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Articles 31 - 60 of 178
Full-Text Articles in Biochemistry, Biophysics, and Structural Biology
Missense Mutations In The Gamma Crystallins And Mechanisms Of Lens Opacity, Wenjuan Hou
Missense Mutations In The Gamma Crystallins And Mechanisms Of Lens Opacity, Wenjuan Hou
Legacy Theses & Dissertations (2009 - 2024)
Cataract, or clouding of the ocular lens, among the most common types of eye diseases, is the leading cause of blindness worldwide. With the opacity or clouding of the lens, light incident on the lens is scattered rather than being transmitted and is thus prevented from focusing on the retina. The lens becomes cataractous due to a large number of reasons, among which aging and genetic mutations are two of the most common factors. Clouding of the center of the lens or nuclear opacity, is the most frequently observed type of age-onset cataract, as well as inherited, congenital cataract [1, …
Study Of Primary Cilium Structure And Intraflagellar Transport, Shufeng Sun
Study Of Primary Cilium Structure And Intraflagellar Transport, Shufeng Sun
Legacy Theses & Dissertations (2009 - 2024)
Primary cilia are hair-like protrusions that stem from the basal bodies in the cytoplasm and extend into the extracellular space to sense signals. Intraflagellar transport (IFT) functions to transport cargo molecules into and out of the ciliary compartment to assemble, maintain, and disassemble the cilia. Accurate knowledge of the three-dimensional (3D) structure of primary cilia and precise details of the IFT profile is the foundation for understanding the sensory functions of primary cilia. This work covers three aspects of primary cilia. Firstly, we obtained and analyzed the overall 3D architecture of the complete primary cilia axoneme region using serial section …
Kinetic Characterization Of Two C-Family Polymerases From The Gram-Positive Bacterium Staphylococcus Aureus, Sean P. Fagan
Kinetic Characterization Of Two C-Family Polymerases From The Gram-Positive Bacterium Staphylococcus Aureus, Sean P. Fagan
Legacy Theses & Dissertations (2009 - 2024)
In this dissertation, I review the fundamental processes and mechanisms for bacterial DNA replication, especially the mechanisms employed by high-fidelity DNA polymerases to replicate the genome. Unlike the prototypical bacterial system from Escherichia coli which uses a single C-family polymerase, DNA polymerase IIIα (Pol IIIα), to replicate the genome, low-GC content Gram-positive bacteria utilize two essential C-family polymerases, PolC and DnaE. PolC and DnaE work cooperatively to replicate the genome, with DnaE initiating synthesis from RNA-primers and PolC performing the bulk synthesis. Although atomic structures of both PolC and Pol IIIα are available, detailed pre-steady state kinetic analysis of the …
Tgfbeta1 And Stat3 As Regulators Of The Ha Synthesis And Signaling Pathway, Brenda Goretty Trevizo
Tgfbeta1 And Stat3 As Regulators Of The Ha Synthesis And Signaling Pathway, Brenda Goretty Trevizo
Legacy Theses & Dissertations (2009 - 2024)
The studies described here explored the role of Transforming Growth Factor Beta-1 (TGFβ1) and Signal Transducer and Activator of Transcription 3 (STAT3) as potential regulators of the Hyaluronic Acid (HA) synthesis and signaling pathway in human mammary cells. Our results support previous findings in which TGFβ1, a well characterized driver of the epithelial-mesenchymal transition (EMT) has been shown to regulate HA synthesis and signaling. Interrogation of The Cancer Genome Atlas (TCGA) indicated HAS2 expression positively correlated with TGFβ1 mRNA expression in breast cancer patients and in breast cancer cell lines. RT-qPCR experiments were used to measure the expression of the …
Understanding The Rage Signaling Pathway And Its Contribution To Diabetic Complications, Leon Vegas Ho
Understanding The Rage Signaling Pathway And Its Contribution To Diabetic Complications, Leon Vegas Ho
Legacy Theses & Dissertations (2009 - 2024)
The binding of advanced glycation end products (AGEs) to the receptor for advanced glycation end products (RAGE) is an important feature of the RAGE signaling pathway that plays a role in the pathogenesis of diabetes. Under high glucose concentration, RAGE expression increases immensely from the formation of a Schiff base by glucose bounded to lysine. This triggers an inflammatory and immune response and upregulates the expression of RAGE and causes an accumulation of AGEs in the body. As a result, this leads to the development of diabetes and other complications such as, atherosclerosis, nephrothapy, and retinopathy. To remedy AGE accumulation, …
Adaptation Of Vibrio Cholerae O1 To Protective, Lipopolysaccharide-Specific Antibodies In The Intestinal Lumen, Danielle Elizabeth Baranova
