Cell and Developmental Biology Commons^™

Regulation Of Genome Architecture By Chromatin Remodeling In The Brain, Jared Vega Goodman

Arts & Sciences Electronic Theses and Dissertations

Brain development requires exquisite control of gene expression to establish and refine the proper circuitry of the nervous system. Gene expression control is under the purview of several cellular processes, including chromatin regulation in the form of DNA modification, histone modification, and nucleosome remodeling. Chromatin remodeling enzymes are the major effectors of nucleosome remodeling. These enzymes are clearly involved in brain development – mutations in chromatin remodeling enzymes are likely causative for neurodevelopmental disorders of cognition. Chromatin remodeling enzymes have discrete molecular functions and binding profiles and similarly control distinct phases of nervous system maturation. Chd4 is a Chd family …

Comprehensive Characterization Of The Genetic And Neoantigen Landscapes Of Follicular Lymphoma Patients Supports The Feasibility Of Personalized Cancer Vaccine Treatments, Cody Alexander Ramirez

Arts & Sciences Electronic Theses and Dissertations

Follicular lymphoma (FL) is the most common indolent non-Hodgkin’s lymphoma; however, it remains incurable with conventional therapies and is poorly responsive to checkpoint blockade. FL arises from B-lymphocytes and develops slowly (and often asymptomatically). A major research focus has been on how to avoid chemotherapy treatments, to limit the potential development of treatment-related side effects, and the risk of therapy-related second cancers. FL also carries an approximately 30% lifetime risk of transforming from an iNHL to more destructive lymphomas, which are associated with poorer prognosis. The most common transformation results in diffuse large B-cell lymphoma (DLBCL). However, many patients may …

The Effects Of Mapk Signaling On The Development Of Cerebellar Granule Cells, Kerry Morgan

University Scholar Projects

The granule cells are the most abundant neuronal type in the human brain. Rapid proliferation of granule cell progenitors results in dramatic expansion and folding of the cerebellar cortex during postnatal development. Mis-regulation of this proliferation process causes medulloblastoma, the most prevalent childhood brain tumor. In the developing cerebellum, granule cells are derived from Atoh1-expressing cells, which arise from the upper rhombic lip (the interface between the roof plate and neuroepithelium). In addition to granule cells, the Atoh1 lineage also gives rise to different types of neurons including cerebellar nuclei neurons. In the current study, I have investigated the …

The Effects Of Mapk Signaling On The Development Of Cerebellar Granule Cells, Kerry Morgan

Honors Scholar Theses

The granule cells are the most abundant neuronal type in the human brain. Rapid proliferation of granule cell progenitors results in dramatic expansion and folding of the cerebellar cortex during postnatal development. Mis-regulation of this proliferation process causes medulloblastoma, the most prevalent childhood brain tumor. In the developing cerebellum, granule cells are derived from Atoh1-expressing cells, which arise from the upper rhombic lip (the interface between the roof plate and neuroepithelium). In addition to granule cells, the Atoh1 lineage also gives rise to different types of neurons including cerebellar nuclei neurons. In the current study, I have investigated the …

Dynamics Of Hybrid Zones At A Continental Scale, Bradley T. Martin

Graduate Theses and Dissertations

Hybridization has traditionally been viewed as a happenstance that negatively impacts populations, but is now recognized as an important evolutionary mechanism that can substantially impact the evolutionary trajectories of gene pools, influence adaptive capacity, and contravene or reinforce divergence. Physiographic processes are important drivers of dispersal, alternately funneling populations into isolation, promoting divergence, or facilitating secondary contact of diverged populations, increasing the potential for hybridization. In North America, glacial-interglacial cycles and geomorphological changes have provided a dynamic backdrop over the last two million years that promoted such oscillations of population contraction and expansion. These biogeographic processes have resulted in regional …

Mapping And Characterization Of Mutagen Sensitivity Genes In Drosophila Malanogaster, Alexis Nystrom

