Development Of Affinity Microcolumns For Drug–Protein Binding Studies In Personalized Medicine: Interactions Of Sulfonylurea Drugs With In Vivo Glycated Human Serum Albumin, 2013 University of Nebraska-Lincoln
Development Of Affinity Microcolumns For Drug–Protein Binding Studies In Personalized Medicine: Interactions Of Sulfonylurea Drugs With In Vivo Glycated Human Serum Albumin, Jeanethe Anguizola, K. S. Joseph, Omar S. Barnaby, Ryan Matsuda, Guadalupe Alvarado, William Clarke, Ronald Cerny, David S. Hage
David Hage Publications
This report used high-performance affinity microcolumns to examine the changes in binding by sulfonylurea drugs to in vivo glycated HSA that had been isolated from individual patients with diabetes. An immunoextraction approach was developed to isolate HSA and glycated HSA from clinical samples, using only 20 μL of plasma or serum and 6–12 nmol of protein to prepare each affinity microcolumn. It was found that the affinity microcolumns could be used in either frontal analysis or zonal elution studies, which typically required only 4–8 min per run. The microcolumns had good stability and allowed data to be obtained for multiple …
Hypoxia-Inducing Factors As Master Regulators Of Stemness Properties And Altered Metabolism Of Cancer- And Metastasis-Initiating Cells., 2013 University of Nebraska Medical Center
Hypoxia-Inducing Factors As Master Regulators Of Stemness Properties And Altered Metabolism Of Cancer- And Metastasis-Initiating Cells., Murielle Mimeault, Surinder K. Batra
Journal Articles: Biochemistry & Molecular Biology
Accumulating lines of experimental evidence have revealed that hypoxia-inducible factors, HIF-1α and HIF-2α, are key regulators of the adaptation of cancer- and metastasis-initiating cells and their differentiated progenies to oxygen and nutrient deprivation during cancer progression under normoxic and hypoxic conditions. Particularly, the sustained stimulation of epidermal growth factor receptor (EGFR), insulin-like growth factor-1 receptor (IGF-1R), stem cell factor (SCF) receptor KIT, transforming growth factor-β receptors (TGF-βRs) and Notch and their downstream signalling elements such as phosphatidylinositol 3'-kinase (PI3K)/Akt/molecular target of rapamycin (mTOR) may lead to an enhanced activity of HIFs. Moreover, the up-regulation of HIFs in cancer cells may …
Preparation Of Phosphonoterephthalic Acids Via Palladium-Catalyzed Coupling Of Aromatic Iodoesters, 2013 University of Dayton
Preparation Of Phosphonoterephthalic Acids Via Palladium-Catalyzed Coupling Of Aromatic Iodoesters, Nathaniel Ivan, Vladimir Benin, Alexander Morgan
Chemistry Faculty Publications
The current article reports in detail the preparation of two phosphonoterephthalic acids: 2-phosphonoterephthalic acid (1) and 2,5-diphosphonoterephthalic acid (2). Efficient, scalable syntheses have been developed for both compounds based on Pd-catalyzed coupling reactions of iodinated terephthalate esters. Phosphonoterephthalic acids are potentially useful as flame-retardant additives or as monomers for the construction of acid-pendant polymer chains.
Reaction Between Polyol-Esters And Phosphate Esters In The Presence Of Metal Carbides, 2013 University of Dayton
Reaction Between Polyol-Esters And Phosphate Esters In The Presence Of Metal Carbides, David W. Johnson, Carolyn Iacullo, John E. Hils
Chemistry Faculty Publications
The reaction of metal carbides with polyol esters found in aerospace lubricants and phosphate esters commonly used as additives was investigated. Carbides were of particular interest since modern materials under consideration at high temperature bearings have surfaces that are primarily metal carbides. Vanadium and chromium carbide were found to react with the ester and phosphate ester by a transesterification reaction, producing an alkyl phosphate which is less stable than the aromatic phosphate esters. In the process, the metal carbide is converted to the metal phosphate and metal polyphosphate, evidenced by the infrared and Raman spectra of the solid residue and …
Discovering Protein Functions And Career Goals: The Suppressor Sike, 2013 Virginia Commonwealth University
Discovering Protein Functions And Career Goals: The Suppressor Sike, Rebekah Rifareal
Auctus: The Journal of Undergraduate Research and Creative Scholarship
Discovering IMSD was accidental. I was having a routine advising appointment and discussing future careers when the topic surfaced. At the time, I had no clue about what I wanted to do, so my advisor suggested that I explore research and encouraged me to apply for the program.
