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New Insights Into The Mechanism Of Dna Replication On Unmodified And Benzo[A]Pyrene Modified Templates Using Surface Plasmon Resonance, Richard George Federley

Wayne State University Dissertations

DNA synthesis is critical to cell survival, and the enzyme DNA polymerase has had a great deal of time to evolve efficient strategies to perform synthesis. A variety of effects are induced by the identity of the incoming dNTP, and its ability to effectively base pair with the templating base. The presence of the next correct dNTP is known to induce a conformational change of the polymerase and lead to an increase in KF-DNA binding. Conversely, the presence of an incorrect dNTP is shown to lead to a destabilization and reduction in the levels of KF-DNA complexes formed. Using surface …

Laser-Assisted Single-Molecule Refolding, Rui Zhao

Wayne State University Dissertations

Non-coding RNAs must fold into precise secondary and tertiary structures in order to perform the biological functions. Due to the flexibility of RNA, the RNA folding energy landscape can be rugged and full of local minimum (kinetic trap). To provide a means to study kinetically trapped RNAs, we have developed a new technique combining single-molecule FRET detection with laser induced temperature jump. We have calibrated the magnitude of the temperature jump with 1˚C accuracy using gold micro-size sensor. The accuracy of temperature calibration was confirmed by close agreement between single-molecule and bulk DNA duplex melting experiments.

HIV 1 DIS RNAs …

Artificial And Natural Nucleic Acid Self Assembling Systems, Marcus Wood

Wayne State University Dissertations

Nucleic acids are good candidates for nanomachine construction. They participate in all the processes of life, and so can function as structural building blocks and dynamic catalysts. However, to use nucleic acids as nanomachines, a better understanding of their material properties, how to design structures using them, and their dynamics is needed. We have tried to address these issues, in a small way, with nucleic acid force field development, an attempt at nanostructural design and synthesis using DNA, and a study of the RNA/protein regulatory dynamics of the tryptophan regulatory attenuation protein.

Development Of Chemical Inducers Of Dimerization For Screening Competitive Histone Deactelyase Inhibitors, Emily Lynn Aubie

Wayne State University Dissertations

Histone Deacetylase (HDAC) proteins are transcriptional regulators that affect histone proteins, which are involved in packaging of DNA into chromosomes. HDACs have been linked to the proliferation of cancer through their role in transcriptional regulation. Due to these findings, HDAC inhibitors have been explored as anti-cancer agents. Several HDAC inhibitors are currently in various stages of clinical trials, and the inhibitor suberoyl anilide hydroxamic acid (SAHA) has been FDA approved for treatment of cutaneous T-Cell lymphoma. Currently, most of the known HDAC inhibitors are non-selective, which causes non-specific binding to the active sites of all HDAC isoforms, including those not …

Synthesis, Redox Properties, And Langmuir Monolayer Formation Of Selected 3d- And 4d- Metalloamphiphiles, Sree Ramadevi Shanmugam

Wayne State University Dissertations

Transition metals containing amphiphilic compounds integrate various geometric, electronic, magnetic, and electrochemical properties together with the film forming properties. These compounds thereby find potential towards the fabrication of responsive films. This dissertation confers the synthesis and analysis of film forming properties of various redox-active metalloamphiphiles. Two new azido and thiocyanto bridged copper-based amphiphiles were synthesized and characterized by IR, UV-visible, and EPR spectroscopies, mass spectrometry, cyclic voltammetry, and elemental analysis. The redox studies show that both these complexes exhibit redox reversibility with only the azido bridged complex showing good redox cycling of about 50 times with minimal decomposition of less …

Structure Function Analysis Of An Adp-Ribosyltransferase Type Iii Effector And Its Rna-Binding Target In Plant Immunity, Byeong-Ryool Jeong, Yan Lin, Anna Joe, Ming Guo, Christin Korneli, Huirong Yang, Ping Wang, Min Yu, Ronald Cerny, Dorothee Staiger, James R. Alfano, Yanhui Xu

Ronald Cerny Publications

Background: HopU1 ADP-ribosylates GRP7, suppressing plant immunity.

Results: The HopU1 structure has two novel loops required for GRP7 recognition, and HopU1 ribosylates GRP7 at an arginine in position 49 disrupting its function.

