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Early Feeding In Lake Trout Fry (Salvelinus Namaycush) As A Mechanism For Ameliorating Thiamine Deficiency Complex, Carrie L. Kozel Jan 2017

Early Feeding In Lake Trout Fry (Salvelinus Namaycush) As A Mechanism For Ameliorating Thiamine Deficiency Complex, Carrie L. Kozel

Graduate College Dissertations and Theses

Recruitment failure of lake trout (Salvelinus namaycush) in the Great Lakes has been attributed in part to the consumption of alewife (Alosa pseudoharengus) by adult lake trout, leading to Thiamine Deficiency Complex (TDC) and early mortality in fry. The current understanding of thiamine deficiency in lake trout fry is based on information from culture and hatchery settings, which do not represent conditions fry experience in the wild and may influence the occurrence of TDC. In the wild, lake trout fry have access to zooplankton immediately following hatching; previous studies found that wild fry begin feeding before complete yolk-sac absorption. However, …


The Role Of Inflammasomes In Asbestos-Induced Mesothelial To Fibroblastic Transition, Joyce K. Thompson Jan 2017

The Role Of Inflammasomes In Asbestos-Induced Mesothelial To Fibroblastic Transition, Joyce K. Thompson

Graduate College Dissertations and Theses

Malignant Mesothelioma (MM) is a fatal disease with a low median survival between 8 to 12 months after diagnosis. MM has a long latency period (10-60 years), is causally related to asbestos exposure, and is refractory to all available modes of therapy. Despite the causal association between asbestos exposure and MM however, the mechanisms by which asbestos induces this deadly disease remain unclear. Chronic inflammation due to the presence of asbestos fibers is believed to play an important role in all aspects of MM pathogenesis, from development to progression and resistance. Chronic inflammation has been shown to promote dysregulated wound …


Transdermal Testosterone For Menopause-Related Hyposexual Desire Disorder: Current Guidelines And Provider Perceptions, Knowledge, And Practice, Kelly Christine White Jan 2017

Transdermal Testosterone For Menopause-Related Hyposexual Desire Disorder: Current Guidelines And Provider Perceptions, Knowledge, And Practice, Kelly Christine White

Graduate College Dissertations and Theses

Hypoactive sexual desire or low libido in women are collectively referred to as hypoactive sexual desire disorder (HSDD). HSDD is estimated to occur in 10% to 15% of adult women. HSDD is likely the most common female sexual dysfunction (FSD) in menopausal women. The hallmark of the diagnosis is personal distress and interpersonal difficulties resulting from low sex drive. Most women will not seek help for this problem. Studies have suggested that primary care providers and gynecologic healthcare providers report not feeling qualified to treat patients with sexual dysfunction, especially HSDD. Testosterone, specifically transdermal testosterone, has been suggested to play …


Predictive Modeling Of Adolescent Cannabis Use From Multimodal Data, Philip Spechler Jan 2017

Predictive Modeling Of Adolescent Cannabis Use From Multimodal Data, Philip Spechler

Graduate College Dissertations and Theses

Predicting teenage drug use is key to understanding the etiology of substance abuse. However, classic predictive modeling procedures are prone to overfitting and fail to generalize to independent observations. To mitigate these concerns, cross-validated logistic regression with elastic-net regularization was used to predict cannabis use by age 16 from a large sample of fourteen year olds (N=1,319). High-dimensional data (p = 2,413) including parent and child psychometric data, child structural and functional MRI data, and genetic data (candidate single-nucleotide polymorphisms, "SNPs") collected at age 14 were used to predict the initiation of cannabis use (minimum six occasions) by age 16. …


Molecular Mechanisms Of Mrna Transport By A Class V Myosin And Cytoplasmic Dynein, Thomas Edward Sladewski Jan 2017

Molecular Mechanisms Of Mrna Transport By A Class V Myosin And Cytoplasmic Dynein, Thomas Edward Sladewski

Graduate College Dissertations and Theses

mRNA localization ensures correct spatial and temporal control of protein synthesis in the cell. Using a single molecule in vitro approach, we provide insight into the mechanisms by which localizing mRNAs are carried by molecular motors on cytoskeletal tracks to their destination.

