Genetics and Genomics Commons^™

The Giant Axolotl Genome Uncovers The Evolution, Scaling, And Transcriptional Control Of Complex Gene Loci, Siegfried Schloissnig, Akane Kawaguchi, Sergej Nowoshilow, Francisco Falcon, Leo Otsuki, Pietro Tardivo, Nataliya Timoshevskaya, Melissa C. Keinath, Jeramiah J. Smith, S. Randal Voss, Elly M. Tanaka

Biology Faculty Publications

Vertebrates harbor recognizably orthologous gene complements but vary 100-fold in genome size. How chromosomal organization scales with genome expansion is unclear, and how acute changes in gene regulation, as during axolotl limb regeneration, occur in the context of a vast genome has remained a riddle. Here, we describe the chromosome-scale assembly of the giant, 32 Gb axolotl genome. Hi-C contact data revealed the scaling properties of interphase and mitotic chromosome organization. Analysis of the assembly yielded understanding of the evolution of large, syntenic multigene clusters, including the Major Histocompatibility Complex (MHC) and the functional regulatory landscape of the Fibroblast Growth …

“Adopt-A-Tissue” Initiative Advances Efforts To Identify Tissue-Specific Histone Marks In The Mare, N. B. Kingsley, Natasha A. Hamilton, Gabriella Lindgren, Ludovic Orlando, Ernest Bailey, Samantha Brooks, Molly Mccue, Theodore S. Kalbfleisch, James N. Macleod, Jessica L. Petersen, Carrie J. Finno, Rebecca R. Bellone

Maxwell H. Gluck Equine Research Center Faculty Publications

No abstract provided.

Changes In Both Trans- And Cis-Regulatory Elements Mediate Insecticide Resistance In A Lepidopteron Pest, Spodoptera Exigua, Bo Hu, He Huang, Songzhu Hu, Miaomiao Ren, Qi Wei, Xiangrui Tian, Mohammed Esmail Abdalla Elzaki, Chris Bass, Jianya Su, Subba Reddy Palli

Entomology Faculty Publications

The evolution of insect resistance to insecticides is frequently associated with overexpression of one or more cytochrome P450 enzyme genes. Although overexpression of CYP450 genes is a well-known mechanism of insecticide resistance, the underlying regulatory mechanisms are poorly understood. Here we uncovered the mechanisms of overexpression of the P450 gene, CYP321A8 in a major pest insect, Spodoptera exigua that is resistant to multiple insecticides. CYP321A8 confers resistance to organophosphate (chlorpyrifos) and pyrethroid (cypermethrin and deltamethrin) insecticides in this insect. Constitutive upregulation of transcription factors CncC/Maf are partially responsible for upregulated expression of CYP321A8 in the resistant strain. Reporter gene assays …

Spatio-Temporal Selection Of Reference Genes In The Two Congeneric Species Of Glycyrrhiza, Yuping Li, Xiaoju Liang, Xuguo Zhou, Yu An, Ming Li, Ling Yuan, Yongqing Li, Ying Wang

Entomology Faculty Publications

Glycyrrhiza, a genus of perennial medicinal herbs, has been traditionally used to treat human diseases, including respiratory disorders. Functional analysis of genes involved in the synthesis, accumulation, and degradation of bioactive compounds in these medicinal plants requires accurate measurement of their expression profiles. Reverse transcription quantitative real-time PCR (RT-qPCR) is a primary tool, which requires stably expressed reference genes to serve as the internal references to normalize the target gene expression. In this study, the stability of 14 candidate reference genes from the two congeneric species G. uralensis and G. inflata, including ACT, CAC, CYP, …

De Novo Whole Genome Assembly Of The Swede Midge (Contarinia Nasturtii), A Specialist Of Brassicaceae, Using Linked-Read Sequencing, Boyd A. Mori, Cathy Coutu, Yolanda H. Chen, Erin O. Campbell, Julian R. Dupuis, Martin A. Erlandson, Dwayne D. Hegedus