Conclusion: HopU1 targets a conserved arginine in GRP7, disabling its ability to bind immunity-related RNA.

Significance: The mechanistic details of how HopU1 recognizes its substrate reveal how HopU1 contributes to pathogenesis.

Establishing An Interdepartmental Fluorescent Microscopy Facility, Marcy Kelly, David Zuzga, Nigel Yarlett

Cornerstone 3 Reports : Interdisciplinary Informatics

No abstract provided.

Interdisciplinary Computational Projects Utilizing The Hpc Cluster, Demos Athanasopoulos

Cornerstone 3 Reports : Interdisciplinary Informatics

No abstract provided.

The Complexity Of Reform Efforts In Science Curriculum And Instruction: A Case Study Of The Illinois Mathematics And Science Academy Chemistry Teacher, Tang Wee Teo

IMSA History

This study explores how teacher-initiated site-based reform in a specialized STEM school is conceptualized and enacted, how and why curriculum reform ideas change in the process of enactment, what qualities of teacher agency are entailed, how these qualities are acquired, interplayed, become generative, and/or are influenced to effect different curriculum reform outcomes, and how different conditions support and further teacher agency to make a more defensible curriculum.

In a critical case study of a highly experienced and qualified science teacher, I follow a teacher who initiated efforts to reform the advanced chemistry curriculum. This teacher wanted to make the curriculum …

Illicit Drug Analysis By Using Ultra-Short Pulses (Thz Spectroscopy), Canan Karaalioglu

Cornerstone 3 Reports : Interdisciplinary Informatics

No abstract provided.

Development Of Biomarkers For Endocrine Disrupting Compounds In The Fathead Minnow, Pimephales Promelas, Tara Frare

Undergraduate Review

Organic waste compounds (OWC’s) are an environmental concern that can have adverse effects on humans, animals, and the environment. Ethinyl estradiol (EE2) is one common OWC and is an active ingredient in oral birth control pills. The presence of EE2 in aquatic environments and drinking water can be linked to decreased fertility and altered physiology in fish. I am developing Q-PCR biomarkers to detect changes in fish at low concentrations before adverse effects occur at higher concentrations. RNA was extracted from twenty fathead minnows that had not been exposed to OWC’s and will be used to synthesize cDNA. Thus far …

Identification Of Proteins That Interact With The Transcription Factor Emx2 In Developing Mouse Neocortex, Jennifer A. Groves

Undergraduate Honors Theses

Neocortex is the largest region of the cerebral cortex in the mammalian brain. It is composed of multiple functional areas that process discrete types of information including visual, somatosensory, and auditory input and motor control output. During embryonic development, the relative size of each area is determined by transcription factors such as EMx2. The goal of our work is to identify proteins that interact with Emx2 to influence its role in neocortical arealization, the process by which the specific areas of the neocortex are formed with discrete boundaries.

Chemical Synthesis Of Peptides And Peptide Thioesters, Indrajeet Sharma

Wayne State University Dissertations

This dissertation describes investigations toward the development of a new chemistry for the block synthesis of peptides and peptidyl thioesters. A direct approach for the Fmoc-SPPS of peptidyl thioesters is also delineated in this thesis.

In the first part of chapter one, the difficulty and importance of chemical synthesis of peptides is explained, and a brief survey of available methods is given. The second part of chapter one presents the challenges inherent in the synthesis of peptidyl thioesters by Fmoc-SPPS.

The second chapter outlines the investigations conducted towards the development of a new chemistry for epimerization-free block synthesis of peptides …

A Turn-On Split-Luciferase Sensor For The Direct Detection Of Poly(Adp-Ribose) As A Marker For Dna Repair And Cell Death, Jennifer L. Furman, Pui-Wing Mok, Shengyi Shen, Cliff I. Stains, Indraneel Ghosh

Cliff Stains Publications

Designed sensors comprising split-firefly luciferase conjugated to tandem poly(ADP-ribose) binding domains allow for the direct solution phase detection of picogram quantities of PAR and for monitoring temporal changes in poly(ADP-ribosyl)ation events in mammalian cells.

Includes Supplementary Material.

