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Articles 91 - 112 of 112
Full-Text Articles in Biochemistry
Selection Of Chemically Modified Rna Aptamers Against The Glua2q Flop Ampa Receptor, Hyojung Seo
Selection Of Chemically Modified Rna Aptamers Against The Glua2q Flop Ampa Receptor, Hyojung Seo
Legacy Theses & Dissertations (2009 - 2024)
The á-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors play an important role in neurotransmission and synaptic plasticity in the central nervous system. Excessive activity of these receptors has been implicated in some neurodegenerative diseases, such as Parkinson's disease, ischemic stroke and amyotrophic lateral sclerosis (ALS). AMPA receptor inhibitors are therefore drug candidates for potential treatment of these neurological disorders and diseases. The objective of my MS thesis work is to develop a stable aptamer so that it can be tested and used in vivo where the aptamer must be exposed to ribonucleases. To do this, I prepared a library containing RNAs with 2'-Fluoro …
Sirtuin 6 : A Review Of Biological Affects And Potential Therapeutic Properties, Jade Beauharnois
Sirtuin 6 : A Review Of Biological Affects And Potential Therapeutic Properties, Jade Beauharnois
Legacy Theses & Dissertations (2009 - 2024)
ABSTRACT: Sirtuins, possessing either histone deacetylase or mono-ribosyltransferase activity, regulate important biological pathways in bacteria, archaea and eukaryotes. The term Sir2 comes from the yeast 'silent mating-type information regulation 2' gene, a gene directing cellular regulation in yeast. Sirtuins have been implicated in aging, regulation of transcription, apoptosis and stress resistance, in addition to energy efficiency and metabolism. In mammals, a variety of sirtuin family members are genetically encoded to include sirtuins 1-7 (SIRT1-SIRT7). SIRT6 is a human sirtuin of interest in a variety of research areas, influencing the genomic instability, metabolic defects and degenerative pathologies associated with aging. Until …
Structure And Function Of Non-Coding Regulatory Rna Domains, Nakesha L. Smith
Structure And Function Of Non-Coding Regulatory Rna Domains, Nakesha L. Smith
Legacy Theses & Dissertations (2009 - 2024)
Ribonucleic acid (RNA) has been found to be a very versatile molecule, exhibiting countless functions and can act as a catalyst in biochemical reactions. These functions have typically been attributed to the unique structures that it forms. Novel non-coding RNAs capable of regulating gene expression are still being discovered, and the scope of the RNA world is still being uncovered. The structure function relationship of two different types of non-coding RNA has been investigated: riboswitches and sxRNAs. UV-monitored thermal denaturation experiments, Nuclear Magnetic Resonance spectroscopy, native gel electrophoresis and an in vivo luciferase assay were used to investigate the structural …
Mechanism Of Inhibition Of The Glua2 Receptors By N-3 Derivatives Of 2,3-Benzodiazepines With C-4 Methyl Group, Congzhou Wang
Mechanism Of Inhibition Of The Glua2 Receptors By N-3 Derivatives Of 2,3-Benzodiazepines With C-4 Methyl Group, Congzhou Wang
Legacy Theses & Dissertations (2009 - 2024)
α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors are one of the three subtypes of ionotropic glutamate receptors. AMPA receptors mediate fast synaptic neurotransmission in the central nervous system (CNS). Over-activation of calcium permeable AMPA receptors causes intracellular calcium overload, which leads to neurodegeneration and cell death. As such, AMPA receptors have been implicated in a number of neurological disorders and diseases, such as epilepsy, amyotrophic lateral sclerosis (ALS), and Parkinson's disease. 2,3-Benzodiazepine derivatives (or GYKI compounds) are a group of structurally similar compounds synthesized as inhibitors of AMPA receptors, and they have been used as potential drug candidates for the treatment of various …
Interactions Of The Human Immunodeficiency Virus Type 1 Nucleocapsid Protein With Non-Hiv-Derived Nucleic Acids : Implications For The Viral Replication Cycle, Abhijit Padmakar Jadhav
Interactions Of The Human Immunodeficiency Virus Type 1 Nucleocapsid Protein With Non-Hiv-Derived Nucleic Acids : Implications For The Viral Replication Cycle, Abhijit Padmakar Jadhav
Legacy Theses & Dissertations (2009 - 2024)
During attempts to develop aptamers that bind to the nucleocapsid protein of HIV-1 (i.e. NCp7) with high affinity, a heretofore unreported property of the protein--the ability to mediate degradation of nucleic acids, was discovered. Using λ DNA as a model nucleic acid system, it was shown that NCp7-mediated degradation of nucleic acids is non-specific, depends on incubation time, the concentration of NCp7, and the presence of divalent and monovalent cations. It was further demonstrated that degradation can be abrogated if NCp7 is pre-incubated with NCp7-inhibitors. Lyophilization of NCp7 can induce irreversible changes in its secondary structure that result in loss …
