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The Localized Manipulation Of The Extracellular Matrix Within 3d Collagen Cell Cultures Using A Biomems Device, Ashley N. Clark
The Localized Manipulation Of The Extracellular Matrix Within 3d Collagen Cell Cultures Using A Biomems Device, Ashley N. Clark
Legacy Theses & Dissertations (2009 - 2024)
Approximately 90% of all cancer related deaths can be attributed to the occurrence of metastasis. There are multiple changes that occur within the tumor microenvironment that have been correlated with the onset of metastasis. Different cell types, extracellular matrices, blood vessels, and soluble factors are some of the various components that make up the complex, heterogeneous microenvironment that exists within a tumor. The dynamic relationship between tumor cells and their surrounding environment makes it an ideal environment to study triggers of metastasis, such as the modification of the extracellular matrix. Changes in the multiple aspects of extracellular matrix composition have …
Impact Of Black Carbon On Global Climate : A Half-Century Of Arctic Black Carbon -- Trends And Sources, Anthony Michael Dejulio
Impact Of Black Carbon On Global Climate : A Half-Century Of Arctic Black Carbon -- Trends And Sources, Anthony Michael Dejulio
Legacy Theses & Dissertations (2009 - 2024)
Abstract
The Genetic Engineering Of Motor Proteins, Rachael M. Hartz
The Genetic Engineering Of Motor Proteins, Rachael M. Hartz
Legacy Theses & Dissertations (2009 - 2024)
Molecular motors are a remarkable feature within living organisms that are responsible for directional mechanical motion, which is driven by adenosine triphosphate (ATP) hydrolysis. Actin-binding molecular motors are of specific interest in the field of nanotechnology as filamentous actin is capable of carrying cargo, such as quantum dots, while it is translocated along a motor coated surface. The binding regions of motor proteins, which are known to interact with actin, such as Myosin, have been thoroughly examined and identified. Rapid genetic engineering of the ATP-hydrolyzing enzyme, adenosine kinase, to incorporate these binding regions is possible through the use of site- …
Btbr-Fvb Chromosome 4 Congenic Displays Rescue Of Behavior And Neuro-Anatomical Phenotypes, Jessica F. Gracias
Btbr-Fvb Chromosome 4 Congenic Displays Rescue Of Behavior And Neuro-Anatomical Phenotypes, Jessica F. Gracias
Legacy Theses & Dissertations (2009 - 2024)
Autism is commonly called the most genetic of neuropsychiatric disorders. Currently, the only diagnostic test is a behavioral evaluation performed by trained physicians and psychologists. There is an urgent need for biomarkers to diagnose autism instead of just relying on behavior and there is also a need to understand the basis of this disorder. One of the theories is that malformation of the corpus callosum is one of the factors that lead to the behavior deficits seen in autism. This theory is based on the fact that human MRI studies have shown that the corpus callosum is absent or malformed …
Post-Translational Modification Regulates Heterogeneous Nuclear Ribonucleoprotein K Function During Axon Outgrowth In Xenopus Laevis, Erica J. Hutchins
Post-Translational Modification Regulates Heterogeneous Nuclear Ribonucleoprotein K Function During Axon Outgrowth In Xenopus Laevis, Erica J. Hutchins
Legacy Theses & Dissertations (2009 - 2024)
The RNA-binding protein, heterogeneous nuclear ribonucleoprotein K (hnRNP K), is required for axon outgrowth. Its suppression in Xenopus embryos causes defects in the translation of mRNAs of multiple cytoskeletal genes. Studies in cell lines have established that hnRNP K shuttles between the nucleus and the cytoplasm to bind and regulate the fates of its target RNAs, from splicing to export and translation. At each step, hnRNP K is regulated through post-translational modifications that alter its nucleic acid and protein interactions, and subcellular localization. Precisely how this happens in developing neurons to coordinate cytoskeletal gene expression with the extracellular signals directing …
2'-O-Methyl Substitutions In The Yeast Telomerase Pseudoknot And Their Effects On Telomerase Activity, Katelyn Mae Jasper
