Life Sciences Commons^™

Investigating Mirna Regulation Of The Human Apobec3 Enzymes, William Dietrich

All Graduate Theses, Dissertations, and Other Capstone Projects

The human apolipoprotein B mRNA editing enzyme catalytic polypeptide 3 (APOBEC3, A3) are a family of proteins consisting of seven enzymes, A3A, B, C, D, F, G and H, which function as cytosine deaminases. The enzymes’ purpose in the cell is to mutate viral DNA during infection hindering or stopping replication of viruses such as human papillomavirus, herpes simplex virus, and HIV-1. Several of the A3 enzymes have also been implicated in contributing to cancers such as head and neck and breast cancers by mutating cellular genomic DNA, making the ability to control A3 expression an attractive target for cancer …

The Effects Of Hybridization On Skeletal Morphology In Two Closely Related Populations Of Rhesus Macaques (Macaca Mulatta): A Geometric Morphometric Approach, Cody Zachery Schumacher

Theses and Dissertations

Precise identification and classification techniques are vital for the field of paleoanthropology to ensure that hominin fossilized remains are labeled accurately. The morphology of extinct hominin specimens will typically be compared to extant nonhuman primate species because of how closely related they are phylogenetically. Observable similarities in their morphological variation can be examined to infer which traits may be a result of evolution and this can update our understanding of their evolutionary relationships. The genus Macaca displays a level of morphological variation that is similar to that seen in the genus Homo, therefore macaques can be used as an analogous …

Molecular Evolution And Biogeography Of The New World Eptesicus Bats, Xueling Yi

Theses and Dissertations

Molecular evolution refers to a broad field of studies ranging from microevolution (e.g., population genetics) to macroevolution (e.g., phylogeny), including the bridging field of phylogeography. In natural populations, molecular studies are also combined with biogeography that links biological diversity with geographic distributions to provide a comprehensive understanding of evolutionary processes. The field of molecular evolution has been largely advanced from early exploratory descriptions to statistical tests on biological hypotheses and integrative analyses using sophisticated modeling. However, studies of molecular evolution still face some unresolved questions and challenges, especially in non-model systems. For example, the application of new technology has largely …

An Investigation Into The Roles Of Aldose Reductase And Acetate Kinase In The Metabolism Of Entamoeba Histolytica, Matthew B. Angel

All Dissertations

Entamoeba histolytica is an amoebic parasite that infects an estimated 90 million people worldwide and causes approximately 100,000 deaths per year. As the causative agent of amoebic dysentery, this food- and water-borne pathogen represents a significant public health burden worldwide, particularly in areas with poor sanitation. While treatments for amoebiasis exist, they are often limited in their effectiveness. Thus, efforts to better understand the biology and physiology of this organism are vital to the development of novel treatments for this disease.

E. histolytica lacks the enzymes for many common metabolic pathways such as the citric acid cycle and oxidative phosphorylation …

Structure And Evolution Of Lizard Immunity Genes, Trent Santonastaso

University of New Orleans Theses and Dissertations

One of the most important gene families to play a role in adaptive immunity is the major histocompatibility complex (MHC). MHC class II loci are considered to be the most variable loci in the vertebrate genome, and studies have shown that this variability can be maintained through complex co-evolutionary dynamics between host and parasite. Despite the rich body of research into the MHC, there is comparatively little understanding of its genomic architecture in reptiles. Similarly, loci associated with innate immunity have received little attention in reptiles compared to other vertebrates. In the first chapter, we investigated the structure and organization …

Profiling Transcription And Retrotransposition Of Mouse L1 Subfamilies, Lingqi Kong

Electronic Theses and Dissertations

Transposable elements, also called jumping genes, comprise almost 45% of the human genome. In contrast, only 1% of the human genome is protein-coding sequences. The function and advantages of maintaining such massive copies of transposable elements in the human genome are still unclear. Long interspersed element 1 (L1), the most substantial group and the only active autonomous transposable element in the human genome, has revealed its unique roles in many diseases. The insertional mutagenesis induced by L1 retrotransposition events could threaten human genomic stability and generate unexpected mutations. L1 overexpression has been documented in both somatic and germline cells and, …

Innate Antibodies, Murine Models, And Evolution: A Study Of Trypanosome Lytic Factor Functions And Their Translational Applications, Joseph P. Verdi

