff, Achilleas Pitsillides, Juan Sebastian Aguirre Patiño, Tamar Sofer, Dan E Arking, Thomas R Austin, Alexa S Beiser, John Blangero, Eric Boerwinkle, Jan Bressler, Joanne E Curran, Lifang Hou, Timothy M Hughes, Sharon L R Kardia, Lenore J Launer, Daniel Levy, Thomas H Mosley, Ilya M Nasrallah, Stephen S Rich, Jerome I Rotter, Sudha Seshadri, Wassim Tarraf, Kevin A González, Vasan Ramachandran, Kristine Yaffe, Paul A Nyquist, Bruce M Psaty, Charles S Decarli, Jennifer A Smith, David C Glahn, Hector M González, Joshua C Bis, Myriam Fornage, Susan R Heckbert, Annette L Fitzpatrick, Chunyu Liu, Claudia L Satizabal

Faculty, Staff and Student Publications

BACKGROUND AND OBJECTIVES: Previous studies suggest that lower mitochondrial DNA (mtDNA) copy number (CN) is associated with neurodegenerative diseases. However, whether mtDNA CN in whole blood is related to endophenotypes of Alzheimer disease (AD) and AD-related dementia (AD/ADRD) needs further investigation. We assessed the association of mtDNA CN with cognitive function and MRI measures in community-based samples of middle-aged to older adults.

METHODS: We included dementia-free participants from 9 diverse community-based cohorts with whole-genome sequencing in the Trans-Omics for Precision Medicine (TOPMed) program. Circulating mtDNA CN was estimated as twice the ratio of the average coverage of mtDNA to nuclear …

Very-Long-Chain Fatty Acids Induce Glial-Derived Sphingosine-1-Phosphate Synthesis, Secretion, And Neuroinflammation, Hyung-Lok Chung, Qi Ye, Ye-Jin Park, Zhongyuan Zuo, Jung-Wan Mok, Oguz Kanca, Sudhir Gopal Tattikota, Shenzhao Lu, Nobert Perrimon, Hyun Kyoung Lee, Hugo J Bellen

Faculty, Staff and Students Publications

VLCFAs (very-long-chain fatty acids) are the most abundant fatty acids in myelin. Hence, during demyelination or aging, glia are exposed to higher levels of VLCFA than normal. We report that glia convert these VLCFA into sphingosine-1-phosphate (S1P) via a glial-specific S1P pathway. Excess S1P causes neuroinflammation, NF-κB activation, and macrophage infiltration into the CNS. Suppressing the function of S1P in fly glia or neurons, or administration of Fingolimod, an S1P receptor antagonist, strongly attenuates the phenotypes caused by excess VLCFAs. In contrast, elevating the VLCFA levels in glia and immune cells exacerbates these phenotypes. Elevated VLCFA and S1P are also …

Dynamic Transcriptomic Responses Of Circulating Immune Cells In Response To Subsequent Days Of Exercise Heat Stress, Soohyun Oh

University Scholar Projects

Acute exercise and chronic training have diverse effects on immune function that are still not well understood. There are remaining questions about how an acute bout of exercise, competition, or repeated training over a period affects an individual’s immune defense system. In a related study, there is evidence that acute exercise may serve as an adjuvant to enhance response to immune function as well as contradicting evidence, including our preliminary data (unpublished). Understanding the fundamental function and gene expression of circulating immune cells in response to acute exercise and in various contexts such as heat stress is critical in understanding …

The Role Of Fto, A Human Rna Demethylase In Perennial Grass Development And Abiotic Stress Responses, Andrew Fiorentino, Qian Hu, Xiaotong Chen, Zhaohui Chen

Honors College Theses

The integration of the human fat mass and obesity associated (FTO) gene into turfgrass is a novel approach at improving cell proliferation and abiotic stress resistance. The FTO protein is an RNA demethylase responsible for epigenetic regulation of the genome. In related rice, the gene is associated with increased crop yield, tiller number, and aerial biomass. It is proposed to work via demethylation of repeat RNA associated with chromatin remodeling, causing widespread transcriptional activation. In this study, the feasibility of using FTO for plant trait modification in perennial grasses is being investigated. Potentially transformed embryogenic calli of creeping bentgrass with …

