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Rab8 Mediates Trpv4 Vesicle Trafficking To The Plasma Membrane In Hgf-Stimulated Mdck Cells, Hillary Jean Haws 2016 Brigham Young University

Rab8 Mediates Trpv4 Vesicle Trafficking To The Plasma Membrane In Hgf-Stimulated Mdck Cells, Hillary Jean Haws

Theses and Dissertations

Epithelial to mesenchymal transition (EMT) is a process whereby epithelial cells, which act collectively through robust cell–cell interactions, take on mesenchymal characteristics, breaking cell–cell junctions to become solitary, invasive and motile. Our previous results show that a transient increase in calcium influxes through TRP channels at the plasma membrane is required for hepatocyte growth factor (HGF)– stimulated EMT. Since this transient increase requires an intact microtubule cytoskeleton, we propose that HGF stimulation results in the mobilization of calcium channels to the plasma membrane from an intracellular compartment via microtubule–dependent vesicle trafficking. Through immunofluorescence, we show that prior to HGF treatment, …


Forward Chemical Genetics Drug Screen Yields Novel Proteases And Proteolytic Inhibitors Of Hgf–Induced Epithelial–Mesenchymal Transition, Jeffrey Thomas Schuler 2016 Brigham Young University

Forward Chemical Genetics Drug Screen Yields Novel Proteases And Proteolytic Inhibitors Of Hgf–Induced Epithelial–Mesenchymal Transition, Jeffrey Thomas Schuler

Theses and Dissertations

Hepatocyte Growth Factor (HGF)–induced Epithelial–Mesenchymal Transition (EMT) is a complex cellular pathway that causes epithelial cell scattering by breaking cell–cell contacts, eliminating apical–basal polarity, and replacing epithelial markers and characteristics with mesenchymal markers. Early EMT events include a brief period of cell spreading, followed by cell compaction and cell–cell contact breaks. A forward chemical genetics drug screen of 50,000 unique compounds measuring HGF–induced cell scattering identified 26 novel EMT inhibitors, including 2 proteolytic inhibitors. Here, we show that B5500–4, one of the EMT inhibitors from the screen, blocks HGF–induced EMT by a predicted blocking of the protease furin, in addition …


Identification And Characterization Of Serum Biomarkers Associated With Breast Cancer Progression, Adhari Abdullah Alzaabi 2016 Brigham Young University

Identification And Characterization Of Serum Biomarkers Associated With Breast Cancer Progression, Adhari Abdullah Alzaabi

Theses and Dissertations

Despite the recognized advances in the treatment of breast cancer, it still accounts for 15% of all cancer-related deaths. 90% of breast cancer deaths are due to unpredicted metastasis. There is neither successful treatment for metastatic patients nor a specific test to predict or detect secondary lesions. Patients with primary tumor will be either over-treated with cytotoxic side effects or under-treated and risk recurrence. This necessitates the need for personalized treatment, which is hard to offer for such heterogeneous disease. Obstacles in treating breast cancer metastasis are mainly due to the gaps exist in the understanding of the molecular mechanism …


Mechanical Conflict System: A Novel Operant Method For The Assessment Of Nociceptive Behavior, Steven E. Harte, Jessica B. Meyers, Renee R. Donahue, Bradley K. Taylor, Thomas J. Morrow 2016 University of Michigan - Ann Arbor

Mechanical Conflict System: A Novel Operant Method For The Assessment Of Nociceptive Behavior, Steven E. Harte, Jessica B. Meyers, Renee R. Donahue, Bradley K. Taylor, Thomas J. Morrow

Physiology Faculty Publications

A new operant test for preclinical pain research, termed the Mechanical Conflict System (MCS), is presented. Rats were given a choice either to remain in a brightly lit compartment or to escape to a dark compartment by crossing an array of height-adjustable nociceptive probes. Latency to escape the light compartment was evaluated with varying probe heights (0, .5, 1, 2, 3, and 4 mm above compartment floor) in rats with neuropathic pain induced by constriction nerve injury (CCI) and in naive control rats. Escape responses in CCI rats were assessed following intraperitoneal administration of pregabalin (10 and 30 mg/kg), morphine …