Graduate Theses

The information contained within DNA is vital to directing all biological processes. All organisms have repair mechanisms in place to repair DNA damage quickly and efficiently. Without these repair pathways, DNA can acquire harmful mutations that can compromise the survival of an organism. Studies of DNA repair in Drosophila melanogaster have focused on mutagen sensitive (mus) mutants, each of which contain a mutation that renders them incapable of performing DNA repair. Since a majority of these mus genes are unmapped, the goal of this project was to determine what genes in the Drosophila melanogaster genome are mus106 and mus108. Presence …

Translational Fidelity And Its Role In Neuronal Homeostasis, Markus Terrey

Electronic Theses and Dissertations

The process of translation, which refers to decoding genetic information from mRNA to protein, is vital for all cellular function. Translational fidelity starts at the level of aminoacylation of transfer RNAs (tRNA). This reaction is catalyzed by aminoacyl tRNA synthetases where each amino acid is transferred to its corresponding cognate tRNA. Because tRNAs harbor the anticodon sequence to decodes a particular mRNA codon, the specific aminoacylation of the tRNA with a cognate amino acid establishes the rules of decoding genetic code into proteins. Aminoacylated tRNAs are then delivered to ribosomes, where ribosomes in a highly organized manner need to accurately …

Genetic Pathway Analysis Of Abnormal Facial Development In Nonsyndromic Cleft Lip And Palate, Lorena Maili

Dissertations & Theses (Open Access)

Nonsyndromic cleft lip with or without cleft palate (NSCLP) is the most common craniofacial birth defect resulting from incomplete fusion of the facial prominences during development, which leaves a gap in the lip, primary palate and/or the secondary palate. NSCLP affects 135,000 NSCLP newborns worldwide each year based on a birth prevalence of 1 per 700 live births. While surgical treatments have dramatically improved, many long-term health issues persist, imposing significant medical, psychosocial and economic burdens. Familial aggregation and segregation analyses suggest genetic contributions underlie NSCLP, but despite decades of study, only a small portion of the NSCLP genetic liability …

Reducing Seed Coat Fiber Content And Pod Shatter, And Engineering Medium Chain Fatty Acids-Containing Oil, In The Oilseed Crop Pennycress ( Thlaspi Arvense L. ), Maliheh Esfahanian

Theses and Dissertations

The overall goal of this thesis was to genetically improve agronomic traits of pennycress (Thlaspi arvense L.; Field Pennycress) and demonstrate the production of value-added designer seed oils to domesticate pennycress and enable its establishment as a new winter annual oilseed/meal/cover crop to be grown in temperate regions of the world. In the U.S. Midwest, pennycress can be double cropped on existing farmland during the time between corn harvest and subsequent planting of soybeans the following spring. Pennycress has the potential to produce 2,000 lbs/acre seeds, which at 33% by weight oil content and 20% protein, would yield 85 gallons/acre …

Insights Into Leptopilina Spp. Immune-Suppressive Strategies Using Mixed-Omics And Molecular Approaches, Brian Wey

Dissertations, Theses, and Capstone Projects

Host-parasite interactions influence the biology of each over the course of evolution. Parasite success allows for the passage of potent virulence strategies from generation to generation. Host success passes stronger immunity and resistance strategies to the following generations as well. Only by studying both partners within their natural contexts can we begin to understand the relationship between the two and how immune mechanisms and virulence strategies interact as a molecular arms race.