Dynein And Dynactin Leverage Their Bivalent Character To Form A High-Affinity Interaction., 2013 Thomas Jefferson University
Dynein And Dynactin Leverage Their Bivalent Character To Form A High-Affinity Interaction., Amanda E Siglin, Shangjin Sun, Jeffrey K Moore, Sarah Tan, Martin Poenie, James D Lear, Tatyana Polenova, John A Cooper, John C Williams
Department of Biochemistry and Molecular Biology Faculty Papers
Cytoplasmic dynein and dynactin participate in retrograde transport of organelles, checkpoint signaling and cell division. The principal subunits that mediate this interaction are the dynein intermediate chain (IC) and the dynactin p150(Glued); however, the interface and mechanism that regulates this interaction remains poorly defined. Herein, we use multiple methods to show the N-terminus of mammalian dynein IC, residues 10-44, is sufficient for binding p150(Glued). Consistent with this mapping, monoclonal antibodies that antagonize the dynein-dynactin interaction also bind to this region of the IC. Furthermore, double and triple alanine point mutations spanning residues 6 to 19 in the yeast IC homolog, …
Possible Steps Of Complete Disassembly Of Post-Termination Complex By Yeast Eef3 Deduced From Inhibition By Translocation Inhibitors., 2013 Thomas Jefferson University
Possible Steps Of Complete Disassembly Of Post-Termination Complex By Yeast Eef3 Deduced From Inhibition By Translocation Inhibitors., Shinya Kurata, Ben Shen, Jun O Liu, Nono Takeuchi, Akira Kaji, Hideko Kaji
Department of Biochemistry and Molecular Biology Faculty Papers
Ribosomes, after one round of translation, must be recycled so that the next round of translation can occur. Complete disassembly of post-termination ribosomal complex (PoTC) in yeast for the recycling consists of three reactions: release of tRNA, release of mRNA and splitting of ribosomes, catalyzed by eukaryotic elongation factor 3 (eEF3) and ATP. Here, we show that translocation inhibitors cycloheximide and lactimidomycin inhibited all three reactions. Cycloheximide is a non-competitive inhibitor of both eEF3 and ATP. The inhibition was observed regardless of the way PoTC was prepared with either release factors or puromycin. Paromomycin not only inhibited all three reactions …
Molecular Determinants Of Epidermal Growth Factor Binding: A Molecular Dynamics Study., 2013 Thomas Jefferson University
Molecular Determinants Of Epidermal Growth Factor Binding: A Molecular Dynamics Study., Jeffrey M Sanders, Matthew E Wampole, Mathew L. Thakur, Eric Wickstrom
Department of Biochemistry and Molecular Biology Faculty Papers
The epidermal growth factor receptor (EGFR) is a member of the receptor tyrosine kinase family that plays a role in multiple cellular processes. Activation of EGFR requires binding of a ligand on the extracellular domain to promote conformational changes leading to dimerization and transphosphorylation of intracellular kinase domains. Seven ligands are known to bind EGFR with affinities ranging from sub-nanomolar to near micromolar dissociation constants. In the case of EGFR, distinct conformational states assumed upon binding a ligand is thought to be a determining factor in activation of a downstream signaling network. Previous biochemical studies suggest the existence of both …
The Tip Of The Tail Needle Affects The Rate Of Dna Delivery By Bacteriophage P22., 2013 University of Utah
The Tip Of The Tail Needle Affects The Rate Of Dna Delivery By Bacteriophage P22., Justin C Leavitt, Lasha Gogokhia, Eddie B Gilcrease, Anshul Bhardwaj, Gino Cingolani, Sherwood R Casjens
Department of Biochemistry and Molecular Biology Faculty Papers