Entomology Faculty Publications

The swede midge, Contarinia nasturtii, is a cecidomyiid fly that feeds specifically on plants within the Brassicaceae. Plants in this family employ a glucosinolate-myrosinase defense system, which can be highly toxic to non-specialist feeders. Feeding by C. nasturtii larvae induces gall formation, which can cause substantial yield losses thus making it a significant agricultural pest. A lack of genomic resources, in particular a reference genome, has limited deciphering the mechanisms underlying glucosinolate tolerance in C. nasturtii, which is of particular importance for managing this species. Here, we present an annotated, scaffolded reference genome of C. nasturtii using linked-read …

Whole-Exome Sequencing And Hipsc Cardiomyocyte Models Identify Myrip, Trappc11, And Slc27a6 Of Potential Importance To Left Ventricular Hypertrophy In An African Ancestry Population, Marguerite R. Irvin, Praful Aggarwal, Steven A. Claas, Lisa De Las Fuentes, Anh N. Do, C. Charles Gu, Andrea Matter, Benjamin S. Olson, Amit Patki, Karen Schwander, Joshua D. Smith, Vinodh Srinivasasainagendra, Hemant K. Tiwari, Amy J. Turner, Deborah A. Nickerson, Dabeeru C. Rao, Ulrich Broeckel, Donna K. Arnett

Epidemiology and Environmental Health Faculty Publications

Background: Indices of left ventricular (LV) structure and geometry represent useful intermediate phenotypes related to LV hypertrophy (LVH), a predictor of cardiovascular (CV) disease (CVD) outcomes.

Methods and Results: We conducted an exome-wide association study of LV mass (LVM) adjusted to height^2.7, LV internal diastolic dimension (LVIDD), and relative wall thickness (RWT) among 1,364 participants of African ancestry (AAs) in the Hypertension Genetic Epidemiology Network (HyperGEN). Both single-variant and gene-based sequence kernel association tests were performed to examine whether common and rare coding variants contribute to variation in echocardiographic traits in AAs. We then used a data-driven …

Physical Mapping Of The Anopheles (Nyssorhynchus) Darlingi Genomic Scaffolds, Míriam Silva Rafael, Leticia Cegatti Bridi, Igor V. Sharakhov, Osvaldo Marinotti, Maria V. Sharakhova, Vladimir A. Timoshevskiy, Giselle Moura Guimarães-Marques, Valéria Silva Santos, Carlos Gustavo Nunes Da Silva, Spartaco Astolfi-Filho, Wanderli Pedro Tadei

Biology Faculty Publications

The genome assembly of Anopheles darlingi consists of 2221 scaffolds (N50 = 115,072 bp) and has a size spanning 136.94 Mbp. This assembly represents one of the smallest genomes among Anopheles species. Anopheles darlingi genomic DNA fragments of ~37 Kb were cloned, end-sequenced, and used as probes for fluorescence in situ hybridization (FISH) with salivary gland polytene chromosomes. In total, we mapped nine DNA probes to scaffolds and autosomal arms. Comparative analysis of the An. darlingi scaffolds with homologous sequences of the Anopheles albimanus and Anopheles gambiae genomes identified chromosomal rearrangements among these species. Our results confirmed that physical mapping …

Comprehensive Analysis Of Nac Transcription Factor Family Uncovers Drought And Salinity Stress Response In Pearl Millet (Pennisetum Glaucum), Ambika Dudhate, Harshraj Shinde, Pei Yu, Daisuke Tsugama, Shashi Kumar Gupta, Shenkui Liu, Tetsuo Takano

Pharmaceutical Sciences Faculty Publications

BACKGROUND: Pearl millet (Pennisetum glaucum) is a cereal crop that possesses the ability to withstand drought, salinity and high temperature stresses. The NAC [NAM (No Apical Meristem), ATAF1 (Arabidopsis thaliana Activation Factor 1), and CUC2 (Cup-shaped Cotyledon)] transcription factor family is one of the largest transcription factor families in plants. NAC family members are known to regulate plant growth and abiotic stress response. Currently, no reports are available on the functions of the NAC family in pearl millet.

