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Articles 151 - 178 of 178
Full-Text Articles in Biochemistry, Biophysics, and Structural Biology
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 …
Gld-1 Represses Its Puf Mrna Targets Prior To/At Initiation Of Translation In The C.Elegans Germline, Gautham Sarathy
Gld-1 Represses Its Puf Mrna Targets Prior To/At Initiation Of Translation In The C.Elegans Germline, Gautham Sarathy
Legacy Theses & Dissertations (2009 - 2024)
The C.elegans germline offers an ideal system to study posttranscriptional regulation of gene expression as it is a major mechanism through which the control over gene expression is achieved. GLD-1 (defective in GermLine Development) is a maxi-KH motif containing RNA binding protein that controls various aspects of germline development from decision over germcell proliferation vs. meiotic entry to the production of mature gametes suggesting that GLD-1 likely controls many mRNA targets.
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 …
Distinct Functions Of The Fshr Ck2 Consensus Sequence And Ck2 Kinase Activity In Fsh Action, Kerri S. Kluetzman
Distinct Functions Of The Fshr Ck2 Consensus Sequence And Ck2 Kinase Activity In Fsh Action, Kerri S. Kluetzman
Legacy Theses & Dissertations (2009 - 2024)
Human reproduction in the female is a complex process requiring coordinated control of gonadotropic hormone signaling in a temporal, spatial and contextually defined manner. Paracrine and autocrine signaling between granulosa cells and oocytes of the developing ovarian follicle result in production of steroids, inhibin and growth factors that dictate maturation, ovulation or atresia. Follicular stimulating hormone (FSH) stimulation of the FSH receptor (FSHR), a G-protein coupled receptor (GPCR) is a key regulator of these processes. Recent developments in GPCR molecular and structural biology have helped define activation and signaling mechanisms that will aid in further defining the etiology of infertility …
The Role Of Trm9 In Stress Responses, Ashish Ravindra Patil
The Role Of Trm9 In Stress Responses, Ashish Ravindra Patil
Legacy Theses & Dissertations (2009 - 2024)
Cells need to respond appropriately to environmental changes in order to maintain homeostasis. The cellular response to an environmental stress is regulated at transcriptional, translational and post translational levels. The tRNA, which acts as an adaptor molecule between the mRNA and the protein, plays an important role in the translational regulation of cellular responses to stress and is one of the most heavily modified biomolecules. In Saccharomyces cerevisiae , the wobble uracil of the tRNA(3'-UCU-5') Arg, tRNA(3'-UUC-5') Glu and certain other specific tRNAs are modified to 5-methoxycarbonylmethyluridine (mcm5U) and 5-methoxycarbonylmethyl-2-thiouridine (mcm5s2U) residues by the tRNA methyltransferase 9 (Trm9). Modifications at …
Regulation Of The Aryl Hydrocarbon Receptor And The Signal Transducer And Activator Of Transcription 1 By Long-Term Estrogen Exposure In Breast Carcinoma Cells, Neal Englert
Legacy Theses & Dissertations (2009 - 2024)
The risk of developing breast cancer is known to be associated with a woman's lifetime exposure to estrogens, both endogenous and exogenous. Increased exposure to estrogens stimulates cellular proliferation, which is a widely accepted theory of estrogen receptor positive mammary carcinogenesis. The molecular mechanisms of gene expression regulation in response to long-term estrogen exposure (LTEE) of MCF-7 breast cancer cells were addressed in this study, with a focus on the aryl hydrocarbon receptor (AHR) and signal transducer and activator of transcription 1 (STAT1).
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 …
Group Ii Intron Dynamics In Heterologous Hosts, Venkata Raghavendra Aditya Chalamcharla
Group Ii Intron Dynamics In Heterologous Hosts, Venkata Raghavendra Aditya Chalamcharla
Legacy Theses & Dissertations (2009 - 2024)
Group II introns are ribozymes with an innate ability to self-splice. They are found predominantly in bacterial and bacterial-derived organellar genomes, but not in the nuclear genomes of eukaryotes. In bacteria, group II introns often behave as mobile retroelements, invading host DNA and exploiting its machinery to complete the retromobility process. The object of my studies is the group II intron found in the Lactococcus lactis relaxase gene. To determine the nature of the group II intron-host relationship, we performed a genetic screen and identified several host factors that affect group II intron retromobility in Escherichia coli, which provides a …
Preparation And Application Of Transgenic And Knockout Mouse Models For Studies On Cytochrome P450 Functions, Yuan Wei
Legacy Theses & Dissertations (2009 - 2024)
The overall objective of this dissertation is to study the in vivo function of microsomal cytochrome P450 monooxygenases (P450s), which metabolize numerous drugs, chemical carcinogens, environmental pollutants, as well as endogenous signaling molecules such as steroid hormones and eicosanoids. The major research tool of this study involves the development of transgenic and knockout mouse models. The specific aims are 1) to study the in vivo function of NADPH-cytochrome P450 reductase (CPR) and CPR-dependent enzymes using a mouse model with a reversible hypomorphic Cpr gene; 2) to study the in vivo function of CYP2A13 with a CYP2A13- transgenic model; and 3) …
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.