In this work, we focus on a natural host-parasite pair, the Drosophila-Leptopilina model. Leptopilina species are parasites of several fruit fly species, including Drosophila melanogaster. This model …

Viropana (Vna) 1, Abijeet Singh Mehta, Panagiotis A. Tsonis, Amit Singh

Components of a Regeneration Toolkit: Notophthalmus viridescens

Viropana (vna) 1

• ID – vna 1

• Details – Gene from a novel protein family belonging to the regeneration toolkit of Notophthalmus viridescens

• Base pairs – 492

Viropana (Vna) 2, Abijeet Singh Mehta, Panagiotis A. Tsonis, Amit Singh

Components of a Regeneration Toolkit: Notophthalmus viridescens

Viropana (vna) 2

• ID – vna 2
• Details – Gene from a novel protein family belonging to the regeneration tool kit of Notophthalmus viridescens
• Base pairs – 396

Viropana (Vna) 5, Abijeet Singh Mehta, Panagiotis A. Tsonis, Amit Singh

Components of a Regeneration Toolkit: Notophthalmus viridescens

Viropana (vna) 5

• ID – vna 5
• Details – Gene from a novel protein family belonging to the regeneration toolkit of Notophthalmus viridescens
• Base pairs – 391

Viropana (Vna) 3, Abijeet Singh Mehta, Panagiotis A. Tsonis, Amit Singh

Components of a Regeneration Toolkit: Notophthalmus viridescens

Viropana (vna) 3

• ID – vna 3
• Details – Gene from a novel protein family belonging to the regeneration toolkit of Notophthalmus viridescens
• Base pairs – 426

Viropana (Vna) 4, Abijeet Singh Mehta, Panagiotis A. Tsonis, Amit Singh

Components of a Regeneration Toolkit: Notophthalmus viridescens

Viropana (vna) 4

• ID – vna 4
• Details – Gene from a novel protein family belonging to the regeneration toolkit of Notophthalmus viridescens
• Base pairs – 501

Transactivation And Mitochondrial Activity Are Affected By High Temperature In C. Elegans Sperm, Jacqueline Mcvay

Scripps Senior Theses

Sexual reproduction has a conserved flaw in that it is temperature sensitive. Exposure to high temperature leads to male infertility, but little is known about the underlying mechanism. Understanding these mechanisms is important for agriculture and reproductive medicine. Using C. elegans, we investigated two potential aspects of male fertility that may be affected by high temperature conditions: activation of sperm by seminal fluid and sperm mitochondrial activity. There are two pathways for sperm activation in C. elegans: the SPE-8 pathway in hermaphrodites and the TRY-5 pathway in male seminal fluid. Hermaphrodite sperm with a mutation in spe-8 can …

Mimicking The Effect Of Prolactin On Stat3/Stat5 Activity In Breast Cancer, Jennifer N. Barbuto, Sarah R. Walker

Honors Theses and Capstones

Signal transducers and activators of transcription (STAT) 3 and 5 are commonly constitutively activated in breast cancer. STAT5 can outcompete STAT3 and reduce cell proliferation and metastasis. STAT5 activation is stimulated by prolactin, a natural hormone that can be harmful at high levels. The aim of this study is to identify some possible previously developed drugs that mimic the effect of prolactin and STAT5 without the added risk in MDA-MB231 breast cancer cells. Using the CLUE database query app and STAT5 up- and downregulation signatures, three drugs (X, K, and M) were chosen based on their similarity in signatures to …

The Origin Of Novel Trait Inferred From Transcriptomic Analysis And A Targeted Gene Approach In The Beetle Horns., Naureen Fatima

Graduate Theses, Dissertations, and Problem Reports

The origin of the evolutionary new trait (evolutionary novelty) and its subsequent evolution is of great interest for biologists in various fields, and beetle horns have been used to address this fundamental biological question. Previous studies on one of the horned beetle species, Onthophagus taurus, that utilized comparative gene expression analyses, suggested legs to be a strong candidate of the origin of horns. At the same time, their horns are secondary sexual traits whose development is regulated by the same gene (doublesex) as genitalia, which also originates from paired appendages such as legs. However, little is known …

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 …

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 …

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 …

A Molecular Toolset For The In Vivo Detection Of A Sulfolobus Islandicus Leucyl Trna Synthetase Paralog, Nicholas Michael Bretz

