Diseases Commons^™

Functional Characterization Of Scaffold Protein Shoc2, Hyein Jang

Theses and Dissertations--Molecular and Cellular Biochemistry

Signaling scaffolds are critical for the correct spatial organization of enzymes within the ERK1/2 signaling pathway and proper transmission of intracellular information. However, mechanisms that control molecular dynamics within scaffolding complexes, as well as biological activities regulated by the specific assemblies, remain unclear.

The scaffold protein Shoc2 is critical for transmission of the ERK1/2 pathway signals. Shoc2 accelerates ERK1/2 signaling by integrating Ras and RAF-1 enzymes into a multi-protein complex. Germ-line mutations in shoc2 cause Noonan-like RASopathy, a disorder with a wide spectrum of developmental deficiencies. However, the physiological role of Shoc2, the nature of ERK1/2 signals transduced through this …

Interleukin-6 And Exercise; Early Evidence Of A Novel Myokine, Brendan Hogg Mr.

Graduate Student Theses, Dissertations, & Professional Papers

Interleukin-6 (IL-6) was first identified as a pleiotropic cytokine, with a host of body-wide functions. Cytokine functions are characterized by chronically elevated levels within various inflammatory states. In this regard, IL-6 is largely associated with the acute phase response to many stimuli and performs specific actions when produced from certain cell types. Accrued evidence indicates IL-6 release from skeletal muscle often includes myokine functions. Novel myokine functions are adaptive in nature, and as compared to inflammatory/cytokine roles, exhibit a transient time course. Following exercise plasma IL-6 peaks and returns to resting levels within 1-2 hours. In contrast, IL-6 is observed …

Wild-Type P53 Enhances Endothelial Barrier Function By Mediating Rac1 Signalling And Rhoa Inhibition, Nektarios Barabutis, Christiana Dimitropoulou, Betsy Gregory, John D. Catravas

Bioelectrics Publications

Inflammation is the major cause of endothelial barrier hyper-permeability, associated with acute lung injury and acute respiratory distress syndrome. This study reports that p53 "orchestrates" the defence of vascular endothelium against LPS, by mediating the opposing actions of Rac1 and RhoA in pulmonary tissues. Human lung microvascular endothelial cells treated with HSP90 inhibitors activated both Rac1- and P21-activated kinase, which is an essential element of vascular barrier function. 17AAG increased the phosphorylation of both LIMK and cofilin, in contrast to LPS which counteracted those effects. Mouse lung microvascular endothelial cells exposed to LPS exhibited decreased expression of phospho-cofilin. 17AAG treatment …

Enhanced Electric Pulse Technology For The Ablation Of Pancreatic Cancer, Siqi Guo, Niculina I. Burcus, Chelsea M. Edelblute, James Hornef, Chunqi Jiang, Karl Schoenbach, Richard Heller, Stephen J. Beebe

Bioelectrics Publications

Electric pulse based technology has been developed and studied as a non-thermal ablation method for local control of pancreatic cancer. Irreversible electroporation (IRE) has shown a significant survival benefit for local advanced pancreatic cancer in clinical trials. However, incomplete ablation with local recurrence and major complications limit the potential of this new technology. We have developed an integrated moderate heating electric pulse delivery system which consists of controllable tumor heating, multi-parameter monitoring and electric pulse delivery. The impedance of tumor is greatly decreased after moderate heating at 42°C for 1–2 min, which does not cause any cell death. Moderate heating …

Objectively Measuring Effects Of Electro-Acupuncture In Parkinsonian Rhesus Monkeys, Rui Zhang, Anders H. Andersen, Peter A. Hardy, Eric Forman, April Evans, Yi Ai, Jin Yue, Guihua Yue, Don M. Gash, Richard Grondin, Zhiming Zhang

Magnetic Resonance Imaging and Spectroscopy Center Faculty Publications

Acupuncture has increasingly been used as an alternative therapy for treatment of Parkinson’s disease (PD). However, the efficacy of acupunture for PD still remains unclear. The present study was designed to objectively and safely monitor anti-parkinsonian effects of electroacupuncture (EA) and brain activity in nonhuman primates modeling human PD. Six middle-aged rhesus monkeys were extensively studied by a computerized behavioral testing battery and by pharmacological MRI (phMRI) scans with specific dopaminergic drug stimulations. All animals were evaluated for behavior and phMRI responses under normal, parkinsonian, parkinsonian with EA treatment and parkinsonian after EA treatment conditions. Stable parkinsonian features were observed …

