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Corticotropin Releasing Factor Receptor Type 1 Signaling In Epilepsy And Traumatic Brain Injury, V V Chakravarthi Narla 2016 The University of Western Ontario

Corticotropin Releasing Factor Receptor Type 1 Signaling In Epilepsy And Traumatic Brain Injury, V V Chakravarthi Narla

Electronic Thesis and Dissertation Repository

Stress increases the frequency by which epileptic seizures occur. Corticotropin-releasing factor (CRF) coordinates neuroendocrine, autonomic and behavioral response to stress. This thesis sought to study the cellular and molecular mechanisms by which CRF regulates the activity of neural circuits in the piriform cortex (PC) in normal and epileptic states. The PC is richly innervated by CRF and 5-HT containing axons arising from the central amygdala and raphe nucleus. CRFR1 and 5-HT2A/CRs have been shown to interact in a manner where CRFR activation subsequently potentiates the activity of 5-HT2A/CRs. The first purpose of this ...


Maintenance Of The Ph Gradient In The Gastric Mucus Layer., Owen Lewis 2016 The University Of Utah

Maintenance Of The Ph Gradient In The Gastric Mucus Layer., Owen Lewis

Annual Symposium on Biomathematics and Ecology: Education and Research

No abstract provided.


Understanding Adipocyte Dynamics Through Mathematical Modeling, Katrina Johnson, Fred Adler 2016 University of Utah

Understanding Adipocyte Dynamics Through Mathematical Modeling, Katrina Johnson, Fred Adler

Annual Symposium on Biomathematics and Ecology: Education and Research

No abstract provided.


Mitochondrial Superoxide Signaling Contributes To Norepinephrine-Mediated T-Lymphocyte Cytokine Profiles., Adam J. Case, Colton T. Roessner, Jun Tian, Matthew C. Zimmerman 2016 University of Nebraska Medical Center

Mitochondrial Superoxide Signaling Contributes To Norepinephrine-Mediated T-Lymphocyte Cytokine Profiles., Adam J. Case, Colton T. Roessner, Jun Tian, Matthew C. Zimmerman

Journal Articles: Cellular & Integrative Physiology

Norepinephrine (NE) produces multifaceted regulatory patterns in T-lymphocytes. Recently, we have shown that NE utilizes redox signaling as evidenced by increased superoxide (O2●-) causally linked to the observed changes in these cells; however, the source of this reactive oxygen species (ROS) remains elusive. Herein, we hypothesized that the source of increased O2●- in NE-stimulated T-lymphocytes is due to disruption of mitochondrial bioenergetics. To address this hypothesis, we utilized purified mouse splenic CD4+ and CD8+ T-lymphocytes stimulated with NE and assessed O2●- levels, mitochondrial metabolism, cellular proliferation, and cytokine profiles. We demonstrate that the increase in O2●- levels in response to ...


Cal And Magi Pdz Protein Regulation Of Crfr1 And 5-Ht2ar Trafficking And Signaling, Maha Mahmoud Hammad 2016 The University of Western Ontario

Cal And Magi Pdz Protein Regulation Of Crfr1 And 5-Ht2ar Trafficking And Signaling, Maha Mahmoud Hammad

Electronic Thesis and Dissertation Repository

PDZ (PSD95/Disc Large/Zona Occludens) domain-containing proteins are scaffolding proteins that play important roles in regulating the activity of G protein-coupled receptors. Corticotropin Releasing Factor Receptor 1 (CRFR1) and Serotonin 2A Receptor (5-HT2AR) are two GPCRs that are commonly associated with mental disorders. Both receptors also contain a class I PDZ-binding motif at the carboxyl terminal tail. In the first chapter, we investigate the effects of CAL (CFTR-associated ligand) on regulating the trafficking and signaling of CRFR1. We demonstrate a role for CAL in inhibiting CRFR1 endocytosis, cell surface expression, and CRF-mediated ERK1/2 signaling via the ...


Suppression Of Ischemia In Arterial Occlusive Disease By Jnk-Promoted Native Collateral Artery Development, Kasmir Ramo, Koichi Sugamura, Siobhan M. Craige, John F. Keaney Jr., Roger J. Davis 2016 University of Massachusetts Medical School

Suppression Of Ischemia In Arterial Occlusive Disease By Jnk-Promoted Native Collateral Artery Development, Kasmir Ramo, Koichi Sugamura, Siobhan M. Craige, John F. Keaney Jr., Roger J. Davis

Davis Lab

Arterial occlusive diseases are major causes of morbidity and mortality. Blood flow to the affected tissue must be restored quickly if viability and function are to be preserved. We report that disruption of the mixed-lineage protein kinase (MLK) - cJun NH2-terminal kinase (JNK) signaling pathway in endothelial cells causes severe blockade of blood flow and failure to recover in the murine femoral artery ligation model of hindlimb ischemia. We show that the MLK-JNK pathway is required for the formation of native collateral arteries that can restore circulation following arterial occlusion. Disruption of the MLK-JNK pathway causes decreased Dll4/Notch signaling, excessive ...


