Genetics and Genomics Commons^™

Caenorhabditis Elegans Rapgef Promotes Synaptic Development Through A Small G Protein Signaling Cascade, Reagan Em Lamb

Theses and Dissertations--Neuroscience

Synaptic dysfunction is a major contributor toward the development of many neurological disorders. For proper development, synapses require a series of signaling pathways to guide them, but not all the mechanisms underlying these processes are understood. Here, we used the neuromuscular junction of Caenorhabditis elegans as a model circuitry for examining underlying pathways that mediate proper development of synapses. We hypothesized that the C. elegans RapGEF2 and RapGEF6 orthologue, PXF-1, contributed toward development of cholinergic synapses at the neuromuscular junction. Using behavioral assays and fluorescence microscopy, we found that pxf-1 mutant animals had decreased neuromuscular junction function and decreased synaptic …

Determining Population Structure In Kentucky Parascaris Univalens Specimens, Constance Finnerty

Theses and Dissertations--Veterinary Science

Parascaris univalens is a highly pathogenic nematode that affects the gastrointestinal system of young horses. When unaddressed, this parasite causes severe intestinal impactions and even death. Parascaris univalens is also found to have an emergence of anthelmintic resistances, causing a concern for horse owners. Despite its clinical significance, very little work has been done on Parascaris univalens to identify its population structure. This study aimed to determine the population structure of Parascaris univalens through Illumina next generation sequencing (NGS) on three hierarchical categorizations: within a horse, within an isolated herd, and within horses in the state of Kentucky. A total …

Genomic Studies Of The Equine Bloodworm, Strongylus Vulgaris, Nichol Ripley

Theses and Dissertations--Veterinary Science

Strongylus vulgaris is the most pathogenic nematode parasite of grazing horses worldwide. This gastrointestinal parasitic nematode is in the family Strongylidae under the subfamily Strongylinae, or Strongylins. While the epidemiology, complete life cycle, and high pathogenicity of the fourth and fifth larval stages of S. vulgaris are well established, we understand very little about its biology. This parasite is renowned for its unique life cycle and capacity to cause arterial damage, leading to significant health and economic impacts for the equine industry. It also is the most intensively documented Strongylin; however, S. vulgaris has yet to gain drug resistance as …

Quantitative Trait Loci Influencing Elemental Content In Grapevine Leaves, Jesse L. Krokower

Graduate Theses/Dissertations

In grapevine, the influence of the plant’s elemental composition (the ionome) on fruit and wine quality is well established, but its genetic underpinnings have received limited scientific attention. In this study, I analyzed the leaf ionome of 131 interspecific F1 hybrid progeny plants from a cross between a Vitis rupestris Scheele (♀) and a Vitis riparia Michx (♂) parents, which were replicated in four different environments: Southwest Missouri, Central Missouri, South Dakota, and New York. I sampled leaves at three different times during the growing season at all four locations and had the concentration of 20 elements measured using ICP-MS. …

Chemical Synthesis Of Sensitive Dna, Komal Chillar

Dissertations, Master's Theses and Master's Reports

Over the past decades, researchers have tried various chemical methods to synthesize modified oligodeoxynucleotides (ODNs, i.e. short segments of DNAs). Traditional ODN synthesis methods require strong basic, and nucleophilic conditions for the deprotection and cleavage of the ODN from the solid support. However, the sensitive ODNs containing labile functionalities are vulnerable to such harsh conditions. Sensitive ODNs have a wide range of applications in research and pharmaceuticals. To synthesize sensitive ODNs, researchers devised different strategies but no practical methods have been developed. To overcome these challenges, we developed alkyl Dim alkyl Dmoc technology. This innovative technology uses weakly basic and …

Exploring 3d Genome Interaction And Epigenetic Regulation Via Swi/Snf Complex And Deep Learning Models, Ruoyun Wang

Dartmouth College Ph.D Dissertations

The three-dimensional organization of the genome is fundamental in regulating gene expression and maintaining cellular function. This organization's complexities, influenced by epigenetic marks and chromatin remodeling complexes, are crucial for understanding genomic regulation. Among these, the SWI/SNF complexes are key, facilitating chromatin accessibility and regulating gene activity across cell types. The first part of my dissertation focuses on SWI/SNF complexes, exploring their role in chromatin remodeling and their impact on 3D genome architecture. Utilizing next-generation sequencing (NGS) techniques, this section investigates the interplay between these complexes and chromatin structure. During my research on the SWI/SNF complex, I was intrigued by …