The Glucose Model Of Mediation: Physiological Bases Of Willpower As Important Explanations For Common Mediation Behavior, Roy F. Baumeister, W. Scott Simpson, Stephen J. Ware, Daniel S. Weber 2016 Pepperdine University

The Glucose Model Of Mediation: Physiological Bases Of Willpower As Important Explanations For Common Mediation Behavior, Roy F. Baumeister, W. Scott Simpson, Stephen J. Ware, Daniel S. Weber

Pepperdine Dispute Resolution Law Journal

Success in life requires the ability to resist urges and control behavior. This ability is commonly called “willpower,” the capacity to overcome impulses and engage in conscious acts of self-control. Social psychologists believe willpower is a finite resource dependent on physiological bases including glucose (from food and drink), sleep and other forms of rest, and the absence of stress. In short, people who are hungry, exhausted, or highly stressed tend to have less willpower than those who are well-fed, well-rested, and relatively stress-free. In addition, a person who exerts self-control (uses willpower) tends to reduce temporarily the amount of willpower …


Efn-4 Functions In Lad-2-Mediated Axon Guidance In Caenorhabditis Elegans, Alicia A. Schwieterman, Cory J. Donelson, Jonathan L. McMurry, Martin L. Hudson 2016 Kennesaw State University

Efn-4 Functions In Lad-2-Mediated Axon Guidance In Caenorhabditis Elegans, Alicia A. Schwieterman, Cory J. Donelson, Jonathan L. Mcmurry, Martin L. Hudson

Faculty Articles

During development of the nervous system, growing axons rely on guidance molecules to direct axon pathfinding. A well-characterized family of guidance molecules are the membrane-associated ephrins, which together with their cognate Eph receptors, direct axon navigation in a contact-mediated fashion. InC. elegans, the ephrin-Eph signaling system is conserved and is best characterized for their roles in neuroblast migration during early embryogenesis. This study demonstrates a role for theC. elegansephrin EFN-4 in axon guidance. We provide both genetic and biochemical evidence that is consistent with theC. elegansdivergent L1 cell adhesion molecule LAD-2 acting as a non-canonical ephrin receptor to EFN-4 to …


Modulating Foveal Representation Can Influence Visual Discrimination In The Periphery, Qing Yu, Won Mok Shim 2016 Dartmouth College

Modulating Foveal Representation Can Influence Visual Discrimination In The Periphery, Qing Yu, Won Mok Shim

Dartmouth Scholarship

A previous study by Williams et al. (2008) provided evidence for a novel form of feedback in the visual system, whereby peripheral information is contained in foveal retinotopic cortex. Beyond its possible implication for peripheral object recognition, few studies have examined the effect of a direct behavioral manipulation of the foveal feedback representation. To address this question, we measured participants' peripheral visual discrimination performance while modulating their foveal representation in a series of psychophysical experiments. On each trial, participants discriminated the identities of briefly presented novel, three-dimensional objects or the orientations of gratings in a peripheral location while fixating at …


Use Of Lecture Capture And Student Performance In Physiology., Chaya Gopalan PhD, Rim M. Hadgu, Sophia Huynh 2016 St. Louis College of Pharmacy

Use Of Lecture Capture And Student Performance In Physiology., Chaya Gopalan Phd, Rim M. Hadgu, Sophia Huynh

SIUE Faculty Research, Scholarship, and Creative Activity

Lecture capture technology is fairly new and has gained interest among higher institutions, faculty and students alike. Live-lecture (LL) is captured in real-time and this recording, LC, is made available for students to access for later use, whether it be for review purpose or to replace a missed class. Student performance was compared between those attending LL only and the other group utilizing LC in addition to LL in two randomly chosen lectures. We found that the overall exam performance was indistinguishable between the LL and the LC groups. Additionally, there was no significant difference in student performance between the …