Exploiting Dna Repair And Er Stress Response Pathways To Induce Apoptosis In Glioblastoma Multiforme: A Dissertation, Jessica L. Weatherbee 2016 University of Massachusetts Medical School

Exploiting Dna Repair And Er Stress Response Pathways To Induce Apoptosis In Glioblastoma Multiforme: A Dissertation, Jessica L. Weatherbee

GSBS Dissertations and Theses

Glioblastoma multiforme (GBM) is a deadly grade IV brain tumor characterized by a heterogeneous population of cells that are drug resistant, aggressive, and infiltrative. The current standard of care, which has not changed in over a decade, only provides GBM patients with 12-14 months survival post diagnosis. We asked if the addition of a novel endoplasmic reticulum (ER) stress inducing agent, JLK1486, to the standard chemotherapy, temozolomide (TMZ), which induces DNA double strand breaks (DSBs), would enhance TMZ’s efficacy. Because GBMs rely on the ER to mitigate their hypoxic environment and DNA repair to fix TMZ induced DSBs, we ...


Cardiovascular And Hematopoietic Responses To Volatile Benzene Exposure., Wesley Tyler Abplanalp 2016 University of Louisville

Cardiovascular And Hematopoietic Responses To Volatile Benzene Exposure., Wesley Tyler Abplanalp

Electronic Theses and Dissertations

The rapid and recent increase in the global epidemic of diabetes and cardiovascular disease suggests a strong component of the environment is contributing. Benzene is a ubiquitous volatile pollutant generated by cigarette smoke, automobile exhaust, wildfires and industrial activities. Consequently, it is found in almost all urban and rural air samples. Benzene is known to cause hematotoxicity and its metabolism generates oxidative stress. Although, benzene has been studied for many years, few investigations have probed what influence benzene exposure may have on other physiological processes. Here we hypothesize that benzene metabolism by hepatic-CYP450 2E1 generates oxidative stress and inflammation, which ...


Long-Term Treatment With Insulin And Retinoic Acid Increased Glucose Usage In L6 Muscle Cells Via Glycogenesis, Matthew Ray Goff 2016 University of Tennessee, Knoxville

Long-Term Treatment With Insulin And Retinoic Acid Increased Glucose Usage In L6 Muscle Cells Via Glycogenesis, Matthew Ray Goff

Doctoral Dissertations

Skeletal muscle glucose metabolism can affect whole body glucose homeostasis significantly. Vitamin A (VA) plays a role in a number of physiological functions including glucose metabolism. However, its role in skeletal muscle glucose metabolism has not been well established. Insulin controls glucose metabolism in the skeletal muscle via the regulations of glucose uptake, glycogenesis, and glycolysis. We hypothesize that insulin and VA signaling pathways may converge to regulate glucose metabolism in skeletal muscle. Here, the effects of retinoic acid (RA) alone and in combination with insulin on glucose utilization in rat L6 muscle cells were studied. L6 cells were treated ...


Protein Kinase Mitogen-Activated Protein Kinase Kinase Kinase Kinase 4 (Map4k4) Promotes Obesity-Induced Hyperinsulinemia, Rachel J. Roth Flach, Laura V. Danai, Marina DiStefano, Mark Kelly, Lorena Garcia Menendez, Agata Jurczyk, Rohit B. Sharma, Dae Young Jung, Jong Hun Kim, Jason K. Kim, Rita Bortell, Laura C. Alonso, Michael P. Czech 2016 University of Massachusetts Medical School

Protein Kinase Mitogen-Activated Protein Kinase Kinase Kinase Kinase 4 (Map4k4) Promotes Obesity-Induced Hyperinsulinemia, Rachel J. Roth Flach, Laura V. Danai, Marina Distefano, Mark Kelly, Lorena Garcia Menendez, Agata Jurczyk, Rohit B. Sharma, Dae Young Jung, Jong Hun Kim, Jason K. Kim, Rita Bortell, Laura C. Alonso, Michael P. Czech

Open Access Articles

Previous studies revealed a paradox whereby mitogen-activated protein kinase kinase kinase kinase 4 (Map4k4) acted as a negative regulator of insulin sensitivity in chronically obese mice, yet systemic deletion of Map4k4 did not improve glucose tolerance. Here, we report markedly reduced glucose-responsive plasma insulin and C-peptide levels in whole body Map4k4-depleted mice (M4K4 iKO) as well as an impaired first phase of insulin secretion from islets derived from M4K4 iKO mice ex vivo After long-term high fat diet (HFD), M4K4 iKO mice pancreata also displayed reduced beta cell mass, fewer proliferating beta cells and reduced islet-specific gene mRNA expression compared ...