Budding yeast serves as a model system for studying the mechanisms of mRNA transport because localizing mRNAs are moved on actin tracks in the cell by a single class V myosin motor, Myo4p. Molecular motors that specialize in cargo transport are generally double-headed so that they can "walk" for many microns without dissociating, a feature known as processivity. …


Protein Kinase Mzeta (Pkm-Ζ) Regulates Kv1.2 Dependent Cerebellar Eyeblink Classical Conditioning, Kutibh Chihabi Jan 2017

Protein Kinase Mzeta (Pkm-Ζ) Regulates Kv1.2 Dependent Cerebellar Eyeblink Classical Conditioning, Kutibh Chihabi

Graduate College Dissertations and Theses

Learning and memory has been a topic that has captured the attention of the scientific and public communities since the dawn of scientific discovery. Without the faculty of memory, mammals cannot experience nor function in the world; among homosapiens specifically, language, relationships, and personal identity cannot be developed (Eysenck, 2012). After all, some philosophers such as John Locke argued we are nothing but a collection of past memories in which we have developed and improved upon (Nimbalkar, 2011).

Understanding the cellular mechanisms behind learning, and the subsequent formation of memory, has been a topic that has garnered scientific interest for …


Evolutionary Innovations In Ants To Thermally Stressful Environments, Andrew D. Nguyen Jan 2017

Evolutionary Innovations In Ants To Thermally Stressful Environments, Andrew D. Nguyen

Graduate College Dissertations and Theses

Temperature is a fundamental environmental force shaping species abundance and distributions through its effects on biochemical reaction rates, metabolism, activity, and reproduction. In light of future climate shifts, mainly driven by temperature increases, how will organisms persist in warmer environments? One molecular mechanism that may play an important role in coping with heat stress is the heat shock response (HSR), which protects against molecular damage. To prevent and repair protein damage specifically, Hsps activate and become up-regulated. However, the functional diversity and relevance of heat shock proteins (Hsps) in extending upper thermal limits in taxonomic groups outside marine and model …


Understanding The Role Of Runx2 In A Breast Cancer Progression Cell Model, Alexandra Ojemann Jan 2017

Understanding The Role Of Runx2 In A Breast Cancer Progression Cell Model, Alexandra Ojemann

Graduate College Dissertations and Theses

Runx2 is a transcription factor required for bone formation and osteoblastic differentiation during normal development and is implicated in metastatic disease during breast cancer progression. Runx2 is highly expressed in many metastatic breast cancers and breast cancer cell lines Knockdown of Runx2 in various breast cancer cell lines restores epithelial characteristics and reduces proliferation, migration, and invasion. However, the role of Runx2 in breast cancer progression from early to late stages is not well understood. The MCF10A derived breast cancer progression model provides the opportunity to study the role of Runx2 in a series of cell lines that progress from …


Activation Of Trpv1 Channel Contributes To Serotonin-Induced Constriction Of Mouse Facial Artery, Bolu Zhou Jan 2017

Activation Of Trpv1 Channel Contributes To Serotonin-Induced Constriction Of Mouse Facial Artery, Bolu Zhou

Graduate College Dissertations and Theses

Tight regulation of cephalic blood circulation is critical under normal physiological conditions, and dysregulation of blood flow to the head occurs in pathophysiological situations such as stroke and migraine headache. The facial artery is an extracranial artery which is one of branches from the external carotid artery territory and its extracranial position indicates its importance in regulating head hemodynamics. Transient receptor potential vanniloid type 1 (TRPV1) is a cation channel permeable to Ca2+ and Na+. Intracellular Ca2+ increase causes vasoconstriction. A previous study indicated the presence of TRPV1 in smooth muscle cells in the facial artery. Protein kinase C (PKC) …


Key Virus-Host Interactions Required For Arenavirus Particle Assembly And Release, Christopher Michael Ziegler Jan 2017

Key Virus-Host Interactions Required For Arenavirus Particle Assembly And Release, Christopher Michael Ziegler

Graduate College Dissertations and Theses

Viruses are infectious agents that must infect the cells of living organisms in order to reproduce. They have relatively simple genomes which encode few proteins but can compensate for their simplicity by hijacking components of their cellular hosts. Arenaviruses, a family of zoonotic viruses carried by rodents, encode only 4 proteins. One of these proteins, Z, is responsible for several functions during the virus life cycle including driving the formation and release of new virus particles at the plasma membrane of infected cells. Relatively little is known about how this viral protein is regulated or the complement of host proteins …


Integrating Human Population Genetics And Genomics To Elucidate The Etiology Of Brain Disorders, Arvis Sulovari Jan 2017

Integrating Human Population Genetics And Genomics To Elucidate The Etiology Of Brain Disorders, Arvis Sulovari