Mw151 Inhibited Il-1Β Levels After Traumatic Brain Injury With No Effect On Microglia Physiological Responses, Adam D. Bachstetter, Zhengqiu Zhou, Rachel K. Rowe, Bin Xing, Danielle S. Goulding, Alyssa N. Conley, Pradoldej Sompol, Shelby Meier, Jose F. Abisambra, Jonathan Lifshitz, D. Martin Watterson, Linda J. Van Eldik 2016 University of Kentucky

Mw151 Inhibited Il-1Β Levels After Traumatic Brain Injury With No Effect On Microglia Physiological Responses, Adam D. Bachstetter, Zhengqiu Zhou, Rachel K. Rowe, Bin Xing, Danielle S. Goulding, Alyssa N. Conley, Pradoldej Sompol, Shelby Meier, Jose F. Abisambra, Jonathan Lifshitz, D. Martin Watterson, Linda J. Van Eldik

Sanders-Brown Center on Aging Faculty Publications

A prevailing neuroinflammation hypothesis is that increased production of proinflammatory cytokines contributes to progressive neuropathology, secondary to the primary damage caused by a traumatic brain injury (TBI). In support of the hypothesis, post-injury interventions that inhibit the proinflammatory cytokine surge can attenuate the progressive pathology. However, other post-injury neuroinflammatory responses are key to endogenous recovery responses. Therefore, it is critical that pharmacological attenuation of detrimental or dysregulated neuroinflammatory processes avoid pan-suppression of inflammation. MW151 is a CNS-penetrant, small molecule experimental therapeutic that restores injury- or disease-induced overproduction of proinflammatory cytokines towards homeostasis without immunosuppression. Post-injury administration of MW151 in a …


Anatomical Variation Of The Ulnar Collateral Ligament And Implications For Joing Stability And Surgical Rehabilitation, Jakob Gamboa, Dr. Jonathan Wisco 2016 Brigham Young University

Anatomical Variation Of The Ulnar Collateral Ligament And Implications For Joing Stability And Surgical Rehabilitation, Jakob Gamboa, Dr. Jonathan Wisco

Journal of Undergraduate Research

In 1974, the first ulnar collateral ligament reconstructive surgery was performed on Los Angeles Dodgers’ pitcher, Tommy John. The damaged ligament of the medial elbow was repaired with tendons from the pitcher’s body. Since then, the surgery has been colloquially termed “Tommy John’s Surgery”, and the alarming increase of the rates of the procedure has now become a concern, being recently called an “epidemic” by the American Sports Medicine Institute1. The procedure possesses risk of complications, and can lead to shortened careers, decreased performance over time2, and can carry a heavy financial toll on individuals and …


Testing The Effect Of Antioxidants On The Pathogenesis Of Alzheimer’S Disease Through The Rage/Nf-Kb Inflammatory Pathway, Harrison Snyder, Jonathan Wisco 2016 Brigham Young University

Testing The Effect Of Antioxidants On The Pathogenesis Of Alzheimer’S Disease Through The Rage/Nf-Kb Inflammatory Pathway, Harrison Snyder, Jonathan Wisco

Journal of Undergraduate Research

The Receptor for Advanced Glycation Endproducts (RAGE) is known to have a role in inflammatory processes. When produced in excess it induces oxidative stress by activating a number of ligand enzymes, resulting in the generation of excessive cytosolic reactive oxidant species. This oxidative stress then stimulates Nuclear Factor Kappa-B (NF-kB), which regulates immune response and inflammation. When RAGE is incorrectly regulated, inflammation occurs in otherwise healthy tissue, a process implicated in neurodegenerative disorders like Alzheimer’s disease. RAGE is found throughout the body and is seen in greater concentration in inflamed tissues; it has also been found in the brain tissue …


Alzheimer’S Disease And The P.V236e Variant In The Apoe Gene, Alton Chad Sorensen, John Kauwe 2016 Brigham Young University

