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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 ...


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 ...


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.


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 ...


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 ...


Skeletal Muscle Function Changes With Aging And Exercise: From The Myosin Molecule To The Whole Muscle, Mark S. Miller 2016 University of Massachusetts Amherst

Skeletal Muscle Function Changes With Aging And Exercise: From The Myosin Molecule To The Whole Muscle, Mark S. Miller

UMass Center for Clinical and Translational Science Research Retreat

As part of the mini-symposium entitled "Advancing Translational Research at the UMass Amherst Center for Personalized Health Monitoring," Dr. Miller's presentation highlights current research initiatives on muscle function changes with aging and exercise.


Exosomes Derived From Alcohol-Treated Hepatocytes Horizontally Transfer Liver Specific Mirna-122 And Sensitize Monocytes To Lps, Fatemeh Momen-Heravi, Shashi Bala, Karen Kodys, Gyongyi Szabo 2016 University of Massachusetts Medical School

Exosomes Derived From Alcohol-Treated Hepatocytes Horizontally Transfer Liver Specific Mirna-122 And Sensitize Monocytes To Lps, Fatemeh Momen-Heravi, Shashi Bala, Karen Kodys, Gyongyi Szabo

Gyongyi Szabo

Hepatocyte damage and inflammation in monocytes/macrophages are central to the pathogenesis of alcoholic hepatitis (AH). MicroRNAs (miRNAs) regulate all of these processes. MiRNA-122 is abundantly expressed in hepatocytes while monocytes/macrophages have low levels. The role of exosomes in AH and possible cross talk between hepatocyte-derived exosomes and immune cells is not explored yet. Here, we show that the number of exosomes significantly increases in the sera of healthy individuals after alcohol binge drinking and in mice after binge or chronic alcohol consumption. Exosomes isolated from sera after alcohol consumption or from in vitro ethanol-treated hepatocytes contained miRNA-122. Exosomes ...


Connecting The Physiological And Behavioral Response To Heat Stress On A Warming Planet, Anastasia Kalyta 2016 Chapman University

Connecting The Physiological And Behavioral Response To Heat Stress On A Warming Planet, Anastasia Kalyta

Student Research Day Abstracts and Posters

Intertidal communities are considered good models of the biological effects of climate change on ecosystems, as their resident organisms are subjected to heat spells during daytime low tides. The increasing heat exposure can elicit behavioral as well as physiological responses in intertidal organisms. We studied the relationship between these responses to heat stress in the blue-banded hermit crab, Pagurus samuelis, by inducing a “heat shock” with elevated water temperature of 29 °C for 2.5 h. The behavioral effect of heat-shock was quantified using a 30-minute feeding assay, measuring the mass of a standard squid pellet consumed by individual hermit ...


Handwashing: A Study Of The History, Methods, And Psychology Surrounding Hand Hygiene, Daniel J. Remillard 2016 Liberty University

Handwashing: A Study Of The History, Methods, And Psychology Surrounding Hand Hygiene, Daniel J. Remillard

Senior Honors Theses

This paper covers three different areas concerning handwashing. First a review of the history of handwashing is done, going from ancient times to its introduction into modern medicine via Dr. Ignaz Semmelweis. This section gives a sobering reminder not to instantly reject data that comes in conflict with prevalent thought.

Then current medical knowledge about handwashing is examined, and the conclusion reached states that handwashing is best done with non-antibacterial soap.

Finally, a review of the psychology of handwashing shows that medical professionals often tend toward neglect if unwatched and unmotivated by an outside source. However, those suffering from obsessive ...


Gene Profiling Of Early And Advanced Liver Disease In Chronic Hepatitis C Patients., Saira Sarfraz Khalid, Saeed Hamid, Anwar Ali Siddiqui, Asaf Qureshi, Nilofer Qureshi 2016 Aga Khan University

Gene Profiling Of Early And Advanced Liver Disease In Chronic Hepatitis C Patients., Saira Sarfraz Khalid, Saeed Hamid, Anwar Ali Siddiqui, Asaf Qureshi, Nilofer Qureshi

Anwar Ali Siddiqui

Purpose: Strong impact of hepatitis C virus (HCV) on normal regulation of cellular processes has been reported that could have significant implications for HCV pathogenesis. We aimed to determine the altered cellular processes during HCV infection with particular reference to advanced disease stages. Methods: Liver biopsy specimens of chronic hepatitis C Patients classified on histological basis as early (fibrosis stage 1-2) or advanced (fibrosis stage 3-4) HCV disease were studied using microarray technology (Affymetrix GeneChip System). For comparison, liver specimens from Patients with non-viral hepatitis (NV-hepatitis) were also analyzed by microarray. Expression data generated were analyzed using software Genespring GX ...