Graduate College Dissertations and Theses

Brain disorders present a significant burden on affected individuals, their families and society at large. Existing diagnostic tests suffer from a lack of genetic biomarkers, particularly for substance use disorders, such as alcohol dependence (AD). Numerous studies have demonstrated that AD has a genetic heritability of 40-60%. The existing genetics literature of AD has primarily focused on linkage analyses in small family cohorts and more recently on genome-wide association analyses (GWAS) in large case-control cohorts, fueled by rapid advances in next generation sequencing (NGS). Numerous AD-associated genomic variations are present at a common frequency in the general population, making these …


Silica Nanoparticles For The Delivery Of Dna And Rnai In Cancer Treatment, Michael Aaron Vrolijk Jan 2017

Silica Nanoparticles For The Delivery Of Dna And Rnai In Cancer Treatment, Michael Aaron Vrolijk

Graduate College Dissertations and Theses

DNA and interfering RNA (RNAi) – short interfering RNA (siRNA) and micro RNA (miRNA) – are promising new cancer therapies, especially for drug resistant lines. However, they require a delivery system in vivo to prevent degradation and off target effects. Silica based nanoparticles, both solid and mesoporous, are a promising option due to their biocompatibility, ease of preparation and morphology control, reproducibility, and facile addition of functional groups including targeting ligands.

After a brief introduction to cancer treatment and review of the current nanoparticle treatments undergoing clinical trials, this thesis details the many methods explored over the past ten years …


Imaging Pain And Brain Plasticity: A Longitudinal Structural Imaging Study, James Hart Bishop Jan 2017

Imaging Pain And Brain Plasticity: A Longitudinal Structural Imaging Study, James Hart Bishop

Graduate College Dissertations and Theses

Chronic musculoskeletal pain is a leading cause of disability worldwide yet the mechanisms of chronification and neural responses to effective treatment remain elusive. Non-invasive imaging techniques are useful for investigating brain alterations associated with health and disease. Thus the overall goal of this dissertation was to investigate the white (WM) and grey matter (GM) structural differences in patients with musculoskeletal pain before and after psychotherapeutic intervention: cognitive behavioral therapy (CBT). To aid in the interpretation of clinical findings, we used a novel porcine model of low back pain-like pathophysiology and developed a post-mortem, in situ, neuroimaging approach to facilitate translational …


Evolution Of Duplicated Han-Like Genes In Petunia X Hybrida., Beck Powers Jan 2017

Evolution Of Duplicated Han-Like Genes In Petunia X Hybrida., Beck Powers

Graduate College Dissertations and Theses

Gene duplications generate critical components of genetic variation that can be selected upon to affect phenotypic evolution. The angiosperm GATA transcription factor family has undergone both ancient and recent gene duplications, with the HAN-like clade displaying divergent functions in organ boundary establishment and lateral organ growth. To better determine the ancestral function within core eudicots, and to investigate their potential role in floral diversification, I conducted HAN-like gene expression and partial silencing analyses in the asterid species petunia (Petunia x hybrida). My results indicate duplication of HAN-like genes at the base of Solanaceae followed by expression diversification within the flower. …


Role Of Community Social Capital For Acute Food Security Following An Extreme Weather Event, Alana N. Chriest Jan 2017

Role Of Community Social Capital For Acute Food Security Following An Extreme Weather Event, Alana N. Chriest

Graduate College Dissertations and Theses

Worsening climate changes effects are predicted to increase the severity and frequency of extreme weather events (EWE), which can disrupt food systems, from the local to global level, and compromise community food security. In the rural U.S., food insecurity, poverty, low economic growth, and population loss are prevalent, and rural communities often lack the physical capital to bolster community resiliency to climate change adaptation. In 2011, Tropical Storm Irene (TS Irene) in Vermont was the most damaging EWE the state’s history. Severely damaged roads, infrastructure, homes, and land, rendered many rural towns isolated for up to several days. The levels …


Magnesium Intake And Depression In U.S. Adults, Emily Tarleton Jan 2017

Magnesium Intake And Depression In U.S. Adults, Emily Tarleton

Graduate College Dissertations and Theses

Research has focused extensively on the negative health effects of inadequate Mg intake, but the extent of the problem of deficiency deserves further exploration. The notion that U.S. adults consume an inadequate amount of magnesium, leading to increased risk for chronic diseases such as depression, is plausible. National Health and Nutrition Examination Surveys (NHANES), which are large, cross-sectional, population-based data sets that assess the health and nutritional status of U.S. adults and children, indicate over half the adult population does not consume adequate amounts of magnesium based on the estimated average requirement (EAR) established by the Institute of Medicine. Using …


