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Synthesis Of Resveratrol Esters And Aliphatic Acids., Stanley Mofor Jing

Electronic Theses and Dissertations

Resveratrol (RV) is a naturally occurring phytoalexin of the stilbenoid family produced by some plant species, and present in grape skin, peanuts, and red wine. It has been found to exhibit anti-cancer, anti-inflammatory, anti-viral, anti-aging, cardio protective, and anti-oxidant properties. Bioavailability is a huge setback that limits the potentials of RV. As a result, efforts have been made to design and synthesize RV esters and aliphatic acids in an attempt to increase its bioavailability, solubility in water, and possibly improving its biological activities. Resveratrol esters, 3,5,4'-triacetyloxystilbene (2) and Methyl 1,1',1''- (3,4',5-stilbenyl)-1,6-hexanedioate (3) have been synthesized. Compound 3 is a new …

Development Of Lps Antagonistic Therapeutics: Synthesis And Evaluation Of Glucopyranoside-Spacer-Amino Acid Motifs, Sophon Kaeothip, Geeta Paranjape, Shana Terrill, Aileen Bongat, Maria Udan, Teerada Kamkhachorn, Hope Johnson, Michael Nichols, Alexei Demchenko

Chemistry & Biochemistry Faculty Works

No abstract provided.

Microfluidic Paper-Based Analytical Devices: From Pocket To Paper-Based Elisa, Andres W. Martinez

Chemistry and Biochemistry

Microfluidic paper-based analytical devices (microPADs) began as a simple idea with an ambitious goal. The idea was to make microfluidic devices out of paper instead of plastic or glass. The goal was to develop low-cost and portable paper-based diagnostic devices to improve healthcare in developing countries. Over the past 6 years, many developments have been made in the emerging field of paper-based microfluidic devices. Reviewing the development of these devices in the Whitesides group at Harvard University (Cambridge, MA, USA) can provide some insight into the future of the field and encourage scientists from a variety of backgrounds to contribute …

In Vivo Liver Endocytosis Followed By Purification Of Liver Cells By Liver Perfusion, Sandhya Gopalakrishnan, Edward N. Harris

Department of Biochemistry: Faculty Publications

The liver is the metabolic center of the mammalian body and serves as a filter for the blood. The basic architecture of the liver is illustrated in figure ¹ in which more than 85% of the liver mass is composed of hepatocytes and the remaining 15% of the cellular mass is composed of Kupffer cells (KCs), stellate cells (HSCs), and sinusoidal endothelial cells (SECs). SECs form the blood vessel walls within the liver and contain specialized morphology called fenestrae within in the cytoplasm. Fenestration of the cytoplasm is the appearance of holes (˜100 μm) within the cells so that the …

Single Cell Analysis For The Characterization Of Cell Populations Using A Live Cell Array, Maureen Ann Walling

Legacy Theses & Dissertations (2009 - 2024)

In the past decade, the shift from whole cell population analyses towards single cell measurement methods and techniques is based on experimental results that reveal significant levels of non-genetic heterogeneity in clonal cell populations. This heterogeneity manifests in multiple aspects of cell activity and is, in part, a result of stochastic noise in processes leading to gene expression, namely transcription and translation. The growing understanding of this occurrence has led to the development of methods to monitor and analyze heterogeneity for a more thorough description of cell populations and overall activity.

Molecular Details Of The Catalytic Activity Of Carboxylesterases, Xiaozhen Yu

Electronic Theses and Dissertations

Carboxylesterases (CEs; EC 3.1.1.1) are ubiquitous enzymes responsible for the detoxification of xenobiotics. CEs hydrolyze carboxyl esters into their corresponding alcohol and carboxylic acid. Because of their biological functions, especially their roles in converting inactive prodrugs, such as the anti-cancer drug CPT-11, to their active metabolites, a good understanding of the mechanism of the hydrolysis reaction will give us a better direction for drug design. In this study, we used a multidisciplinary approach (computational simulation, molecular biology techniques and enzyme kinetic methods) to study the dynamic motions of CEs and the potential role of these motions in the catalytic mechanism …

A Novel In Vivo Protein Refolding Technique, Yuefei Huang

Wayne State University Dissertations

Proteins perform their functions in their native folded states and misfolding of proteins may cause severe diseases, including Alzheimer's disease, Parkinson's disease, prion disease and diabetes. Understanding protein folding is important for us to engineer proteins to treat these diseases. For protein therapeutics, large quantities of properly folded and functional proteins are required. The current technology produces recombinant proteins using either eukaryotic or prokaryotic expression system, both of them have major problems that prevent production of large quantities of properly folded and functional human proteins for protein therapeutics.