RESULTS: Our genome-wide analysis found 151 NAC transcription factor genes (PgNACs) in the pearl millet genome. Thirty-eight …

Characterizing The Physiology And Genetics Of Contact Dependent Growth Inhibiton Systems In Burkholderia Species, Alice Elizabeth Oates

Theses and Dissertations--Microbiology, Immunology, and Molecular Genetics

Contact-dependent growth inhibition (CDI) systems mediate interbacterial competition. The genes encoding these systems are widespread among Gram-negative bacteria, including Burkholderia pathogens. CDI systems of Burkholderia species are composed of two-partner secretion pathway proteins and function to deliver the toxic C-terminus of a polymorphic surface-exposed exoprotein BcpA (Burkholderia CDI protein A) to the cytoplasm of neighboring recipient bacteria upon cell-cell contact. Specific outer and inner membrane proteins facilitate BcpA translocation both out of the donor bacterium and into the recipient cell cytoplasm. Most Burkholderia species-specific CDI translocation factors in recipient cells are unknown. BcpA intoxication functions as a mechanism by …

Cloning And Functional Characterizations Of Circular Rnas From The Human Mapt Locus, Justin R. Welden

Theses and Dissertations--Molecular and Cellular Biochemistry

Under pathophysiological conditions, the microtubule protein tau (MAPT) forms neurofibrillary tangles that are the hallmark of sporadic Alzheimer’s disease as well as familial frontotemporal dementias linked to chromosome 17 (FTDP-17). In this work, I report that MAPT forms circular RNAs through backsplicing of exon 12 to either exon 10 or exon 7 (12→10; 12→7), and that these circular RNAs are translated into proteins.

Using stable cell lines overexpressing the circular tau RNAs 12→7 and 12→10, we have discovered that the tau circular RNA 12→7 is translated in a rolling circle, giving rise to multiple proteins. This circular RNA …

Circadian Rhythmicity And Melatonin Sensitivity In The Human Gut Commensal Bacterium Klebsiella Aerogenes, Kinga Graniczkowska

Theses and Dissertations--Biology

While the expression of circadian rhythms is nearly universal among multicellular eukaryotic organisms, demonstration of this phenomenon in prokaryotes has been largely restricted to photosynthetic cyanobacteria until very recently. Further, growing interest in gastrointestinal microbiomes has revealed a complex temporal relationship between the gastrointestinal clock and the bacterial microbiome within. At least one member of the gut microbiome, Klebsiella (née Enterobacter) aerogenes, responds to the indoleamine hormone melatonin, secreted by the gastrointestinal system itself. Further research revealed that K. aerogenes also expresses a circadian rhythm in motility and gene expression that is temperature compensated. Although rhythmicity is unaltered …

Mechanisms Of Cadmium-Induced And Epidermal Growth Factor Receptor Mutation-Driven Lung Tumorigenesis, Hsuan-Pei Lin

Theses and Dissertations--Toxicology and Cancer Biology

Cadmium (Cd) is a ubiquitous pollutant in the environment and a known carcinogen for lung cancer. Cd has been shown to act as a weak mutagen, which suggests that it may exert tumorigenic effect through non-genotoxic ways, such as epigenetic mechanisms. The goal of this project is to investigate the mechanisms of Cd carcinogenesis focusing on the role of lncRNA dysregulations. The Cd-exposed cells formed significantly more colonies in soft agar, displayed cancer stem cell (CSC)-like property and formed tumors in nude mice. Mechanistically, the lncRNA microarray analysis revealed that chronic Cd exposure dysregulates lncRNA expressions. Q-PCR analysis confirmed the …