2'-O-Methyl Substitutions In The Yeast Telomerase Pseudoknot And Their Effects On Telomerase Activity, Katelyn Mae Jasper
Legacy Theses & Dissertations (2009 - 2024)
Telomerase is a ribonucleoprotein (RNP) complex that synthesizes telomeric repeats at the ends of linear chromosomes to form the DNA–protein complexes known as telomeres. Telomeres protect the ends of chromosomes from degradation during replication due to the end-replication problem. When replication occurs, gaps are created at the beginning of the lagging and leading strands that result in the loss of a small amount of DNA at every replication cycle. By adding thousands of copies of telomeric repeats, the repeats are lost in the replication process and not precious genetic information. The telomerase RNA varies drastically among different species both in …
Developmental Adaptation Hypothesis : Aerobic Capacity, Submaximal Arterial Saturation And Pulmonary Volumes In Peruvian Quechua Natives, Melisa Kiyamu Tsuchiya
Developmental Adaptation Hypothesis : Aerobic Capacity, Submaximal Arterial Saturation And Pulmonary Volumes In Peruvian Quechua Natives, Melisa Kiyamu Tsuchiya
Legacy Theses & Dissertations (2009 - 2024)
The Quechua populations have inhabited the Andes for hundreds of generations. The ability to thrive in this hostile environment, leading an active and healthy life has generated research questions about the special phenotype of Andean highlanders compared to their sea-level counterparts, such as their higher pulmonary volumes and their outstanding work capacity in spite of the challenge of oxygen transport and delivery in hypoxia. In high altitude natives, there have been two main explanations for the origins of the aforementioned traits: genetic adaptation through natural selection and developmental adaptation through the exposure to hypoxia during growth.
Cultural Control And Agency : A Quantitative Analysis Of Mazama Sp. And Odocoileus Sp. Osteological Remains From MayapáN, Yucatan, Mexico, Vivian S. James
Cultural Control And Agency : A Quantitative Analysis Of Mazama Sp. And Odocoileus Sp. Osteological Remains From MayapáN, Yucatan, Mexico, Vivian S. James
Legacy Theses & Dissertations (2009 - 2024)
Mayan management of deer populations at Mayapán in the Yucatán, México has been suggested by historical texts, iconography, and archaeological investigation. Therefore, the main research question of this thesis is: Was deer management or husbandry practiced at Mayapán? Two Cervidae species are identified in the Mayapán faunal assemblage, Odocoileus virginianus (white-tailed deer) and Mazama americana (brocket deer). It is likely that Mazama pandora (Yucatan brocket deer) is also present and possibly another Odocoileus subspecies. Consequently, the second research question of this thesis is: How many deer species or subspecies were present in Postclassic Period Mayapán? There is a considerable non-overlapping …
Role Of P450 Enzymes In Tobacco Dependence And Lung Tumorigenesis, Lei Li
Role Of P450 Enzymes In Tobacco Dependence And Lung Tumorigenesis, Lei Li
Legacy Theses & Dissertations (2009 - 2024)
The overall aim of this study is to better define the roles of P450 enzymes, particularly those in the CYP2A, 2B, and 2F gene subfamilies, in the metabolism and actions of tobacco-related chemicals. Tobacco smoke contains numerous compounds that are deleterious to health, including the primary addictive component nicotine and procarcinogenic compounds, such as naphthalene (NA) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Our main hypotheses are i) that CYP2A and 2B enzymes are largely responsible for nicotine metabolism, and they can impact nicotine dependence; and ii) that CYP2A, 2B, and 2F enzymes play important and tissue-specific roles in NA and NNK bioactivation, leading …
Phage Life History Traits : Regulation Of Pseudomonas Aeruginosa And Evolution Of Phage Resistance Within The Drosophila Melanogaster Host Environment, Heather Lindberg
Phage Life History Traits : Regulation Of Pseudomonas Aeruginosa And Evolution Of Phage Resistance Within The Drosophila Melanogaster Host Environment, Heather Lindberg
Legacy Theses & Dissertations (2009 - 2024)