Adaptation Of Vibrio Cholerae O1 To Protective, Lipopolysaccharide-Specific Antibodies In The Intestinal Lumen, Danielle Elizabeth Baranova
Legacy Theses & Dissertations (2009 - 2024)
The outer membrane (OM) of Gram-negative enteric pathogens like Vibrio cholerae is a barrier against host defense factors, as well as a sensor of physical and chemical stimuli that the bacteria encounter in the gastrointestinal tract. The OM is also the primary target of the mucosal immune response, which consists of secretory antibodies primarily directed against lipopolysaccharide (LPS). ZAC-3 is a monoclonal antibody (MAb) that targets the conserved core/lipid A region of LPS of the pandemic V. cholerae O1 serotype. In a neonatal mouse model, passively administered ZAC-3 IgG has been shown to reduce the ability of V. cholerae to …
Novel Substrate-Free Cholinesterase Based Sensing Of Organophosphorus Compounds, Hailey J. Marini
Novel Substrate-Free Cholinesterase Based Sensing Of Organophosphorus Compounds, Hailey J. Marini
Legacy Theses & Dissertations (2009 - 2024)
The increasing concerns of chemical weapons used by terrorists is growing, creating a need for infield detection methods that can rapidly detect these compounds that are a major health concern for civilians and military personnel. Displacement is a novel concept for the detection of cholinesterase inhibitors, including organophosphorus compounds, that could replace the classical instrumentation methods currently being used for diagnostics.
The Stromal Response In Salivary Gland Injury, Kevin O'Keefe
The Stromal Response In Salivary Gland Injury, Kevin O'Keefe
Legacy Theses & Dissertations (2009 - 2024)
Abstract
Launching The Next Generation : Transcriptional Regulation During Oogenesis, Alicia K. Mccarthy
Launching The Next Generation : Transcriptional Regulation During Oogenesis, Alicia K. Mccarthy
Legacy Theses & Dissertations (2009 - 2024)
Germ cells give rise to gametes and link generations by passing genetic information from parent to offspring. Gametes arise from, in many sexually reproducing organisms, germline stem cells (GSCs) which are set aside early during development. GSCs have an amazing capacity to undergo self-renewal to give rise to a pool of undifferentiated cells, while also differentiating to generate specialized germ cells such as haploid gametes. Upon female GSC differentiation, mitotically dividing germ cells can initiate meiosis, and mature within a follicle. During maturation, the specified oocyte is provided with a trust fund of RNAs and proteins for the next generation …
Targeting The Rage Signaling Pathway To Ameliorate The Complications Of Diabetes, Stephen James Dansereau
Targeting The Rage Signaling Pathway To Ameliorate The Complications Of Diabetes, Stephen James Dansereau
Legacy Theses & Dissertations (2009 - 2024)
Diabetes is a global health epidemic that can be devastating to those afflicted,
Biochemical And Chemical Methods Of Key Derivation For Cryptographic Ciphers, Leif K. Mcgoldrick
Biochemical And Chemical Methods Of Key Derivation For Cryptographic Ciphers, Leif K. Mcgoldrick
Legacy Theses & Dissertations (2009 - 2024)
Cryptography is a vital component of digital communication and digital data in general. The use of cryptography is necessary to support the veracity of data and to protect it from outside parties with malicious intent. Cryptography focuses on two main facets that are vital for this goal: data encryption and user authentication. Encryption protects the data by transforming it into an encrypted text that would not allow someone access without having or breaking the encryption method that was used to make it. User authentication is a multiple part process that allows for one to be able to identify oneself to …
The Guardian Of The Genome : Regulation Of The Enhancer Networks Governing The P53-Mediated Stress Response, Allison Catizone
The Guardian Of The Genome : Regulation Of The Enhancer Networks Governing The P53-Mediated Stress Response, Allison Catizone
Legacy Theses & Dissertations (2009 - 2024)
After fertilization in vertebrates, cells work to build organs, tissues and begin to rapidly differentiate and proliferate. This process is the orchestration of finely tuned signals and perfectly timed gene expression patterns. The first step in gene expression, transcription, is governed by proteins known as transcription factors (TF). TFs are responsible for binding to DNA, altering chromatin structure, and driving activation of other genes based on the organism’s needs. Once the process of development is complete, organisms shift their resources to maintaining homeostasis. Humans regularly encounter outside stressors such as UV radiation, pollution, allergens, and drugs. Cells also accumulate mutations …