Searching The Protein Structure Database For Ligand-Binding Site Similarities Using Cpass V.2, Robert Powers, Jennifer C. Copeland, Jaime L. Stark, Adam Caprez, Ashu Guru, David R. Swanson

Robert Powers Publications

Background: A recent analysis of protein sequences deposited in the NCBI RefSeq database indicates that ~8.5 million protein sequences are encoded in prokaryotic and eukaryotic genomes, where ~30% are explicitly annotated as “hypothetical” or “uncharacterized” protein. Our Comparison of Protein Active-Site Structures (CPASS v.2) database and software compares the sequence and structural characteristics of experimentally determined ligand binding sites to infer a functional relationship in the absence of global sequence or structure similarity. CPASS is an important component of our Functional Annotation Screening Technology by NMR (FAST-NMR) protocol and has been successfully applied to aid the annotation of a number …

New Macrocyclic Glycopeptide Antibiotic For Chiral Hplc Stationary Phases And Ionic Liquids In Analytical Chemistry, Xiaotong Zhang

Chemistry & Biochemistry Dissertations - Archive

The main focus of this dissertation is on the development of new chiral stationary phases for HPLC and GC and the application of ionic liquids in analytical chemistry. They will be discussed separately in two parts. Enantiomeric separations continue to be of great interest to the pharmaceutical industry. It is because drug molecules of opposite chirality often possess distinctive effects in biological environments. Direct chromatography is one of the major techniques used to address the challenge of enantiomeric analysis. Macrocyclic glycopeptides are a very useful class of chiral selectors for HPLC stationary phases because of their broad enantioselectivity. A study …

Slowing Dna Translocation In A Biological Protein Α-Hemolysin Ion Channel, R. Samanthi S. De Zoysa

Chemistry & Biochemistry Dissertations - Archive

During the past decade, nanopore DNA sequencing has emerged as a revolutionary prospect towards a "$1000 genome" goal set by U.S. National Institute of Health. In the nanopore approach, electrophoretic movement of polynucleotide molecules through a nanopore would provide transient current blockades that are unique to each molecule. Since kilobase length DNA can be read directly without amplification or use of costly reagents such as enzymes and fluorescent tags, the nanopore approach can significantly reduce the sequencing cost. However, due to the rapid DNA translocation velocity through the nanopore, accurate detection of single nucleotide bases via the electrophoretically driven approach …

A Survey Of The Chemical Content And Medicinal Activity Of Shrub-Steppe Plants Of The Pacific Northwest, Aaron M. John

Undergraduate Honors Theses

A need for new modes of antibiotic therapy has resulted from the increasing incidence of bacterial resistance to drugs. One approach to this problem involves the search for plant compounds that may help to overcome multi-drug resistance. Many plant genera have been utilized in Native American traditional medicine for their beneficial properties. Such plants include the shrub-steppe genera, Eriogonun and Collomia, which have been used as cold remedies, pain relievers, and for antibiotic-related uses. Limited chemical studies of these genera have revealed medicinally useful compounds such as flavonoids and terpenoids, and further research may result in the identification of …

Variations In Concentrations And Compositions Of Polycyclic Aromatic Hydrocarbons (Pahs) In Coals Related To The Coal Rank And Origin, Susanne Laumann, Vesna Micic Batka, Michael A. Kruge, Christine Achten, Reinhard Sachsenhofer, Jan Schwarzbauer, Thilo Hofmann

Department of Earth and Environmental Studies Faculty Scholarship and Creative Works

The release of unburnt coal particles and associated polycyclic aromatic hydrocarbons (PAHs) may cause adverse impacts on the environment. This study assessed variations in the concentration and composition of PAHs in a set of fifty coal samples from eleven coal basins worldwide. The maximum PAH concentrations at high volatile bituminous rank were recorded in samples from a single basin. Considering the entire sample, the highest PAH concentrations were in fact found outside of this rank range, suggesting that the maceral composition and thus the coal's origin also influenced PAH concentrations. The examination of the PAH compositions revealed that alkylated 2-3 …

Climate Change: The Fork At The End Of Now, Micha Tomkiewicz

Publications and Research

There are many books on global warming written entirely from a layman's perspective, and there is a great deal of scientific literature on this subject. But few if any books attempt to bridge the science to those who lack a rigorous background in mathematics, physics and chemistry-but who may be working on careers in environmental science and policy. The new text is designed to introduce the field of global climate change from a scientific perspective-but written in a way that is accessible to students with some or little science background. It reviews the basic principles of climatic thermodynamics and atmospheric …