Exogenous Fniii 12-14 Regulates Tgf-Β1-Induced Markers, Hilmi M. Humeid

Theses and Dissertations

The extracellular matrix protein Fibronectin (FN) plays an important role in cell contractility, differentiation, growth, adhesion, and migration. The 12th -14th Type III repeats of FN (FNIII 12-14), also referred to as the Heparin-II domain, comprise a highly promiscuous growth factor (GF) binding region. This binding domain aids in cellular signaling initiated from the ECM. Additionally, FN has the ability to assemble into fibrils under certain conditions, mostly observed during cell contractile processes such as those that initiate due to upregulation of Transforming Growth Factor Beta 1 (TGF-β1) [1], [2]. Previous work from our lab has shown that self-assembly of …

5-Ht2b Receptor-Mediated Cardiac Valvulopathy, Pallavi Nistala

Theses and Dissertations

5-HT_2B receptor agonism causes cardiac valvulopathy, a condition characterized by thickening of the heart valves and as a result, regurgitation of blood within the heart. The anti-obesity drug fenfluramine, which was originally prescribed as an anorectic, was withdrawn from the market due to causing cardiac valvulopathy. Fenfluramine, after metabolism by N-dealkylation, produces the metabolite norfenfluramine, which acts as a more potent valvulopathogen. The same was seen with MDMA (ecstasy), a popular drug of abuse, which is metabolized by N-dealkylation to produce MDA, a more potent valvulopathogen. Glennon and co-workers. studied a series of 2,5-dimethoxy-4- substituted phenylisopropylamines (DOX type) hallucinogens …

Multivariate Analysis To Identify Potential Biomarkers For Prognosis And Treatment Resistance In Head And Neck Cancer Patients, Christina Ann Wicker

Theses and Dissertations--Toxicology and Cancer Biology

It is estimated that nearly 50,000 individuals in the United States will be diagnosed with head and neck cancer in 2017 (American Cancer Society www.cancer.org). Ninety percent of oral cancers are head and neck squamous cell carcinoma (HNSCC). Major obstacles in the treatment of HNSCC are recurrence and treatment resistance, which contributes to increased mortality. Therefore, there is increased need to determine genetic alterations in HNSCC that may be ideal novel drug targets, and biomarkers to improve diagnostic and prognostic testing.

Abnormal localization and overexpression of base excision repair protein and transcriptional regulator Apurinic/Apyrimidic endonuclease (APE1) has been associated with …

Surveillance Of South Dakota Mosquito Abundance, Infection Rate, And Insecticide Susceptibility, Geoffrey P. Vincent

Electronic Theses and Dissertations

The aim of this dissertation was to survey and evaluate the abundance, infection rate, and insecticide susceptibility of mosquito fauna present in South Dakota. Mosquito surveillance has been conducted across South Dakota to record and track potential West Nile virus (WNV) vectors from 2004 to 2017. The nuisance mosquito Aedes vexans was found to be the most abundant species overall in the state and most abundant in many of the regions. The WNV vector, Culex tarsalis, was found to be the second most abundant mosquito and the most abundant vector mosquito across the state. However, geospatial variation did exist between …

Pathogenic Mechanisms Of Takotsubo Cardiomyopathy Or Broken Heart Syndrome, Devorah Leah Borisute

The Science Journal of the Lander College of Arts and Sciences

Takotsubo Cardiomyopathy (TTC) is a temporary heart-wall motion abnormality with the clinical presentation of a myocardial infarction. Found predominantly in postmenopausal women, TTC most often appears with apical ballooning and mid-ventricle hypokinesis. Often induced by an emotional or physical stress, TTC is reversible and excluded as a diagnosis in patients with acute plaque rupture and obstructive coronary disease. The transient nature and positive prognosis of this cardiomyopathy leaves a dilemma as to what precipitates it. This paper explores the theories of the pathogenesis of TTC including coronary artery spasm, microvascular dysfunction, and catecholamine excess. A thorough analysis of the pathogenesis …

Is Detection Of Preclinical Alzheimer’S Disease Possible?, Shana Brawer

The Science Journal of the Lander College of Arts and Sciences

No abstract provided.