Although the eukaryotic cells have comprehensive folding machinery that contains chaperones and …

Synthesis, Self-Assembly And Biological Properties Of Self-Folding Cu(Ii) Coordination Polymers, Alejandro Arzola-Rubio

Open Access Theses & Dissertations

The synthesis of materials via molecular self-assembly is a powerful bottom-up approach for fabricating matter in the nano- and micro-meter scales. This methodology involves the spontaneous and reversible organization of small molecules that interact with one another to create larger structures driven by non-covalent interactions such as hydrogen bonding, hydrophobic forces and metal-ligand coordination interactions. In this thesis, the design, synthesis and characterization of a new set of molecules that spontaneously self-organize in water to form three-dimensional nanoscale toroidal structures was investigated. These supramolecular structures were designed with an intrinsic affinity to bind and condense DNA strands with the intent …

The In Situ Function Of A Microbial Community Profiled By Ft-Ir: A Snapshot In Time, Ryan Roberts

Department of Biochemistry: Dissertations, Theses, and Student Research

Photographs of an ecosystem are an important tool in macro-community ecology. The photograph is a permanent record of species phenotype. In microbiology, biochemical activity provides the most descriptive information of an organism’s phenotype. A method for fingerprinting all biochemical activities occurring within a microbial community is analogous to a photograph. Infrared spectroscopy in the region between wavelengths 2500 to 20,000 nm (mid-IR) is a well established instrumental method for fingerprinting the total biochemical profile of axenic cultures. Spectra are complex and sensitive as demonstrated by the ability to discriminate between strains of bacteria, fungi, and algae. This thesis develops the …

The Marine Sponge Metabolite Mycothiazole: A Novel Prototype Mitochondrial Complex I Inhibitor., J Brian Morgan, Fakhri Mahdi, Yang Liu, Veena Coothankandaswamy, Mika B. Jekabsons, Tyler A. Johnson, Koneni V. Sashidhara, Phillip Crews, Dale G. Nagle, Yu-Dong Zhou

Natural Sciences and Mathematics | Faculty Scholarship

A natural product chemistry-based approach was applied to discover small-molecule inhibitors of hypoxia-inducible factor-1 (HIF-1). A Petrosaspongia mycofijiensis marine sponge extract yielded mycothiazole (1), a solid tumor selective compound with no known mechanism for its cell line-dependent cytotoxic activity. Compound 1 inhibited hypoxic HIF-1 signaling in tumor cells (IC(50) 1nM) that correlated with the suppression of hypoxia-stimulated tumor angiogenesis in vitro. However, 1 exhibited pronounced neurotoxicity in vitro. Mechanistic studies revealed that 1 selectively suppresses mitochondrial respiration at complex I (NADH-ubiquinone oxidoreductase). Unlike rotenone, MPP(+), annonaceous acetogenins, piericidin A, and other complex I inhibitors, mycothiazole is a mixed polyketide/peptide-derived compound …

Ampa Receptor Allosterism: Measurement Of The Conformational Changes In The Ligand Binding Domain Of A Functional Receptor, Jennifer Gonzalez-Mcgehee

Dissertations and Theses (Open Access)

Ionotropic glutamate receptors are important excitatory neurotransmitter receptors in the mammalian central nervous system that have been implicated in a number of neuropathologies such as epilepsy, ischemia, and amyotrophic lateral sclerosis. Glutamate binding to an extracellular ligand binding domain initiates a series of structural changes that leads to the formation of a cation selective transmembrane channel, which consequently closes due to desensitization of the receptor. The crystal structures of the AMPA subtype of the glutamate receptor have been particularly useful in providing initial insight into the conformational changes in the ligand binding domain; however, these structures are limited by crystallographic …

Elucidating The Structure Of Protein Aggregates By Raman Spectroscopy, Ludmila A. Popova

Legacy Theses & Dissertations (2009 - 2024)

The structures and properties of amyloid fibrils are of considerable interest due to their associations with numerous neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and transmissible spongiform encephalopaties (prion diseases). Understanding fibrillogenesis at a molecular level requires detailed structural characterization of amyloid fibrils. However amyloid fibrils are difficult objects to study due to their non-crystalline and insoluble nature. These properties make the application of classical tools of structural biology, such as X-Ray crystallography and solution Nuclear Magnetic Resonance spectroscopy, impractical for structural characterization of protein fibrils.