Theses and Dissertations

An ancient and ubiquitous set of enzymes known as the aminoacyl-tRNA synthetases are required for the viability of all organisms. The aminoacyl-tRNA synthetases catalyze the attachment of amino acids onto tRNA molecules. The aminoacylated, or charged, tRNA is then transported and utilized at the ribosome for the synthesis of proteins. The genome of the hyperthermophilic microorganism Sulfolobus islandicus (S. islandicus) harbors a unique leucyl-tRNA synthetase paralog, LeuRS-I, of unknown function. While its duplicate, LeuRS-F, carries out all the classical functions of LeuRS-family enzymes, LeuRS-I fails to charge leucine onto tRNALeu, despite its ability to activate this amino acid and bind …

Single-Fluorophore Sensors For Mechanical Force In Living Cells, Sarah Kricheff

Honors Scholar Theses

Mechanotransduction is the process by which a mechanical stimulus is converted to a cellular signal. This process is heavily influential of cell morphology, differentiation, and behavior. However, altered levels of mechanical stimuli are also found in many pathological contexts. For example, cancerous cells have stiffer surrounding tissue than healthy cells, and research suggests that this alters cell behavior and promotes metastasis. Despite these findings, the cellular processes behind these signaling alterations remain widely unknown. Understanding these cascades is critical, as involved proteins can give us a deeper understanding of the role of mechanotransduction, and certain proteins can potentially be targeted …

The Genome-Wide Roles Of The Lung Lineage Transcription Factor Nkx2-1 In The Regulation Of Opposing Cell Fates In Vivo, Danielle Renae Little

Dissertations & Theses (Open Access)

Lineage transcription factors mark, promote, and maintain multiple distinct cell types originating from a common progenitor. Despite their essential role, how such factors function and bind genome wide to orchestrate the epigenetic changes necessary to form and maintain these identities in vivo is unclear. One lineage transcription factor NK Homeobox 2-1 (NKX2-1) is expressed throughout the lung epithelium during development and was thought to be lost in the extraordinarily thin cell type required for gas exchange– the alveolar type 1 (AT1) cell. Complementing precise genetic knockouts with cell type-specific ChIP-seq, ATAC-seq, and scRNA-seq, our study shows that AT1 and AT2 …

P53 Drives A Transcriptional Program That Elicits A Non-Cell-Autonomous Response And Alters Cell State In Vivo, Sydney Moyer

Dissertations & Theses (Open Access)

Cell stress and DNA damage activate the tumor suppressor p53, triggering transcriptional activation of a myriad of target genes. The molecular, morphological, and physiological consequences of this activation remain poorly understood in vivo. We activated a p53 transcriptional program in mice by deletion of Mdm2, a gene which encodes the major p53 inhibitor. By overlaying tissue-specific RNA-sequencing data from pancreas, small intestine, ovary, kidney, and heart with existing p53 ChIP-sequencing, we identified a large repertoire of tissue-specific p53 genes and a common p53 transcriptional signature of seven genes which included Mdm2 but not p21. Global p53 activation …

Evaluation Of The Xpert Carba-R Nxg Assay For Detection Of Carbapenemase Genes In A Global Challenge Set Of Pseudomonas Aeruginosa Isolates, Fred C. Tenover, Christian M. Gill, Tomefa E. Asempa, Isabella A. Tickler, Caitlin M. Dela Cruz, David P. Nicolau

Biology Faculty Publications

The growing prevalence and diversity of carbapenemase producers among carbapenem-resistant Pseudomonas aeruginosa (CRPA) isolates warrants an expansion of detection capabilities. The purpose of this study was to evaluate the performance of the commercially available Xpert Carba-R (Carba-R) and the research-use-only Xpert Carba-R NxG (Carba-R NxG) in a global collection of P. aeruginosa. The challenge set included 123 P. aeruginosa clinical isolates from 12 countries. Isolates were previously categorized via PCR or whole-genome sequencing. Carbapenemase classes tested include VIM, IMP, NDM, SPM, KPC, and GES. Non-carbapenemase (non-CP)-harboring isolates were also tested (negative control). Isolates were tested using the Carba-R NxG and …