Assesment Of Structure, Function, And Microevolutionary Dynamics Of Extrachromosomal Circular Dna In Chinese Hamster Ovary Cells, Dylan Chitwood

All Dissertations

Chinese hamster ovary (CHO) cell lines are among the most popular expression hosts used in biopharmaceutical manufacturing due to relative ease of culture, capacity to perform human-like post-translational modifications, and non-susceptibility to viruses. However, the intrinsic plasticity of the CHO genome can lead to undesired genetic rearrangements, phenotypic shifts, reduced product quality, and early culture termination that prevents continuous biomanufacturing. A characteristic of plastic and unstable genomes that is poorly understood in CHO cells is extrachromosomal circular DNA (eccDNA). EccDNAs are focal amplifications of the genome that reside in the extranuclear space. These plasmid-like entities are structurally complex and are …

Genetic Investigation Of Spontaneous Harlequin Coat Patterning In A Family Of Finnish Collies, Megan Patterson

Honors College Theses

The merle coat pattern is a pigmentary phenotype of dogs characterized by a dilute background with black patches. Merle is caused by a SINE insertion in PMEL17, a pigmentation gene expressed in melanocytes. The mutation causes aberrant splicing of transcripts and production of an abnormal protein. Harlequin is a dominant modifier of merle that further dilutes the background to white. Harlequin Great Danes have a heterozygous mutation impairing the ubiquitin-proteasome system, suggesting that the inability to degrade aberrant PMEL17 results in melanocyte death. Harlequin is not a recognized coat pattern of the Collie; however, a harlequin phenotype spontaneously appeared in …

Identification Of Sva-Mediated 3’ And 5’ Transductions In Human Genome Sequences, Emily C. Golba

Honors College Theses

Transposable elements (TEs) are sequences of DNA that can move, or transpose, within a genome. Retrotransposons are TEs that propagate via a “copy and paste” mechanism where the elements are transposed to a new genomic location via an RNA intermediate. Short interspersed element (SINE)-VNTR-Alu elements (SVAs) are non-autonomous retrotransposons that use long interspersed element 1 proteins to mobilize. SVAs are currently active in the human genome and often are characterized by the mobilization of sequences adjacent to the 3’ and 5’ ends of insertions, known as transduction events (TDs). TDs were a focus of this study due to their contribution …

Clustering And Analysis Of G Quadruplex Sequences., Aryan Neupane

Electronic Theses and Dissertations

G quadruplex structures are secondary structures located throughout the genome of various organisms with involvement in regulatory functions in different transcription, translation, genome stability, epigenetic regulation as well as cell division. Even with the diverse acknowledgement of G4 structure in vivo, there are no current search tools for G quadruplexes based on already identified G quadruplexes and identified families across different genomes based on sequence diversity. Construction of families of G4 sequences and identifying their polymorphisms within disease and disorders will lead to a better understanding of their functional roles and will further research into the biophysical modeling of interactions …

Mapping The Sos204 ( Suppressor Of Sunn-1 204) Gene In Medicago Truncatula, Rakshya Shah

All Theses

Nodules in legumes allow the plant to form a symbiotic interaction with bacteria, providing access to the inert N₂ in the atmosphere. The Autoregulation of Nodulation Pathway (AON), a negative regulatory feedback mechanism, is a long-distance signaling system which controls the nodule numbers formed on roots, helping the plant conserve energy by not hosting bacterial symbionts beyond those needed by the plant. A forward genetic screen of the EMS mutagenized supernodulating sunn-1 mutant, a weak allele of SUNN in Medicago truncatula, identified 6 lines of heritable suppressor mutants that reduced the nodulating phenotype from supernodulating to wild-type. We used …

Review Of Biomedical Applications Of Cardiovascular Tissue Engineering, Natalie M. Howard