Automated Interpretation Of The Tandem Mass Spectra Of Peptides Using Artificial Neural Networks, Timothy Patrick Manning

Theses

The manual interpretation of mass spectra is a complex and time consuming task. The problem of manually interpreting this data is further exacerbated by the large numbers of mass spectra which can potentially be produced in a single proteoniics experiment. This shows the need for high throughput approaches to the interpretation of mass spectra. Existing automated approaches are however error prone due to the complexity of the task. Accordingly, this thesis discusses and evaluates the application of neural networks to improving the sensitivity, specificity and robustness of current approaches to the automated interpretation of such mass spectral data.

Several neural …

Characterization And Functional Regulation Of Bioactive Peptides In Avian Macrophages And Heterophils, Lakshmi Kannan

Graduate Theses and Dissertations

Oligopeptides and low molecular weight polypeptides play central roles as effectors and signal transducers acting as hormones, neurotransmitters, growth factors, toxins, and antimicrobial factors that are important for the survival of the organism. Owing to the ubiquitous involvement of peptides in many key regulatory processes, we have been interested to identify native peptides in different cells and tissues and understand their functions. To conduct our studies, we used avian macrophages and heterophils as models of specialized cells which constitute central components of innate immunity. These studies involved (a) qualitative identification and characterization of the peptides associated with high intensity mass …

A Locus-Based Paradigm For Generating Systems Biological Inferences From Large Scale Functional Genomics Datasets, Ajish Dominic George

Legacy Theses & Dissertations (2009 - 2024)

Genomics data is growing at a exponential rate. The ability to integrate new results with existing knowledge about genomic biology is rapidly becoming the limiting factor as there no universal language with which to describe genomic functional elements. To integrate and compare new and existing genomic data, we define our basic functional unit of a genome to be a locus -- a set of positional coordinates along any genome with an arbitrary amount of functional annotations attached. The locus concept enables addressing genomic elements and annotations at any level of granularity from entire swaths of chromosomes to single base-positions. We …

History Of The Department Of Biochemistry And Molecular Biology, Gene A. Homandberg

UND Departmental Histories

This departmental history was written on the occasion of the UND Quasquicentennial in 2008.

Giardia Lamblia: Genomic And Molecular Analyses Of Flippase, Diana Leticia Villazana-Kretzer

Open Access Theses & Dissertations

Giardia lamblia, is an intestinal protozoan parasite responsible as a major cause of water-borne intestinal infection in humans (giardiasis). It has been proposed earlier that Giardia has limited lipid synThesis ability and therefore relies on preformed lipid molecules from outside sources. It has also been proposed that lipids are taken up through passive and active transport, and giardial flippasse play a significant role in this process. This study describes the identification and characterization of a putative homologue of flippase gene from Giardia. Flippase is an enzyme that functions as a trans-bilayer transport system facilitating the flip flop diffusion of phospholipids …

Pyridinium Bisretinoids: Synthesis And Photoactivated Cytotoxicity, Junping Gao

Theses and Dissertations

This thesis discusses pyridinium bisretinoid compounds (PBRs), which were prepared for two purposes: 1) to use them as standards for detection of novel fluorophores in human RPE cells, which may be involved in age-related macular degeneration (AMD), and 2) to use them in the development of a targeted and triggered drug delivery system for cancer therapy. We prepared a selection of PBRs using a one-pot biomimetic method; synthesis, mechanisms for formation, and characterization of these compounds is described. We also explored the photoreactivity of three novel PBR compounds and found that these PBRs form oxidation products under blue-light irradiation. The …

Gene Synthesis, Cloning, Expression, Purification And Biophysical Characterization Of The C2 Domain Of Human Tensin, Kiran Sukumar Gajula

Doctoral Dissertations

Tensin is a large "docking" protein found in the adhesive junctions of animal cells and recruited early in the development of cell-substrate contacts. There it binds to the cytoplasmic domain of integrin β1 and caps the barbed ends of filamentous actin. This forms a rational basis for its implication in a direct role in the mechanics of membrane-cytoskeleton interactions. Tensin provides a physical link between the actin cytoskeleton, integrins, and other proteins at the cell-substrate contacts. Its overall biochemical properties are a function of its domain composition and architecture, i.e., the domains that are present and their relative positions in …

A Simple Array Platform For Microrna Analysis And Its Application In Mouse Tissues, Xiaoqing Tang, Jozsef Gal, Xun Zhuang, Wang-Xia Wang, Haining Zhu, Guiliang Tang

