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Full-Text Articles in Physical Sciences and Mathematics

Barth Syndrome: Exploring Cardiac Metabolism With Induced Pluripotent Stem Cell-Derived Cardiomyocytes, Erica M. Fatica, Gina A. Deleonibus, Alisha House, Jillian V. Kodger, Ryan W. Pearce, Rohan R. Shah, Liraz Levi, Yana Sandlers Dec 2019

Barth Syndrome: Exploring Cardiac Metabolism With Induced Pluripotent Stem Cell-Derived Cardiomyocytes, Erica M. Fatica, Gina A. Deleonibus, Alisha House, Jillian V. Kodger, Ryan W. Pearce, Rohan R. Shah, Liraz Levi, Yana Sandlers

Chemistry Faculty Publications

© 2019 by the authors. Licensee MDPI, Basel, Switzerland. Barth syndrome (BTHS) is an X-linked recessive multisystem disorder caused by mutations in the TAZ gene (TAZ, G 4.5, OMIM 300394) that encodes for the acyltransferase tafazzin. This protein is highly expressed in the heart and plays a significant role in cardiolipin biosynthesis. Heart disease is the major clinical manifestation of BTHS with a high incidence in early life. Although the genetic basis of BTHS and tetralinoleoyl cardiolipin deficiency in BTHS-affected individuals are well-established, downstream metabolic changes in cardiac metabolism are still uncovered. Our study aimed to characterize TAZ-induced metabolic perturbations …


End-Point Modification Of Recombinant Thrombomodulin With Enhanced Stability And Anticoagulant Activity, Xia Liu, Mallorie Boron, Yu Zhao, Xue-Long Sun Nov 2019

End-Point Modification Of Recombinant Thrombomodulin With Enhanced Stability And Anticoagulant Activity, Xia Liu, Mallorie Boron, Yu Zhao, Xue-Long Sun

Chemistry Faculty Publications

Thrombomodulin (TM) is an endothelial cell membrane protein that plays essential roles in controlling vascular haemostatic balance. The 4, 5, 6 EGF-like domain of TM (TM456) has cofactor activity for thrombin binding and subsequently protein C activation. Therefore, recombinant TM456 is a promising anticoagulant candidate but has a very short half-life. Ligation of poly (ethylene glycol) to a bioactive protein (PEGylation) is a practical choice to improve stability, extend circulating life, and reduce immunogenicity of the protein. Site-specific PEGylation is preferred as it could avoid the loss of protein activity resulting from nonspecific modification. We report herein …


Cobalt(Ii) Diphenylazodioxide Complexes Induce Apoptosis In Sk-Hep-1 Cells, Norah J. Alghamdi, Lakshmi Balaraman, Kylin A. Emhoff, Ahmed M.H. Salem, Ruhan Wei, Aimin Zhou, W. Christropher Boyd Sep 2019

Cobalt(Ii) Diphenylazodioxide Complexes Induce Apoptosis In Sk-Hep-1 Cells, Norah J. Alghamdi, Lakshmi Balaraman, Kylin A. Emhoff, Ahmed M.H. Salem, Ruhan Wei, Aimin Zhou, W. Christropher Boyd

Chemistry Faculty Publications

The cobalt(II) complex salts [Co(bpy)(az)2](PF6)2 and [Co(az)4](PF6), each bearing the unusual cis-N,N'-diphenylazodioxide ligand, were both screened as possible anticancer agents against SK-HEP-1 liver cancer cells. Both compounds were found to induce substantial apoptosis as an increasing function of concentration and time. Measurement of apoptosis-related proteins indicated that both the extrinsic and intrinsic pathways of apoptosis were activated. The apoptotic activity induced by these salts is not displayed either by simple cobalt(II) salts or complexes or by the free nitrosobenzene ligand. Additionally, these compounds did not induce apoptosis, as assessed by poly(adenosine …


Google Funds Cold Fusion Research; Results Still Negative, David W. Ball Sep 2019

Google Funds Cold Fusion Research; Results Still Negative, David W. Ball

Chemistry Faculty Publications

No abstract provided.