Alzheimer’S Disease And The P.V236e Variant In The Apoe Gene, Alton Chad Sorensen, John Kauwe

Journal of Undergraduate Research

I was interested in trying to validate the findings of the publication by Medway et al. concerning the SNP rs199768005 using data from the Cache Country data set. Unfortunately, of the 4703 people from our data set, only 10 were carriers. Using R statistical analysis, I found that the p-value for this SNP with an association to protect for Alzheimer’s Disease (AD) was not significant. It was similarly not significant in its association with Any AD. I also ran other models to include for factors such as education or age in conjunction with this SNP and its association with AD …


Ligament Microstructure Analysis, Michael Gillespie, Jonathan Wisco 2016 Brigham Young University

Ligament Microstructure Analysis, Michael Gillespie, Jonathan Wisco

Journal of Undergraduate Research

Due to the relatively poor fiber contrast of tendons in comparison with muscles, the anatomical, and therefore, functional relationship of muscle attachments to bones via tendons has not been well mapped. We were interested in mapping the 3D gross anatomical structure of tendons using a MicroScribe 3D digitizer (GoMeasure3D, Amherst, VA), with the goal to compare fibrous architecture between tendons of various types of muscles and muscle classes. We developed a stain made of blue dye and powdered sugar to increase fiber visibility, thus allowing for 3D digitization. This technique was applied to human cadaveric calcaneal tendon and quadriceps tendon.


Analyzing Structural Differences In Quadriceps Femoris Tendon Fibers Using Microscribe Technology, Nathaniel Hainsworth, Jon Wisco 2016 Brigham Young University

Analyzing Structural Differences In Quadriceps Femoris Tendon Fibers Using Microscribe Technology, Nathaniel Hainsworth, Jon Wisco

Journal of Undergraduate Research

Not all tendons and ligaments are created equally. Many have different structural characteristics based on functionality or need for stability. This turns out to be true even between different portions of the same tendon. This project’s purpose was to analyze and compare structural differences between tendon fibers of the patellar portion and quadriceps portion of the quadriceps femoris tendon. We hypothesized that there are significant structural differences between these two portions because they act very different biomechanically, as well as different in the amount of tension/strain put on each portion. We mapped individual tendon fibers of both portions using MicroScribe …


Three-Dimensional Model Of Undocumented Lingual Nerve Branches For The Education Of The International Anatomy, Medical, And Dental Population, Craig D. Clayton, Dr. Jonathan Wisco 2016 Brigham Young University

Three-Dimensional Model Of Undocumented Lingual Nerve Branches For The Education Of The International Anatomy, Medical, And Dental Population, Craig D. Clayton, Dr. Jonathan Wisco

Journal of Undergraduate Research

The floor of the oral cavity is covered by a mucosal layer to protect underlying structures against the digestive events of the mouth. Ducts of the salivary glands open into this mucosa along the lingual frenulum. The lingual nerve from the mandibular division of the trigeminal nerve immediately begins to branch after passing through the foramen ovale, and continues its descent medial to the inferior alveolar nerve. Just superior to the angle of the mandible, the nerve turns anteriorly 90 degrees and continues a lateral to medial path to the anterior of the mouth. It crosses the submandibular salivary duct …


The Role Of Wnt Secretion From Neural Crest Cells In Proper Craniofacial Development, Bradley Haynes, Stark Michael 2016 Brigham Young University

The Role Of Wnt Secretion From Neural Crest Cells In Proper Craniofacial Development, Bradley Haynes, Stark Michael

Journal of Undergraduate Research

Both Wnt signaling and neural crest cells (NCCs) have a well-established role in the development of facial bones and cartilage. Wnt signaling is known to be required for neural crest cell formation; however, Wnt expression originating from the neural crest after their specification by Wnt1 has not been carefully explored. The purpose of our study is to investigate the role of Wnt secretion from NCCs in craniofacial development. Our hypothesis is that loss of Wnt secretion from NCCs will lead to improper craniofacial development and contribute to facial structure abnormalities.