Synthesis Of Peptide-Ligand Conjugates And Their Applications, Nitinkumar Dilipkumar Jabre

Wayne State University Dissertations

Three research areas pertaining to this dissertation, (i) synthesis strategies of peptide-ligand conjugates, (ii) their applications and (iii) chemistry of ferryls were surveyed in the introduction chapter. Next, the divergent and dual divergent strategies for the synthesis of non-heme ligand-peptide conjugates were developed. Using these strategies various peptide-ligand conjugates were synthesized via solution as well as solid phase synthesis. The scope and the functional group compatibility of these strategies were also established. The utility of the dual divergent strategy has been demonstrated by synthesizing a small library of metal-binding LHRH analogues. This work showcased the ability of the dual divergent …

Crystallization And Preliminary X-Ray Crystallographic Analysis Of Ligand-Free And Arginine-Bound Forms Of Thermotoga Maritima Arginine-Binding Protein, Alessia Ruggiero, Jonathan D. Dattelbaum, Anna Pennacchio, Luisa Iozzion, Maria Staiano, Matthew S. Luchansky, Bryan S. Der, Rita Berisio, Sabato D'Auria, Luigi Vitagliano

Chemistry Faculty Publications

The arginine-binding protein from Thermotoga maritima (TmArgBP) is an arginine-binding component of the ATP-binding cassette (ABC) transport system in this hyperthermophilic bacterium. This protein is endowed with an extraordinary stability towards thermal and chemical denaturation. Its structural characterization may provide useful insights for the clarification of structure– stability relationships and for the design of new biosensors. Crystallization trials were set up for both arginine-bound and ligand-free forms of TmArgBP and crystals suitable for crystallographic investigations were obtained for both forms. Ordered crystals of the arginine adduct of TmArgBP could only be obtained by using the detergent LDAO as an additive …

Dynamic Light Scattering And Zeta Potential Of Colloidal Mixtures Of Amelogenin And Hydroxyapatite In Calcium And Phosphate Rich Ionic Milieus, Vuk Uskoković, Roselyn Odsinada, Sonia Djordjevic, Stefan Habelitz

Pharmacy Faculty Articles and Research

The concept of zeta-potential has been used for more than a century as a basic parameter in controlling the stability of colloidal suspensions, irrespective of the nature of their particulate ingredients – organic or inorganic. There are prospects that self-assembly of peptide species and the protein-mineral interactions related to biomineralization may be controlled using this fundamental physicochemical parameter. In this study, we have analyzed the particle size and zeta-potential of the full-length recombinant human amelogenin (rH174), the main protein of the developing enamel matrix, in the presence of calcium and phosphate ions and hydroxyapatite (HAP) particles. As calcium and phosphate …

Insulin Based Inhibitors Of Human Islet Amyloid Polypeptide (Hiapp) And Their Effect On Aggregation Of Hiapp In The Treatment Of Type Ii Diabetes, Ranadheer R. Pesaru

Master's Theses and Doctoral Dissertations

Human islet amyloid polypeptide protein (hIAPP) is secreted by the pancreas along with insulin and is assumed to play a role in pathological development of type II diabetes. It has 37 amino acids in its sequence. Amyloid is formed due to misfolding of the protein, which is cytotoxic to beta cells in the pancreas of type II diabetic patients. The presence of amyloid deposits is also a characteristic feature of a number of other diseases like Alzheimer’s disease and Parkinson’s disease. Since insulin has been reported to interact with hIAPP and block amyloid formation, fragments of insulin were synthesized and …

Characterizing The Oligomeric Structure And Catalytic Activity Of The Dihydroorotase And Aspartate Transcarbamoylase From The Bacterium, Bacillus Anthracis, Reshma Kankanala

Master's Theses and Doctoral Dissertations

Bacteremia refers to bacterial presence in the blood. Bacterial proliferation in the blood requires that the organism adapt its metabolism to available nutrients. Nucleotide precursors that could be used are present at low levels in the blood, and thus the invading bacteria must rely on de novo nucleotide biosynthesis for survival. The dihydroorotase domain is a key enzyme in pyrimidine biosynthesis and a promising drug target. The genes encoding the dihydroorotase (DHOase) and aspartate transcarbamoylase (ATCase) of Bacillus anthracis (B. anthracis) were cloned for expression in Escherichia coli (E. coli). The proteins were purified by affinity …