Natural Kinds And Ceteris Paratis Generalizations: In Praise Of Hunches, W. Christropher Boyd, Richard N. Boyd Jun 2019

Natural Kinds And Ceteris Paratis Generalizations: In Praise Of Hunches, W. Christropher Boyd, Richard N. Boyd

Chemistry Faculty Publications

According to stereotypical logical empiricist conceptions, scientific findings are approximately true (or perhaps true ceteris paribus) law-like generalizations used to predict natural phenomena. They are deployed using topic-neutral, generally reliable inferential principles like deductive or statistical inferences. Natural kinds are the kinds in such generalizations. Chemical examples show that such conceptions are seriously incomplete. Some important chemical generalizations are true often enough, even though not usually true, and they are applied using esoteric topic- and discipline-specific inference rules. Their important methodological role is to underwrite often-enough reliable, often socially implemented, scientifically informed guessing about chemical phenomena. Some chemical natural …


A Non-Natural Nucleotide Uses A Specific Pocket To Selectively Inhibit Telomerase Activity, Wilnelly Hernandez-Sanchez, Wei Huang, Brian Plucinsky, Nelson Garcia-Vazquez, Nathaniel J. Robinson, William P. Schiemann, Anthony J. Berdis, Emmanuel Skordalakes, Derek J. Taylor Apr 2019

A Non-Natural Nucleotide Uses A Specific Pocket To Selectively Inhibit Telomerase Activity, Wilnelly Hernandez-Sanchez, Wei Huang, Brian Plucinsky, Nelson Garcia-Vazquez, Nathaniel J. Robinson, William P. Schiemann, Anthony J. Berdis, Emmanuel Skordalakes, Derek J. Taylor

Chemistry Faculty Publications

Telomerase, a unique reverse transcriptase that specifically extends the ends of linear chromosomes, is up-regulated in the vast majority of cancer cells. Here, we show that an indole nucleotide analog, 5-methylcarboxyl-indolyl-2′-deoxyriboside 5′-triphosphate (5-MeCITP), functions as an inhibitor of telomerase activity. The crystal structure of 5-MeCITP bound to the Tribolium castaneum telomerase reverse transcriptase reveals an atypical interaction, in which the nucleobase is flipped in the active site. In this orientation, the methoxy group of 5-MeCITP extends out of the canonical active site to interact with a telomerase-specific hydrophobic pocket formed by motifs 1 and 2 in the fingers domain and …


A Quantitative Lc-Ms/Ms Method For Determination Of A Small Molecule Agonist Of Epha2 In Mouse Plasma And Brain Tissue, Bo Zhong, Yaxin Li, Nethrie Idippily, Aaron Petty, Bin Su Ph.D., Bingcheng Wang Apr 2019

A Quantitative Lc-Ms/Ms Method For Determination Of A Small Molecule Agonist Of Epha2 In Mouse Plasma And Brain Tissue, Bo Zhong, Yaxin Li, Nethrie Idippily, Aaron Petty, Bin Su Ph.D., Bingcheng Wang

Chemistry Faculty Publications

Compound 27 {1, 12‐bis[4‐(4‐amino‐6,7‐dimethoxyquinazolin‐2‐yl)piperazin‐1‐yl]dodecane‐1,12‐dione} is a novel small molecule agonist of EphA2 receptor tyrosine kinase. It showed much improved activity for the activation of EphA2 receptor compared with the parental compound doxazosin. To support further pharmacological and toxicological studies of the compound, a method using liquid chromatography and electrospray ionization tandem mass spectrometry (LC–MS/MS) has been developed for the quantification of this compound. Liquid–liquid extraction was used to extract the compound from mouse plasma and brain tissue homogenate. Reverse‐phase chromatography with gradient elution was performed to separate compound 27 from the endogenous molecules in the matrix, followed by …


Tracking Decitabine Incorporation Into Malignant Myeloid Cell Dna In Vitro And In Vivo By Lc-Ms/Ms With Enzymatic Digestion, Sujatha Chilakala, Ye Feng, Lan Li, Reda Mahfouz, Ebrahem Quteba, Yogen Saunthararajah, Yan Xu Mar 2019

