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Pharmacological And Non-Pharmacological Treatments For The Neonatal Abstinence Syndrome (Nas)., A. K. Mangat, G. M. Schmölzer, W. K. Kraft

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Neonatal abstinence syndrome is defined by signs and symptoms of withdrawal that infants develop after intrauterine maternal drug exposure. All infants with documented in utero opioid exposure, or a high pre-test probability of exposure should have monitoring with a standard assessment instrument such as a Finnegan Score. A Finnegan score of >8 is suggestive of opioid exposure, even in the absence of declared use during pregnancy. At least half of infants in most locales can be treated without the use of pharmacologic means. For this reason, symptom scores will drive the decision for pharmacologic therapy. Nevertheless, all infants, regardless of …

Cyclin D1 Integrates G9a-Mediated Histone Methylation., Zhiping Li, Xuanmao Jiao, Gabriele Di Sante, Adam Ertel, Mathew C. Casimiro, Min Wang, Sanjay Katiyar, Xiaoming Ju, D. V. Klopfenstein, Aydin Tozeren, William Dampier, Iouri Chepelev, Albert Jeltsch, Richard G. Pestell

Department of Cancer Biology Faculty Papers

Lysine methylation of histones and non-histone substrates by the SET domain containing protein lysine methyltransferase (KMT) G9a/EHMT2 governs transcription contributing to apoptosis, aberrant cell growth, and pluripotency. The positioning of chromosomes within the nuclear three-dimensional space involves interactions between nuclear lamina (NL) and the lamina-associated domains (LAD). Contact of individual LADs with the NL are dependent upon H3K9me2 introduced by G9a. The mechanisms governing the recruitment of G9a to distinct subcellular sites, into chromatin or to LAD, is not known. The cyclin D1 gene product encodes the regulatory subunit of the holoenzyme that phosphorylates pRB and NRF1 thereby governing cell-cycle …

Identification Of Novel Regulatory Genes In Apap Induced Hepatocyte Toxicity By A Genome-Wide Crispr-Cas9 Screen., Katherine Shortt, Daniel P. Heruth, Nini Zhang, Weibin Wu, Shipra Singh, Ding-You Li, Li Qin Zhang, Gerald J. Wyckoff, Lei S Qi, Craig A. Friesen, Shui Qing Ye

Manuscripts, Articles, Book Chapters and Other Papers

Acetaminophen (APAP) is a commonly used analgesic responsible for more than half of acute liver failure cases. Identification of previously unknown genetic risk factors would provide mechanistic insights and novel therapeutic targets for APAP-induced liver injury. This study used a genome-wide CRISPR-Cas9 screen to evaluate genes that are protective against, or cause susceptibility to, APAP-induced liver injury. HuH7 human hepatocellular carcinoma cells containing CRISPR-Cas9 gene knockouts were treated with 15 mM APAP for 30 minutes to 4 days. A gene expression profile was developed based on the 1) top screening hits, 2) overlap of expression data from APAP overdose studies, …

Critical Role Of Post-Transcriptional Regulation For Ifn-Γ In Tumor-Infiltrating T Cells, Fiamma Salerno, Aurelie Guislain, Julian J. Freen-Van Heeren, Benoit P. Nicolet, Howard A. Young, Monika C. Wolkers

United States Public Health Resources

Protective T cell responses against tumors require the production of Interferon gamma (IFN-γ). However, tumor-infiltrating T cells (TILs) gradually lose their capacity to produce IFN-γ and therefore fail to clear malignant cells. Dissecting the underlying mechanisms that block cytokine production is thus key for improving T cell products. Here we show that although TILs express substantial levels of Ifng mRNA, post-transcriptional mechanisms impede the production of IFN-γ protein due to loss of mRNA stability. CD28 triggering, but not PD1 blocking antibodies, effectively restores the stability of Ifng mRNA. Intriguingly, TILs devoid of AU-rich elements within the 3ʹuntranslated region maintain stabilized …