Muscle Synergy During A Single Leg Standing Test In Ambulatory Children With Cerebral Palsy, Brennan L. Smith

Theses and Dissertations--Kinesiology and Health Promotion

INTRODUCTION: Cerebral Palsy (CP) is a sensorimotor disorder characterized by dysfunctional motor coordination, balance problems, and loss of selective motor control. Motor coordination exhibited as co-contraction, has been subjectively quantified using gait analysis, but recent studies have begun to objectively analyze the amount of co-contraction by collecting electromyography (EMG) data. Center of pressure excursion (COPE) measurements collected during a single leg standing test (SLST) have shown to be more valid measurements of balance in populations with motor disabilities than a SLST alone. A recent study has correlated increased COPE velocity with a lower fall risk as determined by reported fall …

Discovery Of New Antimicrobial Options And Evaluation Of Aminoglycoside Resistance Enzyme-Associated Resistance Epidemic, Selina Y. L. Holbrook

Theses and Dissertations--Pharmacy

The extensive and sometimes incorrect and noncompliant use of various types of antimicrobial agents has accelerated the development of antimicrobial resistance (AMR). In fact, AMR has become one of the greatest global threat to human health in this era. The broad-spectrum antibiotics aminoglycosides (AGs) display excellent potency against most Gram-negative bacteria, mycobacteria, and some Gram-positive bacteria, such as Staphylococcus aureus. The AG antibiotics amikacin, gentamicin, kanamycin, and tobramycin are still commonly prescribed in the U.S.A. for the treatment of serious infections. Unfortunately, bacteria evolve to acquire resistance to AGs via four different mechanisms: i) changing in membrane permeability to …

Role Of Sex Chromosomes In Sexual Dimorphism Of Angii-Induced Abdominal Aortic Aneurysms, Yasir Alsiraj

Theses and Dissertations--Pharmacology and Nutritional Sciences

Abdominal aortic aneurysms (AAAs), a permanent dilation in the abdominal region of the aorta, is a highly sexually dimorphic disease. AAAs prevalence is ranging from 4-10 fold higher in males than females. Defining the mechanistic basis for reduced (in females) or increased (in males) AAA formation and progression may uncover potential therapeutic targets. The majority of studies examining sexual dimorphism focus on the role of sex hormones. However, genes residing on sex chromosomes, in addition to sex hormones, may contribute to sexual dimorphism of AAAs. For example, the X chromosome contains about 5% of the whole genome, but the role …

Insulin-Like Growth Factor-1 Overexpression Mediates Hippocampal Remodeling And Plasticity Following Tbi, Erica Latrice Littlejohn

Theses and Dissertations--Physiology

Every year over 2.5 million traumatic brain injuries (TBI) occur and are the leading cause of death and disability among adolescents. There are no approved treatments for TBI. Survivors suffer from persistent cognitive impairment due to posttraumatic tissue damage and disruption of neural networks which significantly detract from their quality of life. Posttraumatic cognitive impairment depends in part on the brain's limited ability to repair or replace damaged cells. Immature neurons in the hippocampus dentate gyrus, a brain region required for learning and memory, are particularly vulnerable to TBI. Insulin-like growth factor-1 (IGF1) is a potential therapeutic for TBI because …

Mechanisms And Potential Therapy On Disrupted Blood Pressure Circadian Rhythm In Diabetes, Tianfei Hou

Theses and Dissertations--Pharmacology and Nutritional Sciences

Arterial blood pressure (BP) undergoes a 24-hour oscillation that peaks in the active day and reaches a nadir at night during sleep in humans. Reduced nocturnal BP fall (also known as non-dipper) is the most common disruption of BP circadian rhythm and is associated with increased risk of untoward cardiovascular events and target organ injury. Up to 75% of diabetic patients are non-dippers. However, the mechanisms underlying diabetes associated non-dipping BP are largely unknown. To address this important question, we generated a novel diabetic db/db-mPer2^Luc mouse model (db/db-mPer2^Luc) that allows quantitatively measuring of mPER2 protein oscillation …

