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Pharmacy Faculty Articles and Research

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Full-Text Articles in Endocrine System Diseases

Actionable Patient Safety Solution (Apss) #3c: Improve Prevention Of Severe Hypoglycemia, Jerika Lam, Steven Barker, Michael Ramsay, Ariana Longley, Joe Kiani Jan 2017

Actionable Patient Safety Solution (Apss) #3c: Improve Prevention Of Severe Hypoglycemia, Jerika Lam, Steven Barker, Michael Ramsay, Ariana Longley, Joe Kiani

Pharmacy Faculty Articles and Research

This report presents a plan of action for introducing a "program to reduce errors in the recognition and treatment of [severe hypoglycemia]".


Advances And Perspectives In Genetics Of Congenital Thyroid Disorders Associated With Thyroglobulin Gene Mutations, Héctor M. Targovnik, Cintia E. Citterio, Sofi Siffo, Carina M. Rivolta Dec 2016

Advances And Perspectives In Genetics Of Congenital Thyroid Disorders Associated With Thyroglobulin Gene Mutations, Héctor M. Targovnik, Cintia E. Citterio, Sofi Siffo, Carina M. Rivolta

Pharmacy Faculty Articles and Research

Dyshormonogenesis due to thyroglobulin (TG) gene mutations is a rare cause of congenital hypothyroidism with an estimated incidence of approximately 1 in 100,000 newborns. The TG gene is organized in 48 exons, spanning over 270 kb on human chromosome 8q24. The human TG mRNA is 8.5 Kb long and the preprotein monomer is composed of a 19 amino acids signal peptide followed by a 2749 residues polypeptide. Until now, one hundred seventeen deleterious mutations in the human TG gene have been identified and characterized, originating structural changes in the protein that alter the normal protein folding, assembly and …


Advances And Perspectives In Genetics Of Congenital Thyroid Disorders, Héctor M. Targovnik, Cintia E. Citterio, Sofi Siff, Carina M. Rivolta Sep 2016

Advances And Perspectives In Genetics Of Congenital Thyroid Disorders, Héctor M. Targovnik, Cintia E. Citterio, Sofi Siff, Carina M. Rivolta

Pharmacy Faculty Articles and Research

"Congenital hypothyroidism (CH) is the most frequent endocrine disease in infants, affects about 1 in 3,000 newborns and is characterized by elevated levels of thyroidstimulating hormone (TSH) as a consequence of reduced thyroid function. It is also one of the most common preventable causes of cognitive and motor deficits. Prevention of CH is based on carrier identification, genetic counseling and prenatal diagnosis. In neonates a complete diagnosis of CH should include clinical examination, biochemical thyroid tests, thyroid ultrasound, radioiodine or technetium scintigraphy and perchlorate discharge test (PDT). In the last two decades, considerable progress has been made in identifying the …


Regulation Of Polycystin-1 Function By Calmodulin Binding, Nicholas Doerr, Yidi Wang, Kevin R. Kipp, Guangyi Liu, Jesse J. Benza, Vladimir Pletnev, Tengis S. Pavlov, Alexander Staruschenko, Ashraf M. Mohieldin, Maki Takahashi, Surya M. Nauli, Thomas Weimbs Aug 2016

Regulation Of Polycystin-1 Function By Calmodulin Binding, Nicholas Doerr, Yidi Wang, Kevin R. Kipp, Guangyi Liu, Jesse J. Benza, Vladimir Pletnev, Tengis S. Pavlov, Alexander Staruschenko, Ashraf M. Mohieldin, Maki Takahashi, Surya M. Nauli, Thomas Weimbs

Pharmacy Faculty Articles and Research

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a common genetic disease that leads to progressive renal cyst growth and loss of renal function, and is caused by mutations in the genes encoding polycystin-1 (PC1) and polycystin-2 (PC2), respectively. The PC1/PC2 complex localizes to primary cilia and can act as a flow-dependent calcium channel in addition to numerous other signaling functions. The exact functions of the polycystins, their regulation and the purpose of the PC1/PC2 channel are still poorly understood. PC1 is an integral membrane protein with a large extracytoplasmic N-terminal domain and a short, ~200 amino acid C-terminal cytoplasmic tail. …