The Underdeveloped Innate Immunity In Embryonic Stem Cells: The Molecular Basis And Biological Perspectives From Early Embryogenesis, Yan-Lin Guo

Faculty Publications

Embryonic stem cells (ESCs) have been intensively studied as a promising cell source for regenerative medicine. The rapid advancements in the field have not only proven the feasibility of ESC‐based cell therapy, but also led to a better understanding of pluripotent stem cells (PSCs) as a unique cell population at an early stage of embryogenesis. Recent studies have revealed that both human and mouse ESCs have attenuated innate immune responses to infectious agents and inflammatory cytokines. These findings raise interesting questions about the rationale for ESCs, the PSCs experimentally derived from preimplantation stage embryos, to not have an innate defense …

Roles For The Uptake2 Transporter Oct3 In Regulation Of Dopaminergic Neurotransmission And Behavior, Paul J. Gasser

Biomedical Sciences Faculty Research and Publications

Transporter-mediated uptake determines the peak concentration, duration, and physical spread of released monoamines. Most studies of monoamine clearance focus on the presynaptic uptake₁ transporters SERT, NET and DAT. However, recent studies have demonstrated the expression of the uptake₂ transporter OCT3 (organic cation transporter 3), throughout the rodent brain. In contrast to NET, DAT and SERT, OCT3 has higher capacity and lower affinity for substrates, is sodium-independent, and is multi-specific, with the capacity to transport norepinephrine, dopamine, serotonin and histamine. OCT3is insensitive to inhibition by cocaine and antidepressant drugs but is inhibited directly by the glucocorticoid hormone corticosterone. Thus, …

4-D Computational Modeling Of Cardiac Outflow Tract Hemodynamics Over Looping Developmental Stages In Chicken Embryos, Katherine Courchaine, Mackenzie J. Gray, Kaitlin Beel, Kent L. Thornburg, Sandra Rugonyi

OHSU-PSU School of Public Health Faculty Publications and Presentations

Cardiogenesis is interdependent with blood flow within the embryonic system. Recently, a number of studies have begun to elucidate the effects of hemodynamic forces acting upon and within cells as the cardiovascular system begins to develop. Changes in flow are picked up by mechanosensors in endocardial cells exposed to wall shear stress (the tangential force exerted by blood flow) and by myocardial and mesenchymal cells exposed to cyclic strain (deformation). Mechanosensors stimulate a variety of mechanotransduction pathways which elicit functional cellular responses in order to coordinate the structural development of the heart and cardiovascular system. The looping stages of heart …

A Paleolithic Diet Lowers Resistant Starch Intake But Does Not Affect Serum Trimethylamine-N-Oxide Concentrations In Healthy Women, Angela Genoni, Johnny Lo, Philippa Lyons-Wall, Mary C. Boyce, Claus T. Christophersen, Anthony Bird, Amanda Devine

Research outputs 2014 to 2021

The Paleolithic diet excludes two major sources of fibre, grains and legumes. However, it is not known whether this results in changes to resistant starch (RS) consumption. Serum trimethylamine-N-oxide (TMAO) is produced mainly from colonic fermentation and hepatic conversion of animal protein and is implicated in CVD, but changes in RS intake may alter concentrations. We aimed to determine whether intake of RS and serum concentrations of TMAO varied in response to either the Paleolithic or the Australian Guide to Healthy Eating (AGHE) diets and whether this was related to changes in food group consumption. A total of thirty-nine women …

The Morphology And Evolution Of The Primate Brachial Plexus, Brian M. Shearer

Dissertations, Theses, and Capstone Projects

Primate evolutionary history is inexorably linked to the evolution of a broad array of locomotor adaptations that have facilitated the clade’s invasion of new niches. Researchers studying the evolution of primates and of their individual locomotor adaptations have traditionally relied on bony morphology – a practical choice given the virtual non-existence of any other type of tissue in the fossil record. However, this focus downplays the potential importance of the many other structures involved in locomotion, such as muscle, cartilage, and neural tissue, which may each be influenced by separate selective forces because of their different roles in facilitating movement. …