Antibody Dependent Enhancement Of Visceral Leishmaniasis, Alan K. Mcnolty

All Master's Theses

Leishmaniasis is a parasitic disease caused by protozoans of the genus Leishmania. This vector-born disease, transmitted by biting phlebotomine sandflies, typically manifests in one of three ways. The cutaneous form of the disease is characterized by localized lesions of the skin and is by far the most common manifestation. The visceral form of the disease is caused by parasitic infiltration of internal organs, particularly the spleen, liver, and bone marrow. The mucocutaneous form is caused by parasitic infection of the mucosa in the nose or mouth. While cutaneous leishmaniasis (CL) is often self-healing, visceral leishmaniasis (VL) is fatal if …

Comparative Genetic And Genomic Analysis Of The Novel Fusellovirus Sulfolobus Spindle-Shaped Virus 10, David Andrew Goodman, Kenneth M. Stedman

Biology Faculty Publications and Presentations

Viruses that infect thermophilic Archaea are unique in both their structure and genetic makeup. The lemon-shaped fuselloviruses—which infect members of the order Sulfolobales, growing optimally at 80 C and pH 3—are some of the most ubiquitous and best studied viruses of the thermoacidophilic Archaea. Nonetheless, much remains to be learned about these viruses. In order to investigate fusellovirus evolution, we have isolated and characterized a novel fusellovirus, Sulfolobus spindle-shaped virus 10 (formerly SSV-L1). Comparative genomic analyses highlight significant similarity with both SSV8 and SSV9, as well as conservation of promoter elements within the Fuselloviridae. SSV10 encodes five ORFs with no …

Serum Tumor Necrosis Factor-Alpha Associates With Myocardial Oxygen Demand And Exercise Tolerance In Postmenopausal Women, Stephen J. Carter, David R. Bryan, William H. Neumeier, Stephen P. Glasser, Gary R. Hunter

Internal Medicine Faculty Publications

The functional implications of serum tumor necrosis factor-alpha (TNF-α), a marker of oxidative stress, on hemodynamic parameters at rest and during physical exertion are unclear. The aims of this investigation were to examine the independent associations of TNF-α on myocardial oxygen demand at rest and during submaximal exercise, while also evaluating the association of TNF-α on exercise tolerance. Forty, postmenopausal women, provided blood samples and completed a modified-Balke protocol to measure maximal oxygen uptake (VO_2max). Large artery compliance was measured by pulse contour analyses while rate-pressure product (RPP), an index of myocardial oxygen demand, was measured at rest …

Novel Survivin Inhibitor For Suppressing Pancreatic Cancer Cells Growth Via Downregulating Sp1 And Sp3 Transciption Factors, Myrna Hurtado, Umesh T. Sankpal, Aboubacar Kaba, Shahela Mahammad, Jaya Chhabra, Deondra T. Brown, Raj K. Gurung, Alvin A. Holder, Jamboor K. Vishwanatha, Riyaz Basha

Chemistry & Biochemistry Faculty Publications

Background/Aims: Targeting survivin, an anti-apoptotic protein and mitotic regulator, is considered as an effective therapeutic option for pancreatic cancer (PaCa). Tolfenamic acid (TA) showed anti-cancer activity in pre-clinical studies. A recent discovery demonstrated a copper(II) complex of TA (Cu-TA) can result in higher activity. In this study, the ability of Cu-TA to inhibit survivin and its transcription factors, Specificity protein (Sp) 1 and 3 in PaCa cell lines and tumor growth in mouse xenograft model were evaluated.

Methods: Cell growth inhibition was measured in MIA PaCa-2 and Panc1 cells for 2 days using CellTiter-Glo kit. Sp1, Sp3 and survivin expression …

Lack Of Delayed-Type Hypersensitivity In Striped Bass (Morone Saxatilis), Jessica Shannon Miller

Biological Sciences Theses & Dissertations

Mycobacteriosis is a fatal disease in fishes caused by acid-fast bacteria in the genus Mycobacterium. This disease impacts aquaculture, aquariums, and wild fishes. Unfortunately, there are currently no non-lethal diagnostic tests for mycobacterial infection in fishes. Type IV delayed type hypersensitivity (DTH) responses in vivo and in vitro are currently used for the non-lethal detection of mycobacterial infections in humans and in animals; however, there is little information available on DTH responses in fishes. In this work, we examine in vivo DTH response in Striped Bass (Morone saxatilis), an important U.S. Eastern seaboard fish species, experimentally …