Genetic Mouse Models Of Liver Disease: Potential Roles Of Zhx2 (Afr1) And Afr2 In Damage And Regeneration, Courtney P. Turpin

Theses and Dissertations--Pharmacology and Nutritional Sciences

The liver is the largest internal organ in mammals and responsible for carrying out various processes, including lipid and carbohydrate metabolism, detoxification of chemicals, and production of serum proteins. Liver damage, which can be caused by a variety of agents including viral infection, environmental toxins, alcohol and excessive dietary fats, can cause dysregulation of these critical functions, leading to worsening liver pathophysiology and impacting health. However, the liver has the remarkable ability to regenerate when damaged. Hepatocytes, which comprise a majority of liver cells, are relatively quiescent under healthy conditions. Upon injury, remaining hepatocytes can proliferate to recover from liver …

Distribution And Diversity Of Heliothine And Other Lepidopteran Nudiviruses, Emrah Ozel

Theses and Dissertations--Entomology

Helicoverpa zea nudivirus 2 (HzNV-2) is the only known sterilizing and sexually-transmitted insect virus and causes pathological symptoms in H. zea reproductive tissues. HzNV-2 has features that make it a candidate as a H. zea (corn earworm) control agent, such as the ability to cause asymptomatic (latent) and symptomatic (lytic) infections and the ability to influence mating behavior of its host to favor virus spread. HzNV pathology has been studied and its genome sequenced, however, its prevalence in natural populations is largely unknown. In this study, we developed and used a low-cost PCR-based molecular survey to investigate HzNV-2 prevalence and …

Novel Computational Methods For Cancer Genomics Data Analysis, Jinpeng Liu

Theses and Dissertations--Computer Science

Cancer is a genetic disease responsible for one in eight deaths worldwide. The advancement of next-generation sequencing (NGS) technology has revolutionized the cancer research, allowing comprehensively profiling the cancer genome at great resolution. Large-scale cancer genomics research has sparked the needs for efficient and accurate Bioinformatics methods to analyze the data. The research presented in this dissertation focuses on three areas in cancer genomics: cancer somatic mutation detection; cancer driver genes identification and transcriptome profiling on single-cell level.

NGS data analysis involves a series of complicated data transformation that convert raw sequencing data to the information that is interpretable by …

Molecular Mechanisms Regulating Optic Fissure Fusion During Zebrafish Eye Development, Megan Weaver

Theses and Dissertations--Biology

Vertebrate retinal development requires timely and precise fusion of the optic fissure. Failure of this event leads to congenital vision impairment in the form of coloboma. Recent studies have suggested hyaloid vasculature to be involved in OF fusion. In order to examine this link, we analyzed optic fissure fusion and hyaloid vasculogenesis in the zebrafish pax2a noi mutant line. We first determined that pax2a^-/- embryos fail to accumulate F-actin in the optic fissure prior to basement membrane (BM) degradation. Furthermore, using 3D and live imaging we observed reduced OF hyaloid vascularization in pax2a^-/- embryos. When examining the connection …

Periocular Mesenchyme Heterogeneity During Morphogenesis Of The Vertebrate Ocular Anterior Segment, Kristyn L. Van Der Meulen

Theses and Dissertations--Biology

The vertebrate eye is a complex organ, responsible for the primary sense with which we interact with our environment: vision. Development of the eye is a tightly regulated process, controlled by a vast network of genes. This process begins with eye morphogenesis, when the eye structure is formed through a series of morphogenetic movements and culminates in the creation of the optic cup, lens, and presumptive optic stalk. Next, retinal differentiation creates the critical cell layers of the retina needed to process light waves that enter the eye, including rod and cone photoreceptors, interneurons, and support cells. Failure in either …

Southern Pine Beetle-Specific Rna Interference Demonstrates No Effects On Nontarget Insects, Hannah Marie Hollowell

Theses and Dissertations--Entomology

The endemic southern pine beetle (SPB), Dendroctonus frontalis Zimmermann, is a highly destructive bark beetle that has devastated coniferous forests of the southern United States for decades. Traditional management strategies have been unable to respond effectively to largescale SPB outbreaks, prompting exploration of novel techniques including RNA interference (RNAi). Double-stranded RNAs (dsRNAs) are effective at triggering gene silencing and inducing mortality in SPB, but determining delivery methods and demonstrating specificity of the treatments is necessary before this technology may progress to deployment.