The Effects Of Hypothalamic Brain-Derived Neurotrophic Factor On Catecholaminergic Regulation Of Cardiovascular Function., Nicholas Christopher Cruickshank Jan 2017

The Effects Of Hypothalamic Brain-Derived Neurotrophic Factor On Catecholaminergic Regulation Of Cardiovascular Function., Nicholas Christopher Cruickshank

Graduate College Dissertations and Theses

Considerable evidence supports the claim that a hyperactive sympathetic nervous system (SNS) is involved in most cases of human hypertension, and therefore a more thorough understanding of the central regulation of the SNS may help elucidate novel therapeutic options. The PVN is a key region in SNS regulation of blood pressure (BP) and heart rate (HR). Stimulation of the parvocellular PVN neurons has been shown to enhance sympathetic outflow and thereby increase BP. Brain-derived neurotrophic factor (BDNF), a modulator of neuronal activity is upregulated in the paraventricular nucleus of the hypothalamus (PVN) in response to several hypertensive stimuli such as …


Functional And Mechanistic Consequences Of Dual Oxidase 1 Suppression In Lung Cancer, Andrew Charles Little Jan 2017

Functional And Mechanistic Consequences Of Dual Oxidase 1 Suppression In Lung Cancer, Andrew Charles Little

Graduate College Dissertations and Theses

The NADPH oxidase homolog, dual oxidase 1 (DUOX1), is an H2O2 producing transmembrane enzyme highly expressed in the airway epithelium. DUOX1-dependent redox signaling has been characterized to regulate many homeostatic processes in the lung epithelium, such as host defense, wound healing, and type II immune responses. Intriguingly, DUOX1 has been found to be suppressed in many epithelial cancers, including lung cancer, by hypermethylation of its promoter. Epigenetic silencing of DUOX1 in cancer is paradoxical to the understanding that tumors harbor elevated levels of reactive oxygen species (ROS), suggesting that DUOX1 may be a tumor suppressor.

Since DUOX1 loss occurs in …


Assessing The Efficacy Of Two Species Of Silver Fly, Leucopis Argenticollis And L. Piniperda, As Biological Control Agents Of Hemlock Woolly Adelgid, Adelges Tsugae, Kyle Motley Jan 2017

Assessing The Efficacy Of Two Species Of Silver Fly, Leucopis Argenticollis And L. Piniperda, As Biological Control Agents Of Hemlock Woolly Adelgid, Adelges Tsugae, Kyle Motley

Graduate College Dissertations and Theses

Adelges tsugae Annand is a non-native invasive insect threatening the survival of eastern hemlock (Tsuga canadensis) and Carolina hemlock (T. caroliniana). A. tsugae is established in over half of the total range of eastern hemlock and the entire range of Carolina hemlock. Its continued spread, establishment and associated hemlock mortality make research into biological control of A. tsugae crucial. Field surveys of predators associated with A. tsugae in the Pacific Northwest identified a strong correlation between A. tsugae abundance with Laricobius nigrinus and two species of silver fly, Leucopis argenticollis and Leucopis piniperda. Flies in the genus Leucopis are known …


Assessment Of A Function For Threonyl-Trna Synthetase In Angiogenesis In A Mouse Ovarian Cancer Model, Peibin Wo Jan 2017

Assessment Of A Function For Threonyl-Trna Synthetase In Angiogenesis In A Mouse Ovarian Cancer Model, Peibin Wo

Graduate College Dissertations and Theses

Despite the high mortality rate of ovarian cancer, there are few selective biomarkers that detect its progression and none have become successful targets for therapy. A complex microenvironment that promotes angiogenesis, reduces immune responses and alters the integrity of the surrounding matrix is involved through the biology of ovarian cancer. Previous studies done by our lab and collaborators indicated that extracellular threonyl-tRNA synthetase (TARS) is a pro-angiogenic mediator of the ovarian tumor microenvironment, which is secreted in response to inflammatory signals, and actively promotes angiogenesis. In order to better understand the mechanisms underlying the angiogenic effects of TARS in ovarian …


Quantifying Tree Response To Alterations In Pollution Deposition And Climate Change In The Northeastern Us, Alexandra M. Kosiba Jan 2017

Quantifying Tree Response To Alterations In Pollution Deposition And Climate Change In The Northeastern Us, Alexandra M. Kosiba

Graduate College Dissertations and Theses

Understanding tree physiological responses to climate change is critical for quantifying forest carbon, predicting species' range change, and forecasting growth trajectories. Continued increases in temperature could push trees into conditions to which they are ill adapted -- such as decreased depth of winter snow cover, altered water regimes, and a lengthened effective growing season. A complicating factor is that in the northeastern United States, climate change is occurring on a backdrop of acid deposition and land-use change. In this dissertation, I used three studies to investigate the spatiotemporal nuances of resultant tree and sapling physiology to environmental change.