Controlling Platelet Secretion To Modulate Hemostasis And Thrombosis, Smita Joshi

Theses and Dissertations--Molecular and Cellular Biochemistry

Upon vascular injury, activated blood platelets fuse their granules to the plasma membrane and release cargo to regulate the vascular microenvironment, a dynamic process central to platelet function in many critical processes including hemostasis, thrombosis, immunity, wound healing, angiogenesis etc. This granule- plasma membrane fusion is mediated by a family of membrane proteins- Soluble N-ethyl maleimide Attachment Receptor Proteins(SNAREs). SNAREs that reside on vesicle (v-SNAREs) /Vesicle-Associated Membrane Proteins(VAMPs) interact with target/t-SNAREs forming a trans-bilayer complex that facilitates granule fusion. Though many components of exocytic machinery are identified, it is still not clear how it could be manipulated to prevent …

Neurological Involvement Associated With Plasmodium Vivax Malaria From Pakistan, Yousaf Abdullah Khan, Usman Hameed Mian, Najia Karim Ghanchi, Ali Bin Sarwar Zubairi, Mohammad Asim Beg

Department of Pathology and Laboratory Medicine

Plasmodium vivax is the most common specie causing malaria outside Africa with approximately 13.8 million reported cases worldwide. We report case of P. vivax infection with cerebral involvement. A nine year old boy presented with high grade fever accompanied by projectile vomiting and abnormal behavior later he developed seizures, shock, and unconsciousness. P. vivax monoinfection was diagnosed based on peripheral smears and PCR. After antimalarial therapy, patient made full recovery. Current case highlights increasing trend of cerebral complications caused by P. vivax.

Exploring H.Pylori Seropositivity As A Risk Factor For Type 2 Diabetes, Virginia Chaidez, Yumou Qiu

Department of Nutrition and Health Sciences: Faculty Publications

Background: In the US, the percentage of adults with diagnosed diabetes are higher in members of racial and ethnic minority groups compared to non-Latino Whites. Understanding why such disparities exist has been less forthcoming.

Methods: Secondary data analysis was conducted using the National Health and Nutrition Examination Survey (NHANES) 1999-2000 cross-sectional data.

Results: H.pylori seropositivity was highest in Mexican Americans (43.7%), lowest in non- Hispanic Whites (18.1%). Diabetes was highest in non-Hispanic Blacks (5.9%); lowest in non-Hispanic whites (4.3%). H.pylori seropositivity was associated with greater likelihood of having type 2 diabetes (1.927, 95% CI 1.142, 3.257) compared to H.pylori negative …

Evaluation Of A Handheld Gluten Detection Device, Steve L. Taylor, Julie A. Nordlee, Shyamali Jayasena, Joseph L. Baumert

Department of Food Science and Technology: Faculty Publications

A portable, handheld gluten detection device, the Nima sensor, is now available for consumers wishing to determine if gluten is present in food. By United States regulation, gluten-free foods should contain < 20 ppm of gluten. Thirteen gluten-free foods (muffins, three different types of bread, three different types of pasta, puffed corn snack, ice cream, meatballs, vinegar and oil salad dressing, oatmeal, and dark chocolate) were prepared; each food was spiked on a weight-to-weight basis with gluten levels of 0, 5, 10, 20, 30, 40, and 100 ppm before processing or preparation. Unprocessed and processed foods were tested with the handheld gluten sensor and by two gluten-specific enzyme-linked immunosorbent assays (ELISAs) on the basis of the R5 and G12 monoclonal antibodies, respectively. The portable gluten detection device detected gluten in all food types at the 30-ppm addition level, failing to detect gluten in only 5 (6.4%) of 78 subsamples. At the 20-ppm addition level, the portable gluten detection device failed to detect gluten in one type of pasta but detected gluten residues in 63 (87.5%) of 72 other subsamples. The device was able to detect gluten at the 10-ppm addition level in 9 of the 13 food matrices (41 of 54 subsamples, 75.9%) but not in the three types of pasta and the puffed corn snack. The gluten-sensing device did not perform reliably at the 5-ppm addition level in 11 of 13 food matrices (exceptions: ice cream and muffins). In contrast, the ELISA methods were highly reliable at gluten addition levels of ≥ 10 ppm in all food matrices. The portable gluten detection device yielded a low percentage of false-positive results (4 of 111, 3.6%) in these food matrices. Thus, this handheld portable gluten sensor performed reliably in the detection of gluten in foods having ≥ 20 ppm of added gluten with only 18 (5.9%) of 306 failures, if results of the one type of pasta are excluded. The device worked with greater reliability as the gluten levels in the foods increased.