Honors College Theses

Tissue engineering can be defined as processes that aim to generate three-dimensional functional tissues in vitrothat have been favorably altered according to the structural, biochemical, electrophysiological, and biomechanical properties of the desired tissue before implantation into the human body. In relation to cardiac tissues, these properties would include the ability to conduct action potentials, withstand systolic pressure, permit sufficient O₂ and CO₂penetration, sufficient vascularization to supply nutrients for cellular activity, surface topology that enables cellular communication, and more. As heart diseases and instances of myocardial infarction continue to rise worldwide, there is an increasing need for …

Development Of Three Novel Edna Assays For Detecting Coastal Sharks, Kristina Dawn Flanigan

Electronic Theses and Dissertations

Environmental DNA (eDNA) analysis is an emerging, non-invasive community monitoring tool. This study aimed to determine if eDNA methods can be reliably used in a large brackish, partially mixed estuary by developing and testing three novel eDNA primers, for Sandbar Sharks (Carcharhinus plumbeus), Blacknose Sharks (Carcharhinus acronotus), and Bonnetheads (Sphyrna tiburo). These primers were designed to target 109, 156, and 120 base pair (bp) fragments, respectively, of the highly conserved NAD2 gene in the mitochondrial genome of each species. Primer function was validated through testing against 102 known genomic source samples and 25 filtered water samples from aquaria in which …

Transcriptional Regulation Of Stem Cell Function In The Drosophila Central Nervous System, Amalia S. Parra

Biology ETDs

Development of multicellular organisms depends on coordination of various molecular mechanisms to ensure proper tissue size and structure. This is accomplished through intrinsic and extrinsic cues that regulate cell growth and proliferation both spatially and temporally. These well-coordinated signals are present from early developmental stages and remain active throughout development to ensure tissue structure is appropriate for function. This is particularly important in early cell types that form specialized lineages such as stem cells or those found throughout the body such as epithelia. While much progress has been made in understanding growth regulatory mechanisms, several fundamental aspects remain unknown. This …

Genetic Investigation Of Spontaneous Harlequin Coat Patterning In A Family Of Australian Shepherds, Katherine Grace Singleton

Honors College Theses

In dogs, a white base coat with black patches is termed harlequin patterning. In the Great Dane, harlequin is caused by a mutation in the ubiquitin-proteasome system, a highly complex process through which damaged proteins are degraded1. All harlequins are also heterozygous for the Merle allele of SILV, which harbors a retrotransposon that leads to production of abnormal protein2. In melanocytes with impaired protein degradation, aberrant SILV is thought to cause cell death, resulting in the characteristic white base coat of a harlequin dog1. We identified a novel, spontaneous form of harlequin patterning in a family of Australian shepherds. To …

Investigating The Role Of Cnag_05113 In The Carnitine Biosynthesis Pathway In Cryptococcus Neoformans., Jasmine Meltzer, Rodrigo Catalan-Hurtado, Perry Kezh, Kerry Smith

Honors College Theses

Cryptococcus neoformans, the leading cause of fungal meningitis, is a fungal pathogen that causes severe infection of the central nervous system in patients with compromised immune systems, typically caused by HIV/AIDS. C. neoformans infections are present in developed countries including the United States, but most fatalities occur in sub-Saharan Africa where antiretroviral therapy, the treatment for HIV/AIDS, is less accessible. Current treatments for severe cryptococcal infections are extensive and outdated. There is a critical need for an improved understanding of the fungus and new targeted therapies. Our goal is to identify metabolic pathways important to the survival of C. …

Genetic Implications Of Language Acquisition, Marissa Renee Ciccarini

Honors Scholar Theses

The argument about whether language acquisition is "nature" or "nurture" has been long debated. Linguists have concluded that it requires the two, but how much does language acquisition rely on nature? Children show the capacity to learn languages quickly and without much effort. While research suggests that infants absorb many visual and verbal cues in their environment, biological structures are the underlying component of how this knowledge is gathered and organized. The genetics that code for specific neurophysiological pathways affect how people interact with their environment and where information is stored, forming the basis for these biological structures. Genetic research …

