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Articles 1 - 23 of 23
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Evolutionary Analysis Of Host Proteins Cd4, Cxcr4 And Ccr5, And Hiv/Siv Gp12, Lana Bunning
Evolutionary Analysis Of Host Proteins Cd4, Cxcr4 And Ccr5, And Hiv/Siv Gp12, Lana Bunning
Biological Sciences
The acquired immune deficiency syndrome, AIDS, is a growing epidemic in the United States and the world. Since its discovery in 1981, the virus that causes AIDS, human immunodeficiency virus (HIV), has escalated. .Certain African ape (i.e., chimpanzees and gorillas) and monkey species are known to harbor forms of the virus termed SIV (simian immunodeficiency virus). Chimpanzees are the natural hosts of the SIV strains from which HIV-I evolved, but do not rapidly progress to AIDS, unlike their human relatives. In the wild, gorillas have been observed to harbor SIV, but this species' disease progression is currently unknown. As the …
The Role Of Trna Modification Systems In The Cellular Stress Response, Margaret Daly
The Role Of Trna Modification Systems In The Cellular Stress Response, Margaret Daly
Biological Sciences
Transfer RNA(tRNA) is a small chain of nucleotides that participates in protein synthesis by pairing its anticodon with an mRNA codon and transferring an amino acid to a growing polypeptide chain. tRNA methyltransferases are a group of enzymes that can modify nucleosides in or around the anticodon, as well as at other parts of the tRNA. Recently, some of these modifications have been reported to enhance the translation of proteins that help the cell respond to and/or repair DNA damage. We hypothesize that the modifications catalyzed by some of the tRNA methyltransferases (Trms) stabilize the interaction between the mRNA codon …
Effects Of Carbachol And Vitamin C On Submandibular Salivary Gland Branching Morphogenesis, Nasiratu Larry
Effects Of Carbachol And Vitamin C On Submandibular Salivary Gland Branching Morphogenesis, Nasiratu Larry
Biological Sciences
The Submandibular Salivary Gland (SMG) is formed by iterative branching of epithelial cells into secretory acinar endbuds and branched ducts that are extensively innervated by parasympathetic nerves which can influence gland development. Carbarrylcholine or carbachol, (an acetylcholine neurotransmitter analog), is a drug that binds to and activates the acetylcholine receptor. Previous research has suggested that carbachol on SMGs might delay ductal differentiation and affect actin localization in cells lining the lumen of ducts. Vitamin C has been shown to enhance matrix protein synthesis, which may accelerate cell differentiation. My goal was to test whether and how carbachol or modulation of …
Biomonitoring Of Perfluorochemicals In Human Blood, Breast Milk, Saliva, And Urine, Lin Tao
Biomonitoring Of Perfluorochemicals In Human Blood, Breast Milk, Saliva, And Urine, Lin Tao
Legacy Theses & Dissertations (2009 - 2024)
Perfluorochemicals (PFCs) have been used as surfactants and surface protectors in a large number of consumer products. PFCs have been reported to elicit adverse health effects in laboratory animals and humans, and have been detected in foodstuffs and in human bodies. In this dissertation, analytical methods were developed for the determination of trace levels of PFCs in human blood, dried blood spot, breast milk, saliva, and urine. An assessment of human exposure to PFCs was performed by analyzing human specimens collected from the United States and several Asian countries. Blood, breast milk, and dried blood spots were found to be …
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 …
Genetic And Non-Genetic Factors That Cause Inter-Individual Variations In Cyp2a13 Gene Expression, Hong Wu
Genetic And Non-Genetic Factors That Cause Inter-Individual Variations In Cyp2a13 Gene Expression, Hong Wu
Legacy Theses & Dissertations (2009 - 2024)
The overall goal of this dissertation is to investigate the mechanisms underlying the large interindividual variations in susceptibility to lung carcinogenesis. We focused on CYP2A13, a respiratory tract-specifically expressed enzyme, which is the most efficient P450 towards bioactivation of a tobacco-related carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). The expression level of CYP2A13 varies substantially among human lung samples. Our central hypothesis is that CYP2A13 expression level is affected by both genetic regulators and non-genetic factors. The specific aims are 1) to identify the mechanisms underlying the decreased allelic expression of a CYP2A13 allele (7520C>G); 2) to identify frequent single-nucleotide polymorphisms (SNPs), associated …
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.