Tracking Decitabine Incorporation Into Malignant Myeloid Cell Dna In Vitro And In Vivo By Lc-Ms/Ms With Enzymatic Digestion, Sujatha Chilakala, Ye Feng, Lan Li, Reda Mahfouz, Ebrahem Quteba, Yogen Saunthararajah, Yan Xu

Chemistry Faculty Publications

The DNA hypomethylating agents decitabine and 5-azacytidine are the only two drugs approved for treatment of all subtypes of the myeloid malignancy myelodysplastic syndromes (MDS). The key to drug activity is incorporation into target cell DNA, however, a practical method to measure this incorporation is un-available. Here, we report a sensitive and specific LC-MS/MS method to simultaneously measure decitabine incorporation and DNA hypomethylation. A stable heavy isotope of 2'-deoxycytidine was used as an internal standard and one-step multi-enzyme digestion was used to release the DNA bound drug. Enzyme-released decitabine along with other mononucleosides were separated by a reverse-phase C-18 column …


Analysis Of Oxygen-18 Labeled Phosphate To Study Positional Isotope Experiments Using Lc-Qtof-Ms, Sujatha Chilakala, Iteen Cheng, Ireen Lee, Yan Xu Feb 2019

Analysis Of Oxygen-18 Labeled Phosphate To Study Positional Isotope Experiments Using Lc-Qtof-Ms, Sujatha Chilakala, Iteen Cheng, Ireen Lee, Yan Xu

Chemistry Faculty Publications

A method is proposed in this paper for the determination of oxygen-18 labeled phosphate so that positional isotope experiments using sensitive and rapid liquid chromatography–QTOF–mass spectrometry (LC-QTOF-MS) experiments can be carried out. The positional isotope exchange technique is a useful tool in understanding the mechanisms and kinetics of many enzyme-catalyzed reactions. Detection of the positions and concentration of these exchanged isotopes is the key. Gas chromatography–mass spectrometry (GC-MS) and nuclear magnetic resonance imaging are commonly used analytical techniques for measurement of 18O/16O, 31P and 15N isotope enrichment. Since these techniques either require a time-consuming derivatization …


Cold Fusion Thirty Years Later, David W. Ball Jan 2019

Cold Fusion Thirty Years Later, David W. Ball

Chemistry Faculty Publications

In March 1989, the claim of a revolutionary discovery in nuclear energy production galvanized the scientific community. It turned into a classic case of pathological science—and a textbook example of the self-correcting nature of science.


Coordination Chemistry Of N,N’- Azodoxides, Lakshmi Balaraman Jan 2019

Coordination Chemistry Of N,N’- Azodoxides, Lakshmi Balaraman

ETD Archive

The coordination chemistry of nitric oxide (NO) with transition metals has been extensively investigated, but that of organic NO derivatives as ligands less so. Some nitrosoalkanes RNO and nitrosoarenes ArNO are in equilibrium with dimeric species known as N,N'–azodioxides, R(O)NN(O)R or Ar(O)NN(O)Ar. The cis diastereomers of azodioxides have been proposed to act as bidentate chelating ligands for both main-group and transition metals, but only three azodioxide complexes, a dicationic iron (II) complex, a neutral scandium (III) complex, and a dicationic calcium (II) complex, have thus far been structurally characterized before our work in this area. The delocalized π system of …


Reactivity Of Molybdenum And Tungsten Sulfido Complexes With First-Series Transition Metals, Khalil Mudarmah Jan 2019

Reactivity Of Molybdenum And Tungsten Sulfido Complexes With First-Series Transition Metals, Khalil Mudarmah

ETD Archive

Ammonium tetrathiomolybdate (ATTM) is an important compound in bioinorganic chemistry, with medicinal applications. Metal complexes of sulfur-containing ligands have been widely used as building block in biology and inorganic chemistry. This project aims to increase the number of Mo-S and W-S complexes that may contribute to fields such as bioinorganic and medicinal chemistry, by the preparation of heterometallic complexes containing both Mo or S and a metal of the first transition series. The homobimetallic complex anion salts (Et4N)2[Mo2(S)2(μ-S)2(edt)2] (1) and (Et4N)2[W2(S)2(μ-S)2(edt)2] (2) have been prepared from ATTM and ammonium tetrathiotungstate (ATTW) in order to start our work. The overnight treatment …