Dissertations, Theses, and Capstone Projects

Trypanosome lytic factors (TLFs) are primate-specific antimicrobial protein complexes that lyse African trypanosome parasites by delivering the channel-forming toxin APOL1 to the invading microorganisms. Human serum contains two TLFs that are delivered to the parasite by separate mechanisms, only one of which has been characterized. TLF1 is endocytosed by a receptor that is typically blocked by other serum factors in vivo, suggesting that TLF2 is the more relevant lytic factor in the context of trypanosome immunity. TLF2 is non-covalently associated with polyclonal immunoglobulin M (IgM) antibodies, which we report here to be involved in the uptake mechanism. The TLF2-IgMs …

Targeted-Ion Mass Spectrometry For The Identification Of Forensically Relevant Biological Fluids And Samples From Sexual Assault Evidence, Heather Erin Mckiernan

Electronic Theses and Dissertations

Forensic practitioners have long sought efficient and reliable means for identifying those samples that are best suited for successful genetic profiling. Traditional serological screening methodologies rely upon enzyme activity and antibody-based serological tests. These tests can be consumptive, laborious and costly while reliance on antibody-based serological testing can be prone to error. Positive results resulting from non-target biological fluids, the potential for cross- reactivity and non-specific binding events yield merely presumptive results. This has led forensic biologists to omit serological testing, at least in the case of sexual assault kit samples, in favor of Y-Screen assays. While these Y-Screen approaches …

Molecular Homology & The Ancient Genetic Toolkit: How Evolutionary Development Could Shape Your Next Doctor's Appointment, Elizabeth G. Plender

Regis University Student Publications (comprehensive collection)

Homology, i.e. the biological pattern of “sameness,” is a pervasive facet of evolution at both the organismic and molecular levels of organization. While traditionally interpreted at the anatomical scale, shared molecular phenotypes across vastly divergent species hint at the presence of a deeply conserved, ancient genetic “toolkit” characteristic of the animal kingdom. Through careful examination of the nuanced homologues implicated in comparative embryology, evolutionary developmental biologists provide a holistic approach to understanding how homologous patterns of gene regulation translate to anatomical similarities among animal species. My summer research project in the Division of Developmental Biology at Cincinnati Children’s hospital aimed …

Transcriptomics Of Learning, Pablo Iturralde

Theses

Learning is a basic and important component of behavior yet we have very little empirical information about the interaction between mechanisms of learning and evolution. In our work, we are testing hypotheses about the neurogenetic mechanisms through which animal learning abilities evolve. We are able to test this directly by using experimentally evolved populations of flies, which differ in learning ability. These populations were previously evolved within the lab by creating worlds with different patterns of change following theoretically predicted effects on which enhanced learning will evolve. How has evolution acted to modulate genes and gene expression in the brain …

The Heart Of The Madder: An Important Prehistoric Pigment And Its Botanical And Cultural Roots, Michelle Laberge

Theses and Dissertations

In recent years, an interest in natural botanical dye sources has prompted new research into the cultivation and processing of prehistoric dye plants. Advances in chemical analyses of ancient European textiles have provided more information about dye plants such as woad (Isatis tinctoria) weld (Reseda luteola) and madder (Rubia tinctorum), which were important sources of color in early textile production. Evidence of madder dye has been reported in the archaeological record of the European Bronze and Iron Ages in textiles preserved in the Hallstatt salt mines, Scandinavian bog sites and other elite European burials but the picture of madder usage …

Crystal Structure Of Apobec3a Bound To Single-Stranded Dna Reveals Structural Basis For Cytidine Deamination And Specificity, Takahide Kouno, Tania V. Silvas, Brendan J. Hilbert, Shivender Shandilya, Markus-Frederik Bohn, Brian A. Kelch, William E. Royer, Mohan Somasundaran, Nese Kurt Yilmaz, Hiroshi Matsuo, Celia A. Schiffer

Celia A. Schiffer

Nucleic acid editing enzymes are essential components of the immune system that lethally mutate viral pathogens and somatically mutate immunoglobulins, and contribute to the diversification and lethality of cancers. Among these enzymes are the seven human APOBEC3 deoxycytidine deaminases, each with unique target sequence specificity and subcellular localization. While the enzymology and biological consequences have been extensively studied, the mechanism by which APOBEC3s recognize and edit DNA remains elusive. Here we present the crystal structure of a complex of a cytidine deaminase with ssDNA bound in the active site at 2.2 A. This structure not only visualizes the active site …

A Novel Population Of Cardiovascular Progenitors Persist In Neonates As Mesendodermal Cells, Julia Kim