Investigation Of Occurrence, Elimination And Degradation Of Pharmaceutical And Personal Care Products In Drinking Water Using Liquid Chromatography-Tandem Mass Spectrometry, Chuan Wang

Doctoral Dissertations

"Pharmaceutical and personal care products have benefited humans and animals around the world. However, their presence in natural and treated water system as emerging contaminates may have potentially adverse effects on the aquatic environment and cause development of bacterial resistance. In this research project, a comprehensive liquid chromatography tandem mass spectrometry method has been developed and validated for the analysis of sixteen pharmaceutical compounds using solid phase extraction. Treated and untreated water samples collected across Missouri from water treatment facilities were analyzed to access the distribution of sixteen pharmaceutical compounds in both winter and summer seasons. The results of the …

Cyclopentadienone Conversions To Terephthalates And Cycloadditions Of Alkynes And Azides, Sarah E. Bragg

Browse all Theses and Dissertations

Cyclopentadienone derivatives can be converted via a Diels-Alder reaction to multifunctional terephthalate derivatives, which can then be converted to poly(phenylene vinylene) derivatives. It was demonstrated that terephthalate derivatives can be simply and reproducibly synthesized from 2,5-diethoxycarbonyl-3,4-diphenylcyclopentadienone with a variety of acetylenes, having yields ranging from 63% to quantitative yields. The terephthalate derivatives synthesized varied from oils to crystalline solids, but were readily isolated and generally had high rates of completion despite expected steric factors. Terephthalate derivatives with pendent acetylenes were formed in reactions with as low as a 3:1 ratio of diacetylene to cyclopentadienone. A terephthalate derivative with a pendent …

Novel Trisubstituted Arylidene Oxindoles With Potent Anti-Apoptotic Properties, Paul J. Repasky

Browse all Theses and Dissertations

Apoptosis is a highly complex, multi-step cellular pathway utilized to initiate cell suicide. The family of enzymes largely responsible for the process is the cystienyl aspartic acid proteases (caspases). This study details the design and synthesis of a new class of small molecule caspase inhibitors, namely arylidene oxindoles, which are comparable to the isatin family of inhibitors but which offer the advantage of incorporating three points of variability into the basic scaffold. Moreover, whereas the mode of action of isatins against caspases has been demonstrated to involve nucleophilic addition of the cysteine residue of the enzymes to the C-3 ketone …

Self-Assembly Of Amyloid Aggregates Simulated With Molecular Dynamics, Workalemahu Mikre Berhanu

Electronic Theses and Dissertations

Amyloids are highly ordered cross-β sheet aggregates that are associated with many diseases such as Alzheimer‟s, type II diabetes and prion diseases. Recently a progress has been made in structure elucidation, environmental effects and thermodynamic properties of amyloid aggregates. However, detailed understanding of how mutation, packing polymorphism and small organic molecules influence amyloid structure and dynamics is still lacking. Atomistic modeling of these phenomena with molecular dynamics (MD) simulations holds a great promise to bridge this gap. This Thesis describes the results of MD simulations, which provide insight into the effects of mutation, packing polymorphism and molecular inhibitors on amyloid …

High Resolution Hybrid Mass Spectrometry For The Determination Of Marine Biotoxins, Azaspiracids, And Their Biotransformation Products., Zuzana Skrabakova

Theses

Azaspiracids (AZAs), polyether marine toxins, are produced by marine microalgae and accumulate in filter-feeding bivalve molluscs, such as mussels, clams, oysters and scallops, while grazing on phytoplankton, from which they derive nutrition. Although being discovered quite recently, AZAs have caused several human intoxication events and thus became a problem for health authorities and shellfish industries. The rapid development of highly sensitive liquid chromatography multiple tandem mass spectrometry (LC-MS/MS, LC-MS") methods enabled the identification of numerous AZA analogues and added to the control of shellfish contamination. Tandem mass spectrometry techniques, while being highly selective and sensitive for determination of AZAs in …