The Influence Of Unpredictable, Fragmented Parental Signals On The Developing Brain, Laura M. Glynn, Tallie Z. Baram

Psychology Faculty Articles and Research

Mental illnesses originate early in life, governed by environmental and genetic factors. Because parents are a dominant source of signals to the developing child, parental signals - beginning with maternal signals in utero - are primary contributors to children’s mental health. Existing literature on maternal signals has focused almost exclusively on their quality and valence (e.g. maternal depression, sensitivity). Here we identify a novel dimension of maternal signals: their patterns and especially their predictability/unpredictability, as an important determinant of children’s neurodevelopment. We find that unpredictable maternal mood and behavior presage risk for child and adolescent psychopathology. In experimental models, fragmented/unpredictable …

The Tenets Of Teneurin: Conserved Mechanisms Regulate Diverse Developmental Processes In The Drosophila Nervous System, Alison T. Depew, Michael A. Aimino, Timothy J. Mosca

Department of Neuroscience Faculty Papers

To successfully integrate a neuron into a circuit, a myriad of developmental events must occur correctly and in the correct order. Neurons must be born and grow out toward a destination, responding to guidance cues to direct their path. Once arrived, each neuron must segregate to the correct sub-region before sorting through a milieu of incorrect partners to identify the correct partner with which they can connect. Finally, the neuron must make a synaptic connection with their correct partner; a connection that needs to be broadly maintained throughout the life of the animal while remaining responsive to modes of plasticity …

Transdisciplinarity At The Boundaries: Exploring A Sylvan Metaphor For Health, Peter J. Whitehouse

Faculty Scholarship

Transdisciplinarity is an action oriented intellectual and ethical endeavor to address complex ecological, economic, and political challenges that humans face. Language is viewed as a powerful tool for necessary cultural change. Blending art and science looking for the difficult to define but critically important hidden spaces between apparently rigid conceptual structures is a core of transdisciplinarity. Metaphor is a particular powerful tool for examining boundaries and developing creative blends of structures and processes. Forests are biologically and culturally critical to life on the planet. In this paper we explore, a performance character named Sylvanus, the Tree Doctor, named after the …

Itch Nuclear Translocation And H1.2 Polyubiquitination Negatively Regulate The Dna Damage Response, Lufen Chang, Lei Shen, Hu Zhou, Jing Gao, Hangyi Pan, Li Zheng, Brian Armstrong, Yang Peng, Guang Peng, Binhua P. Zhou, Steven T. Rosen, Binghui Shen

Molecular and Cellular Biochemistry Faculty Publications

The downregulation of the DNA damage response (DDR) enables aggressive tumors to achieve uncontrolled proliferation against replication stress, but the mechanisms underlying this process in tumors are relatively complex. Here, we demonstrate a mechanism through which a distinct E3 ubiquitin ligase, ITCH, modulates DDR machinery in triple-negative breast cancer (TNBC). We found that expression of a nuclear form of ITCH was significantly increased in human TNBC cell lines and tumor specimens. Phosphorylation of ITCH at Ser257 by AKT led to the nuclear localization of ITCH and ubiquitination of H1.2. The ITCH-mediated polyubiquitination of H1.2 suppressed RNF8/RNF168-dependent formation of 53BP1 foci, …

Absence Of Endothelial Α5Β1 Integrin Triggers Early Onset Of Experimental Autoimmune Encephalomyelitis Due To Reduced Vascular Remodeling And Compromised Vascular Integrity, Ravi Kant, Sebok K. Halder, Gregory J. Bix, Richard Milner