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 …
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 …
Regulation Of Gene Expression Through Ribosome-Associated Proteins, Clare Margaret Miller
Regulation Of Gene Expression Through Ribosome-Associated Proteins, Clare Margaret Miller
Legacy Theses & Dissertations (2009 - 2024)
Translation is a crucial mechanism for generating proteins to carry out cellular processes and for ensuring proper cell functions. Ribosomes are at the center of translation and are complex pieces of machinery. They consist of at least 80 core eukaryotic ribosomal proteins, which are conserved from prokaryotes, and four ribosomal RNAs (rRNAs): 18S, 28S, 5,8A 5S. In addition, numerous translation factors aid the ribosome in protein production. While ribosomes are typically described by these core features, they are known to exist in a heterogenous pool with variations in protein composition, modifications of rRNA, and an assortment of non-ribosomal proteins that …
The Influence Of Mir-322 On Skeletal Muscle Differentiation, Miles Alexander Soyer
The Influence Of Mir-322 On Skeletal Muscle Differentiation, Miles Alexander Soyer
Legacy Theses & Dissertations (2009 - 2024)
Skeletal muscle plays a crucial role in coordinating voluntary movement and accounts for nearly 50% of total body mass. Dysregulation in skeletal muscle development is known to cause muscle degenerative diseases including the devastating Duchenne Muscular Dystrophy (DMD). The majority of the biological studies investigating muscle development were based on myogenic transcription factors and signaling molecules including: Pax7, Myf5, MyoD, WNT, TGF-β and BMP. After the discovery of non-coding RNAs including microRNAs, it was postulated that these molecules could regulate gene expression and thus affect differentiation and development. MicroRNAs are small non-coding RNAs (~17-25 nucleotides) that regulate gene expression negatively …
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 …
Of Donuts And Promo : In Silico Approaches To Identification Of Transcriptional Regulators Of Salivary Acinar Differentiation, Connor Cillian Duffy
Of Donuts And Promo : In Silico Approaches To Identification Of Transcriptional Regulators Of Salivary Acinar Differentiation, Connor Cillian Duffy
Legacy Theses & Dissertations (2009 - 2024)
The salivary gland is an organ often taken for granted by most people. However, its proper function is essential for several everyday activities, such as speaking, swallowing, and tasting. As such, impaired salivary gland function, such as that caused by Sjögren’s Syndrome or radiotherapy for head and neck cancers, can lead to a significantly reduced quality of life. The cells that produce saliva in salivary glands are known as acinar cells, which arise from proacinar cells generated during embryonic development. As such, in studying the promoter regions of proacinar and acinar genes, it may be possible to identify common transcription …
Post-Translational Modifications And Functional Studies Of Dksa In Escherichia Coli, Andrew Charles Isidoridy
Post-Translational Modifications And Functional Studies Of Dksa In Escherichia Coli, Andrew Charles Isidoridy
Legacy Theses & Dissertations (2009 - 2024)
DksA is a bacterial gene regulator that functions synergistically with the stress alarmone ppGpp to mediate the stringent response. DksA also functions independently of ppGpp to regulate transcription of a number of genes. DksA function is dependent on its binding affinity to RNA polymerase and requires specific interactions between RNAP and catalytic amino acids located on the coiled coil tip, D74 and A76. While much of the previous work on DksA has focused on understanding the mechanisms of action and the numerous gene targets for transcriptional regulation, little is known about the mechanisms by which DksA expression and function may …
Inteins From Pathogenic Microbes As Regulatory Elements And Potential Drug Targets, Cathleen Maria Schiraldi
Inteins From Pathogenic Microbes As Regulatory Elements And Potential Drug Targets, Cathleen Maria Schiraldi
Legacy Theses & Dissertations (2009 - 2024)
Inteins are self-splicing elements that orchestrate the autocatalytic process of protein splicing, during which the intein excises itself from a host polypeptide. This multistep reaction involves a series of coordinated nucleophilic attacks and peptide bond rearrangements that remove the intein and reassemble the flanking halves, called exteins, to form the mature host protein. Some inteins are also mobile elements, and can spread to the same or ectopic sites using an internal homing endonuclease domain.