Concepts In Animal Parasitology: Example Chapter Section, Manuscript Of The Aspidogastrea By Klaus Rohde, Klaus Rohde

Concepts in Animal Parasitology

This is an example chapter section for Concepts in Animal Parasitology. It is a manuscript of the section titled The Aspidogastrea, written by by Klaus Rohde. This is an example of a section written without using the optional template for Parts 2-5 of the textbook. The associated images are included in a supplemental file.

Ccl11 As A Biomarker For The In Vivo Diagnosis Of Chronic Traumatic Encephalopathy, Robert Weissenfels

CMC Senior Theses

Chronic traumatic encephalopathy is the neurodegenerative disease that is ascribed to the long term development of cognitive, behavioral, emotional, and motor deficits as a result of the exposure to high amounts of sub concussive traumatic brain injuries. The disease has gained recent popularity in the media for its prevalence in American football as a response to recent research that has suggested the prominence of the disease in nearly every NFL player that is examined post mortem. This has produced a growing concern for the consequences of head impact and participation in contact sports. Despite media attention, little is currently known …

Cortactin Phosphorylation By Casein Kinase 2 Regulates Actin Related Protein 2/3 Complex Activity And Invadopodia Function, Steven Michael Markwell

Graduate Theses, Dissertations, and Problem Reports (ETD)

Malregulation of the actin cytoskeleton enhances tumor cell motility and invasion. The actin-binding protein cortactin facilitates branched actin network formation through activation of the actin-related protein (Arp) 2/3 complex. Arp2/3 complex activation is responsible for driving increased migration and extracellular matrix (ECM) degradation by governing invadopodia formation and activity. While cortactin-mediated activation of Arp2/3 complex and invadopodia regulation has been well established, signaling pathways responsible for governing cortactin binding to Arp2/3 are unknown. In this dissertation we identify casein kinase (CK) 2α phosphorylation of cortactin as a negative regulator of Arp2/3 binding. CK2α directly phosphorylates cortactin at a conserved threonine …

Towards Understanding The Role Of Small Mammals In The Transmission Of Lyme Disease In Virginia, Usa, Robert K. Rose, Laura Bitzer, Wayne Hynes, Holly D. Gaff, Robyn Nadolny, Jory Brinkerhoff

Biological Sciences Faculty Publications

Larvae and nymphs of many species of ticks select small mammals, reptiles, and birds as hosts. Since 2011, we have examined more than 1,000 small mammals of 10 species and collected a small tissue sample as well as all visible ticks; rates of infestation range from 18% in harvest mice to 53% in meadow voles. Identification of immature ticks is challenging and requires molecular or genetic methods beyond classification as being from the genus Ixodes or another genus. Ixodes ticks include Ixodes scapularis, the species that transmits the Lyme disease-causing bacterium Borrelia burgdorferi to humans. Of the approximately 2,300 ticks …

Novel Insights Into The Contribution Of Cellular Senescence To Cancer Therapy: Reversibility, Dormancy And Senolysis., Tareq Saleh

Theses and Dissertations

Cellular senescence a specialized form of growth arrest that contributes to the pathogenesis of several aging-related disorders including cancer. While by definition tumor cells are considered immortalized, they can undergo senescence when exposed to conventional and targeted cancer therapy. Therapy-Induced Senescence (TIS) represents a fundamental response to therapy and impacts its outcomes. However, TIS has been considered a positive therapeutic goal since senescent tumor cells are expected to enter a state of permanent growth abrogation. In this work we examined the hypothesis that a subpopulation of senescent cells can re-acquire proliferative potential after a state of senescent dormancy, indicating that …