Combination Therapy With Trastuzumab And Niraparib: Quantifying Early Proliferative Alterations In Her2+ Breast Cancer Models, Ameer Mansur, Patrick N. Song, Yun Lu, Andrew C. Burns, Luke Sligh, Eddy S. Yang, Anna G. Sorace

Markey Cancer Center Faculty Publications

HER2–targeted treatments have improved survival rates in HER2+ breast cancer patients, yet poor responsiveness remains a major clinical obstacle. Recently, HER2+ breast cancer cells, both resistant and responsive to HER2–targeted therapies, have demonstrated sensitivity to poly–(ADP– ribose) polymerase (PARP) inhibition, independent of DNA repair deficiencies. This study seeks to describe biological factors that precede cell viability changes in response to the combination of trastuzumab and PARP inhibition. Treatment response was evaluated in HER2+ and HER2– breast cancer cells. Further, we evaluated the utility of 3′–Deoxy–3′–[18F]–fluorothymidine positron emission tomography ([18F]FLT–PET) imaging for early response assessment in a HER2+ patient derived xenograft …

A Dna-Peptide Crosslink (Dpc) Increases Mutagenicity In Sos-Induced Escherichia Coli, Alessandra Bassani

Honors Scholar Theses

Bacteria, such as Escherichia coli, have an inducible system in response to DNA damage termed the SOS response. This system is activated when the replicative DNA polymerase (Pol) III encounters a lesion, uncouples from DNA helicase, and single-stranded DNA (ssDNA) accumulates at the replication fork. In this study, we investigated DNA-peptide crosslink (DpC), a common lesion that results from cross-linking of proteins or peptides, UV irradiation, and alkylating agents. To increase survival following formation of a lesion, the SOS response can utilize homologous recombination, translesion synthesis (TLS), or excision repair. With TLS, the levels of DNA Pol II, IV, …

Gene Expression Changes Linked To Phenylpropanoid-Based Resistance To Fusarium Head Blight Of Wheat, Shiv Singla

Department of Plant Pathology: Dissertations, Theses, and Student Research

Fusarium graminearum is a devastating pathogen of wheat that causes Fusarium head blight (FHB) and contaminates the grain with the mycotoxin deoxynivalenol (DON). Resistance to FHB is quantitative and it is important to identify additional genes conferring resistance against it. The goal of this thesis was to examine if the constitutive expression of two sorghum phenylpropanoid pathway genes, SbCCoAOMT (encoding caffeoyl-CoA O-methyltransferase) and SbC3’H (encoding p-coumarate 3-hydroxylase), in the moderately-susceptible spring wheat CB037 can provide Type-I and Type-II resistance to F. graminearum and determine the underlying mechanisms of the enhanced resistance. The constitutive expression lines (CCoAOMT413, CCoAOMT421, C3H112, …

A Review Of How Bioinformatics And Genome Sequencing Are Affecting Precision Medicine, Taylor S. Hickey

Honors Program: Senior Projects (Public)

Advancement in genomic sequencing and bioinformatics methods have been affecting biomedical research through precision medicine, especially in the area of cancer. Vaccine therapies can be developed using neoantigens that target specific mutations in tumors. The goals of this research are to identify mutations that lead to cancer and then define subpopulations in which patients can easily be identified. The future goal is to have targeted vaccines that are specific to each subpopulation ready to be used in treatment of their cancer. Limitations to reaching these goals have been due to tumor heterogeneity, cancer location, and difficulty in creating neoantigens for …

Validating A New In Vivo Model To Study Als, Izabela J. Cimachowska

Student Theses and Dissertations

Buildup of oxidative stress and mitochondrial dysfunction are well known characteristics of both sporadic and hereditary amyotrophic lateral sclerosis (ALS). While both forms of the disease seem to arise from common cellular dysfunction, the genetic disease is studied to a much greater extent. Engineering novel animal models of the sporadic form of the disease is crucial for development of druggable targets to treat ALS and understand the underlying mechanisms. Interestingly, accumulation of oxidative stress by exacerbated emission of reactive oxygen species (ROS) from presynaptic mitochondria is a hallmark of both hereditary and sporadic ALS. Previous work by our laboratory showed …