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 …
Multiple Antibiotic Resistant Staphylococcus Spp. In Environmental Settings, Stephen Shost
Multiple Antibiotic Resistant Staphylococcus Spp. In Environmental Settings, Stephen Shost
Legacy Theses & Dissertations (2009 - 2024)
Ninety staphylococci carrying the mecA gene, including 17 strains of methicillin-resistant Staphylococcus aureus (MRSA), were isolated from environmental settings within New York State. Waterborne staphylococci harboring mecA were isolated from multiple sources: the Hudson River near a combined sewage overflow; urban streams; freshwater and marine beaches; a swimming pool; swimming pool decks; combined sewage; as well as wastewater treatment plant (WWTP) primary sewage influent, mixed liquor, aeration water, and final (unchlorinated) effluent. Environmental MRSA strains were isolated from beach water (n=3); swimming pool deck water (n=1); Hudson River water (n=2); combined sewage (n=3); as well as wastewater treatment plant mixed …
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 …
Live-Cell Studies On Mitotic Slippage In Humans, Daniela A. Brito
Live-Cell Studies On Mitotic Slippage In Humans, Daniela A. Brito
Legacy Theses & Dissertations (2009 - 2024)
Checkpoints are regulatory pathways that control the order and timing of specific cell-cycle events. In the presence of unattached/weakly-attached kinetochores, the mitotic checkpoint (MC) arrests cells in mitosis by inhibiting the degradation of cyclin B, the regulatory subunit of Cdk1 (cyclin dependent kinase 1). Checkpoints do not arrest cells permanently, and escaping mitosis with an unsatisfied MC requires cyclin B/Cdk1 inactivation. In yeast, this occurs through an “adaptation” mechanism involving inhibitory phosphorylations and/or Cdk1-inhibitors. To determine how vertebrate cells escape mitosis when the MC cannot be satisfied I conducted live-cell imaging and immunofluorescence studies on nocodazole-treated rat kangaroo (PtK) and …
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 …
Effect Of Anti-Lipopolysaccharide Iga Antibodies On The Virulence And Physiology Of Salmonella Enterica And Shigella Flexneri, Stephen J. Forbes
Effect Of Anti-Lipopolysaccharide Iga Antibodies On The Virulence And Physiology Of Salmonella Enterica And Shigella Flexneri, Stephen J. Forbes
Legacy Theses & Dissertations (2009 - 2024)
Secretory IgA (SIgA) antibodies directed against the serotype-specific, O-antigen of lipopolysaccharide (LPS) are the primary determinants of mucosal immunity to enteric bacterial pathogens, including of Salmonella enterica serovar Typhimurium and Shigella flexneri. While the singular importance of SIgA in preventing enteric infections is recognized, the underlying mechanisms by which these antibodies protect the mucosal epithelium remains poorly understood. In this study, I demonstrated that Sal4, a protective, anti-LPS specific monoclonal IgA, is a potent inhibitor of S. Typhimurium flagella-based motility and type three secretion (T3S) mediated entry into epithelial cells. Sal4's effects on motility and invasion occurred rapidly (<15 min), and were independent of agglutination. I also present evidence the protective anti-LPS, monoclonal IgA, IgAC5, reduced S. flexneri T3S of IpaB and IpaC. Concurrent with the IgA-induced reduction in T3S, there was a decrease in both the proton motive force and ATP levels in both bacterial species examined. I also report that Sal4 and IgAC5 have effects on the bacterial envelope. Scanning, transmission, and cyro-electron microscopy revealed dramatic antibody-mediated alterations in the topology of the outer membrane (OM) of S.Typhimurium and S. flexneri. Furthermore, Sal4-treatment caused a ~5 fold increase in O-antigen, and elevated levels of lipid A, released into culture supernatants, consistent with the loss of LPS. Correspondingly, the OM of antibody-treated bacteria was ~50% more permeable than control cells. Based on these data, I proposed that Sal4 binding to the LPS destabilizes the outer leaflet of the OM of S. Typhimurium, thereby compromising the integrity of the bacterial envelope, disrupting bioenergetics by physical and/or mechanical stress, and arresting both flagella-based motility and T3S. This study reveals a previously unrecognized capacity of SIgA to "disarm" enteric pathogens in mucosal secretions, thereby preventing colonization and invasion of the intestinal epithelium.