Evaluation Of Fingerprint Content For Forensic Crime Scene Analysis And Drug Metabolite Detection, Erica Kathryn Brunelle
Evaluation Of Fingerprint Content For Forensic Crime Scene Analysis And Drug Metabolite Detection, Erica Kathryn Brunelle
Legacy Theses & Dissertations (2009 - 2024)
With respect to criminal investigations, one key piece of evidence that often gets overlooked are fingerprints. For years, fingerprint samples have been believed to be useful only for matching purposes using their unique ridges, shapes, and sizes. With the rapid growth of forensic science, it has become evident that the development of fingerprint analysis has been stagnant. The traditional approach has been advantageous for the identification of many individuals; however, many fingerprint samples have been labeled “unusable” due to smudging, smearing, or any one of a myriad of reasons that could cause inconclusive matches. These samples can, however, still be …
Epitranscriptomic Writer Systems And Codon Bias Regulate The Response To Environmental Stress, Andrea Leonardi
Epitranscriptomic Writer Systems And Codon Bias Regulate The Response To Environmental Stress, Andrea Leonardi
Legacy Theses & Dissertations (2009 - 2024)
Epitranscriptomic marks in the form of enzyme-catalyzed modifications to RNA nucleosides can be important regulators of translation and play integral roles in the response to stress. Dynamic changes in tRNA modification status can regulate the translation of stress response proteins whose transcripts have distinct codon biases. The epitranscriptomic writer Alkylation repair homolog 8 (ALKBH8) plays a crucial part in the translation of codon biased transcripts, as it regulates stop codon recoding, which is a specialized form of translation used to generate selenoproteins. ALKBH8 modifies the wobble uridine of selenocysteine tRNA (tRNASec) to promote the decoding of an internal UGA codon …
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 …
Sers For Protein Detection At A Single Molecule Level For Developing A New Medical Diagnostics Platform, Lamyaa Almehmadi
Sers For Protein Detection At A Single Molecule Level For Developing A New Medical Diagnostics Platform, Lamyaa Almehmadi
Legacy Theses & Dissertations (2009 - 2024)
A two-step process of protein detection at a single molecule level using Surface Enhanced Raman Spectroscopy (SERS) was developed as a new platform for medical diagnostics in this proof-of-concept study. First, a protein molecule was bound to a linker in the bulk solution and then this adduct was chemically reacted with the SERS substrate. Traut’s Reagent (TR) was used to thiolate Bovine serum albumin (BSA) in solution followed by chemical cross linking to a gold surface through a sulfhydryl group. A Glycine-TR adduct was used as a control sample to identify the protein contribution to the SER spectra. Gold SERS …
Defining And Harnessing Nature's Selection Of Geranylation In Rna Modification, Phensinee Haruehanroengra
Defining And Harnessing Nature's Selection Of Geranylation In Rna Modification, Phensinee Haruehanroengra
Legacy Theses & Dissertations (2009 - 2024)
Natural RNAs utilize extensive chemical modifications to diversify their structures and functions. Geranylated-2-thiouridine is a special hydrophobic tRNA modification that has been discovered very recently in several bacteria, namely E. coli, E. aerogenes, P. aeruginosa and S. typhimurium by Liu group. It has been found as a post-transcription modification on the wobble position of anticodon of tRNAs specific for glutamic acid, glutamine and lysine. Geranylated-tRNA was shown to correct the frameshifting during the translation of E. coli. However, the reason of the existing of the modification is still largely unclear. To understand why nature incorporates such a hydrophobic group in …