Plant and Soil Sciences Faculty Publications

MicroRNAs (miRNAs) are a novel class of small noncoding RNAs that regulate gene expression at the post-transcriptional level and play a critical role in many important biological processes. Most miRNAs are conserved between humans and mice, which makes it possible to analyze their expressions with a set of selected array probes. Here, we report a simple array platform that can detect 553 nonredundant miRNAs encompassing the entire set of miRNAs for humans and mice. The platform features carefully selected and designed probes with optimized hybridization parameters. Potential cross-reaction between mature miRNAs and their precursors was investigated. The array platform was …

Retrocyclin Rc-101 Overcomes Cationic Mutations On The Heptad Repeat 2 Of Hiv-1 Gp41, Christopher Fuhrman

Electronic Theses and Dissertations

Retrocyclin RC-101, a θ-defensin with lectin-like properties, potently inhibits infection by many HIV-1 subtypes by binding to the heptad repeat (HR)-2 region of gp41 and preventing six-helix bundle formation. In the present study, we used in silico computational exploration to identify residues of HR2 that interacted with RC-101 and then analyzed the HIV-1 Sequence Database at LANL for residue variations in the HR1 and HR2 segments that could plausibly impart in vivo resistance. Docking RC-101 to gp41 peptides in silico confirmed its strong preference for HR2 over HR1, and implicated residues crucial for its ability to bind HR2. We mutagenized …

The Influence Of Adenoviral Infection And The Group Via Calcium-Independent Phospholipase A2 On Hepatic Lipid Metabolism, William Palmer Wilkins Iii

Theses and Dissertations

Sterol regulatory element-binding proteins (SREBP) are transcription factors that regulate genes involved in lipid metabolism especially in the liver. Therefore, hepatic SREBP is significant regulator of systemic lipid metabolism. Evidence demonstrates that insulin and dietary unsaturated fatty acid (UFA) regulate SREBP1 expression and subsequent SREBP1-mediated gene transcription, events that in many instances result in modulation of systemic fatty acid and triglyceride (TG) homeostasis. A series of investigations was designed to uncover novel regulators of SREBP1. Dietary and exogenous addition of UFA has been shown to regulate SREBP function yet, an endogenous source of UFA capable of modulating SREBP remains elusive. …

Androgen-Induced Recruitment Of Rna Polymerase Ii To A Nuclear Receptor–P160 Coactivator Complex, Maggie C. Louie, Hong Qiong Yang, Ai-Hong Ma, Wei Xu, June X. Zou, Hsing-Jien Kung, Hong-Wu Chen

Collected Faculty Scholarship

The androgen receptor, like other nuclear receptors, activates target genes by binding to hormone-responsive enhancers. Here we demonstrate that androgen induces robust recruitment of androgen receptor, members of the p160 coactivator family, and CREB-binding protein/p300 specifically at the distant enhancer of prostate-specific antigen (PSA) gene. Unexpectedly, we found that RNA polymerase II (Pol II) is directly recruited to the enhancer in a hormone-dependent manner, independent of the proximal promoter, and that the isolated PSA enhancer can mediate efficient androgen induction of transcription. Inhibition of the Pol II carboxyl-terminal domain kinase activity with low concentrations of flavopiridol blocks Pol II transfer …

Developmental And Hormonal Regulation Of The Expression Of Cytosolic Phospholipase A2 Protein Levels In Baboon Placenta, Kathleen Elizabeth Dunstan

Chemistry & Biochemistry Theses & Dissertations

Cytosolic phospholipase A₂ ( cPLA₂) specifically catalyzes the release of arachidonate from membrane phospholipids, thus initiating synthesis of prostaglandins, thromboxanes, and other eicosanoids. The human and nonhuman primate placenta actively synthesize high levels of eicosanoids which play both an autocrine and paracrine role in placental function. Previous studies in Dr. Miriam D. Rosenthal's laboratory have shown that cPLA₂ mRNA levels are developmentally regulated. The present study was designed to determine whether placental cPLA₂ protein levels increased during gestation. Since the marked increases in estrogen levels during normal pregnancy have been shown to enhance morphological and …

Nerve Tissue-Specific Human Glutamate Dehydrogenase That Is Thermolabile And Highly Regulated By Adp / P. Shashidharan, Donald D. Clarke, Naveed Ahmed, Nicholas Moschonas, And Andreas Plaitakis Department Of Neurology, Mount Sinai School Of Medicine, New York; Department Of Chemistry, Fordham University, Bronx New York, Usa; And Department Of Biology And School Of Health Sciences, University Of Crete, Crete, Greece, P. Shashidharan, Donald Dudley Clarke Phd, Naveed Ahmed, Nicholas Moschonas