I evaluated three SPB-specific dsRNAs on model nontarget insects to assess potential lethal effects, sublethal effects such as …

Leveraging Transcriptomic Approaches To Identify Differences In Genetic Programming Driving Two Distinct Wound Healing Mechanisms, Regeneration And Fibrosis, In Acomys And Mus, Shishir K. Biswas

Theses and Dissertations--Biology

Why can some animals and others cannot? This fundamental question has fueled scientists studying regeneration for hundreds of years since early observations in crayfish, salamanders and many other organisms. While most contemporary work in regeneration is done in a handful of species including salamanders, zebrafish and flatforms, these organisms lack a closely-related, non-regenerating sister species from which unique genetic differences can be identified. Additionally, while much has been learned from these organisms, they do not share fundamental biological traits with mammals (endothermy, metabolism and immune system) which limits the ability to translate this research for clinical medicine. To this end, …

Leveraging Chemical And Computational Biology To Probe The Cellulose Synthase Complex, B. Kirtley Amos

Theses and Dissertations--Plant and Soil Sciences

Cellular expansion in plants is a complex process driven by the constraint of internal cellular turgor pressure by an expansible cell wall. The main structural element of the cell wall is cellulose. Cellulose is vital to plant fitness and the protein complex that creates it is an excellent target for small molecule inhibition to create herbicides. In the following thesis many small molecules (SMs) from a diverse library were screened in search of new cellulose biosynthesis inhibitors (CBI). Loss of cellular expansion was the primary phenotype used to search for putative CBIs. As such, this was approached in a forward …

Loss-Of-Function Genomic Variants Highlight Potential Therapeutic Targets For Cardiovascular Disease, Jonas B. Nielsen, Oren Rom, Ida Surakka, Sarah E. Graham, Wei Zhou, Tanmoy Roychowdhury, Lars G. Fritsche, Sarah A. Gagliano Taliun, Carlo Sidore, Yuhao Liu, Maiken E. Gabrielsen, Anne Heidi Skogholt, Brooke Wolford, William Overton, Ying Zhao, Jin Chen, He Zhang, Whitney E. Hornsby, Akua Acheampong, Austen Grooms, Amanda Schaefer, Gregory J. M. Zajac, Luis Villacorta, Jifeng Zhang, Ben Brumpton, Mari Løset, Vivek Rai, Pia R. Lundegaard, Morten S. Olesen, Kent D. Taylor, Donna K. Arnett

Epidemiology and Environmental Health Faculty Publications

Pharmaceutical drugs targeting dyslipidemia and cardiovascular disease (CVD) may increase the risk of fatty liver disease and other metabolic disorders. To identify potential novel CVD drug targets without these adverse effects, we perform genome-wide analyses of participants in the HUNT Study in Norway (n = 69,479) to search for protein-altering variants with beneficial impact on quantitative blood traits related to cardiovascular disease, but without detrimental impact on liver function. We identify 76 (11 previously unreported) presumed causal protein-altering variants associated with one or more CVD- or liver-related blood traits. Nine of the variants are predicted to result in loss-of-function of …

Epigenetic Regulation Of Prostate Cancer, Ruixin Wang, Xiaoqi Liu

Toxicology and Cancer Biology Faculty Publications

Prostate cancer is (PCa) the second leading cause of cancer death in males in the United State, with 174,650 new cases and 31,620 deaths estimated in 2019. It has been documented that epigenetic deregulation such as histone modification and DNA methylation contributes to PCa initiation and progression. EZH2 (enhancer of zeste homolog 2), the catalytic subunit of the Polycomb Repressive Complex (PRC2) responsible for H3K27me3 and gene repression, has been identified as a promising target in PCa. In addition, overexpression of other epigenetic regulators such as DNA methyltransferases (DNMT) is also observed in PCa. These epigenetic regulators undergo extensive post-translational …