Due to the increase in antibiotic resistant bacteria, there has been renewed interest in using bacteriophage to treat bacterial infections (phage therapy). This body of work examined different aspects related to the interaction between bacteria and phage within a host using the system of Drosophila melanogaster infected with Pseudomonas aeruginosa, which is then treated with lytic bacteriophage. Using this system four specific areas were addressed: I) How in vitro phage life history traits may be predictive of in vivo therapeutic efficacy, II) How the in vivo phage/bacteria dynamics differ for two different phages throughout the course of infection, III) How …
The Role Of Progesterone Receptor In The Development Of The Mesocortical Dopaminergic Pathway, Jari Willing
The Role Of Progesterone Receptor In The Development Of The Mesocortical Dopaminergic Pathway, Jari Willing
Legacy Theses & Dissertations (2009 - 2024)
The mesocortical dopaminergic pathway, comprised of projections from the ventral tegmental area (VTA) to the prefrontal cortex (PFC), mediates many of the most complex forms of cognitive behaviors and has been associated with clinical disorders such as ADHD and schizophrenia. While this circuit continues to develop throughout much of the lifespan, there is a rapid period of maturation, early in development, in which this circuit is highly sensitive to disruption. Steroid hormone receptors are powerful transcription factors, capable of affecting a variety of neurodevelopmental processes and are expressed in many regions throughout the developing brain. Specifically, the nuclear progesterone receptor …
Functional Roles Of The Insulin-Regulated Glucose Transporter-4 In The Hippocampus, Jiah Pearson-Leary
Functional Roles Of The Insulin-Regulated Glucose Transporter-4 In The Hippocampus, Jiah Pearson-Leary
Legacy Theses & Dissertations (2009 - 2024)
Although a great deal of research has elucidated both localization and function of many glucose transporters (GluTs) throughout the brain, the function of brain insulin-responsive glucose transporter-4 (GluT4) remains unclear (McEwen & Reagan, 2004). Because type 2 diabetes mellitus (T2DM; insulin resistance, i.e., impaired insulin signaling) is a risk factor for Alzheimer's disease (AD), and because the signaling mechanisms insulin uses to mediate hippocampal processes and memory are unclear, a major purpose of this dissertation was to determine whether hippocampal GluT4, which is responsible for insulin's glucoregulatory and canonical effects in the periphery, is necessary for insulin's effects in the …
Ecology Of Earthworms In Riparian Habitats, Rebecca Annette Pinder
Ecology Of Earthworms In Riparian Habitats, Rebecca Annette Pinder
Legacy Theses & Dissertations (2009 - 2024)
Research on earthworm ecology in North America has shifted from a focus on agricultural systems to investigations of their impacts on forested ecosystems. Many of the earthworms (family Lumbricidae, Megascolecidae, and Sparganophilidae) found so far appear to be groups of exotic species, many recently arrived from Eurasia. My preliminary research established their presence along forested headwater stream banks, previously assumed to be earthworm-free zones. These riparian areas are integral landscape elements that influence many downstream processes. This dissertation is the first to examine four aspects of earthworm ecology in riparian zones: species composition and distributions; community structure of earthworm assemblages; …
Development And Assessment Of Analytical Methods For Monitoring Current And Historical Exposures To Manganese : Blood, Urine, And Teeth, Meredith Lyn Praamsma
Development And Assessment Of Analytical Methods For Monitoring Current And Historical Exposures To Manganese : Blood, Urine, And Teeth, Meredith Lyn Praamsma
Legacy Theses & Dissertations (2009 - 2024)
Manganese, as an essential trace element, is a cofactor in numerous enzymes that aid in bone growth, cholesterol synthesis, and carbohydrate metabolism. Manganese can become toxic with overexposure, potentially leading to neurodegenerative effects and the disease manganism. Manganese concentrations in blood and urine have been widely used in monitoring current exposure and now there is interest in using manganese concentrations in teeth for monitoring historical exposure, especially in utero and in early childhood.