Sanders-Brown Center on Aging Faculty Publications

Early in the development of multiple sclerosis (MS) and its mouse model experimental autoimmune encephalomyelitis (EAE), vascular integrity is compromised. This is accompanied by a marked vascular remodeling response, though it is currently unclear whether this is an adaptive vascular repair mechanism or is part of the pathogenic process. In light of the well-described angiogenic role for the α5β1 integrin, the goal of this study was to evaluate how genetic deletion of endothelial α5 integrin (α5-EC-KO mice) impacts vascular remodeling and repair following vascular disruption during EAE pathogenesis, and how this subsequently influences clinical progression and inflammatory demyelination. Immunofluorescence staining …

Circular Rna Circnol10 Inhibits Lung Cancer Development By Promoting Sclm1-Mediated Transcriptional Regulation Of The Humanin Polypeptide Family, Aruo Nan, Lijian Chen, Nan Zhang, Yangyang Jia, Xin Li, Hanyu Zhou, Yihui Ling, Zhishan Wang, Chengfeng Yang, Sijin Liu, Yiguo Jiang

Toxicology and Cancer Biology Faculty Publications

circNOL10 is a circular RNA expressed at low levels in lung cancer, though its functions in lung cancer remain unknown. Here, the function and molecular mechanism of circNOL10 in lung cancer development are investigated using in vitro and in vivo studies, and it is shown that circNOL10 significantly inhibits the development of lung cancer and that circNOL10 expression is co‐regulated by methylation of its parental gene Pre‐NOL10 and by splicing factor epithelial splicing regulatory protein 1 (ESRP1). circNOL10 promotes the expression of transcription factor sex comb on midleg‐like 1 (SCML1) by inhibiting transcription factor ubiquitination and thus also affects regulation …

Biotransformed Metabolites Of The Hop Prenylflavanone Isoxanthohumol, Hyun Jung Kim, Soon-Ho Yim, Fubo Han, Bok Yun Kang, Hyun Jin Choi, Da-Woon Jung, Darren R. Williams, Kirk R. Gustafson, Edward J. Kennelly, Ik-Soo Lee

Publications and Research

A metabolic conversion study on microbes is known as one of the most useful tools to predict the xenobiotic metabolism of organic compounds in mammalian systems. The microbial biotransformation of isoxanthohumol (1), a major hop prenylflavanone in beer, has resulted in the production of three diastereomeric pairs of oxygenated metabolites (2–7). The microbial metabolites of 1 were formed by epoxidation or hydroxylation of the prenyl group, and HPLC, NMR, and CD analyses revealed that all of the products were diastereomeric pairs composed of (2S)- and (2R)- isomers. The structures of these metabolic compounds were elucidated to be (2S,200S)- and (2R,200S)-40 …

The Promises And Challenges Of Erythropoietin For Treatment Of Alzheimer's Disease, Jiahong Sun, Jan Michelle Martin, Victoria Vanderpoel, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Alzheimer’s disease (AD) is the most prevalent neurodegenerative disorder in the world, and intracellular neurofibrillary tangles and extracellular amyloid-beta protein deposits represent the major pathological hallmarks of the disease. Currently available treatments provide some symptomatic relief but fail to modify primary pathological processes that underlie the disease. Erythropoietin (EPO), a hematopoietic growth factor, acts primarily to stimulate erythroid cell production, and is clinically used to treat anemia. EPO has evolved as a therapeutic agent for neurodegeneration and has improved neurological outcomes and AD pathology in rodents. However, penetration of the blood–brain barrier (BBB) and negative hematopoietic effects are the two …

The Effect Of Nonassociative Learning On Oxidative Stress In Caenorhabditis Elegans: A Potential Application For Alzheimer’S Disease Research, Gillian Patton