Loma Linda University Electronic Theses, Dissertations & Projects

The rise in mortality due to cardiovascular disease has increased the need to develop an efficient regenerative therapeutic for heart failure. Numerous cell-based therapies have been investigated for myocardial regeneration; however, an optimal progenitor has yet to be discovered. Identifying a resident cell population with enhanced ability to differentiate into multiple lineages would greatly contribute to the field of stem cell-based regenerative therapy. Evidence suggests that endogenous cardiovascular progenitor cells (CPCs) that have been isolated from the heart itself express ISL1, KDR, and MESP1, and are capable of differentiating into all major cardiac lineages. The earlier developmental stage at which …

Evolutionary Genetic Aspects Of Host Association In Generalist Ectoparasites, Benoit Talbot

Electronic Thesis and Dissertation Repository

Despite the use of the host for dispersal by most parasite species, the extremely loose relationship typical between highly mobile hosts and generalist ectoparasites may lead to very different gene flow patterns between the two, leading in turn to different spatial genetic structure, and potentially different demographic history. I examined how similar gene flow patterns are between Cimex adjunctus, a generalist ectoparasite of bats present throughout North America, and two of its key bat hosts. I first analyzed the continent-scale genetic structure and demographic history of C. adjunctus and compared it to that of two of its hosts, the …

Mitochondrial Heteroplasmy Contributes To The Dynamic Atovaquone Resistance Response In Plasmodium Falciparum, Sasha Victoria Siegel

USF Tampa Graduate Theses and Dissertations

Of the considerable challenges researchers face in the control and elimination of malaria, the development of antimalarial drug resistance in parasite populations remains a significant hurdle to progress worldwide. Atovaquone is used in combination with proguanil (Malarone) as an antimalarial treatment in uncomplicated malaria, but is rendered ineffective by the rapid development of atovaquone resistance during treatment. Previous studies have established that de novo mutant parasites confer resistance to atovaquone with a substitution in amino acid 268 in the cytochrome b gene encoded by the parasite mitochondrial genome, yet much is still unknown about how this resistance develops, and whether …

Single-Cell Transcriptional Analysis Of Normal, Aberrant, And Malignant Hematopoiesis In Zebrafish, Finola E. Moore, Elaine G. Garcia, Riadh Lobbardi, Esha Jain, Qin Tang, John C. Moore, Mauricio Cortes, Aleksey Molodtsov, Melissa Kasheta, Christina C. Luo, Amaris J. Garcia, Ravi Mylvaganam, Jeffrey A. Yoder, Jessica S. Blackburn, Ruslan I. Sadreyev, Craig J. Ceol, Trista E. North, David M. Langenau

Molecular and Cellular Biochemistry Faculty Publications

Hematopoiesis culminates in the production of functionally heterogeneous blood cell types. In zebrafish, the lack of cell surface antibodies has compelled researchers to use fluorescent transgenic reporter lines to label specific blood cell fractions. However, these approaches are limited by the availability of transgenic lines and fluorescent protein combinations that can be distinguished. Here, we have transcriptionally profiled single hematopoietic cells from zebrafish to define erythroid, myeloid, B, and T cell lineages. We also used our approach to identify hematopoietic stem and progenitor cells and a novel NK-lysin 4⁺ cell type, representing a putative cytotoxic T/NK cell. Our platform …

The Evolution Of The Viral Rna Sensor Oas1 In Old World Monkeys And Cetartiodactyls, Ian Fish

Dissertations, Theses, and Capstone Projects

Animals produce an array of sensors patrolling the intracellular environment poised to detect and respond to viral infection. The oligoadenylate synthetase family of enzymes comprises a crucial part of this innate immune response, directly signaling endonuclease activity responsible for inhibiting viral replication. Oligoadenylate synthetase 1 plays a vital role in animal susceptibility to pathogens including flaviviruses such as dengue, West Nile, and hepatitis c virus. This thesis includes a population level analysis of OAS1 diversity within macaque and baboon species followed by a broader survey of the gene in nineteen Old World monkeys. My research found that at the species …

The Lineage-Specific Evolution Of Aquaporin Gene Clusters Facilitated Tetrapod Terrestrial Adaptation, Roderick Nigel Finn, François Chauvigné, Jón Baldur Hlidberg, Christopher P. Cutler, Joan Cerdà

Department of Biology Faculty Publications

A major physiological barrier for aquatic organisms adapting to terrestrial life is dessication in the aerial environment. This barrier was nevertheless overcome by the Devonian ancestors of extant Tetrapoda, but the origin of specific molecular mechanisms that solved this water problem remains largely unknown. Here we show that an ancient aquaporin gene cluster evolved specifically in the sarcopterygian lineage, and subsequently diverged into paralogous forms of AQP2, -5, or -6 to mediate water conservation in extant Tetrapoda. To determine the origin of these apomorphic genomic traits, we combined aquaporin sequencing from jawless and jawed vertebrates with broad taxon assembly of …