Liquid Chromatography - Mass Spectrometric Analysis Of Clinicallyand Pharmacologically Relevant Molecules, Raghavi Kakarla Jan 2019

Liquid Chromatography - Mass Spectrometric Analysis Of Clinicallyand Pharmacologically Relevant Molecules, Raghavi Kakarla

ETD Archive

Liquid Chromatography-Mass Spectrometry is an advanced analytical technique that offers high sensitivity and specificity and has been increasingly used for analysis of a wide variety of compounds including clinically and pharmacologically relevant molecules. In this dissertation we describe qualitative and quantitative liquid chromatographic mass spectrometric methods to analyze both small molecules and larger macromolecules that provide useful insights into diagnosis and management of several diseases. An LCMS(/MS) analytical method includes extraction of analytes of interest from the matrix followed by liquid chromatographic separation and mass spectrometric detection. Chapter I describes pre-analytical workflows and sample pretreatment techniques and theories underlying LC-MS …


Development Of An Spr Method To Monitor The Chemical Interaction Of Dna With A Small Reactive Molecule: Peroxynitrite As An Example, Divya Sharma Jan 2019

Development Of An Spr Method To Monitor The Chemical Interaction Of Dna With A Small Reactive Molecule: Peroxynitrite As An Example, Divya Sharma

ETD Archive

Peroxynitrite is an anion with the formula ONOO-. It is an unstable structural isomer of nitrate, NO3-. Although its conjugate acid (ONOOH) is highly reactive, it is quite relatively stable in basic solutions. Generation of peroxynitrite in-vivo occurs through the diffusion-controlled reaction between superoxide anion and nitric oxide free radical. It is a strong oxidizing and nitrating agent, and its formation has been correlated with many pathological conditions. Because of its oxidizing properties, peroxynitrite can damage a wide array of molecules in cells, including DNA and proteins. Reactions of peroxynitrite with DNA, proteins, and lipids, trigger a wide array of …


In-Quest Of Biomarkers For Alzheimer’S Disease And Pharmacokinetic Profile Of Anticancer Agents Using Lc-Ms In Human Plasma, Chandana Mannem Jan 2019

In-Quest Of Biomarkers For Alzheimer’S Disease And Pharmacokinetic Profile Of Anticancer Agents Using Lc-Ms In Human Plasma, Chandana Mannem

ETD Archive

In this dissertation work, a semi-quantitative assay using a lipidomics approach and an absolute quantitative assay using liquid chromatography-mass spectrometry techniques were developed (LC-MS). In the lipidomics approach, ultra-high pressure liquid chromatography in tandem with quadrupole time of flight (UHPLC-QTOF) mass spectrometry was used to profile, compare and quantitate the human plasma lipids in Alzheimer’s disease subjects (AD) and normal cognitive controls (NCCs). The purpose of this study is to identify potential plasma lipid markers of AD and to explore the relationships between AD and lipid pathways in humans by using bioinformatic tools. The plasma samples of study subjects were …


Development Of An Spr Method To Monitor The Chemical Interaction Of Dna With A Small Reactive Molecule: Peroxynitrite As An Example, Divya Sharma Jan 2019

Development Of An Spr Method To Monitor The Chemical Interaction Of Dna With A Small Reactive Molecule: Peroxynitrite As An Example, Divya Sharma

ETD Archive

Peroxynitrite is an anion with the formula ONOO-. It is an unstable structural isomer of nitrate, NO3-. Although its conjugate acid (ONOOH) is highly reactive, it is quite relatively stable in basic solutions. Generation of peroxynitrite in-vivo occurs through the diffusion-controlled reaction between superoxide anion and nitric oxide free radical. It is a strong oxidizing and nitrating agent, and its formation has been correlated with many pathological conditions. Because of its oxidizing properties, peroxynitrite can damage a wide array of molecules in cells, including DNA and proteins. Reactions of peroxynitrite with DNA, proteins, and lipids, trigger a wide array of …