Vitamin K2 (Menaquinone) Supplementation And Its Benefits In Cardiovascular Disease, Osteoporosis, And Cancer, Grant S. Buchanan, MD, Thomas Melvin, Brandon Merritt, Charles Bishop, MD, Franklin D. Shuler, MD, PhD 2016 Marshall University, Joan C. Edwards School of Medicine

Vitamin K2 (Menaquinone) Supplementation And Its Benefits In Cardiovascular Disease, Osteoporosis, And Cancer, Grant S. Buchanan, Md, Thomas Melvin, Brandon Merritt, Charles Bishop, Md, Franklin D. Shuler, Md, Phd

Marshall Journal of Medicine

Vitamin K is known to play an essential role in the coagulation cascade; however, a growing body of research has found that a subtype of this vitamin, vitamin K2 (menaquinone) may have a beneficial effect in osteoporosis, cardiovascular disease, and cancer. This purpose of this article is to provide a comprehensive review of recent literature regarding menaquinone and its role in human health. This review discusses the physiology of menaquinone, its clinical benefits in cardiovascular disease, osteoporosis, and cancer, and how it may interact with certain medications. The authors conclude that menaquinone supplementation has been shown to improve carboxylation ...


Osteopetrorickets Due To Snx10 Deficiency In Mice Results From Both Failed Osteoclast Activity And Loss Of Gastric Acid-Dependent Calcium Absorption, Liang Ye, Leslie R. Morse, Li Zhang, Hajime Sasaki, Jason C. Mills, Paul R. Odgren, Greg Sibbel, James R.L. Stanley, Gee Wong, Ariane Zamarioli, Ricardo A. Battaglino 2016 The Forsyth Institute

Osteopetrorickets Due To Snx10 Deficiency In Mice Results From Both Failed Osteoclast Activity And Loss Of Gastric Acid-Dependent Calcium Absorption, Liang Ye, Leslie R. Morse, Li Zhang, Hajime Sasaki, Jason C. Mills, Paul R. Odgren, Greg Sibbel, James R.L. Stanley, Gee Wong, Ariane Zamarioli, Ricardo A. Battaglino

Paul R. Odgren PhD

Mutations in sorting nexin 10 (Snx10) have recently been found to account for roughly 4% of all human malignant osteopetrosis, some of them fatal. To study the disease pathogenesis, we investigated the expression of Snx10 and created mouse models in which Snx10 was knocked down globally or knocked out in osteoclasts. Endocytosis is severely defective in Snx10-deficient osteoclasts, as is extracellular acidification, ruffled border formation, and bone resorption. We also discovered that Snx10 is highly expressed in stomach epithelium, with mutations leading to high stomach pH and low calcium solubilization. Global Snx10-deficiency in mice results in a combined phenotype: osteopetrosis ...


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

Ellen Moomaw

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 ...


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

Ellen Moomaw

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 ...


Promoter-Enhancer Looping At The Pparγ2 Locus During Adipogenic Differentiation Requires The Prmt5 Methyltransferase, Scott E. LeBlanc, Qiong Wu, Pallavi Lamba, Said Sif, Anthony N. Imbalzano 2016 University of Massachusetts Medical School

Promoter-Enhancer Looping At The Pparγ2 Locus During Adipogenic Differentiation Requires The Prmt5 Methyltransferase, Scott E. Leblanc, Qiong Wu, Pallavi Lamba, Said Sif, Anthony N. Imbalzano

Imbalzano Lab

PPARγ2 is a critical lineage-determining transcription factor that is essential for adipogenic differentiation. Here we report characterization of the three-dimensional structure of the PPARγ2 locus after the onset of adipogenic differentiation and the mechanisms by which it forms. We identified a differentiation-dependent loop between the PPARγ2 promoter and an enhancer sequence 10 kb upstream that forms at the onset of PPARγ2 expression. The arginine methyltransferase Prmt5 was required for loop formation, and overexpression of Prmt5 resulted in premature loop formation and earlier onset of PPARγ2 expression. Kinetic studies of regulatory factor interactions at the PPARγ2 promoter and enhancer revealed enhanced ...