Contribution Of The Transcription Factor Red Nac To Low Nitrogen Phenotypes In Poplar, Shane Alexander Spence

Dissertations, Master's Theses and Master's Reports

Greenhouse grafting and field trials were conducted to examine the contribution of the RED NAC transcription factor on low nitrogen phenotypes in hybrid poplar (P. tremula x P. alba). Reciprocal grafting trials showed both root and shoot expression contribute to phenotype under low nitrogen conditions, and shoot expression has a leading role in contribution to low-nitrogen phenotype. The impact of RED NAC expression level on auxin polar transport was investigated using a DR5::GUS auxin-responsive reporter gene line as rootstock for RED NAC modified scions. Pilot studies indicate the rate of auxin transport from apex to roots is slower through shoots …

A Multimolecular Perspective On The Success Of Wolf Recovery And Relocation, Samuel D. Hervey

Dissertations, Master's Theses and Master's Reports

With global biodiversity in decline and many species isolated in fragmented habitats, conservation efforts increasingly rely on natural recolonization and translocation to restore ecosystems. These strategies face challenges such as genetic erosion and habitat limitations, highlighting the need for effective monitoring practices. This research assesses the success of wolf recovery initiatives by examining long-term genetic and genomic health using both traditional and advanced molecular methods. First, we investigated the genetic health of 19 gray wolves (Canis lupus) relocated to Isle Royale National Park to restore ecosystem balance. Initial genetic assessments with microsatellites found that these wolves had genetic diversity metrics …

Inflammation And Tumor Progression: The Differential Impact Of Saa In Breast Cancer Models, Daniel Wilhelm Olivier, Carla Eksteen, Manisha Du Plessis, Louis De Jager, Lize Engelbrecht, Nathaniel Wade Mcgregor, Preetha Shridas, Frederick C. De Beer, Willem J. S. De Villiers, Etheresia Pretorius, Anna-Mart Engelbrecht

Saha Cardiovascular Research Center Faculty Publications

Background: Previous research has shown that the Serum Amyloid A (SAA) protein family is intricately involved in inflammatory signaling and various disease pathologies. We have previously demonstrated that SAA is associated with increased colitis disease severity and the promotion of tumorigenesis. However, the specific role of SAA proteins in breast cancer pathology remains unclear. Therefore, we investigated the role of systemic SAA1 and SAA2 (SAA1/2) in a triple-negative breast cancer mouse model.

Methods: Syngeneic breast tumors were established in wild-type mice, and mice lacking the SAA1/2 (SAADKO). Subsequently, tumor volume was monitored, species survival determined, the inflammatory profiles of mice …

Identification And Characterization Of Two Novel Kcnh2 Mutations Contributing To Long Qt Syndrome, Anthony Owusu-Mensah, Jacqueline Treat, Joyce Bernardi, Ryan Pfeiffer, Robert Goodrow, Bright Tsevi, Victoria Lam, Michel Audette, Jonathan M. Cordeiro, Makarand Deo

Electrical & Computer Engineering Faculty Publications

We identified two different inherited mutations in KCNH2 gene, or human ether-a-go-go related gene (hERG), which are linked to Long QT Syndrome. The first mutation was in a 1-day-old infant, whereas the second was in a 14-year-old girl. The two KCNH2 mutations were transiently transfected into either human embryonic kidney (HEK) cells or human induced pluripotent stem-cell derived cardiomyocytes. We performed associated multiscale computer simulations to elucidate the arrhythmogenic potentials of the KCNH2 mutations. Genetic screening of the first and second index patients revealed a heterozygous missense mutation in KCNH2, resulting in an amino acid change (P632L) in the …

Cyp6g2 Is The Major P450 Epoxidase Responsible For Juvenile Hormone Biosynthesis In Drosophila Melanogaster, Qiangqiang Jia, Liu Yang, Jiamin Wen, Suning Liu, Di Wen, Wei Luo, Weihua Wang, Subba R. Palli, Li Sheng

Entomology Faculty Publications

Background Juvenile hormones (JH) play crucial role in regulating development and reproduction in insects. The most common form of JH is JH III, derived from MF through epoxidation by CYP15 enzymes. However, in the higher dipterans, such as the fruitfly, Drosophila melanogaster, a bis-epoxide form of JHB3, accounted most of the JH detected. Moreover, these higher dipterans have lost the CYP15 gene from their genomes. As a result, the identity of the P450 epoxidase in the JH biosynthesis pathway in higher dipterans remains unknown.

