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Articles 1 - 15 of 15

Full-Text Articles in Biochemistry, Biophysics, and Structural Biology

Mechanisms Of Dna Synthesis And Fidelity By Y-Family Translesion And C-Family Replicative Polymerases, Purba Mukherjee Jan 2014

Mechanisms Of Dna Synthesis And Fidelity By Y-Family Translesion And C-Family Replicative Polymerases, Purba Mukherjee

Legacy Theses & Dissertations (2009 - 2024)

Since the discovery of the DNA polymerase by Arthur Kornberg nearly 60 years ago, there have been great advances in understanding the involvement of polymerases in replication and repair. Years of genetic, biochemical and structural studies have lead to the classification of DNA-dependent DNA polymerases into six families: A, B, C, D, X and Y. In this work, I have focussed on two different families, C and Y. Hence this work is divided into two parts. Part one discusses the studies on Y-family polymerases. All Y-family polymerases are involved in replicating past DNA lesions. The ability to tolerate unnatural nucleotides …


Mediation Of Recurrent Hypoglycemia's Physiological And Behavioral Effects In The Hippocampus By Glucocorticoids, Danielle Osborne Jan 2014

Mediation Of Recurrent Hypoglycemia's Physiological And Behavioral Effects In The Hippocampus By Glucocorticoids, Danielle Osborne

Legacy Theses & Dissertations (2009 - 2024)

Recurrent hypoglycemia (RH) occurs with the over administration of insulin resulting in severe hypoglycemia on a repetitive basis. This occurs most commonly among Type I Diabetics who rely on exogenous insulin replacement for management of their disease; however it is becoming increasingly common among Type II Diabetics. Although cognitive deficits are reported during hypoglycemia, the period following restoration of euglycemia has been denoted by improved hippocampally-mediated short-term and working memory in humans and rodents, respectively. RH is also associated with an altered glucocorticoid secretion profile in response to hypoglycemia. In vitro and in vivo approaches were utilized with the goal …


Regulation Of Ty1 Retrovirus-Like Transposon Rna Localization And Translation, Ryan Joseph Palumbo Jan 2014

Regulation Of Ty1 Retrovirus-Like Transposon Rna Localization And Translation, Ryan Joseph Palumbo

Legacy Theses & Dissertations (2009 - 2024)

Replication of the Ty1 retrovirus-like transposon of the yeast Saccharomyces cerevisiae is stringently regulated to reduce the frequency of deleterious retrotransposition events. However, under stress conditions, Ty1 retrotransposition can lead to adaptive genomic alterations. To characterize host regulation of Ty1 retrotransposition, I analyzed ribosome profiling data and showed that Ty1 RNA is efficiently translated. Moreover, the ribosome biogenesis factors BUD21, DBP7, HCR1, LOC1, MRT4, and PUF6 are required for optimal expression of the Ty1 protein Gag.


Monitoring Ligand-Induced Nucleic Acid Conformational Changes Using Ion Mobility Spectrometry-Mass Spectrometry, Bill Kenneth Redick Jan 2014

Monitoring Ligand-Induced Nucleic Acid Conformational Changes Using Ion Mobility Spectrometry-Mass Spectrometry, Bill Kenneth Redick

Legacy Theses & Dissertations (2009 - 2024)

Three-dimensional structures of biopolymers frequently dictate the biological role those molecules play. As such, investigation into structure of nucleic acids can provide important information pertaining to how those nucleic acids work. Many nucleic acid species, especially single-stranded RNA, fold into unique structures that allow them to function properly. Metals, and other cationic species, are often bound to the nucleic acid to make folding into the proper structure more favorable by neutralizing the negative charge on the nucleic acid imparted by the phosphate group. This investigation explores tertiary structure of nucleic acids that have been folded in the presence of ligands …


Raman Spectroscopy Of Blood Serum And Cerebrospinal Fluid And Multivariate Data Analysis For Alzheimer's Disease Diagnostics, Elena Ryzhikova Jan 2014

Raman Spectroscopy Of Blood Serum And Cerebrospinal Fluid And Multivariate Data Analysis For Alzheimer's Disease Diagnostics, Elena Ryzhikova