Mechanism Of Chimeric Vaccine Mediated Immune Suppression Of Human Dendritic Cells, Jacques Christian Mbongue 2016 Loma Linda University

Mechanism Of Chimeric Vaccine Mediated Immune Suppression Of Human Dendritic Cells, Jacques Christian Mbongue

Loma Linda University Electronic Theses, Dissertations & Projects

Type 1 diabetes mellitus is a chronic inflammatory disease in which insulin producing β-cells of the pancreatic islets are killed by autoreactive cells of the immune system in response to a loss of tolerance. Dendritic cells (DC) interact predominantly with naïve T cells to regulate the delicate balance between immunity and tolerance required to maintain immunological homeostasis. In this dissertation, immature human dendritic cells (iDC) were inoculated with a chimeric fusion protein vaccine containing the pancreatic β-cell auto-antigen proinsulin linked to a mucosal adjuvant the cholera toxin B subunit (CTB-INS). Proteomic analysis of vaccine inoculated DCs revealed strong up-regulation of ...


Hill's Diagrammatic Method And Reduced Graph Powers, Gregory D. Smith, Richard Hammack 2016 The College of William & Mary

Hill's Diagrammatic Method And Reduced Graph Powers, Gregory D. Smith, Richard Hammack

Biology and Medicine Through Mathematics Conference

No abstract provided.


Microfluidic Platforms To Study Host-Microbiome Interactions, Abhinav Sharma, Neil Forbes, Jungwoo Lee 2016 University of Massachusetts Amherst

Microfluidic Platforms To Study Host-Microbiome Interactions, Abhinav Sharma, Neil Forbes, Jungwoo Lee

UMass Center for Clinical and Translational Science Research Retreat

About three-quarters of human body surface is exposed to dense microbial population along the gastro-intestinal tract (GIT) that accommodates around 80% of immune cells. The GIT is one of the most critical sites for metabolic and immunologic homeostasis in the body. While large-scale genomic analysis and germ-free mice have been widely used, they are limited to capture the dynamic functional interaction between host-microbiome in a humanized setting. in-vitro recapitulation of GIT physiology can be a powerful alternative for hypothesis testing in diseases like IBD and cancer.

As a first step, we developed a simple transwell assembly to closely emulate GIT ...


Prenylated Retinal Ciliopathy Protein Rpgr Regulates Ciliary Localization Of Joubert Syndrome-Associated Protein Inpp5e In Cooperation With Pde6, Wei Zhang, Kollu N. Rao, Linjing Li, Manisha Anand, Hemant Khanna 2016 University of Massachusetts Medical School

Prenylated Retinal Ciliopathy Protein Rpgr Regulates Ciliary Localization Of Joubert Syndrome-Associated Protein Inpp5e In Cooperation With Pde6, Wei Zhang, Kollu N. Rao, Linjing Li, Manisha Anand, Hemant Khanna

UMass Center for Clinical and Translational Science Research Retreat

Ciliary dysfunction is an underlying cause of severe human disorders (collectively called ciliopathies), such as retinitis pigmentosa (RP), Joubert Syndrome (JBTS), and Bardet-Biedl Syndrome. Ciliary proteins form distinct functional networks for localization to cilia as well as regulation of ciliary function. However, not much is known about the mechanism of ciliary localization and function of RPGR (retinitis pigmentosa GTPase regulator), a ciliary protein frequently associated with RP worldwide. Using tandem mass spectrometry analysis, we show that RPGR interacts with two JBTS-associated proteins: PDE6Π (delta subunit of Phosphodiesterase; a prenyl-binding protein) and INPP5E (inositol polyphosphate-5-phosphatase 5E; a ciliary cargo). Whereas PDE6Π ...


Geometric Control Of Yap-Dependent Mechanotransduction: A Proposed Model, Ngozi A. Eze, Heather A. Cirka, Kristen L. Billiar 2016 Worcester Polytechnic Institute

Geometric Control Of Yap-Dependent Mechanotransduction: A Proposed Model, Ngozi A. Eze, Heather A. Cirka, Kristen L. Billiar

UMass Center for Clinical and Translational Science Research Retreat

The Billiar lab is interested in the interplay between mechanical tension and programmed cell death (namely, apoptosis) in cells growing on micro-contact printed aggregates. The Billiar lab uses a bioinspired hydrogel to develop an in vitro model for mechanosensitive signaling in mammalian cells. The micro-contact printed cell aggregates experience a loss of tensional homeostasis at the center of the aggregates, which results in selective cell death at the center, but not periphery of the aggregates, followed by calcification, similar to excised diseased aortic valves. However, the subcellular mechanisms responsible for transducing the mechanical cues from the loss of tensional homeostasis ...


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