Journal of the South Carolina Academy of Science

Alzheimer’s disease results in learning and memory deficits due to toxic changes in the brain caused by amyloid-β plaques and oxidative stress. Oxidative stress is caused by the overproduction of free radicals, which are uncharged molecules containing an unpaired valence electron. Nonassociative learning is a type of cognitive processing that only uses one stimulus instead of two related stimuli. Cognitive processing promotes neural growth and learning, while Alzheimer’s inhibits it. The purpose of this study was to test how nonassociative learning impacts oxidative stress and thus, if it might be considered as a potential treatment option for Alzheimer’s disease. It …

Impaired Nuclear Export Of Polyglutamine-Expanded Androgen Receptor In Spinal And Bulbar Muscular Atrophy., Frederick J. Arnold, Anna Pluciennik, Diane E. Merry

Department of Biochemistry and Molecular Biology Faculty Papers

Spinal and bulbar muscular atrophy (SBMA) is a neuromuscular disease caused by polyglutamine (polyQ) expansion in the androgen receptor (AR). Prior studies have highlighted the importance of AR nuclear localization in SBMA pathogenesis; therefore, in this study, we sought to determine the role of AR nuclear export in the pathological manifestations of SBMA. We demonstrate here that the nuclear export of polyQ-expanded AR is impaired, even prior to the formation of intranuclear inclusions of aggregated AR. Additionally, we find that promoting AR export with an exogenous nuclear export signal substantially reduces its aggregation and blocks hormone-induced toxicity. Moreover, we show …

The Effect Of Flavonoid Galangin On The Cell Viability And Toxicity Of Mcf-7 Human Breast Cancer Cells Exposed To Polycyclic Aromatic Hydrocarbons (Pahs), Abhimanyu Sailesh

Journal of the South Carolina Academy of Science

Polycyclic aromatic hydrocarbons (PAHs) are chemical compounds ubiquitous in the environment; many of which are known human and animal carcinogen. The purpose of this study was to investigate MCF-7 epithelial breast cancer cells’ viability and toxicity following a short-term in vitro exposure to a cocktail of PAHs and benzo[a]pyrene (B[a]P) separately in the presence and absence of varying concentrations of flavonoid galangin. It was predicted that presence of galangin will completely or partially block the damaging effects of PAHs. It was hypothesized that exposing the cells to 7 µM cocktail of PAHs or 10 µM B[a]P in the presence of …

The Effect Of Acetaminophen (Analgesic) And Diphenhydramine (Antihistamine) On Nociception Response Of Caenorhabditis Elegans, Heart Rate Of Eisenia Fetida, And Mortality Of Both E. Fetida And C. Elegans, Vamsi Gorrepati

Journal of the South Carolina Academy of Science

Pharmaceutical pollution continues to increase each year but its adverse effects on the environment are still largely unknown. Pharmaceuticals can enter the terrestrial ecosystem when animal manure and sewage sludge are applied to land as a fertilizer or when irrigated with contaminated water. To understand the extent to which common drugs impact the ecosystem, two commonly polluting pharmaceuticals, acetaminophen and diphenhydramine, which have been found in many cities such as Chicago, Dallas, and most notably The Great Lakes, were studied. Various concentrations were tested on E. fetida and C. elegans. Indicators such as heart rate were observed for E. …

Effectiveness Of Plant Species For Removing Atmospheric Ammonia, Marife B. Anunciado, Sheryll B. Jerez, Hans Williams, Joey Bray, Dean W. Coble, Rena Saito

Faculty Publications

Six plant species of Yaupon, Eastern red cedar, American holly, Arizona cypress, Arborvitae and Roughleaf dogwood were utilized to determine their effectiveness in the removal of atmospheric ammonia. All species were exposed to three ammonia levels (1, 5 and 10 ppm) in an environmental chamber. Foliar ammonia content was quantified using an enzymatic technique. The effects of exposure to ammonia on the physiological responses (e.g. photosynthetic activity, stomatal conductance, and transpiration rate) of plants in ambient condition were also determined using an open design photosynthetic gas exchange system. Foliar ammonia content was significantly different among the six plant species (p<0.0001) with Eastern red cedar exhibiting the highest content. The physiological responses differed significantly depending on the plant species and the ammonia treatment level. The photosynthetic response of plants to the presence of ammonia was mixed. At low exposure level, all species except Arborvitae had decreased photosynthetic activity, reducing by as much as 44.5% for Yaupon. At the highest concentration, however, Yaupon’s photosynthetic activity improved by about 10%. Exposure to ammonia caused increased stomatal conductance and transpiration rate on American holly and Arizona cypress, making them more susceptible to water loss.

