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Full-Text Articles in Life Sciences
Ampa And Kainate Receptor-Potentiating Rna Aptamers, Janet L. Lynch
Ampa And Kainate Receptor-Potentiating Rna Aptamers, Janet L. Lynch
Legacy Theses & Dissertations (2009 - 2024)
Glutamate receptors act to bring about excitatory transmission in the central nervous system. The receptors are divided into two groups: ionotropic and metabotropic glutamate receptors. Ionotropic glutamate receptors are ion channels which are activated by an agonist such as glutamate or kainate. The main receptors in the ionotropic glutamate receptor family are the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), kainate and N-methyl-D-aspartate (NMDA) receptors. In the central nervous system ionotropic glutamate receptors are found both pre- and postsynaptically. It has been found that most AMPA and NMDA receptors are postsynaptic receptors while the kainate receptors can be pre- or postsynaptic. Underactivity of these …
Development Of Dual Functional Dna/Rna Nanostructures For Drug Delivery, Vibhav Amit Valsangkar
Development Of Dual Functional Dna/Rna Nanostructures For Drug Delivery, Vibhav Amit Valsangkar
Legacy Theses & Dissertations (2009 - 2024)
In addition to the traditional biochemical functions, DNA and RNA have been increasingly studied as building blocks for the formation of various 2D and 3D nanostructures. DNA has emerged as a versatile building block for programmable self-assembly. DNA-based nanostructures have been widely applied in biosensing, bioimaging, drug delivery, molecular computation and macromolecular scaffolding. A variety of strategies have been developed to functionalize these nanostructures. The major advantage is that DNA is a very stable molecule and its base-pairing properties can be easily utilized to control and program the formation of desired nanostructures. In addition, some of these DNA/RNA nanostructures have …
Development Of Small Molecule Antibiotics Against A Conserved Rna Gene Regulatory Element In Gram-Positive Bacteria, Ville Yrjö Petteri Väre
Development Of Small Molecule Antibiotics Against A Conserved Rna Gene Regulatory Element In Gram-Positive Bacteria, Ville Yrjö Petteri Väre
Legacy Theses & Dissertations (2009 - 2024)
Bacterial infections and the rise of antibiotic resistance, especially multidrug resistant strains, have generated a clear need for discovery of novel therapeutics. Most antibiotics in use today are derivatives of previous antibiotics to which resistance mechanisms already exist, and traditionally they have a single target: either a protein or rRNA. Gram-positive bacteria regulate the expression of several essential genes or operons using a mechanism called the T-box. The T-box is a structurally conserved riboswitch-like gene regulator in the 5’-untranslated region (UTR) of numerous essential genes of Gram-positive bacteria. T-boxes are stabilized by cognate, unacylated tRNA ligands, allowing the formation of …
Significance Of Rna 2'-5' Linkage And Metal-Ion Mediated Base Pairs, Fusheng Shen
Significance Of Rna 2'-5' Linkage And Metal-Ion Mediated Base Pairs, Fusheng Shen
Legacy Theses & Dissertations (2009 - 2024)
It has been known that the template-directed RNA chemical replication reaction produces mixture of backbones containing both 3’-5’ and 2’-5’ linkages. This backbone heterogeneity has been a significant problem in studying the emergence of RNA World from the prebiotic chemistry. However, very recently, it is reported that FMN binding aptamer and a hammerhead ribozyme are still able to retain considerable functions in the presence of certain 2’-5’ linkages, indicating that RNA backbones may be quite flexible and this backbone heterogeneity problem may not be as severe as originally thought. This finding also brings two related important questions: First, how does …
Transcriptional Regulation Of Dksa In E. Coli, Daniel Thomas Woods
Transcriptional Regulation Of Dksa In E. Coli, Daniel Thomas Woods
Legacy Theses & Dissertations (2009 - 2024)