Structure-Activity Relationship Of 2,3-Benzodiazepin-4-Ones As Noncompetitive Ampa Receptor Antagonists, Mohammad Shaban Qneibi
Structure-Activity Relationship Of 2,3-Benzodiazepin-4-Ones As Noncompetitive Ampa Receptor Antagonists, Mohammad Shaban Qneibi
Legacy Theses & Dissertations (2009 - 2024)
2,3-Benzodiazepin-4-one (BDZ-11) derivatives are a special group of 2,3-benzodiazepine compounds. These compounds have been previously synthesized as AMPA receptor inhibitors, and they are also potential drugs for the treatment of various neurological diseases involving excessive AMPA receptor activity. AMPA receptors are a subtype of glutamate ion channel proteins and are responsible for the majority of excitatory neurotransmission in the mammalian central nervous system. Specifically, they are critically involved in neuronal development and brain activities, including learning and memory. Overstimulation of AMPA receptors is associated with some neurological diseases such as ALS, stroke and Alzheimer's disease. Despite the fact that hundreds …
Modeling The Ecological Niche Of The Nigeria-Cameroon Chimpanzee Under Climate Change, Paul Ryan Sesink Clee
Modeling The Ecological Niche Of The Nigeria-Cameroon Chimpanzee Under Climate Change, Paul Ryan Sesink Clee
Legacy Theses & Dissertations (2009 - 2024)
Ecological niche theory states that a set of environmental conditions exists that a species relies upon in order to survive and reproduce. Collectively, these variables define a species' niche, which includes a species' dispersal abilities and its range. Ecological niche modeling predicts the distributions of species by using information from environmental variables across geographic space, making it a valuable tool for studying how environment affects population dynamics. With accurate species presence data and geospatial information that describe its known habitat, ENMs can effectively map a species' realized niche across geographical space, and for closely related taxa, be used to understand …
Characterizing The Effects Of Glutaraldehyde On The Ryanodine Receptor Calcium Release Channel, Joshua Dov Strauss
Characterizing The Effects Of Glutaraldehyde On The Ryanodine Receptor Calcium Release Channel, Joshua Dov Strauss
Legacy Theses & Dissertations (2009 - 2024)
Ryanodine receptors (RyR) are large intracellular calcium release channels, which
New Tools To Study Amyloid Fibrils And Intrinsically Disordered Proteins In Vitro And In Vivo, Jacqueline D. Washington
New Tools To Study Amyloid Fibrils And Intrinsically Disordered Proteins In Vitro And In Vivo, Jacqueline D. Washington
Legacy Theses & Dissertations (2009 - 2024)
Amyloid fibrils are β-sheet-rich protein aggregates commonly found in the organs and tissues of patients with various amyloid-associated diseases. The structure of insulin fibrils was characterized by deep ultraviolet resonance Raman and Nuclear Magnetic Resonance spectroscopy combined with hydrogen-deuterium exchange. Our new approach of combining NMR and Raman spectroscopy with molecular dynamic simulations for characterizing amyloid fibrils provided exclusive knowledge about fibril structure at amino acid residue resolution.
Y-Family Dna Polymerases : Mechanism Of Single-Base Deletion And Effect Of Pcna Interaction, Yifeng Wu
Y-Family Dna Polymerases : Mechanism Of Single-Base Deletion And Effect Of Pcna Interaction, Yifeng Wu
Legacy Theses & Dissertations (2009 - 2024)
Translesional synthesis (TLS) by specialized Y-family DNA polymerases is a DNA damage tolerance pathway to bypass DNA lesions that have not been repaired by other DNA repair mechanisms. Despite their valuable lesion bypass ability, the Y-family DNA polymerases display a much lower fidelity upon replicating undamaged DNA. Their activity therefore needs to be well regulated in the cell. In our first project, we examined how an archaeal Y-family DNA polymerase, Dpo4, makes single-base deletions during replication. Dpo4 belongs to the DinB subfamily which is known to make single-base deletions. Although previous studies suggested that it uses a dNTP-stabilized misalignment mechanism, …
Assessment Of Human Exposure To Perchlorate And Perfluoroalkyl Substances In The United States : Biomonitoring And Environmental Monitoring Approaches, Qian Wu
Legacy Theses & Dissertations (2009 - 2024)
Perchlorate is an oxidant in solid fuels and explosives and is produced in large quantities worldwide. Perchlorate is a ubiquitous environmental contaminant and is present in water, food, indoor environment and humans. Human exposure to perchlorate is a concern due to its ability to disrupt the thyroid gland functions.