Chemistry Faculty Publications

Glutamate dehydrogenase (GDH), an enzyme that is central to the metabolism of glutamate, is present at high levels in the mammalian brain. Studies on human leukocytes and rat brain suggested the presence of two GDH activities differing in thermal stability and allosteric regulation, but molecular biological investigations led to the cloning of two human GDH-specific genes encoding highly homologous polypeptides. The first gene, designated GLUD1, is expressed in all tissues (housekeeping GDH), whereas the second gene, designated GLUD2, is expressed specifically in neural and testicular tissues. In this study, we obtained both GDH isoenzymes in pure form by expressing a …

The Lipooligosaccharides Of Haemophilus Ducreyi Are Highly Sialylated, William Melaugh, A A. Campagnari, B W. Gibson

Chemistry Faculty Publications

The major lipooligosaccharides of the sexually transmitted pathogen Haemophilus ducreyi 35000 have been previously found to terminate in N-acetyllactosamine and sialyl-N-acetyllactosamine, Neu5Ac alpha 2-->3Gal beta 1-->4GlcNAc (W. Melaugh, N. J. Phillips, A. A. Campagnari, M. V. Tullius, and B. W. Gibson, Biochemistry 33: 13070-13078, 1994). In this study, mass spectrometry and composition analyses have shown that the lipooligosaccharides from three other H. ducreyi strains also contain N-acetyllactosamine and are highly sialylated (approximately 30 to 50%), although one African strain was found to contain neither of these structural features.

Study Of Existing Information Concerning Water Quality Within Lake Mead, Vicki Scharnhorst, Southern Nevada Water Authority

Publications (WR)

The purpose of Task 010A15M of the Southern Nevada Water Authority (SNWA) Treatment and Transmission Facility (TTF) contract is to conduct a study of existing information concerning water quality within Lake Mead and identify additional water quality studies that are needed to supplement existing data. The objective of this task is not to discuss treatability of the raw water source; this is addressed by Task 010A18M, "Define Water Treatment Requirements." In addition, a narrative on the effect of pending Safe Drinking Water Act amendments and a determination of treated water quality goals is included in Task 010A16M, "Review Safe Drinking …

Use Of Pyocin To Select A Haemophilus Ducreyi Variant Defective In Lipooligosaccharide Biosynthesis, A A. Campagnari, R Karalus, M A. Apicella, William Melaugh, A J. Lesse, B W. Gibson

Chemistry Faculty Publications

Haemophilus ducreyi, a cause of genital ulcer disease in developing countries, appears to facilitate the heterosexual transmission of the human immunodeficiency virus in Africa. Despite an increase in studies of this gram-negative human pathogen, little is known about the pathogenesis of chancroid. Our studies have shown that the lipooligosaccharides (LOS) of H. ducreyi may play an important role in ulcer formation. Monoclonal antibody and mass spectrometric analyses identified a terminal trisaccharide present on H. ducreyi LOS that is immunochemically similar to human paragloboside. This epitope is present on the LOS of Neisseria gonorrhoeae, and it may be the site of …

The Isolation And Identification Of Polyphenolics From Grape Seeds And Their Activity Towards Specific Cell Lines, Joseph A. Reddy

Chemistry & Biochemistry Theses & Dissertations

Grape seed extract is being marketed in France for cardiovascular use and skin care. The active constituents of both these drugs are certain polyphenols called procyanidins. A similar seed extract has now been obtained from Virginia Chardonnay grape seeds. Ten of the major components in this extract have been isolated in their pure form by the semi-preparative HPLC separation on a YMC ODS-AQ (Octadecylsilane-AQ) column. The ODS-Aq column has been shown to have a better resolving capacity compared to the Spherisorb ODS (Octadecylsilane) column previously described in the literature. This has been attributed to the ODSAQ support which has both …

Proto-Oncogene Regulation By Growth Factors In Bone Cells, Harold Lyndon Merriman

Loma Linda University Electronic Theses, Dissertations & Projects

Previous studies have shown that bone cells in culture produce a number of growth factors that are important in bone regulation. Chick and mouse primary calvarial cultures consist of a mixture of cell types that make it difficult to interpret the results from these model systems. In contrast, MC3T3-E1 cells are a clonal mouse osteoblast-like cell line. Since MC3T3-E1 cells consist of a single population of calvarial cells, they make an ideal system in which to study the autocrine effects of bone growth factors.

Based on this work, MC3T3-E1 cells are now known to produce IGF-I, TGF-beta and IGF-II in …