The P22-like bacteriophages have short tails. Their virions bind to their polysaccharide receptors through six trimeric tailspike proteins that surround the tail tip. These short tails also have a trimeric needle protein that extends beyond the tailspikes from the center of the tail tip, in a position that suggests that it should make first contact with the host's outer membrane during the infection process. The base of the needle serves as a plug that keeps the DNA in the virion, but role of the needle during adsorption and DNA injection is not well understood. Among the P22-like phages are needle …
Structural Implications For Selective Targeting Of Parps., 2013 Thomas Jefferson University
Structural Implications For Selective Targeting Of Parps., Jamin D Steffen, Md, Jonathan Brody, Md, Roger S Armen, Md, John M Pascal, Md
Department of Biochemistry and Molecular Biology Faculty Papers
Poly(ADP-ribose) polymerases (PARPs) are a family of enzymes that use NAD(+) as a substrate to synthesize polymers of ADP-ribose (PAR) as post-translational modifications of proteins. PARPs have important cellular roles that include preserving genomic integrity, telomere maintenance, transcriptional regulation, and cell fate determination. The diverse biological roles of PARPs have made them attractive therapeutic targets, which have fueled the pursuit of small molecule PARP inhibitors. The design of PARP inhibitors has matured over the past several years resulting in several lead candidates in clinical trials. PARP inhibitors are mainly used in clinical trials to treat cancer, particularly as sensitizing agents …
Time-Stepping For Laser Ablation, 2013 Embry-Riddle Aeronautical University
Time-Stepping For Laser Ablation, Harihar Khanal, David Autrique, Vasilios Alexiades
Publications
Nanosecond laser ablation is a popular technique, applied in many areas of science and technology such as medicine, archaeology, chemistry, environmental and materials sciences. We outline a computational model for radiative and collisional processes occurring during ns-laser ablation, and compare the performance of various low and high order time-stepping algorithms.
Hydrodynamic Modeling Of Ns-Laser Ablation, 2013 TU Kaiserslautern
Hydrodynamic Modeling Of Ns-Laser Ablation, David Autrique, Vasilios Alexiades, Harihar Khanal
Publications
Laser ablation is a versatile and widespread technique, applied in an increasing number of medical, industrial and analytical applications. A hydrodynamic multiphase model describing nanosecond-laser ablation (ns- LA) is outlined. The model accounts for target heating and mass removal mechanisms as well as plume expansion and plasma formation. A copper target is placed in an ambient environment consisting of helium and irradiated by a nanosecond-laser pulse. The effect of variable laser settings on the ablation process is explored in 1-D numerical simulations.
Biomarkers Of Disease : Concentrations In The Serum Of Women During Natural And Stimulated Ovarian Cycles And During Early Pregnancy, 2013 Edith Cowan University
Biomarkers Of Disease : Concentrations In The Serum Of Women During Natural And Stimulated Ovarian Cycles And During Early Pregnancy, Melissa Stemp
Theses: Doctorates and Masters
Molecular biomarkers are chemical signatures that all cell types possess. They are used in medicine to evaluate both normal biological events and pathogenic processes. A series of biomarkers associated with cancer of the breast, ovaries and other parts of the female reproductive tract and the monitoring of pregnancy were measured in disease‐free women. The biomarkers measured were prostate specific antigen (PSA), CA125, CA15‐3, CA72‐4, and pregnancy associated plasma protein‐a (PAPP‐A). The patterns of change during natural and stimulated ovarian cycles and early pregnancy were investigated to determine if these biomarkers could reflect normal events relating to ovulation and implantation/placentation. In …
Amalgamation Of Nucleosides And Amino Acids In Antibiotic Biosynthesis, 2013 University of Kentucky
Amalgamation Of Nucleosides And Amino Acids In Antibiotic Biosynthesis, Sandra H. Barnard