First, I …


Development And Implementation Of Methods To Study Crystallization In Cheese, Gil Fils Tansman Jan 2017

Development And Implementation Of Methods To Study Crystallization In Cheese, Gil Fils Tansman

Graduate College Dissertations and Theses

Dissolved compounds and ions, including mineral elements and products of microbial metabolism, are present in many cheeses in relatively high concentrations. These dissolved substances may precipitate from the aqueous phase of cheese to form sparingly soluble crystals that can impart a crunchy, gritty, or sandy texture on the cheese. In the present work, optical and diffractometric methods were optimized for use with cheese samples to identify crystal phases in several cheese varieties. These techniques, which included powder X-ray diffractometry (PXRD), single crystal X-ray diffractometry (SCXRD), and petrographic microscopy (PM) have traditionally been used on geological specimens that are quite different …


Social And Emotional Dimensions Of Succession Planning For Family Forest Owners In The Northeastern United States, Hallie E. Schwab Jan 2017

Social And Emotional Dimensions Of Succession Planning For Family Forest Owners In The Northeastern United States, Hallie E. Schwab

Graduate College Dissertations and Theses

Keeping forestland intact has emerged as a critical policy objective at state and federal levels. This target has been supported by substantial public investment. The collective impact from the bequest decisions of millions of landowning individuals and families has the potential to affect the extent and functionality of future forests in the United States. Despite a growing body of research devoted to studying these transitions in forest ownership, much remains unknown about how family forest owners make decisions in this arena. The social and emotional dimensions of woodland succession planning have been particularly under-examined. This thesis explores the process of …


Changes In Threonyl-Trna Synthetase Expression And Secretion In Response To Endoplasmic Reticulum Stress By Monensin In Ovarian Cancer Cells, Jared Louis Hammer Jan 2017

Changes In Threonyl-Trna Synthetase Expression And Secretion In Response To Endoplasmic Reticulum Stress By Monensin In Ovarian Cancer Cells, Jared Louis Hammer

Graduate College Dissertations and Theses

Aminoacyl-tRNA synthetases (ARS) are a family of enzymes that catalyze the charging of amino acids to their cognate tRNA in an aminoacylation reaction. Many members of this family have been found to have secondary functions independent of their primary aminoacylation function. Threonyl-tRNA synthetase (TARS), the ARS responsible for charging tRNA with threonine, is secreted from endothelial cells in response to both vascular endothelial growth factor (VEGF) and tumor necrosis factor-α (TNF-α), and stimulates angiogenesis and cell migration. Here we show a novel experimental approach for studying TARS secretion, and for observing the role of intracellular TARS in the endoplasmic reticulum …


Assessing Community Dynamics And Colonization Patterns Of Tritatoma Dimidiata And Other Biotic Factors Associated With Chagas Disease Prevalence In Central America, Lucia Consuelo Orantes Jan 2017

Assessing Community Dynamics And Colonization Patterns Of Tritatoma Dimidiata And Other Biotic Factors Associated With Chagas Disease Prevalence In Central America, Lucia Consuelo Orantes

Graduate College Dissertations and Theses

Chagas disease is caused by the parasite Trypanosoma cruzi and transmitted by multiple triatomine vectors across the Americas. In Central America, the predominant vector is Triatoma dimidiata, a highly adaptable and genetically diverse Hemiptera. In this research, we used a novel reduced-representation DNA sequencing approach to discover community dynamics among multiple biotic factors associated with Chagas disease in Central America, and assess the infestation patterns of T. dimidiata after seasonal and chemical disturbances in Jutiapa, Guatemala. For our first study, we used a hierarchical sampling design to obtain multi-species DNA data found in the abdomens of 32 T. dimidiata …


Interaction Of Stocking Density And The Feeding Environment In Lactating Holstein Dairy Cows, Mackenzie Andrew Campbell Jan 2017

Interaction Of Stocking Density And The Feeding Environment In Lactating Holstein Dairy Cows, Mackenzie Andrew Campbell

Graduate College Dissertations and Theses

Stocking density serves as a sub-clinical stressor impacting natural behavior and affective state of dairy cows. However, cows rarely experience stocking density as an isolated stressor. Understanding the effects of stocking density with additional management stressors such as low-fiber diets or feed restriction is the next step in alleviating stress and improving the well-being of lactating dairy cows housed in freestall barns. The overall goal of this dissertation was to evaluate the interaction of stocking density and the feeding environment on short-term production, behavioral, ruminal fermentation, and stress responses of lactating dairy cattle.