The Impact Of Environment On Virulence Of The Pathogenic Yeast Cryptococcus Gattii, Deborah Jean Springer
The Impact Of Environment On Virulence Of The Pathogenic Yeast Cryptococcus Gattii, Deborah Jean Springer
Legacy Theses & Dissertations (2009 - 2024)
Four serotypes of Cryptococcus are responsible for most human and animal infections. C. gattii , serotype B and C, are the primary the causative agent of cryptococcosis in immune competent individuals whilst, C. neoformans var. neoformans serotype D, and C. neoformans var. grubii serotype A are most prevalent in immunocompromised hosts world-wide. C. gattii is recognized as a species distinct from C. neoformans based on differences in clinical manifestations, morphology, biological characteristics, and environmental niche. We used the plant model Arabidopsis thaliana plants and plant derived substrates as a model to explore C. gattii interactions in its ecological niche. C. …
A Locus-Based Paradigm For Generating Systems Biological Inferences From Large Scale Functional Genomics Datasets, Ajish Dominic George
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 …
Opportunism And Diversity In The Lifestyle Of A Group Ii Intron, Arthur R. Beauregard
Opportunism And Diversity In The Lifestyle Of A Group Ii Intron, Arthur R. Beauregard
Legacy Theses & Dissertations (2009 - 2024)
Group II introns are mobile retroelements. They invade the cognate intron-minus gene in an efficient process known as retrohoming. They can also retrotranspose to ectopic sites at low frequency. Retrohoming occurs by the intron RNA reverse-splicing into double-stranded DNA (dsDNA) through an endonuclease-dependent pathway. However, in retrotransposition in Lactoccocus lactis, the intron inserts predominantly into single-stranded DNA (ssDNA), in an endonuclease-independent manner. Unlike in L. lactis, in Escherichia coli the Ll.LtrB intron retrotransposes frequently into dsDNA, and the process is dependent on the endonuclease activity of the intron-encoded protein. Further, the endonuclease-dependent integrations preferentially occurred around the origin and terminus …
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.
An Rnai Screen Targeting The Protein Tyrosine Kinases Identifies Bruton's Tyrosine Kinase (Btk) As A Breast Cancer Cell Survival Factor, Cheryl Lynne Eifert
An Rnai Screen Targeting The Protein Tyrosine Kinases Identifies Bruton's Tyrosine Kinase (Btk) As A Breast Cancer Cell Survival Factor, Cheryl Lynne Eifert
Legacy Theses & Dissertations (2009 - 2024)
The receptor protein tyrosine kinases (RPTKs) and the non- receptor protein tyrosine kinases (PTKs) are among the most commonly up-regulated genes found in all types of cancers. Although, a large body of data implicates a majority of tyrosine kinases (TKs) in cancer, few have been extensively evaluated for any potential therapeutic benefit in any of the many subtypes of breast cancer. We have used RNA interference (RNAi) to perform a large-scale loss-of-function analysis to facilitate the identification of individual factors necessary for the survival of an ErbB2 positive breast cancer cell line. We have found that 30% of the TKs …
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 …
Molecular Evolution Of Genes Underlying Phenotypic Differences Between Humans And Chimpanzees, Santhoshi Bandla
Molecular Evolution Of Genes Underlying Phenotypic Differences Between Humans And Chimpanzees, Santhoshi Bandla
Legacy Theses & Dissertations (2009 - 2024)
Chimpanzees (Pan troglodytes) and bonobos (P. paniscus) are often used as models to study the genetic and morphological changes on the lineage leading to the modern humans (Homo sapiens). Results of this dissertation suggest that, in comparison to other hominoids, chimpanzees and bonobos are more derived in their relative testes sizes and promiscuous mating systems. Phylogenetic analysis of genes that might underlie increased testes size revealed that, in addition to being a sex-determining gene, SRY displays Pan-specific amino acid replacements that make it a compelling candidate as a testes-size determining gene. Strikingly, SRY and another candidate gene, DMRT3, display patterns …
Study Of Dynamic Processes In Protein Synthesis Using Heterogeneous Ribosome Specimens, Jie Fu
Study Of Dynamic Processes In Protein Synthesis Using Heterogeneous Ribosome Specimens, Jie Fu
Legacy Theses & Dissertations (2009 - 2024)
Single-particle reconstruction from cryo-electron microscopy (cryo-EM) images is a widely used technique in studying the structure of macromolecular complexes. This technique allows the visualization of molecules in their native hydrated state. The heterogeneity of two-dimensional projection images, resulting from the co-existence of different states of a macromolecular complex, remains a major obstacle, as it impairs the validity of reconstruction and limits the progress toward higher resolution. On the other hand, co-existing structures, if successfully extracted from a single dataset, can provide valuable information about the equilibrium and dynamics of the biological system being studied.