Whole Genome Sequencing Identified A 16 Kilobase Deletion On Eca13 Associated With Distichiasis In Friesian Horses, E. A. Hisey, H. Hermans, Z. T. Lounsberry, F. Avila, R. A. Grahn, K. E. Knickelbein, S. A. Duward-Akhurst, M. E. Mccue, Theodore S. Kalbfleisch, M. E. Lassaline, W. Back, R. R. Bellone

Veterinary Science Faculty Publications

BACKGROUND: Distichiasis, an ocular disorder in which aberrant cilia (eyelashes) grow from the opening of the Meibomian glands of the eyelid, has been reported in Friesian horses. These misplaced cilia can cause discomfort, chronic keratitis, and corneal ulceration, potentially impacting vision due to corneal fibrosis, or, if secondary infection occurs, may lead to loss of the eye. Friesian horses represent the vast majority of reported cases of equine distichiasis, and as the breed is known to be affected with inherited monogenic disorders, this condition was hypothesized to be a simply inherited Mendelian trait.

RESULTS: A genome wide association study (GWAS) …

Genetic-Based Hypertension Subtype Identification Using Informative Snps, Yuanjing Ma, Hongmei Jiang, Sanjiv J. Shah, Donna K. Arnett, Marguerite R. Irvin, Yuan Luo

Epidemiology and Environmental Health Faculty Publications

In this work, we proposed a process to select informative genetic variants for identifying clinically meaningful subtypes of hypertensive patients. We studied 575 African American (AA) and 612 Caucasian hypertensive participants enrolled in the Hypertension Genetic Epidemiology Network (HyperGEN) study and analyzed each race-based group separately. All study participants underwent GWAS (Genome-Wide Association Studies) and echocardiography. We applied a variety of statistical methods and filtering criteria, including generalized linear models, F statistics, burden tests, deleterious variant filtering, and others to select the most informative hypertension-related genetic variants. We performed an unsupervised learning algorithm non-negative matrix factorization (NMF) to identify hypertension …

The P-Glycoprotein Repertoire Of The Equine Parasitic Nematode Parascaris Univalens, Alexander P. Gerhard, Jürgen Krücken, Emanuel Heitlinger, I. Jana I. Janssen, Marta Basiaga, Sławomir Kornaś, Céline Beier, Martin K. Nielsen, Richard E. Davis, Jianbin Wang, Georg Von Samson-Himmelstjerna

Maxwell H. Gluck Equine Research Center Faculty Publications

P-glycoproteins (Pgp) have been proposed as contributors to the widespread macrocyclic lactone (ML) resistance in several nematode species including a major pathogen of foals, Parascaris univalens. Using new and available RNA-seq data, ten different genomic loci encoding Pgps were identified and characterized by transcriptome-guided RT-PCRs and Sanger sequencing. Phylogenetic analysis revealed an ascarid-specific Pgp lineage, Pgp-18, as well as two paralogues of Pgp-11 and Pgp-16. Comparative gene expression analyses in P. univalens and Caenorhabditis elegans show that the intestine is the major site of expression but individual gene expression patterns were not conserved between the two nematodes. In P. …

Genome Diversity And The Origin Of The Arabian Horse, Elissa J. Cosgrove, Raheleh Sadeghi, Florencia Schlamp, Heather M. Holl, Mohammad Moradi-Shahrbabak, Seyed Reza Miraei-Ashtiani, Salma Abdalla, Ben Shykind, Mats H. T. Troedsson, Monika Stefaniuk-Szmukier, Anil Prabhu, Stefania Bucca, Monika Bugno-Poniewierska, Barbara Wallner, Joel Malek, Donald C. Miller, Andrew G. Clark, Douglas F. Antczak, Samantha A. Brooks