Saliva As A Diagnostic Biological Fluid And The Human Salivary Proteome, Jessica Ghassan Emsies
Saliva As A Diagnostic Biological Fluid And The Human Salivary Proteome, Jessica Ghassan Emsies
Legacy Theses & Dissertations (2009 - 2024)
Saliva is a unique biologic fluid that contains a varying spectrum of proteins, nucleic acids, electrolytes, and hormones.31 It is an exocrine secretion of the salivary glands which is hypotonic in nature with a pH of 7.2-7.4.31 Saliva plays an important role in the oral cavity.33 It lubricates, hydrates, and bathes the oral cavity, therefore, aiding speech and mastication.33 Saliva forms a barrier on the teeth, protects against demineralization, and aids in remineralization.33 Saliva is required for chewing and food bolus preparation, it contains enzymes necessary for digestion, and mediates the sense of taste.33 It also helps wound healing and …
Premature Rho-Dependent Transcription Termination In Escherichia Coli : Link To Translation And Gene Regulation, Gabriele Baniulyte
Premature Rho-Dependent Transcription Termination In Escherichia Coli : Link To Translation And Gene Regulation, Gabriele Baniulyte
Legacy Theses & Dissertations (2009 - 2024)
Transcription termination factor Rho is an essential protein in Escherichia coli and related bacteria. The primary function of Rho is to clear unproductive RNA polymerases from the DNA template to minimize negative effects associated with uncontrolled transcription. Although most of the Rho termination events are constitutive, premature Rho-mediated termination was observed at 3% of all affected transcripts indicating active regulation of Rho activity. In this work, we investigated the regulatory mechanism behind premature Rho-dependent transcription termination in two unrelated genes: suhB and topAI. We show that in both cases transcription is terminated inside the coding gene as a consequence of …
Rack1 Is A Critical Component In Ires-Mediated Translation, Ethan Asher Lafontaine
Rack1 Is A Critical Component In Ires-Mediated Translation, Ethan Asher Lafontaine
Legacy Theses & Dissertations (2009 - 2024)
Due to its sheer number of interacting partners, core ribosomal protein RACK1 is a key player in many cellular processes and has been shown to play a vital role of translation initiation of the Hepatitis C virus RNA. The HCV 5′ untranslated region contains an internal ribosome entry site. IRES-mediated translation is a process employed in eukaryotes by select viruses and some cellular mRNAs by which translation initiation bypasses the canonical mRNA cap-dependent pathway by means of an RNA secondary structure (the IRES). While cap-dependent translation requires the recruitment of a suite of initiation factors, IRES-mediated translation requires few to …
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 …
Cyclic Adenosine Monophosphate Signaling In Mycobacterium Tuberculosis : New Insights Into A Universal Second Messenger, Richard Mcpherson Johnson
Cyclic Adenosine Monophosphate Signaling In Mycobacterium Tuberculosis : New Insights Into A Universal Second Messenger, Richard Mcpherson Johnson
Legacy Theses & Dissertations (2009 - 2024)
Despite being the focus of intense research for many years Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), remains the deadliest bacterial pathogen plaguing mankind today. Humans are the sole host and reservoir for Mtb, and Mtb has coevolved closely with its human host for thousands of years. Mtb currently infects over two billion people worldwide and over 1.5 million people die from TB each year, arguably making Mtb the most successful bacterial pathogen on the planet.