Dna Repair Fidelity And Cancer : Structural And Kinetic Insights From Dna Polymerase Beta Mutator Variants, Chelsea Lynne Gridley
Dna Repair Fidelity And Cancer : Structural And Kinetic Insights From Dna Polymerase Beta Mutator Variants, Chelsea Lynne Gridley
Legacy Theses & Dissertations (2009 - 2024)
DNA polymerases are essential for genome replication and DNA repair in all living organisms. Precise DNA replication is critical for the preservation of genomic stability. Any insult, endogenous/exogenous, to cellular DNA requires properly functioning repair polymerases. In eukaryotes, DNA polymerase beta, a small enzyme (39 kDa), plays an important role in DNA repair during the base excision repair pathway. Pol beta catalyzes the incorporation of nucleotides in small stretches (1-6 nucleotides) of damaged double-stranded DNA. Should gap-filling synthesis by pol beta be compromised, mutations in genomic DNA accumulate, which are frequently linked to human diseases, including cancers. For this reason, …
Amyloid Fibril Polymorphism : Structure, Supramolecular Chiraliy And Spontaneous Interconversion, Dzmitry Kurouski
Amyloid Fibril Polymorphism : Structure, Supramolecular Chiraliy And Spontaneous Interconversion, Dzmitry Kurouski
Legacy Theses & Dissertations (2009 - 2024)
Specific protein aggregation has been linked to more than 25 severe human maladies including prion, Alzheimer's, and Parkinson's diseases. These important malfunctions are often referred to as 'conformational' disorders and result from the conversion of a normal isoform of a protein into a specific b-sheet rich polymeric amyloid form. This work elaborates a comprehensive characterization of amyloids and dedicated to the investigation of the fibril polymorphism using advanced microscopic tools, such as Atomic Force and Scanning Electron microcopies, together with several vibrational spectroscopy techniques, such as Raman, Infrared and Vibrational Circular Dichroism. A new type of protein folding-aggregation phenomenon, spontaneous …
Single Cell Analysis For The Characterization Of Cell Populations Using A Live Cell Array, Maureen Ann Walling
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.
Structural Interactions And Dynamics Of Disease Related Proteins By Using Nmr Spectroscopy, Shadakshara Swamy Puttamadappa
Structural Interactions And Dynamics Of Disease Related Proteins By Using Nmr Spectroscopy, Shadakshara Swamy Puttamadappa
Legacy Theses & Dissertations (2009 - 2024)
Nuclear Magnetic Resonance (NMR) is a powerful spectroscopic technique to study the structure, molecular interactions, and dynamics of proteins. Modern NMR instrumentation, advancements in experimental techniques and revolutionary developments in recombinant DNA technology have made NMR a versatile and very convenient tool for biomolecule characterization.
In-Cell And In Vitro Studies Of Disease Related Protein-Protein Interactions Using Nmr-Spectroscopy, Andres Yudiel Maldonado
In-Cell And In Vitro Studies Of Disease Related Protein-Protein Interactions Using Nmr-Spectroscopy, Andres Yudiel Maldonado
Legacy Theses & Dissertations (2009 - 2024)
The receptor for advanced glycation end products (RAGE) is a multiligand cell surface macromolecule that plays a central role in the etiology of diabetes, inflammation, and neurodegeneration. The cytoplasmic domain of RAGE, ctRAGE, is critical for RAGE-dependent signal transduction. As the most membrane proximal event, mDia1 binds to ctRAGE and is essential for RAGE ligand-stimulated phosphorylation of AKT and cell proliferation/migration. We show that ctRAGE contains an unusual alpha-turn that mediates the mDia1-ctRAGE interaction and is required for RAGE dependent signaling. The results establish a novel mechanism through which an extracellular signal initiated by RAGE ligands regulates RAGE signaling in …
Advanced Statistical Methods For Biochemical And Forensic Applications Of Raman Spectroscopy, Vitali Sikirzhytski
Advanced Statistical Methods For Biochemical And Forensic Applications Of Raman Spectroscopy, Vitali Sikirzhytski
Legacy Theses & Dissertations (2009 - 2024)
This work is dedicated to the development and application of advanced statistical methods for biochemical and forensic applications of Raman spectroscopy. We developed a new concept of multidimensional Raman signatures for forensic identification of body fluid traces, which was successfully applied to the study of dried blood, semen, saliva, sweat and vaginal fluid stains. Several alternative advanced chemometric techniques were also successfully tested for the problems of pure body fluids discrimination and mixture analysis. Studies of body fluid mixtures with low blood and semen concentrations indicated that the detection limit of a minor contributor was as low as a few …
Structure And Function Of Coding And Non-Coding Rna Domains, Fei Liu
Structure And Function Of Coding And Non-Coding Rna Domains, Fei Liu
Legacy Theses & Dissertations (2009 - 2024)