Application Of Sihler’S Stain To Expose Cardiac Conduction Nerve Fibers, Adam Jorgensen, Jonathan J. Wisco 2016 Brigham Young University

Application Of Sihler’S Stain To Expose Cardiac Conduction Nerve Fibers, Adam Jorgensen, Jonathan J. Wisco

Journal of Undergraduate Research

Arrhythmia is a serious heart condition that affects 14 million people in the United Statesi, and is characterized by irregular frequency of atrial and ventricular beats.ii The most serious effects of arrhythmia include sudden cardiac arrest and stroke.iii About 383,000 cases of cardiac arrest are recorded annually in the United States alone.iv In a report complied in 2011 by the World Health Organization, stroke has the second highest death rate of any disease worldwide, ending the lives of 6.1 million people annually.v Recent developments in cardiac ablation have helped in the treatment of arrhythmia …


Novel G-Protein Coupled Receptor Expression And Modulation Of Synaptic Plasticity, Michael Thayer Christensen, Dr. Jeff Edwards 2016 Brigham Young University

Novel G-Protein Coupled Receptor Expression And Modulation Of Synaptic Plasticity, Michael Thayer Christensen, Dr. Jeff Edwards

Journal of Undergraduate Research

According to the Centers for Disease Control and Prevention, Alzheimer’s disease – infamously known for its patients’ loss of memory and other intellectual abilities – is the sixth most common cause of death in the United States. Sadly this is just one of many ailments people experience that result in learning and memory loss. Why do so many suffer from these neurodegenerative states? One fundamental problem is that the complex learning and remembering process is not well understood. A specific brain region called the hippocampus is involved in short-term declarative memory; however, many of its intricate signaling pathways that mediate …


Confirming The Spatial Relationship Between Iron, Tau Protein, And Amyloid Beta Within The Subiculum As A Means To Better Detect Alzheimer’S Disease With Magnetic Resonance Imaging, Brandon Herrington, Jonathan Wisco 2016 Brigham Young University

Confirming The Spatial Relationship Between Iron, Tau Protein, And Amyloid Beta Within The Subiculum As A Means To Better Detect Alzheimer’S Disease With Magnetic Resonance Imaging, Brandon Herrington, Jonathan Wisco

Journal of Undergraduate Research

As the 6th leading cause of death in the United States1, and because of the significant deterioration it causes in the quality of life of its victims, Alzheimer’s disease is an area where research to improve its early diagnosis is paramount to establishing new treatments. Alzheimer’s disease appears to show its effects at a particularly early stage within the hippocampus2. More specifically, the subicular area of the hippocampus is noted as a region that is subjected to more severe pathological changes due to the disease3. Braak staging is a method used to classify, …


Isothermal Titration Calorimetry Uncovers Substrate Promiscuity Of Bicupin Oxalate Oxidase From Ceriporiopsis Subvermispora, Hassan Rana, Patricia Moussatche, Lis Souza Rocha, Ellen W. Moomaw 2016 Kennesaw State University

Isothermal Titration Calorimetry Uncovers Substrate Promiscuity Of Bicupin Oxalate Oxidase From Ceriporiopsis Subvermispora, Hassan Rana, Patricia Moussatche, Lis Souza Rocha, Ellen W. Moomaw

Faculty Articles

Isothermal titration calorimetry (ITC) may be used to determine the kinetic parameters of enzymecatalyzed reactions when neither products nor reactants are spectrophotometrically visible and when the reaction products are unknown. We report here the use of the multiple injection method of ITC to characterize the catalytic properties of oxalate oxidase (OxOx) from Ceriporiopsis subvermispora (CsOxOx), a manganese dependent enzyme that catalyzes the oxygen-dependent oxidation of oxalate to carbon dioxide in a reaction coupled with the formation of hydrogen peroxide. CsOxOx is the first bicupin enzyme identified that catalyzes this reaction. The multiple injection ITC method of measuring OxOx activity involves …


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