Theses and Dissertations--Pharmacy
The rapid increase in antibiotic resistance demands the identification of novel antibiotics with novel targets. One potential antibacterial target is the biosynthesis of peptidoglycan cell wall, which is both ubiquitous and necessary for bacterial survival. Both the caprazamycin-related compounds A-90289 and muraminomicin, as well as the capuramycin-related compounds A-503083 and A-102395 are potent inhibitors of the translocase I enzyme, one of the key enzymes required for cell wall biosynthesis. The caprazamycin-related compounds contain a core nonproteinogen b-hydroxy-a-amino acid referred to as 5’-C-glycyluridine (GlyU). Residing within the biosynthetic gene clusters of the aforementioned compounds is a shared open reading …
Copper Triflate-Mediated Synthesis Of 1,3,5-Triarylpyrazoles In [Bmim][Pf6] Ionic Liquid And Evaluation Of Their Anticancer Activities, 2013 Birla Institute of Technology and Science
Copper Triflate-Mediated Synthesis Of 1,3,5-Triarylpyrazoles In [Bmim][Pf6] Ionic Liquid And Evaluation Of Their Anticancer Activities, V. Kameshwara Rao, Rakesh Tiwari, Bhupender S. Chhikara, Amir Nasrolahi Shirazi, Keykavous Parang, Anil Kumar
Pharmacy Faculty Articles and Research
A simple, efficient, and environment friendly protocol for the synthesis of 1,3,5-triarylpyrazoles and 1,3,5-triarylpyrazolines in [bmim][PF6] ionic liquid mediated by Cu(OTf)2 is described. The reaction protocol gave 1,3,5-triarylpyrazoles in good to high yields (71–84%) via a one-pot addition–cyclocondensation between chalcones and arylhydrazines, and oxidative aromatization without the requirement for an additional oxidizing reagent. The catalyst can be reused for up to four cycles without much loss in the catalytic activity. The pyrazoles (4a–o) and pyrazolines (3a–n) were evaluated for their antiproliferative activity in SK-OV-3, HT-29, and HeLa human cancer cells lines. Among all the compounds, 3b inhibited cell proliferation of …
Alterations In Glutathione Levels And Apoptotic Regulators Are Associated With Acquisition Of Arsenic Trioxide Resistance In Multiple Myeloma, 2012 Departments of Hematology and Medical Oncology and Cell Biology, Emory University School of Medicine and Winship Cancer Institute, Atlanta, Georgia
Alterations In Glutathione Levels And Apoptotic Regulators Are Associated With Acquisition Of Arsenic Trioxide Resistance In Multiple Myeloma, Shannon M. Matulis, Alejo A. Morales, Lucy Yehiayan, Kelvin P. Lee, Yong Cai, Lawrence H. Boise
Department of Chemistry and Biochemistry
Arsenic trioxide (ATO) has been tested in relapsed/refractory multiple myeloma with limited success. In order to better understand drug mechanism and resistance pathways in myeloma we generated an ATO-resistant cell line, 8226/S-ATOR05, with an IC50 that is 2–3-fold higher than control cell lines and significantly higher than clinically achievable concentrations. Interestingly we found two parallel pathways governing resistance to ATO in 8226/S-ATOR05, and the relevance of these pathways appears to be linked to the concentration of ATO used. We found changes in the expression of Bcl-2 family proteins Bfl-1 and Noxa as well as an increase in cellular glutathione (GSH) …
Targeting Astrocytes Ameliorates Neurologic Changes In A Mouse Model Of Alzheimer's Disease, 2012 University of Kentucky
Targeting Astrocytes Ameliorates Neurologic Changes In A Mouse Model Of Alzheimer's Disease, Jennifer L. Furman, Diana M. Sama, John C. Gant, Tina L. Beckett, M. Paul Murphy, Adam D. Bachstetter, Linda J. Van Eldik, Christopher M. Norris
Pharmacology and Nutritional Sciences Faculty Publications