As a versatile molecule, RNA exhibits an astonishing variety of functional activities, which is typically attributed to its particular structure-forming capacity. There are an increasing number of established roles and systems where RNA structures, in particular, RNA pseudoknots, affect specific biological processes based on their structural features. The structure-function-relationships of RNA in three systems has been invesgated: the telomerase RNA pseudoknot domain from S. cerevisiae, a poteintial unusual H-type pseudoknot forming region near the 3'-splice-site in the influenza virus NS1 mRNA, and the 5'-untranslated-region of the CC16 mRNA where mutations in the wildtype sequence have been related to asthma. UV-monitored …
Design And Application Of Composite Rna Aptamers, Shengchun Wang
Design And Application Of Composite Rna Aptamers, Shengchun Wang
Legacy Theses & Dissertations (2009 - 2024)
aptamers are being developed as an essential tool in many fields of biological research. Their utility is not limited to being protein inhibitors; a lot of novel functions can be realized. However, in vivo application of RNA aptamers still faces many challenges. The aim of this dissertation is to design and apply composite aptamers in multiple expression and delivery systems to address some critical issues, such as correct folding, high level production, degradation by nucleases, excessive consumption of cellular resource and potential toxic effect.
Homologous And Heterologous Crystallin Protein Interactions As The Molecular Basis Of Inherited Cataract, Priya Ranjan Banerjee
Homologous And Heterologous Crystallin Protein Interactions As The Molecular Basis Of Inherited Cataract, Priya Ranjan Banerjee
Legacy Theses & Dissertations (2009 - 2024)
Age-related cataract is the most common cause of blindness worldwide. Nearly fifty percent of Americans above the age of 75 are diagnosed with this disease (http://www.nei.nih.gov/eyedata/pbd_tables.asp), and surgical intervention is the sole method of treatment at present (http://www.nei.nih.gov/healthyvision/objective/cataracts.asp). In the developing world, even this treatment is not readily available. These are compelling reasons to search for better treatments to delay, prevent or arrest cataract formation. Recent evidence suggests that age-related cataracts also have a genetic component. Therefore, determining the mechanisms underlying genetic cataracts with a known association to a protein-mutation is one important strategy towards understanding the molecular basis for …
Biophysical Investigations Of The Molecular Basis Of Cataract Associated With The R76s Mutation In Human Gammad-Crystallin, Vurghun Ahmadov
Biophysical Investigations Of The Molecular Basis Of Cataract Associated With The R76s Mutation In Human Gammad-Crystallin, Vurghun Ahmadov
Legacy Theses & Dissertations (2009 - 2024)
Cataract disease results when the eye lens becomes opaque and scatters a significant part of the incoming light into the eye. The lens contains very high concentrations of the lens proteins, called crystallins, which are present at concentrations comparable to those found in protein crystals (about 400-600 mg/mL). Chemical modifications of the crystallins, such as oxidation and deamidation, or genetic mutations are known to result in increased light-scattering in vitro, and are implicated in cataract formation in vivo. Here we present the in vitro work on a mutant protein of human gammaD crystallin (HGD), namely R76S (i.e. Arg 76 to …
The Alliinase And Lachrymatory Factor Synthase Systems In Petiveria Alliacea, Quan He
The Alliinase And Lachrymatory Factor Synthase Systems In Petiveria Alliacea, Quan He
Legacy Theses & Dissertations (2009 - 2024)
Isolation and characterization of an alliinase and a lachrymatory factor synthase from the Amazonian medicinal plant Petiveria alliacea is reported. The alliinase is unusual in that it is heteromeric, whereas all previous reports of characterized alliinases have shown them to be monomers or homomultimers. The protein possesses 5 subunits: two alpha subunits which are glycosylated and connected by a disulfide bond, and beta, gamma and delta subunits. The alliinase exhibits broad substrate specificity, reacting with S-substituted-L-cysteine sulfoxides with aromatic, aliphatic, alkenyl and polar side chains. The alliinase-mediated breakdown of a variety of cysteine sulfoxide derivatives yields transitory sulfenic acid intermediate …
Saturation Transfer Difference Nmr Studies : Pyrazinamide And Pyrazinamide Analogs Coordinating With Mycobacterium Tuberculosis Fatty Acid Synthase I (Fas I), Halimah Sayahi
Legacy Theses & Dissertations (2009 - 2024)
One third of the world's population is infected with M. tuberculosis, the causative agent of tuberculosis (TB) that claims the life of approximately 2 million people every year. The rapid spread of multidrug-resistance tuberculosis as well the emergence of extensively drug resistance strains that are resistant to virtually any known antibiotic, has transformed this once curable disease into a major public health challenge. To regain control of this disease and the associated mortality and morbidity new antibiotics are urgently needed.