Genetic Basis Of Hybrid Sterility Between Drosophila Pseudoobscura And D. Persimilis, Alannah J.P. Mattice

Electronic Thesis and Dissertation Repository

Speciation is the underlying process that leads to formation of new species, and therefore is the basis of biodiversity. Genes involved in each stage of speciation, such as those involved in interspecies sterility, remain elusive. Male hybrid sterility and postzygotic isolation between Drosophila pseudoobscura and D. persimilis was examined in this study through backcrossing of female hybrids into each parental line (introgression), selecting for a sterile sperm phenotype, needle-eye sperm. Sperm phenotypes did not separate through backcrossing; instead, males presented with multiple sperm phenotypes. A relationship between the phenotypes observed and the potential genes involved was examined through whole genome …

Identification And Characterization Of Novel Genes And Genetic Interactions That Influence Iba Metabolism, Vanessica Jawahir

Dissertations

Indole-3-butyric acid (IBA) is an endogenous storage auxin important for maintaining appropriate indole-3-acetic acid (IAA) levels that influences primary root elongation and lateral root development. IBA is metabolized into free IAA in the peroxisome in a multistep process similar to fatty acid β-oxidation. Although many components specific to IBA metabolism and peroxisome function have been identified, our understanding is incomplete. I sought to identify novel components of IBA metabolism or peroxisome function by conducting a forward genetic screen for Arabidopsis thaliana plants with enhanced resistance to IBA. I identified Long chain acyl-CoA synthetase 4 (LACS4) as a novel gene functioning …

Herb-Layer Dynamics In An Old-Growth Forest: Vegetation–Environment Relationships And Response To Invasion-Related Perturbations, Taylor M. Buskey, Margaret E. Maloney, Julia I. Chapman, Ryan W. Mcewan

Biology Faculty Publications

Temperate forests of eastern North America are subject to multiple invasions from non-native species that have the potential to drive long-term dynamics in biodiversity. Garlic mustard (Alliaria petiolata (M. Bieb.) Cavara and Grande) is an invasive plant in many deciduous forests, and management efforts often focus on removing this species to initiate native species restoration. Agrilus planipennis Fairmaire (emerald ash borer; Coleoptera: Buprestidae) is a non-native insect pest that has caused substantial loss of ash trees (Fraxinus spp. L.) in North America. Our goal was to understand how the herbaceous layer in an old-growth forest responded to the removal of …

Does The Presence Of Multiple Β-Lactamases In Gram-Negative Bacilli Impact The Results Of Antimicrobial Susceptibility Tests And Extended-Spectrum Β-Lactamase And Carbapenemase Confirmation Methods?, Fred C. Tenover, Caitlin M. Dela Cruz, Scott Dewell, Victoria M. Le, Isabella A. Tickler

Biology Faculty Publications

Objectives: Many multidrug-resistant Gram-negative bacilli (MDR-GNB) harbour multiple β-lactamases. The aim of this study was to assess the impact of multiple β-lactamase carriage on the accuracy of susceptibility tests and extended-spectrum β-lactamase (ESBL) and carbapenemase confirmation methods.

Methods: A total of 50 MDR-GNB, of which 29 carried multiple β-lactamases, underwent broth microdilution (BMD) and disk diffusion (DD) testing as well as confirmation tests for ESBLs and carbapenemases. Whole-genome sequencing (WGS) was used for β-lactamase gene identification.

Results: Categorical agreement of BMD and DD testing results ranged from 86.5 to 97.7% for 10 β-lactam agents. BMD and DD algorithms for ESBL …