Astrocytes are the most abundant cell type in the brain and play a critical role in maintaining healthy nervous tissue. In Alzheimer's disease (AD) and most other neurodegenerative disorders, many astrocytes convert to a chronically "activated" phenotype characterized by morphologic and biochemical changes that appear to compromise protective properties and/or promote harmful neuroinflammatory processes. Activated astrocytes emerge early in the course of AD and become increasingly prominent as clinical and pathological symptoms progress, but few studies have tested the potential of astrocyte-targeted therapeutics in an intact animal model of AD. Here, we used adeno-associated virus (AAV) vectors containing the astrocyte-specific …
Muc4 And Muc1 Expression In Adenocarcinoma Of The Stomach Correlates With Vessel Invasion And Lymph Node Metastasis: An Immunohistochemical Study Of Early Gastric Cancer., 2012 Kagoshima University
Muc4 And Muc1 Expression In Adenocarcinoma Of The Stomach Correlates With Vessel Invasion And Lymph Node Metastasis: An Immunohistochemical Study Of Early Gastric Cancer., Yukihiro Tamura, Michiyo Higashi, Sho Kitamoto, Seiya Yokoyama, Masahiko Osako, Michiko Horinouchi, Takeshi Shimizu, Mineo Tabata, Surinder K. Batra, Masamichi Goto, Suguru Yonezawa
Journal Articles: Biochemistry & Molecular Biology
We have previously reported that MUC4 expression is a poor prognostic factor in various carcinomas. Our previous study also showed that MUC1 expression in gastric cancers, including the early and advanced stages is a poor prognostic factor. In the present study, the expression profiles of MUC4 and MUC1 were examined by immunohistochemistry (IHC) using two anti-MUC4 monoclonal antibodies (MAbs), 8G7 and 1G8, and anti-MUC1 MAb DF3 in 104 gastrectomy specimens of early gastric adenocarcinoma with submucosal invasion (pT1b2), including 197 histological subtype lesions. Before the IHC study of the human specimens, we evaluated the specificity of the two MAbs by …
Aging-Associated Dysfunction Of Akt/Protein Kinase B: S-Nitrosylation And Acetaminophen Intervention, 2012 Marshall University
Aging-Associated Dysfunction Of Akt/Protein Kinase B: S-Nitrosylation And Acetaminophen Intervention, Miaozong Wu, Anjaiah Katta, Murali Gadde, Hua Liu, Sunil Kakarla, Jacqueline Fannin, Satyanarayana Paturi, Ravi Arvapalli, Kevin Rice, Yeling Wang, Eric Blough
Ravi K. Arvapalli
Background: Aged skeletal muscle is characterized by an increased incidence of metabolic and functional disorders, which if allowed to proceed unchecked can lead to increased morbidity and mortality. The mechanism(s) underlying the development of these disorders in aging skeletal muscle are not well understood. Protein kinase B (Akt/PKB) is an important regulator of cellular metabolism and survival, but it is unclear if aged muscle exhibits alterations in Akt function. Here we report a novel dysfunction of Akt in aging muscle, which may relate to S-nitrosylation and can be prevented by acetaminophen intervention. Principal Findings: Compared to 6- and 27-month rats, …
Stem Cell Transplantation Increases Antioxidant Effects In Diabetic Mice, 2012 Marshall University
Stem Cell Transplantation Increases Antioxidant Effects In Diabetic Mice, Ming Li, Luca Vanella, Yuming Zhang, Ming Shi, Takashi Takaki, Joseph I. Shapiro M.D., Susuma Ikehera
Biochemistry and Microbiology
Intra bone marrow-bone marrow transplantation (IBM- BMT) + thymus transplantation (TT) has been shown to reduce the incidence of graft versus host disease (GVHD) and restore donor-derived T cell function. In addition, an increase in insulin sensitivity occurred in db/db mice after IBM-BMT+TT treatment. Heme oxygenase (HO)-1 is a stress inducible enzyme which exert antioxidant, antiapoptotic, and immune-modulating properties. We examined whether IBM-BMT+TT could modulate the expression of HO-1 in the kidneys of db/db mice. Six-week-old db/db mice with blood glucose levels higher than 250 mg/dl were treated with IBM-BMT+TT. Six weeks later, the db/db mice showed decreased body weight, …