DksA is a global transcription factor that binds RNAP directly to regulate the expression of many genes and operons, including ribosomal RNA, in a ppGpp-dependent or ppGpp–independent manner. It is also involved in facilitating the process of DNA replication by removing stalled transcription elongation complexes that could block the progress of the replication fork. In addition, DksA is important for colonization, establishment of biofilms, and pathogenesis. In order to sustain these various functions, an adequate level of cellular DksA is required. This work tested the hypothesis that the E. coli dksA is substantially regulated at the level of transcription. Using …
Circular Rna : A Review Of History, Diseases, And Diagnostic Potential, Daniel Conley
Circular Rna : A Review Of History, Diseases, And Diagnostic Potential, Daniel Conley
Legacy Theses & Dissertations (2009 - 2024)
Abstract
Technology Development For Detection Of Circulating Disease Biomarkers From Liquid Biopsies Using Multifunctional Nanomaterials, Mustafa Balcioglu
Technology Development For Detection Of Circulating Disease Biomarkers From Liquid Biopsies Using Multifunctional Nanomaterials, Mustafa Balcioglu
Legacy Theses & Dissertations (2009 - 2024)
Despite the advance health care, devastating health conditions such as cancer and infectious diseases that affect populations worldwide are too often not diagnosed until morbid symptoms become apparent in the late phase. Obtaining an early and accurate diagnosis that reveal a hidden lethal threat before the disease becomes complicated may dramatically reduce the severity of its impact on the patient’s life and increase the probability of survival. For example, in the case of ovarian cancer, which is the fifth most common malignancy and the fifth leading cause of cancer mortality in women in the US, the 5-year relative survival is …
Mass Spectrometric Analysis And Machine Learning Enable Microorganism Classification Based On Rna Posttranscriptional Modifications, Colin Christopher Aldrich
Mass Spectrometric Analysis And Machine Learning Enable Microorganism Classification Based On Rna Posttranscriptional Modifications, Colin Christopher Aldrich
Legacy Theses & Dissertations (2009 - 2024)
RNA post-transcriptional modifications (PTMs) are dynamic features that can be up- or down-regulated by the health and metabolic state of a cell. These covalent modifications are installed and removed on RNA nucleosides by enzymes controlled by the activation and deactivation of specific genes. The goal of this research was to demonstrate that RNA PTMs can serve as a unique feature for the classification/identification of microorganisms. We utilized a scheme based on electrospray ionization mass spectrometry (ESI-MS) to obtain global PTM profiles from total RNA extracted from various microorganisms in optimal growth conditions as well as Salmonella typhimurium (S. typhimurium) spiked …
The Structural Heterogeneity And Dynamics Of Base Stacking And Unstacking In Nucleic Acids, Ada Anna Sedova
The Structural Heterogeneity And Dynamics Of Base Stacking And Unstacking In Nucleic Acids, Ada Anna Sedova
Legacy Theses & Dissertations (2009 - 2024)
Base stacking provides stability to nucleic acid duplexes, and base unstacking is involved in numerous biological functions related to nucleic acids, including replication, repair, transcription, and translation. The patterns of base stacking and unstacking in available nucleic acid crystal structures were classified after separation into their individual single strand dinucleotide components and clustering using a k-means-based ensemble clustering method. The A- and B-form proximity of these dinucleotide structures were assessed to discover that RNA dinucleotides can approach B-form-like structures. Umbrella sampling molecular dynamics simulations were used to obtain the potential of mean force profiles for base unstacking at 5'-termini for …
Novel Nmr Based Technologies To Study Macromolecular Structures, Subhabrata Majumder
Novel Nmr Based Technologies To Study Macromolecular Structures, Subhabrata Majumder
Legacy Theses & Dissertations (2009 - 2024)
Nuclear Magnetic Resonance Spectroscopy (NMR) is one of the principle tools in structural biology to probe macromolecular structures and interactions. The atomic resolution afforded by this technique has been widely used to probe protein-protein, and protein-ligand interactions in-vitro. However, the natural milieu of the proteins is the living cell and the cellular cytoplasm is extremely heterogeneous. The NMR studies of folded protein in-cell, till now, have been limited by non-specific interactions of the cytosol. This thesis outlays a general methodology to study protein structure/interactions inside the living cells using NMR. In a closely related objective, it also describes the use …