Results In this study, we show that Cyp6g2 serves as the major JH epoxidase responsible for …

Go West: Population Genomics Reveals Unexpected Population Fluctuations And Little Gene Flow In Western Hemisphere Populations Of The Predatory Lady Beetle, Hippodamia Convergens, Arun Sethuraman, Schyler O. Nunziata, Angela Jones, John J. Obrycki, David W. Weisrock

Entomology Faculty Publications

Hippodamia convergens—the convergent lady beetle, has been used extensively in aug- mentative biological control of aphids, thrips, and whiteflies across its native range in North America, and was introduced into South America in the 1950s. Overwintering H. convergens populations from its native western range in the United States are com- mercially collected and released across its current range in the eastern USA, with little knowledge of the effectiveness of its augmentative biological control. Here we use a novel ddRADseq-based SNP/haplotype discovery approach to estimate its range- wide population diversity, differentiation, and recent evolutionary history. Our results indicate (1) significant population …

N(Alpha)-Acetyltransferase 40-Mediated Histone Acetylation Plays An Important Role In Ecdysone Regulation Of Metamorphosis In The Red Flour Beetle, Tribolium Castaneum, Sharath Chandra Gaddelapati, Smitha George, Anilkumar Moola, Karthi Sengodan, Subba Reddy Palli

Entomology Faculty Publications

Histone acetylation, a crucial epigenetic modification, is governed by histone acetyltransferases (HATs), that regulate many biological processes. Functions of HATs in insects are not well understood. We identified 27 HATs and determined their functions using RNA interference (RNAi) in the model insect, Tribolium castaneum. Among HATs studied, N-alpha-acetyltransferase 40 (NAA40) knockdown caused a severe phenotype of arrested larval development. The steroid hormone, ecdysone induced NAA40 expression through its receptor, EcR (ecdysone receptor). Interestingly, ecdysone-induced NAA40 regulates EcR expression. NAA40 acetylates histone H4 protein, associated with the promoters of ecdysone response genes: EcR, E74, E75, and HR3, and causes an increase …

The Mechanoreceptor Piezo Is Required For Spermatogenesis In Bombyx Mori, Zhongjie Zhang, Xiaojing Liu, Bo Hu, Kai Chen, Ye Yu, Chenxin Sun, Dalin Zhu, Hua Bai, Subba Reddy Palli, Anjiang Tan

Entomology Faculty Publications

Background The animal sperm shows high diversity in morphology, components, and motility. In the lepidopteran model insect, the silkworm Bombyx mori, two types of sperm, including nucleate fertile eupyrene sperm and anucleate unfertile apyrene sperm, are generated. Apyrene sperm assists fertilization by facilitating the migration of eupyrene spermatozoa from the bursa copulatrix to the spermatheca. During spermatogenesis, eupyrene sperm bundles extrude the cytoplasm by peristaltic squeezing, while the nuclei of the apyrene sperm bundles are discarded with the same process, forming matured sperm.

Results In this study, we describe that a mechanoreceptor BmPiezo, the sole Piezo ortholog in B. mori, …

Structural And Functional Consequences Of Pde6 Prenylation In Rod And Cone Photoreceptors, Faezeh Moakedi

Graduate Theses, Dissertations, and Problem Reports (ETD)

Phosphodiesterase-6 (PDE6) serves as a pivotal component in the phototransduction pathways of both cone and rod photoreceptors. In cones, PDE6 consists of tetrameric subunits: inhibitory (γ') and catalytic (α'). The catalytic subunit, PDE6α', contains a C-terminal prenylation motif. Deletion of this motif is associated with achromatopsia (ACHM), a form of color blindness. The mechanisms underlying the disease and the roles of PDE6 lipidation in vision remain elusive. Meanwhile, rod PDE6 is composed of α and β catalytic subunits and γ inhibitory subunits, with alterations in the C-terminal "prenylation motif" of PDE6β linked to retinitis pigmentosa (RP) pathology. In this comprehensive …