The first two studies (Chapter 2 and …


Technical Assistance And Farming At The Rural-Urban Interface: A Study Of Farmer Utilization And Related Attitudes, Elijah Massey Jan 2017

Technical Assistance And Farming At The Rural-Urban Interface: A Study Of Farmer Utilization And Related Attitudes, Elijah Massey

Graduate College Dissertations and Theses

The rural-urban interface (RUI) is a complex landscape impacted by a variety of social and economic processes. Substantial U.S. agricultural production occurs at the RUI despite non-farm development pressure. Notably, at a time when U.S. farming is increasingly dominated by a shrinking number of large scale operations, RUI agricultural production occurs primarily on small and medium farms. Importantly, RUI farms exhibit greater diversity in terms of operator demographics, production type, and marketing channels, than their large-scale counterparts.

A critical resource in the persistence of diverse RUI farms is Technical Assistance (TA). While TA is provided by a number of different …


New Approaches To Heterocycle Synthesis: A Greener Route To Structurally Complex Protonated Azomethine Imines, And Their Use In 1,3-Dipolar Cycloadditions, Ram Chandra Dhakal Jan 2017

New Approaches To Heterocycle Synthesis: A Greener Route To Structurally Complex Protonated Azomethine Imines, And Their Use In 1,3-Dipolar Cycloadditions, Ram Chandra Dhakal

Graduate College Dissertations and Theses

1-Aza-2-azoniaallene salts are reactive intermediates that undergo [3+2] cycloaddition with many different types of multiple bonds. For the past several years, the Brewer group has studied the reactivity of these intermediates in intramolecular reactions, and have discovered that these cationic heteroallenes can react through a variety of other, mechanistically distinct, pathways to give different classes of nitrogen heterocycles. For example, prior work in the Brewer group revealed that 1-aza-2-azoniaallene salts could react in an intramolecular [4+2] cycloaddition reaction to give protonated azomethine imine salts containing a 1,2,3,4-tetrahydrocinnoline scaffold. Further study of the scope and limitations of this Diels-Alder-like reaction are …


The Cardiovascular Epidemiology And Genome-Wide Associations Of Biomarkers Of Innate And Adaptive Immunity: Scd163 And Sil2ra, Jon Peter Durda Jan 2017

The Cardiovascular Epidemiology And Genome-Wide Associations Of Biomarkers Of Innate And Adaptive Immunity: Scd163 And Sil2ra, Jon Peter Durda

Graduate College Dissertations and Theses

Cardiovascular disease (CVD) is a major cause of morbidity and mortality in the U.S. and worldwide. Atherosclerosis, the buildup of plaque in the arteries, is a common cause of CVD. For many years, research in atherosclerosis was focused on lipid metabolism and the accumulation of low-density lipoprotein in the arteries. While this research set public health guidelines for lipid management, lipid concentration was not the only factor influencing atherosclerosis and CVD events. Many scientists, as far back as the 1850’s recognized the role of inflammation in the progression of atherosclerotic disease. The continuous low levels of immune activation in the …


The Biochemical Characterization Of Human Histidyl-Trna Synthetase And Disease Associated Variants, Jamie Alyson Abbott Jan 2017

The Biochemical Characterization Of Human Histidyl-Trna Synthetase And Disease Associated Variants, Jamie Alyson Abbott

Graduate College Dissertations and Theses

Human histidyl-tRNA synthetase (HARS) is an aminoacyl-tRNA synthetase (AARS) that catalyzes the attachment of the amino acid histidine to histidyl-tRNA (tRNAHis) in a two-step reaction that is essential for protein translation. Currently, two human diseases, Usher Syndrome IIIB (USH3B) and an inherited peripheral neuropathy, Charcot Marie Tooth Syndrome (CMT), have been linked genetically to single point mutations in the HARS gene. The recessive HARS USH3B mutation encodes an Y454S substitution localized at the interface between the anticodon-binding domain and the catalytic domain of the opposing subunit. Patients with Usher Syndrome IIIB lose their sight and hearing during their second decade …