Legacy Theses & Dissertations (2009 - 2024)

The efficient and accurate diagnosis at the early stages of dementia is a key moment for effective treatment and productive research to find a new ways to combat the disease. It is especially true for Alzheimer's disease (AD) for which there is no effective cure, but several treatments are known to allow slowing down the degenerative processes. Alzheimer's disease (AD) displays only non-specific clinical symptoms of mental decline for decades after the initiation and is very challenging to differentiate even at the later stages when it becomes very aggressive. Despite the great need, current diagnostic tests are unable to diagnose …


Modeling The Early, Aging-Related Changes In Human Recombinant Gammas-Crystallin In Vitro, Christiana Oluwaseun Salami Jan 2014

Modeling The Early, Aging-Related Changes In Human Recombinant Gammas-Crystallin In Vitro, Christiana Oluwaseun Salami

Legacy Theses & Dissertations (2009 - 2024)

Cataract is the leading cause of blindness in the world. Cataractous lenses scatter a significant part of the light entering the eye. Cataract can be of several types: Age-related cataract, secondary cataract, traumatic cataract, congenital cataract, and radiation cataract. Age-related cataract is the most common type of cataract. Several factors contribute to age-onset cataract; among them are the Post-Translational Modifications (PTMs) to the major lens proteins or crystallins, which constitute about 80-90% of the protein content of the lens. Predominant PTMs of the crystallins are oxidation, deamidation, phosphorylation, glycation, and disulfide crosslinking, which tend to increase as the lens ages.


Probing Secondary And Tertiary Rna Folding Using Force And Temperature, William Stephenson Jan 2014

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 …


Crosstalk Between Vitamin D₃- And Testosterone-Mediated Signaling In Prostate Cancer Cells, Wei-Lin Winnie Wang Jan 2014

Crosstalk Between Vitamin D₃- And Testosterone-Mediated Signaling In Prostate Cancer Cells, Wei-Lin Winnie Wang

Legacy Theses & Dissertations (2009 - 2024)

Contrary to the common belief that prostate cancer is a hormone dependent disease, the incidence of prostate cancer and associated mortality actually increases significantly after serum androgen levels decline. This led us to hypothesize that androgen depletion in elder men is an underlying cause for the development and progression of prostate cancer. In addition, serum vitamin D3 levels also decline in older men. Epidemiological and experimental data support an anti-neoplastic activity of vitamin D3 in colorectal and breast cancers through regulation of cell proliferation, apoptosis, cell differentiation and metastasis. The effects of vitamin D3 on prostate cancer …


A Structural And Functional Comparison Of Human Immunodeficiency Virus Type 1 Nucleocapsid Protein (Ncp7) And Other Retroviral Nucleocapsid Proteins, Christopher Richard Cavender Jan 2014

A Structural And Functional Comparison Of Human Immunodeficiency Virus Type 1 Nucleocapsid Protein (Ncp7) And Other Retroviral Nucleocapsid Proteins, Christopher Richard Cavender

Legacy Theses & Dissertations (2009 - 2024)

Human immunodeficiency virus type 1 (HIV-1) is a retrovirus belonging to the lentivirus genus of the orthoretrovirinae family. HIV-1 is widely known for causing acquired immunodeficiency syndrome (AIDS) in humans and being responsible for 1.8 million deaths due to AIDS associated illnesses in 201016.


Molecular Actions Of The Novel Histone Deacetylase Inhibitor Cg-1521 In Models Of Inflammatory Breast Cancer, Namita Chatterjee Jan 2014

Molecular Actions Of The Novel Histone Deacetylase Inhibitor Cg-1521 In Models Of Inflammatory Breast Cancer, Namita Chatterjee

Legacy Theses & Dissertations (2009 - 2024)

Inflammatory breast cancer (IBC) is a rare and particularly lethal form of breast cancer. Despite aggressive therapeutic approaches, the 5-year survival rate is only 34%. As this disease is severely understudied, we have investigated the therapeutic potential of the novel hydroxamic acid-derived histone deacetylase inhibitor (HDACi), CG-1521 in comparison to a structurally similar compound, Trichostatin A (TSA) in two IBC cell lines: SUM149PT and SUM190PT. In these cells, CG-1521 and TSA induce dose- and time-dependent induction of cell cycle arrest and apoptosis regardless of the presence of 17β-estradiol (E2). Interestingly, the cell lines have considerably different sensitivities to these treatments …