Contemporary Vs. Traditional Dna-Based Mutation Testing To Detect Hereditary Breast And Ovarian Cancer Syndrome (Hboc) In Women: A Meta Narrative Review, Hannah Olivia Cantu, Jacob Hipp, Nyela Y. Lopez, Duc Duy Nguyen

Research Methods Poster Session 2024

No abstract provided.

The Genetic Diversity Of An Endangered Buttercup, Ranunculus Triternatus, Ryan Garcia

All Master's Theses

Ranunculus triternatus, a rare endemic species of the Columbia River Gorge, faces conservation challenges due to its limited range and fragmented populations. This study assesses the genetic diversity of R. triternatus and compares it with its widespread congener, Ranunculus glaberrimus, using inter-primer binding site (iPBS) markers. Genetic data from 80 individuals across eight populations were analyzed using Nei’s genetic diversity, Shannon’s diversity index, and AMOVA. Results showed R. triternatus had higher genetic diversity than western populations of R. glaberrimus, with eastern populations of R. glaberrimus displaying greater diversity than western ones. PCA, UPGMA, and STRUCTURE analysis revealed …

Genetic Diversity Of Paxistima Canbyi A. Gray: Conserving A Rare Plant Species Endemic To The Eastern United States, Isaac Buabeng

Master’s Theses

Premise: The glacial cycles of the Pleistocene period likely had a profound impact on the genetic diversity and phylogeographic patterns of numerous plant taxa in North America. However, the genetic diversity of rare, limestone-endemic woody species has not been highlighted. This study assesses genetic diversity in Paxistima canbyi A. Gray (Canby’s mountain lover or rat stripper), a rare limestone endemic small woody plant.

Methods: We investigated the genetic diversity of P. canbyi using genomic Single Nucleotide Polymorphism (SNP) data from 165 individuals from 14 populations sampled from across the entire range distribution. We first; de novo assembled the SNP …

Robust Phylogenetic Regression, Richard Adams, Zoe Cain, Raquel Assis, Michael Degiorgio

Entomology and Plant Pathology Faculty Publications and Presentations

Modern comparative biology owes much to phylogenetic regression. At its conception, this technique sparked a revolution that armed biologists with phylogenetic comparative methods (PCMs) for disentangling evolutionary correlations from those arising from hierarchical phylogenetic relationships. Over the past few decades, the phylogenetic regression framework has become a paradigm of modern comparative biology that has been widely embraced as a remedy for shared ancestry. However, recent evidence has shown doubt over the efficacy of phylogenetic regression, and PCMs more generally, with the suggestion that many of these methods fail to provide an adequate defense against unreplicated evolution—the primary justification for using …

Harnessing Microrna-Enriched Extracellular Vesicles For Liquid Biopsy, Song Yi Ko, Wonjae Lee, Honami Naora

Faculty, Staff and Student Publications

Extracellular microRNAs (miRNAs) can be detected in body fluids and hold great potential as cancer biomarkers. Extracellular miRNAs are protected from degradation by binding various proteins and through their packaging into extracellular vesicles (EVs). There is evidence that the diagnostic performance of cancer-associated extracellular miRNAs can be improved by assaying EV-miRNA instead of total cell-free miRNA, but several challenges have hampered the advancement of EV-miRNA in liquid biopsy. Because almost all types of cells release EVs, cancer cell-derived EVs might constitute only a minor fraction of EVs in body fluids of cancer patients with low volume disease. Furthermore, a given …

The Genetic Basis Of Two Reproductive Traits In Monkeyflowers: Stigma Closure And Corolla Carotenoids, Rachel Anne Halperin