Structural Biology Of The Receptor For Advanced Glycation End Products (Rage), Jing Xue
Structural Biology Of The Receptor For Advanced Glycation End Products (Rage), Jing Xue
Legacy Theses & Dissertations (2009 - 2024)
The receptor for advanced glycated end products (RAGE), due to its location in the major histocompatibility complex class III (MHC III) region, suggests its involvement in immune responses. Because RAGE has been linked to complications of diabetes and chronic inflammation, the severity of Alzheimer's disease and cancer, it's significant to understanding the biological mechanism of signal transduction of RAGE.
Neutralizing Antibodies Against The Ricin Toxin Binding Subunit (Rtb), Anastasiya Yermakova
Neutralizing Antibodies Against The Ricin Toxin Binding Subunit (Rtb), Anastasiya Yermakova
Legacy Theses & Dissertations (2009 - 2024)
Ricin is a toxin that is naturally produced by the seeds of the castor bean plant Ricinus communis, and is part of a family of A-B toxins that includes Shiga, cholera, and anthrax toxins. The toxin consists of two subunits, RTA and RTB, which are linked by a disulfide bond. RTA is an RNA N-glycosidase that selectively targets and inactivates 28S ribosomal RNA, thereby arresting protein synthesis and leading to cell death. RTB is a galactose/ N-acetylgalactosamine-specific lectin that mediates attachment, entry, and intracellular trafficking of ricin in host cells. Currently, there is no approved vaccine or therapeutics available against …
Molecular Biochemical Study Of The Cataract-Associated Mutants In Human Gammad-Crystallin, Cindy Yeung
Molecular Biochemical Study Of The Cataract-Associated Mutants In Human Gammad-Crystallin, Cindy Yeung
Legacy Theses & Dissertations (2009 - 2024)
Cataract is a vision impairment disease that leads to light scattering and opacity of the eye lens. It is recognized as the most prevalent cause of blindness. Most cataracts occur due to aging, but those that occur in childhood or in young adults are typically of genetic origin. In the young (developing) eye, post–surgical complications such as glaucoma are common after cataract surgery. Hence there is a great need to develop non-surgical intervention strategies for the treatment of cataract. Here, two cataract-associated mutants of human γD-crystallin (HGD): i) Arg76 to Ser (R76S) and ii) a truncation mutation at Trp156 (W156X …
Function And Regulation Of Intestinal P450 Enzymes : Insights From Conditional Cytochrome P450 Reductase Knockout Mouse Models, Yi Zhu
Legacy Theses & Dissertations (2009 - 2024)
The overall goal of this thesis work was to investigate the function and regulation of intestinal P450 enzymes (P450s). The central hypotheses are that 1) small intestinal (SI) P450s play an important role in the first-pass clearance of oral drugs and in bioactivation of chemicals that cause intestinal toxicity, 2) endogenous regulatory compounds produced by intestinal P450s are important for protection against chemical-induced colon inflammation, and 3) there is a cross talk between the liver and the SI that helps to maintain the overall xenobiotic-metabolism capacity of the digestive tract.