Tubular Cell And Keratinocyte Single-Cell Transcriptomics Applied To Lupus Nephritis Reveal Type I Ifn And Fibrosis Relevant Pathways, E. Der, H. Suryawanshi, P. Morozov, M. Kustagi, Goilav, Ranabathou, P. Izmirly, A. Davidson, R. Furie, F. Zhang, +57 Additional Authors

Journal Articles

© 2019, The Author(s), under exclusive licence to Springer Nature America, Inc. The molecular and cellular processes that lead to renal damage and to the heterogeneity of lupus nephritis (LN) are not well understood. We applied single-cell RNA sequencing (scRNA-seq) to renal biopsies from patients with LN and evaluated skin biopsies as a potential source of diagnostic and prognostic markers of renal disease. Type I interferon (IFN)-response signatures in tubular cells and keratinocytes distinguished patients with LN from healthy control subjects. Moreover, a high IFN-response signature and fibrotic signature in tubular cells were each associated with failure to respond to …

Mus Musculus Deficient For Secretory Antibodies Show Delayed Growth With An Altered Urinary Metabolome, K. R. Simpfendorfer, N. Wang, D. L. Tull, D. P. De Souza, A. Nahid, A. Mu, D. M. Hocking, J. S. Pedersen, O. L. Wijburg, R. A. Strugnell, +1 Additional Author

Journal Articles

© 2019 The Author(s). Background: The polymeric immunoglobulin receptor (pIgR) maintains the integrity of epithelial barriers by transporting polymeric antibodies and antigens through the epithelial mucosa into the lumen. In this study, we examined the role of pIgR in maintaining gut barrier integrity, which is important for the normal development in mice. Methods: Cohorts of pIgR -/- mice and their wildtype controls were housed under Specific Pathogen Free (SPF) conditions and monitored for weight gain as an indicator of development over time. The general physiology of the gastrointestinal tract was analysed using immunohistochemistry in young (8-12 weeks of age) and …

Ca2+ Sensor Synaptotagmin-1 Mediates Exocytosis In Mammalian Photoreceptors, Justin J. Grassmeyer, Asia L. Cahill, Cassandra L. Hays, Cody Barta, Rolen M. Quadros, Channabasavaiah B. Gurumurthy, Wallace B. Thoreson

Journal Articles: Pharmacology & Experimental Neuroscience

To encode light-dependent changes in membrane potential, rod and cone photoreceptors utilize synaptic ribbons to sustain continuous exocytosis while making rapid, fine adjustments to release rate. Release kinetics are shaped by vesicle delivery down ribbons and by properties of exocytotic Ca²⁺ sensors. We tested the role for synaptotagmin-1 (Syt1) in photoreceptor exocytosis by using novel mouse lines in which Syt1 was conditionally removed from rods or cones. Photoreceptors lacking Syt1 exhibited marked reductions in exocytosis as measured by electroretinography and single-cell recordings. Syt1 mediated all evoked release in cones, whereas rods appeared capable of some slow Syt1-independent release. Spontaneous …

Intranasal Peptide-Based Fpva-Klh Conjugate Vaccine Protects Mice From Pseudomonas Aeruginosa Acute Murine Pneumonia, Emel Sen-Kilic, Catherine B. Blackwood, Dylan T. Boehm, Wiliam T. Witt, Aaron C. Malkowski, Justin R. Bevere, Ting Y. Wong, Jesse M. Hall, Shelby D. Bradford, Melinda E. Varney, Fredrick Heath Damron, Mariette Barbier