Improving The Microbial Source Tracking Toolbox : Evaluating The Use Of Selective Enrichments And Artificial Sweeteners In A Multi-Tiered Approach, Stacey A. Helming Jan 2014

Improving The Microbial Source Tracking Toolbox : Evaluating The Use Of Selective Enrichments And Artificial Sweeteners In A Multi-Tiered Approach, Stacey A. Helming

Legacy Theses & Dissertations (2009 - 2024)

Microbial contamination of surface waters is a public health concern world-wide, with non-point source fecal input contributing to millions of cases of waterborne illness annually. Numerous techniques have been proposed to monitor for non-point source fecal contamination, but few studies have explored the correlation of multiple chemical and microbial fecal source tracking markers in ambient waters. Therefore, the purpose of these studies was to evaluate the use of multiple "ideal" markers of fecal contamination and improve upon any analytical techniques required to identify species-specific fecal contamination in surface waters. The use of selective enrichments to improve the sensitivity of end-point …


Mechanistic Studies Of C- And Y-Family Dna Polymerases, Indrajit Lahiri Jan 2014

Mechanistic Studies Of C- And Y-Family Dna Polymerases, Indrajit Lahiri

Legacy Theses & Dissertations (2009 - 2024)

DISSERTATION ABSTRACT


Molecular Actions Of The Vitamin D Receptor In Breast Cancer, Erika Laporta Jan 2014

Molecular Actions Of The Vitamin D Receptor In Breast Cancer, Erika Laporta

Legacy Theses & Dissertations (2009 - 2024)

1,25-Dihydroxyvitamin D (1,25D) exerts anti-cancer actions through the vitamin D receptor (VDR) but the specific targets that mediate these effects remain to be defined. In these studies, growth and genomic responses to 1,25D were evaluated in a cellular model system derived from mammary tumors generated in VDR knockout (KO) and wildtype (WT) mice. WT145 cells (derived from WT tumors) expressed VDR and were growth inhibited by 1,25D, whereas KO240 cells (derived from VDRKO tumors) lacked VDR and were not growth inhibited by 1,25D. KO240 cell clones stably expressing VDR (KOhVDR cells) were sensitized to 1,25D mediated growth arrest. Genomic profiling …


Mechanisms Of Age-Related Inflammation And Cancer : The Synergistic Effect Of Oxidants And Calcium, Donald A. Mccarthy Jan 2014

Mechanisms Of Age-Related Inflammation And Cancer : The Synergistic Effect Of Oxidants And Calcium, Donald A. Mccarthy

Legacy Theses & Dissertations (2009 - 2024)

The accumulation of senescent cells during the process of aging has been implicated as causal in numerous age-related pathologies. Senescent cells adopt a secretory phenotype consisting of many factors including matrix remodeling enzymes, growth factors, cytokines, and chemokines. Their secretory nature is the primary reason that they are associated with disease, but it remains unclear why they become so inflammatory. Using primary human fibroblasts cultured to senescence, we mechanistically determined why senescent cells are such potent inducers of inflammation. Our findings indicate that the early production of the cytokine Interleukin 1-α (IL-1α) is central to this transition. We found that …


Ph Regulation And The Assessment Of Renal Injury Biomarkers In A Warm Perfusion Renal Allograft Preservation System, Aaron Meyer Jan 2014

Ph Regulation And The Assessment Of Renal Injury Biomarkers In A Warm Perfusion Renal Allograft Preservation System, Aaron Meyer

Legacy Theses & Dissertations (2009 - 2024)

A shortage of viable kidneys available for transplantation exists today, as the number of individuals waiting for a kidney transplant continues to grow while the number of kidneys available each year for transplantation has remained stagnant. The development of technology that will allow for transplantation of organs that currently may be considered too damaged for transplant will provide access to a large number of donors who have experienced traumatic injury deaths resulting in loss of cardiac function. These potential donors account for the majority of all traumatic injury deaths in intensive care units, however their organs have experienced a degree …