Exposure To Persistent Organic Pollutants And Metabolic Diseases, Zafar Zayirovich Aminov
Exposure To Persistent Organic Pollutants And Metabolic Diseases, Zafar Zayirovich Aminov
Legacy Theses & Dissertations (2009 - 2024)
Background: The metabolic syndrome (MetS) is a group of diseases that tend to occur together, including diabetes, hypertension, central obesity, cardiovascular disease and hyperlipidemia. Exposure to persistent organic pollutants (POPs) such as polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) have been associated with increased risk of development of several of the components of the MetS.
The Sxrna Platform : Biophysical Characterization Of Trans-Acting Rna Switches For Gene Expression Control, Christine Bazinet
The Sxrna Platform : Biophysical Characterization Of Trans-Acting Rna Switches For Gene Expression Control, Christine Bazinet
Legacy Theses & Dissertations (2009 - 2024)
In the past decade, microRNAs (miRNAs) have become a hot topic in biochemical research. These very short ~ 22 nucleotide strands of RNA have been recognized as a functional RNA group and found to play a key role in mediating gene regulation along with RNA-binding proteins (RBPs). For example, by binding to the histone stem-loop (HSL) region of the target mRNA, normally in the 3'- untranslated region (UTR), gene expression can either be activated or deactivated for up or down regulation of the gene product. The majority of miRNAs have been found to down regulate gene expression upon binding to …
Protein Structures Under Physiological Conditions, Karl Michael Bertrand
Protein Structures Under Physiological Conditions, Karl Michael Bertrand
Legacy Theses & Dissertations (2009 - 2024)
My research focused on the evaluation of protein structures and protein dynamics inside eukaryotic cells under physiological conditions. The primary analyses of my research involved the use of in-cell Nuclear Magnetic Resonance spectroscopy using Heteronuclear Single Quantum Coherence experiments. This allowed me to visualize protein structures at an atomic resolution level, as well as, study the interactions of these proteins with small molecules.
Mutational Analysis Of An Rna Aptamer, Deblina Biswas
Mutational Analysis Of An Rna Aptamer, Deblina Biswas
Legacy Theses & Dissertations (2009 - 2024)
Aptamers are oligonucleotide molecules (DNA or RNA) that are selected against specific target proteins, nucleic acids or small molecules by using the well established technique of SELEX (Systemic Evolution of Ligands by Exponential Enrichment). Their ability to bind with high affinity and specificity has opened up a wide arena of scientific applications. Aptamers have been shown to have many potential therapeutic and bioanalytical contributions such as in the treatment of diseases like cancer, cardiovascular and other major ailments. The aim of this dissertation is to study and analyze double transversion involving 4 bases in a RNA aptamer molecule: MinB4-au-flipS clamp …
Evolution And Expression Of The Lysozyme And Beta1,4-Galactosyltransferase Families In Mammals : Possible Roles In Fertilization, Jason Michael Biegel
Evolution And Expression Of The Lysozyme And Beta1,4-Galactosyltransferase Families In Mammals : Possible Roles In Fertilization, Jason Michael Biegel
Legacy Theses & Dissertations (2009 - 2024)
Understanding the specificity of sperm-egg recognition during mammalian fertilization has been a topic of intense study for many years, and yet the biochemical basis for this process is still largely unknown. Mammalian eggs are covered by thick glycoprotein coats, called zona pellucida (ZP), which contain glycans of varying structures that must be specifically recognized, and presumably cleaved, for fertilization to occur. Various experiments have implicated B1,4-galactosyltransferase 1 (B4GalT1) in the ability of mouse sperm to bind the ZP. Here I present evidence that additional members of the B4GalT family (specifically B4GalT3 and B4GalT4) are present on mouse and rat sperm, …
(S)-Trifluoroselenomethionine : A New Non-Natural Amino Acid With Enhanced Methioninase-Induced Cytotoxicity Toward Human Colon Cancer Cells, Stephene Nathele Lodge
(S)-Trifluoroselenomethionine : A New Non-Natural Amino Acid With Enhanced Methioninase-Induced Cytotoxicity Toward Human Colon Cancer Cells, Stephene Nathele Lodge
Legacy Theses & Dissertations (2009 - 2024)
Abstract