Protein Composition And Movements Of Membrane Swellings Associated With Primary Cilia, Ashraf M. Mohieldin, Hanan S. Haymour, Shao T. Lo, Wissam A. Aboualaiwi, Kimberly F. Atkinson, Christopher J. Ward, Min Gao, Oliver Wessely, Surya M. Nauli Feb 2015

Protein Composition And Movements Of Membrane Swellings Associated With Primary Cilia, Ashraf M. Mohieldin, Hanan S. Haymour, Shao T. Lo, Wissam A. Aboualaiwi, Kimberly F. Atkinson, Christopher J. Ward, Min Gao, Oliver Wessely, Surya M. Nauli

Pharmacy Faculty Articles and Research

Dysfunction of many ciliary proteins has been linked to a list of diseases, from cystic kidney to obesity and from hypertension to mental retardation. We previously proposed that primary cilia are unique communication organelles that function as microsensory compartments that house mechanosensory molecules. Here we report that primary cilia exhibit membrane swellings, which based on their unique ultrastructure and motility, could be mechanically regulated by fluid-shear stress. Together with the ultrastructure analysis of the bulb, which contains monosialodihexosylganglioside (GM3), our results show that ciliary membrane swelling has a distinctive set of functional proteins, including GM3 synthase (GM3S), bicaudal-c1 (Bicc1) and …


The Cell's Antenna And Bending With The Flow, Surya M. Nauli, Kimberly F. Atkinson, Sarmed H. Kathem Jan 2015

The Cell's Antenna And Bending With The Flow, Surya M. Nauli, Kimberly F. Atkinson, Sarmed H. Kathem

Pharmacy Faculty Articles and Research

Polycystic kidney disease (PKD) is the most common life-threatening genetic disease worldwide – affecting about 12.5 million people. Patients with the condition have multiple fluid-filled cysts in their kidneys that lead to a massive enlargement of the organ and gradual worsening of its function, as well as complete failure in many cases. The lack of available treatment means patients may eventually require regular dialysis or a kidney transplant.


Dopaminergic Signaling Within The Primary Cilia In The Renovascular System, Kimberly F. Atkinson, Samred H. Kathem, Xingjian Jin, Brian S. Muntean, Wissam A. Aboualaiwi, Andromeda M. Nauli, Surya M. Nauli Jan 2015

Dopaminergic Signaling Within The Primary Cilia In The Renovascular System, Kimberly F. Atkinson, Samred H. Kathem, Xingjian Jin, Brian S. Muntean, Wissam A. Aboualaiwi, Andromeda M. Nauli, Surya M. Nauli

Pharmacy Faculty Articles and Research

Activation of dopamine receptor type-5 (DR5) has been known to reduce systemic blood pressure, most likely by increasing renal vasodilation and enhancing natriuresis in the kidney. However, the mechanism of DR5 in natriuresis and vasodilation was not clearly known. We have previously shown that DR5 is localized to primary cilia of proximal renal epithelial and vascular endothelial cells. We here show that selective activation of DR5 specifically induces calcium influx only in the primary cilia, whereas non-selective activation of dopamine receptor induces calcium fluxes in both cilioplasm and cytoplasm. Cilia-independent signaling induced by thrombin only shows calcium signaling within cytoplasm. …


Primary Cilia Regulates The Directional Migration And Barrier Integrity Of Endothelial Cells Through The Modulation Of Hsp27 Dependent Actin Cytoskeletal Organization, Thomas J. Jones, Ravi K. Adapala, Werner J. Geldenhuys, Chris Bursley, Wissam A. Aboualaiwi, Surya M. Nauli, Charles K. Thodeti Jan 2012