Veterinary Science Faculty Publications

The Arabian horse, one of the world's oldest breeds of any domesticated animal, is characterized by natural beauty, graceful movement, athletic endurance, and, as a result of its development in the arid Middle East, the ability to thrive in a hot, dry environment. Here we studied 378 Arabian horses from 12 countries using equine single nucleotide polymorphism (SNP) arrays and whole-genome re-sequencing to examine hypotheses about genomic diversity, population structure, and the relationship of the Arabian to other horse breeds. We identified a high degree of genetic variation and complex ancestry in Arabian horses from the Middle East region. Also, …

A Transcriptional Regulatory Network Of Rsv3-Mediated Extreme Resistance Against Soybean Mosaic Virus, Lindsay C. Demers, Neelam R. Redekar, Aardra Kachroo, Sue A. Tolin, Song Li, M. A. Saghai Maroof

Plant Pathology Faculty Publications

Resistance genes are an effective means for disease control in plants. They predominantly function by inducing a hypersensitive reaction, which results in localized cell death restricting pathogen spread. Some resistance genes elicit an atypical response, termed extreme resistance, where resistance is not associated with a hypersensitive reaction and its standard defense responses. Unlike hypersensitive reaction, the molecular regulatory mechanism(s) underlying extreme resistance is largely unexplored. One of the few known, naturally occurring, instances of extreme resistance is resistance derived from the soybean Rsv3 gene, which confers resistance against the most virulent Soybean mosaic virus strains. To discern the regulatory mechanism …

Frontotemporal Dementia Nonsense Mutation Of Progranulin Rescued By Aminoglycosides, Lisha Kuang, Kei Hashimoto, Eric J. Huang, Matthew S. Gentry, Haining Zhu

Molecular and Cellular Biochemistry Faculty Publications

Frontotemporal dementia (FTD) is an early onset dementia and is characterized by progressive atrophy of the frontal and/or temporal lobes. FTD is highly heritable with mutations in progranulin accounting for 5-26% of cases in different populations. Progranulin is involved in endocytosis, secretion and lysosomal processes, but its function under physiological and pathological conditions remains to be defined. Many FTD-causing nonsense progranulin mutations contain a premature termination codon (PTC), thus progranulin haploinsufficiency has been proposed as a major disease mechanism. Currently, there is no effective FTD treatment or therapy.

Aminoglycosides are a class of antibiotics that possess a less known function …

Epigenetic Implications In Inorganic Arsenic-Mediated Carcinogenesis, Meredith Eckstein

Theses and Dissertations--Molecular and Cellular Biochemistry

Chronic, low dose exposure to inorganic arsenic (iAs) is a public health concern throughout the world, contributing to the development of many diseases, including lung cancer. Several mechanisms for iAs-mediated carcinogenesis have been proposed, of which the production of reactive oxygen species and formation of chromosomal aberrations are the most studied. Another equally important, yet less studied mechanism is dysregulation of epigenetic marks. “Epigenetics” refers to changes that occur on the DNA and chromatin that do not alter base pair identity, but alter compaction, expression, and regulation of specific DNA sequences. There are several types of epigenetic marks including histone …

The Roles Of Polar Cell Extensions In Drosophila Micropyle Formation, Bradford Hull

Theses and Dissertations--Biology

The Drosophila micropyle is a conserved formation utilized to allow sperm passage past the robust eggshell structure for fertilization. Micropyle formation follows a unique acellular tubulogenesis method where it is secreted and shaped by specialized follicle cells including the border cells and polar cells. In late oogenesis, the polar cells form extensions that are necessary to create the micropyle pore through which sperm enters. Previous work established that polar cell extension presence is required for micropyle pore formation. We investigated temporal requirements of extensions throughout chorion deposition and found extensions are required during the beginning and middle of choriogenesis, but …