Undergraduate Theses, Professional Papers, and Capstone Artifacts

Abstract

The interactions between pollinators and flowers have long been a driving force for the evolution of many physical floral traits. Traits such as flower shape, size, color, and smell are just some of these traits that evolve because of these interactions. This evolution does not only occur in the more obvious morphological floral traits, however, but also in more subtle traits like touch sensitive stigma closure. In hundreds of Lamiales species, the bilobed stigma, the organ that receives pollen from pollinators, closes rapidly upon touch. Theory and experiments show that this novel dynamic reproductive trait increases pollen export and …

Re-Programming Transcription Factor Function For Neuroscience Research Of Addiction: Investigating The Role Of Zinc Finger Proteins In Driving Cocaine Reinforcement In Mice, Joseph A. Picone

Theses and Dissertations

Administration of addictive drugs like cocaine or morphine initiates aberrant gene transcription within brain reward circuitry neurons, which contributes to the lasting behavioral maladaptations that define addiction. The drug-induced expression and function of key brain transcription factors (TFs) is one major mechanism through which these drugs are able to regulate transcription, and as a consequence, lasting damaging drug-related behaviors including compulsive drug use. The goal of this dissertation is to more fully understand the molecular mechanistic drug-specific actions of TFs within the rodent nucleus accumbens (NAc). The findings from these studies could serve as the basis to identify novel candidate …

Strategies For Improving The Performance Of Prediction Models For Response To Immune Checkpoint Blockade Therapy In Cancer, Tiantian Zeng, Jason Z. Zhang, Arnold Stromberg, Jin Chen, Chi Wang

Markey Cancer Center Faculty Publications

Immune checkpoint blockade (ICB) therapy holds promise for bringing long-lasting clinical gains for the treatment of cancer. However, studies show that only a fraction of patients respond to the treatment. In this regard, it is valu- able to develop gene expression signatures based on RNA sequencing (RNAseq) data and machine learning meth- ods to predict a patient’s response to the ICB therapy, which contributes to more personalized treatment strategy and better management of cancer patients. However, due to the limited sample size of ICB trials with RNAseq data available and the vast number of candidate gene expression features, it is …

Vaginal Lactobacillus Fatty Acid Response Mechanisms Reveal A Metabolite-Targeted Strategy For Bacterial Vaginosis Treatment, Paul C. Blainey, Seth M. Bloom, Douglas S. Kwon

Markey Cancer Center Faculty Publications

Bacterial vaginosis (BV), a common syndrome characterized by Lactobacillus-deficient vaginal microbiota, is associated with adverse health outcomes. BV often recurs after standard antibiotic therapy in part because antibiotics promote microbiota dominance by Lactobacillus iners instead of Lactobacillus crispatus, which has more beneficial health associations. Strategies to promote L. crispatus and inhibit L. iners are thus needed. We show that oleic acid (OA) and similar long-chain fatty acids simultaneously inhibit L. iners and enhance L. crispatus growth. These phenotypes require OA-inducible genes conserved in L. crispatus and related lactobacilli, including an oleate hydratase (ohyA) and putative fatty acid efflux pump (farE). …

Therapeutic Potential Of Berberine In Attenuating Cholestatic Liver Injury: Insights From A Psc Mouse Model, Yanyan Wang, Derrick Zhao, Lianyong Su, Yun-Ling Tai, Grayson W. Way, Jing Zeng, Qianhua Yan, Ying Xu, Xuan Wang, Emily C. Gurley, Xi-Qiao Zhou, Jinze Liu, Jinpeng Liu, Weidong Chen, Philip B. Hylemon, Huiping Zhou

Markey Cancer Center Faculty Publications

Background and aims

Primary sclerosing cholangitis (PSC) is a chronic liver disease characterized by progressive biliary inflammation and bile duct injury. Berberine (BBR) is a bioactive isoquinoline alkaloid found in various herbs and has multiple beneficial effects on metabolic and inflammatory diseases, including liver diseases. This study aimed to examine the therapeutic effect of BBR on cholestatic liver injury in a PSC mouse model (Mdr2 −/− mice) and eluci‑ date the underlying mechanisms.