Primary Cilia Regulates The Directional Migration And Barrier Integrity Of Endothelial Cells Through The Modulation Of Hsp27 Dependent Actin Cytoskeletal Organization, Thomas J. Jones, Ravi K. Adapala, Werner J. Geldenhuys, Chris Bursley, Wissam A. Aboualaiwi, Surya M. Nauli, Charles K. Thodeti

Pharmacy Faculty Articles and Research

Cilia are mechanosensing organelles that communicate extracellular signals into intracellular responses. Altered functions of primary cilia play a key role in the development of various diseases including polycystic kidney disease. Here, we show that endothelial cells from the oak ridge polycystic kidney (Tg737orpk/orpk) mouse, with impaired cilia assembly, exhibit a reduction in the actin stress fibers and focal adhesions compared to wild type. In contrast, endothelial cells from polycystin-1 deficient mice (pkd1null/null), with impaired cilia function, display robust stress fibers and focal adhesion assembly. We found that the Tg737orpk/orpk cells exhibit impaired directional migration and endothelial cell monolayer permeability compared …


Calcium-Mediated Mechanisms Of Cystic Expansion, Shakila Abdul-Majeed, Surya M. Nauli Oct 2011

Calcium-Mediated Mechanisms Of Cystic Expansion, Shakila Abdul-Majeed, Surya M. Nauli

Pharmacy Faculty Articles and Research

In this review, we will discuss several well-accepted signaling pathways toward calcium-mediated mechanisms of cystic expansion. The second messenger calcium ion has contributed to a vast diversity of signal transduction pathways. We will dissect calcium signaling as a possible mechanism that contributes to renal cyst formation. Because cytosolic calcium also regulates an array of signaling pathways, we will first discuss cilia-induced calcium fluxes, followed by Wnt signaling that has attributed to much-discussed planar cell polarity. We will then look at the relationship between cytosolic calcium and cAMP as one of the most important aspects of cyst progression. The signaling of …


Multiple Protein Kinases Determine The Phosphorylated State Of The Small Heat Shock Protein, Hsp27, In Sh-Sy5y Neuroblastoma Cells, Linda A. Dokas, Amy M. Malone, Frederick E. Williams, Surya M. Nauli, William S. Messer Jr. Jul 2011

Multiple Protein Kinases Determine The Phosphorylated State Of The Small Heat Shock Protein, Hsp27, In Sh-Sy5y Neuroblastoma Cells, Linda A. Dokas, Amy M. Malone, Frederick E. Williams, Surya M. Nauli, William S. Messer Jr.

Pharmacy Faculty Articles and Research

In SH-SY5Y human neuroblastoma cells, the cholinergic agonist, carbachol, stimulates phosphorylation of the small heat shock protein 27 (HSP27). Carbachol increases phosphorylation of both Ser-82 and Ser-78 while the phorbol ester, phorbol-12, 13-dibutyrate (PDB) affects only Ser-82. Muscarinic receptor activation by carbachol was confirmed by sensitivity of Ser-82 phosphorylation to hyoscyamine with no effect of nicotine or bradykinin. This response to carbachol is partially reduced by inhibition of protein kinase C (PKC) with GF 109203X and p38 mitogen-activated protein kinase (MAPK) with SB 203580. In contrast, phosphorylation produced by PDB is completely reversed by GF 109203X or CID 755673, an …


Ciliary Dysfunction In Polycystic Kidney Disease: An Emerging Model With Polarizing Potential, Robert J. Kolb, Surya M. Nauli May 2008

Ciliary Dysfunction In Polycystic Kidney Disease: An Emerging Model With Polarizing Potential, Robert J. Kolb, Surya M. Nauli

Pharmacy Faculty Articles and Research

The majority of different cell types in the human body have a cilium, a thin rod-like structure of uniquely arranged microtubules that are encapsulated by the surface plasma membrane. The cilium originates from a basal body, a mature centriole that has migrated and docked to the cell surface. The non-motile cilia are microtubule-based organelles that are generally considered sensory structures. The purpose of this review is to discuss the practicality of the ciliary hypothesis as a unifying concept for polycystic kidney disease and to review current literature in the field of cilium biology, as it relates to mechanosensation and planar …