A Homogenizing Process Of Selection Has Maintained An 'Ultra-Slow' Acetylation Nat2 Variant In Humans, Blandine Patillon, Pierre Luisi, Estella S. Poloni, Sotiria Boukouvala, Pierre Darlu, E. Genin, Audrey Sabbagh

Human Biology Open Access Pre-Prints

N-acetyltransferase 2 (NAT2) is an important enzyme involved in the metabolism of a wide spectrum of naturally occurring xenobiotics, including therapeutic drugs and common environmental carcinogens. Extensive polymorphism in NAT2 gives rise to a wide interindividual variation in acetylation capacity which influences individual susceptibility to various drug-induced adverse reactions and cancers. Striking patterns of geographic differentiation have been described for the main slow acetylation variants of the NAT2 gene, suggesting the action of natural selection at this locus. In the present study, we took advantage of the whole-genome sequence data available from the 1000 Genomes project to investigate the …

Role Of Cardiac Catecholamines In Embryos And Adults Under Stress, Candice Baker

Electronic Theses and Dissertations

Cardiovascular disease is responsible for the loss of one life every 38 seconds and accounts for 26.6 percent of all infants that die of congenital birth defects. Adrenergic hormones are critically important regulators of cardiovascular physiology in embryos and adults. They are key mediators of stress responses and have profound stimulatory effects on cardiovascular function, and dysregulation of adrenergic function has been associated with many adverse cardiac conditions, including congenital malformations, arrhythmias, ischemic heart disease, heart failure, and sudden cardiac death. Despite intensive study, the specific roles these hormones play in the developing heart is not well-understood. Further, there is …

The Role Of Gnrh-Ii And Its Receptor In Testicular Function, Amy Desaulniers

Department of Animal Science: Dissertations, Theses, and Student Research

The second mammalian isoform of GnRH (GnRH-II) has been linked to regulation of cell proliferation, feed intake, and the interaction between energy balance and reproductive behavior. In contrast to the native form of GnRH (GnRH-I), GnRH-II is an inefficient modulator of gonadotropin secretion. Unlike many species, a functional receptor (GnRHR-II) specific to this ligand has been discovered in the pig that may be directly involved in testosterone production. Therefore, our objective was to identify the role of GnRH-II and its receptor in testicular function. First, there was 6-fold more GnRHR-II protein in the testis than anterior pituitary gland of boars. …

Characterization Of Innate Immunity In The Female Reproductive Tract For The Prevention Of Hiv Acquisition, Colleen Eade

Electronic Theses and Dissertations

Human immunodeficiency virus (HIV) infects 30 million people worldwide. In sub-Saharan Africa, the region most affected by HIV, women comprise 60% of the infected population. Heterosexual transmission is a major mode of viral acquisition, mandating further research of the process and prevention of HIV acquisition via the female reproductive tract (FRT). The FRT is a dynamic environment, protected by host immune mechanisms and commensal microbes. The disruption of either of these elements can increase susceptibility to HIV. Accordingly, one common risk factor for HIV acquisition is the microbial shift condition known as bacterial vaginosis (BV), which is characterized by the …

Sirt1 Regulation Of The Heat Shock Response In An Hsf1-Dependent Manner And The Impact Of Caloric Restriction, Rachel Rene Raynes

USF Tampa Graduate Theses and Dissertations

The heat shock response (HSR) is the cell's molecular reaction to protein damaging stress and is critical in the management of denatured proteins. Activation of HSF1, the master transcriptional regulator of the HSR, results in the induction of molecular chaperones called heat shock proteins (HSPs). Transcription of hsp genes is promoted by the hyperphosphorylation of HSF1, while the attenuation of the HSR is regulated by a dual mechanism involving negative feedback inhibition from HSPs and acetylation at a critical lysine residue within the DNA binding domain of HSF1, which results in a loss of affinity for DNA. SIRT1 is a …

Composition And Evolution Of The Vertebrate And Mammalian Selenoproteomes, Marco Mariotti, Perry G. Ridge, Yan Zhang, Alexei V. Lobanov, Thomas H. Pringle, Roderic Guigo, Dolph L. Hatfield, Vadim N. Gladyshev

Department of Biochemistry: Faculty Publications

Background: Selenium is an essential trace element in mammals due to its presence in proteins in the form of selenocysteine (Sec). Human genome codes for 25 Sec-containing protein genes, and mouse and rat genomes for 24.