Methods

Mdr2−/− mice (12–14 weeks old, both sexes) received either BBR (50 mg/kg) or control solution daily for eight weeks via oral gavage. Histological and serum biochemical …

Mechanisms Of Γδ T Cell Accumulation In Visceral Adipose Tissue With Aging, Sujata Mukherjee, Maria E. C. Bruno, Jason Oakes, Gregory S. Hawk, Arnold Stromberg, Donald A. Cohen, Marlene E. Starr

Markey Cancer Center Faculty Publications

γδ T cells are resident in visceral adipose tissue (VAT) where they show an age- associated increase in numbers and contribute to local and systemic chronic inflammation. However, regulation of this population and mechanisms for the age-dependent accumulation are not known. In this study, we identified a progressive trend of γδ T cell accumulation in VAT over the lifespan in mice and explored physiological mechanisms contributing to accumulation. Using isochronic parabiotic pairs of wild-type (WT) and T cell receptor delta knockout (TCRδ KO) mice at young and old age, we confirmed that VAT γδ T cells are predominately a tissue-resident …

A Novel Protozoa Parasite-Derived Protein Adjuvant Is Effective In Immunization With Cancer Cells To Activate The Cancer-Specific Protective Immunity And Inhibit The Cancer Growth In A Murine Model Of Colorectal Cancer, Rajesh Mani, Chloe G. Martin, Kanal E. Balu, Qingding Wang, Piotr G. Rychahou, Tadahide Izumi, B. Mark Evers, Yasuhiro Suzuki

Markey Cancer Center Faculty Publications

Cancer-specific CD8+ cytotoxic T cells play important roles in preventing cancer growth, and IFN-γ, in addition to IL-12 and type I interferon, is critical for activating CD8+ cytotoxic T cells. We recently identified the capability of the amino-terminus region of dense granule protein 6 (GRA6Nt) of Toxoplasma gondii, an intracellular protozoan parasite, to activate IFN-γ production of microglia, a tissue-resident macrophage population. Therefore, in the present study, we examined whether recombinant GRA6Nt protein (rGRA6Nt) functions as an effective adjuvant to potently activate cancer-specific protective immunity using a murine model of MC38 colorectal cancer (CRC). When mice were immunized with non-replicable …

Ribosome Hibernation Factor Induces Antibiotic Persisters Of Mycobacterium Tuberculosis In Neutrophil-Rich Lung Lesions, Jamie Corro

Electronic Theses & Dissertations (2024 - present)

Mycobacterium tuberculosis (Mtb), the etiological agent of tuberculosis, is a prescient global health threat and the leading cause of death by an infectious agent. Treatment of Mtb infection involves administering 2-4 antibiotics for a minimum of 6 months. This extended drug regimen is required to target a subpopulation of persistent bacilli. As their name implies, these bacteria can “persist” by acquiring nonhereditary and transient antibiotic tolerance. Although the precise mechanism is unknown, it’s often attributed to slowing cellular growth and metabolic processes. During zinc deprivation, bacteria can remodel their ribosomes by replacing their zinc-binding paralogues containing the CXXC motif (C+) …

Transcription And Translation Regulation Of Germ Cell To Maternal Transition, Noor Kotb

Electronic Theses & Dissertations (2024 - present)

In sexually reproducing organisms, the process of gametogenesis produces mature eggs and sperms required for fertilization to occur. The egg's quality is crucial for the healthy development of the next generation, making oogenesis a tightly regulated process with multiple benchmarks. To investigate the intricacies of oogenesis, we utilized the Drosophila oogenesis system as our primary model. This choice was motivated by several factors. Firstly, the process of egg development in Drosophila is conserved across species, making it a valuable proxy for understanding oogenesis in other organisms, including humans. Secondly, Drosophila melanogaster has long been established as a powerhouse in genetic …

Genetic Engineering Of Escherichia Coli For The Production Of Riboflavin, Adeyemi Adesanwo

Graduate Research Theses & Dissertations

Riboflavin, a water-soluble vitamin B2, is essential for the growth and reproduction of living organisms. However, humans and animals lack a riboflavin synthesis pathway and must rely on diets derived from plants and microbes for this essential vitamin. To meet our needs for vitamin B2, industrial riboflavin production is currently being pursued using strains of Bacillus subtilis. The fermentation process is successful, but improvements are needed for better substrate-to-product conversion yield. To this end, it is imperative to develop alternative microbial strains for cost-effective riboflavin production.

Due to its simple growth requirement, well-understood genetic background, and widely available genetic tools, …