Rna Aptamer Mediated Manipulation Of The 70 Kilodalton Heat Shock Protein Chaperone Machinery, Deepak Thirunavukarasu
Rna Aptamer Mediated Manipulation Of The 70 Kilodalton Heat Shock Protein Chaperone Machinery, Deepak Thirunavukarasu
Legacy Theses & Dissertations (2009 - 2024)
Protein quality control involves refolding of damaged proteins and facilitating degradation of irreparable proteins. Understanding the protein quality control mechanism is critical, since defects in it has been implicated in a number of age-related diseases like neurodegenerative diseases and also in cancer. A vast network of molecular chaperones and proteolytic systems collaborate to maintain protein quality control. The 70 kilodalton Heat shock protein (Hsp70) is a highly conserved and ubiquitous chaperone, which interacts with a variety of protein substrates including newly synthesized polypeptides, unfolded, partially misfolded and native proteins to maintain protein quality control. Hsp70 chaperone function is coupled to …
Probing Secondary And Tertiary Rna Folding Using Force And Temperature, William Stephenson
Probing Secondary And Tertiary Rna Folding Using Force And Temperature, William Stephenson
Legacy Theses & Dissertations (2009 - 2024)
RNA folding is the process whereby a single stranded RNA molecule assumes its three-dimensional functional conformation. Along with the protein folding problem, the RNA folding problem remains as one of the great unsolved problems in biophysics. Generally RNA folding occurs in a hierarchical manner whereby the sequence of an RNA (primary structure) determines which regions will form helical segments (secondary structure) before further rearrangement and base pairing of secondary structure motifs (tertiary structure). Due to the intimate connection between structure and function within molecular biology, increased familiarity with the thermodynamic and kinetic factors that govern RNA folding will permit the …
2'-O-Methyl Substitutions In The Yeast Telomerase Pseudoknot And Their Effects On Telomerase Activity, Katelyn Mae Jasper
2'-O-Methyl Substitutions In The Yeast Telomerase Pseudoknot And Their Effects On Telomerase Activity, Katelyn Mae Jasper
Legacy Theses & Dissertations (2009 - 2024)
Telomerase is a ribonucleoprotein (RNP) complex that synthesizes telomeric repeats at the ends of linear chromosomes to form the DNA–protein complexes known as telomeres. Telomeres protect the ends of chromosomes from degradation during replication due to the end-replication problem. When replication occurs, gaps are created at the beginning of the lagging and leading strands that result in the loss of a small amount of DNA at every replication cycle. By adding thousands of copies of telomeric repeats, the repeats are lost in the replication process and not precious genetic information. The telomerase RNA varies drastically among different species both in …
Ultraviolet Resonance Raman Spectroscopy For Characterization Of Rna Structure And Thermodynamics, Joseph Dustin Handen
Ultraviolet Resonance Raman Spectroscopy For Characterization Of Rna Structure And Thermodynamics, Joseph Dustin Handen
Legacy Theses & Dissertations (2009 - 2024)
Raman spectroscopy is a technique well suited for the study of biological molecules such as proteins, peptides, or RNAs. By utilizing an ultraviolet resonance Raman (UVRR) instrument, we are afforded a tremendous increase in sensitivity because of resonance enhancement. Additionally, this technique does not require any labeling. Moreover, this technique is better suited for studying biological systems than infrared absorption due to reduced interference from water. In this study, we apply techniques we have developed for the study of protein and peptide fibrillation to a model RNA homodimer. We demonstrate that UVRR spectroscopy is uniquely suited to monitoring the free …
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 …
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.
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 …
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 …