Methodology/Principal Findings: We characterized the selenoproteomes of 44 sequenced vertebrates by applying gene prediction and phylogenetic reconstruction methods, supplemented with the analyses of gene structures, alternative splicing isoforms, untranslated regions, SECIS elements, and pseudogenes. In total, we detected 45 selenoprotein subfamilies. 28 of them were found in mammals, and 41 in bony fishes. We define the ancestral vertebrate (28 proteins) and mammalian …

Opposing Roles Of The Μ-Opioid And Nociceptin/Orphanin Fq Receptors In Oligodendrocyte Development And Myelination, Allison Vestal-Laborde

Theses and Dissertations

While the classical function of myelin is to facilitate saltatory conduction, this membrane and the myelin-making oligodendrocytes (OLGs) are now recognized as regulators of plasticity and remodeling in the central nervous system (CNS). Thus, OLG maturation and myelination are highly vulnerable processes along CNS development. We previously showed that rat brain myelination is altered by perinatal exposure to buprenorphine, an opioid analogue in clinical trials for the treatment of pregnant opioid addicts. We now found that the in vivo effects on myelination could result from direct alteration in the balance between μ-opioid receptor (MOR) and nociceptin/orphanin FQ receptor (NOPR) activities …

Lafora Disease E3-Ubiquitin Ligase Malin Is Related To Trim32 At Both The Phylogenetic And Functional Level, Carlos Romá-Mateo, Daniel Moreno, Santiago Vernia, Teresa Rubio, Travis M. Bridges, Matthew S. Gentry, Pascual Sanz

Molecular and Cellular Biochemistry Faculty Publications

BACKGROUND: Malin is an E3-ubiquitin ligase that is mutated in Lafora disease, a fatal form of progressive myoclonus epilepsy. In order to perform its function, malin forms a functional complex with laforin, a glucan phosphatase that facilitates targeting of malin to its corresponding substrates. While laforin phylogeny has been studied, there are no data on the evolutionary lineage of malin.

RESULTS: After an extensive search for malin orthologs, we found that malin is present in all vertebrate species and a cephalochordate, in contrast with the broader species distribution previously reported for laforin. These data suggest that in addition to forming …

Mechanisms Of Alpha]-Synuclein-Induced Neurodegenertaion In Parkinson's Disease And Stroke, Cherine Belal

Electronic Theses and Dissertations

Parkinson’s disease (PD) is a debilitating neurodegenerative disorder affecting one million Americans. Despite its social and economic impact, the pathological cascades that lead to neuron dysfunction and degeneration in PD are poorly understood. Endoplasmic reticulum (ER) stress has been implicated as an initiator or contributing factor in neurodegenerative diseases including PD. The ER is an organelle central to protein folding and intracellular Ca2+ homeostasis. Perturbations of these functions result in ER stress and upregulation of ER stress proteins, of which some have been implicated in counteracting ER stress-induced cell death. The mechanisms that lead to ER stress and how ER …

Molecular Cloning And Characterization Of The Porcine Fto Promoter And Coding Regions.Pdf, Jinming Huang, Yunzhou Yang, Gang Liu, Jibin Zhang, Xinxing Dong, Ying Bai, Meiying Fang

Jibin Zhang

Evolution Of Lactate Dehydrogenase Genes In Primates, With Special Consideration Of Nucleotide Organization In Mammalian Promoters, Zack Papper

Wayne State University Dissertations

Concomitant with an increase in brain volume and mass, the allocation of energetic resources to the brain increased during stem anthropoid evolution, leading to humans. One mechanism by which this allocation may have occurred is through greater use of lactate as a neuronal fuel. Both the production of lactate, and conversion to pyruvate for use in aerobic metabolism, are catalyzed, in part, by the tetrameric enzyme lactate dehydrogenase (LDH). The two primary LDH genes, LDHA and LDHB, confer different rates of substrate turnover to the LDH enzyme, and these rates lend to the argument that LDHA supports anaerobic while LDHB …

Smart Stimulation: Zoo Conservation For 21st Century Zoos, Lauren Retallack

WWU Honors College Senior Projects

According to a 1992 survey, "an estimated 102 million people, more than attend professional football, baseball, and basketball games combined, visit 162 accredited North American zoos and aquariums each year" (2). People frequent zoos for a variety of reasons, from entertaining children for a few hours, to learning about the wildlife which inhabits their region and foreign places. Regardless of intent, once at the zoo, visitors are presented with a unique opportunity to learn about conservation and the plights of endangered species. It is the job of zoo directors, keepers, staff, and volunteers to get people thinking about conservation while …