The Thioredoxin Trx-1 Regulates The Major Oxidative Stress Response Transcription Factor, Skn-1, In Caenorhabditis Elegans, Katie C. McCallum 2016 The University of Texas Graduate School of Biomedical Sciences at Houston

The Thioredoxin Trx-1 Regulates The Major Oxidative Stress Response Transcription Factor, Skn-1, In Caenorhabditis Elegans, Katie C. Mccallum

UT GSBS Dissertations and Theses (Open Access)

The ability to respond to hostile environmental conditions is critical for the survival of an organism. Oxidative stress is an adverse state in which reactive oxygen species (ROS) accumulate to a harmful level and, if left unresolved, can lead to cellular dysfunction and organismal disease. Sophisticated detoxification systems, characterized by a battery of enzymatic antioxidants, are utilized to neutralize ROS thereby reducing stress. However, ROS are also purposefully produced by designated cellular enzymes to facilitate the signaling and regulation of critical physiological processes. Therefore, both the production and neutralization of ROS must be tightly controlled. Indeed, the expression of detoxification ...


Exploring The Effect Of Novel Small Molecules On Oligodendrocyte Precursor Proliferation, Sagune Sakya 2016 University of Connecticut - Storrs

Exploring The Effect Of Novel Small Molecules On Oligodendrocyte Precursor Proliferation, Sagune Sakya

University Scholar Projects

Gliomas, a type of brain tumor, can be difficult to treat and have a poor survival rate. One pathway that leads to glioma formation is excessive signaling by platelet derived growth factors (PDGF) through PDGF receptor α (PDGFRα). Through this research, I found that novel compounds that downregulate PDGFRα decrease proliferation of Oli-neu cells, an oligodendrocyte precursor cell model, and identified signaling pathways through which these compounds may exert their effect. Further investigation may identify targets for development of glioma treatments.


Programming Heart Disease: Does Poor Maternal Nutrition Alter Expression Of Cardiac Markers Of Proliferation, Hypertrophy, And Fibrosis In Offspring?, Cathy Chun 2016 University of Connecticut

Programming Heart Disease: Does Poor Maternal Nutrition Alter Expression Of Cardiac Markers Of Proliferation, Hypertrophy, And Fibrosis In Offspring?, Cathy Chun

Honors Scholar Theses

Maternal malnutrition can affect fetal organogenesis, metabolic processes, and factors involved in developmental regulation. Of the many physiological effects poor maternal nutrition can induce in offspring, one of the most important organs affected is the heart. Cardiovascular disease has been associated with poor maternal diet. It also been suggested that hypertension can originate during impaired intrauterine growth and development. Hypertension can trigger hypertensive heart disease and is associated with numerous heart complications. We hypothesized that poor maternal nutrition would alter critical growth factors associated with normal heart development, specifically, insulin-like growth factor (IGF)-1, IGF-2, transforming growth factor (TGF)β ...


The Effect Of Transformed Escherichia Coli On The Mouse Intestine Microbiome: The Microbial Metabolic Enhancement Hypothesis, Bryar P. Kader 2016 Liberty University

The Effect Of Transformed Escherichia Coli On The Mouse Intestine Microbiome: The Microbial Metabolic Enhancement Hypothesis, Bryar P. Kader

Senior Honors Theses

Metabolic disorders affect around thirty-four percent of the population in the United States. Among these disorders is lactose intolerance, which results from diminished production of the human lactase enzyme. This disorder and others like it are genetically determined and cannot be cured. However, the use of transformed bacteria implanted in the colon may provide a means by which the faulty pathway can be bypassed. To test whether transformed bacteria have the capability to aid in the digestion of normally indigestible compounds, a transformed strain of Escherichia coli overexpressing the beta-galactosidase enzyme encoded by the lacZ gene was colonized in the ...


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