Faculty & Staff Scholarship

Pseudomonas aeruginosa is an opportunistic pathogen causing acute and chronic respiratory infections associated with morbidity and mortality, especially in patients with cystic fibrosis. Vaccination against P. aeruginosa before colonization may be a solution against these infections and improve the quality of life of at-risk patients. To develop a vaccine against P. aeruginosa, we formulated a novel peptide-based P. aeruginosa subunit vaccine based on the extracellular regions of one of its major siderophore receptors, FpvA. We evaluated the effectiveness and immunogenicity of the FpvA peptides conjugated to keyhole limpet hemocyanin (KLH) with the adjuvant curdlan in a murine vaccination and challenge …

Measurement Precision And Reliability Of Supraspinatus Tendon Strain Using Speckle Track Analysis Of Ultrasound Images, Gregory Alan Mcclanahan

Theses, Dissertations and Capstones

Introduction: Ultrasound speckle tracking is an emergent method in studying musculoskeletal physiology and disease. For a method to be effective and useful, it needs to be precise and reliable. The precision and reliability of supraspinatus tendon strain measurements have not been explored. The purpose of this study was to examine the precision and reliability of speckle tracking to measure supraspinatus tendon strain.

Methods: Forty-two (42) participants participated in this study. Five (5) ultrasound images of the participant’s right shoulder supraspinatus tendon were collected during a maximal voluntary isometric abduction contraction. Cine loop video files of the 5 imaging trials …

Mechanistic Study Of Diatrizoic Acid Induced Proximal Tubule Cytotoxicity, Dakota Blake Ward

Theses, Dissertations and Capstones

Radiocontrast media (RCM) are necessary for many diagnostic procedures such as arteriography, percutaneous coronary intervention (PCI), and computed tomography. Contrast-induced acute kidney injury (CI-AKI) is the third most common cause of hospital-associated kidney damage accounting for 10-25% of cases worldwide. The mechanisms of contrast-induced renal impairment are not entirely known, but diminished renal hemodynamics, inflammatory responses, and direct cytotoxicity have been hypothesized. The purpose of this study was to investigate the mechanisms of direct cytotoxicity observed in HK-2 cells following treatment with diatrizoic acid (DA) and to determine the source of this damage. Mitochondrial function, endoplasmic reticulum (ER) stress, oxidative …

Regulation Of Na-K-Atpase By Arachidonic Acid Metabolites In Intestinal Epithelial Cells, Niraj Nepa

Theses, Dissertations and Capstones

The integral membrane protein sodium potassium adenosine triphosphate (Na-K-ATPase), has been extensively studied in various animal cell models. Na-K-ATPase is a multifunctional enzyme which plays a significant role in cellular physiology by regulating electrochemical potential, cell volume, pH, cytosolic calcium, and many nutrient and electrolyte transport processes. As such, it has been implicated in the pathogenesis of inflammatory bowel diseases (IBD) and has been shown to play a vital role in the malabsorption of nutrients and electrolytes. In this context, a significant amount of research has been done over the last two decades to understand the mechanisms of alteration of …

Interplay Between Genetic Predisposition And Diet In Advancing Obesity And Type 2 Diabetes In The Tallyho Mouse, Jacaline Parkman

Theses, Dissertations and Capstones

Obesity is a global epidemic, affecting all ages. It is one of the leading causes of preventable death, as it increases the risk of type 2 diabetes (T2D), hypertension, cardiovascular disease, nonalcoholic fatty liver disease, and some cancers. Obesity is a complex disease that is caused by a combination of genetic and environmental factors such as diets high in fat and sedentary life style. Despite our increased knowledge of obesity development and progression, current obesity treatments have not stopped the rise in obesity rates. There are still many unknowns related to the underlying mechanisms of obesity that need to be …