Three-Dimensional Hydrogel Cell Culture Systems For Modeling Neural Tissue, John P. Frampton
Three-Dimensional Hydrogel Cell Culture Systems For Modeling Neural Tissue, John P. Frampton
Legacy Theses & Dissertations (2009 - 2024)
Two-dimensional (2-D) neural cell culture systems have served as physiological models for understanding the cellular and molecular events that underlie responses to physical and chemical stimuli, control sensory and motor function, and lead to the development of neurological diseases. However, the development of three-dimensional (3-D) cell culture systems will be essential for the advancement of experimental research in a variety of fields including tissue engineering, chemical transport and delivery, cell growth, and cell-cell communication. In 3-D cell culture, cells are provided with an environment similar to tissue, in which they are surrounded on all sides by other cells, structural molecules …
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.
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 …
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 …
Proactive Procreation : Ethical Implications Of New Genetic Technologies For Parental Obligations To Future Offspring, L Syd M. Johnson
Proactive Procreation : Ethical Implications Of New Genetic Technologies For Parental Obligations To Future Offspring, L Syd M. Johnson
Legacy Theses & Dissertations (2009 - 2024)
This dissertation examines the ethical implications of recent genetic innovations, particularly preimplantation genetic diagnosis, for the obligations and duties of parents to future children. I critique common but uncompelling objections to the use of genetic information, diagnosis, and technology to influence the characteristics of future offspring, and conclude that genetic selection and enhancement are not different in kind or degree from other means of selection, direction, and enhancement that parents engage in to shape the lives of their children. Procreation is morally risky -- it risks imposing substantial burdens on persons who would not otherwise have to bear those burdens, …
Identification Of B-Cell Epitopes On Domain 4 Of Anthrax Protective Antigen, Cassandra D. Kelly-Cirino
Identification Of B-Cell Epitopes On Domain 4 Of Anthrax Protective Antigen, Cassandra D. Kelly-Cirino
Legacy Theses & Dissertations (2009 - 2024)
Protective Antigen (PA) is the receptor binding subunit common to both Lethal (LT) and Edema (ET) toxins, which contribute to the mortality associated with Bacillus anthracis infection. While recombinant PA (rPA) is likely to be an important constituent of second generation anthrax vaccines, evaluating the effectiveness of candidate vaccines is currently difficult, because the specific B cell epitopes involved in toxin neutralization have not been completely defined. The only well characterized antibody, 14B7, has been shown to disrupt the association of PA with the anthrax toxin receptors (ATR) by binding to domain 4 of PA. I hypothesized that other domain …
Anatomical Substrates Of Central Nervous System Plasticity Induced By Spinal Cord Reflex Conditioning And Sensorimotor Cortex Stimulation, Shreejith Pillai
Anatomical Substrates Of Central Nervous System Plasticity Induced By Spinal Cord Reflex Conditioning And Sensorimotor Cortex Stimulation, Shreejith Pillai
Legacy Theses & Dissertations (2009 - 2024)
ABSTRACT
Generation And Maintenance Of Protective Igm Responses During Intracellular Bacterial Infection, Rachael Denise Racine
Generation And Maintenance Of Protective Igm Responses During Intracellular Bacterial Infection, Rachael Denise Racine
Legacy Theses & Dissertations (2009 - 2024)
It is widely accepted that IgM provides the first line of defense against during microbial infection prior to the generation of high-affinity, isotype-switched antibodies, which is the hallmark of long-lived lived immunity and immunological memory. The overall objective of these studies was to address the role of IgM in the generation and maintenance of protective immunity during intracellular bacterial infection. We have identified a population of CD11clo plasmablasts that were responsible for nearly all of the antigen-specific IgM production in the spleen. Moreover, selective depletion of the CD11c-expressing B cells during acute infection resulted in a complete loss in the …
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 …
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. …