Elucidating The Structure Of Protein Aggregates By Raman Spectroscopy, Ludmila A. Popova
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.
Role Of Cyp2a5 In Drug Metabolism, Chemical Toxicity, And Maintenance Of Steroid Hormone Homeostasis : Insights From Studies On A Novel Cyp2a5-Null Mouse Model, Xin Zhou
Legacy Theses & Dissertations (2009 - 2024)
The central hypothesis is that CYP2A5 plays an important role in the metabolism of xenobiotic substrates, and in the toxicity induced by over-exposure to drugs, as well as in the metabolism of endogenous compounds and regulation of steroid hormone homeostasis. The specific aims are: 1) to generate and characterize a Cyp2a5-null mouse; 2) to determine the role of CYP2A5 in the systemic clearance of nicotine and cotinine; and 3) to explore the mechanisms underlying the resistance of the lateral nasal gland (LNG) of male Cyp2g1-null/Cyp2a5-low mouse and Cyp2a5-null mouse to acetaminophen (AP) toxicity.
Genetically Engineered Repetitive Polypeptides : Design, Synthesis, Characterization, And Applications, Natalya I. Topilina
Genetically Engineered Repetitive Polypeptides : Design, Synthesis, Characterization, And Applications, Natalya I. Topilina
Legacy Theses & Dissertations (2009 - 2024)
This work is dedicated to the investigation of protein folding with the emphasis on the aggregation and amyloid fibrils formation. The focus of the research is to elucidate the relationship between polypeptide chain sequence and folding/aggregation properties. For this purpose, i) libraries of the de novo macromolecular repetitive β-sheet forming polypeptides were designed, and ii) the strategy for their rapid creation was developed. The strategy enables retention of a basic polypeptide core, yet allowing variations in the repetitive sequence, degree of polymerization and distribution of specific amino acids. The polypeptides were expressed in E. coli, purified, and characterized by various …
Secondary Structures And Thermodynamic Properties Of Ampa Receptor Aptamers, Sabarinath Jayaseelan
Secondary Structures And Thermodynamic Properties Of Ampa Receptor Aptamers, Sabarinath Jayaseelan
Legacy Theses & Dissertations (2009 - 2024)
Using systematic evolution of ligands by exponential enrichment (SELEX), our lab previously selected a class of competitive RNA aptamers against the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors. One aptamer in this class was found to have a minimal, functional sequence of 58 nucleotides. In vitro transcription generates two RNA transcripts with the same sequence, which we named M1 and M2, both of which are required to work together to inhibit the AMPA receptors. Although the M1 and M2 species have the same sequence, they cannot be interconverted through unfolding by denaturation/refolding by renaturation. To probe the secondary structures and the thermodynamic …
The Recognition And Folding Of Ncp7 (Nucleocapsid Protein) With Tardna And Psi Site Rna Hairpin Structures From Hiv-1 : A Spin Label Study, Yan Sun
Legacy Theses & Dissertations (2009 - 2024)
The nucleocapsid (NC) protein NCp7 of the human immunodeficiency virus type 1(HIV 1) is a small basic protein with two zinc finger motifs. NCp7 has key roles in virus replication and structure, which rely on its interactions with nucleic acids. We investigated the interaction of NCp7 with Transactivation Response Element (TAR) DNA which is critical for minus strand transfer during the HIV 1 reverse transcription. The EPR spin probe nitroxide was used as the reporter. Binding of NCp7 to TARDNA caused TARDNA condensation, as inferred from the probe tumbling time which markedly increased to several nanoseconds at a 4:1 NCp7 …