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

Investigation Of Alcohol-Induced Changes In Hepatic Histone Modifications Using Mass Spectrometry Based Proteomics, Crystina Leah Kriss Apr 2018

Investigation Of Alcohol-Induced Changes In Hepatic Histone Modifications Using Mass Spectrometry Based Proteomics, Crystina Leah Kriss

Graduate Theses and Dissertations

Alcohol liver disease (ALD) is a major health concern throughout the world. Currently, in the United States, 17 million people suffer from alcoholism, of which 1.4 million people are receiving treatment [1, 2]. The link between ethanol metabolism, reactive oxygen species (ROS) and liver injury in ALD has been well characterized over the last couple decades [3-10]. Ethanol metabolism relies on the availability of the cofactor NAD+ for the oxidation of ethanol into acetate, consequently causing alterations in redox potential. Redox dysfunction within the mitochondria can affect multiple pathways important in maintaining cellular homeostasis. Chapter 1 provides an introduction ...


Disorder Levels Of C-Myb Transactivation Domain Regulate Its Binding Affinity To The Kix Domain Of Creb Binding Protein, Anusha Poosapati Nov 2017

Disorder Levels Of C-Myb Transactivation Domain Regulate Its Binding Affinity To The Kix Domain Of Creb Binding Protein, Anusha Poosapati

Graduate Theses and Dissertations

Intrinsically disordered proteins (IDPs) do not form stable tertiary structures like their ordered partners. They exist as heterogeneous ensembles that fluctuate over a time scale. Intrinsically disordered regions and proteins are found across different phyla and exert crucial biological functions. They exhibit transient secondary structures in their free state and become folded upon binding to their protein partners via a mechanism called coupled folding and binding. Some IDPs form alpha helices when bound to their protein partners. We observed a set of cancer associated IDPs where the helical binding segments of IDPs are flanked by prolines on both the sides ...


Uncovering Transcriptional Activators And Targets Of Hsf-1 In Caenorhabditis Elegans, Jessica Brunquell Apr 2017

Uncovering Transcriptional Activators And Targets Of Hsf-1 In Caenorhabditis Elegans, Jessica Brunquell

Graduate Theses and Dissertations

In order to survive, cells must be able to cope with a variety of environmental stressors. The heat shock response (HSR) is a pro-survival mechanism employed by cells in response to protein denaturing stress, such as heat. Since its discovery in 1960, the heat shock response has been found to be regulated by the transcription factor heat shock factor 1 (HSF1). During periods of increased stress, HSF1 undergoes a multi-step process of activation that involves homotrimerization, DNA-binding, and post-translational regulatory modifications, all of which ultimately function to control the transcription of chaperone genes. These chaperone genes encode molecular chaperone proteins ...


Mechanisms Of Ikbke Activation In Cancer, Sridevi Challa Jan 2017

Mechanisms Of Ikbke Activation In Cancer, Sridevi Challa

Graduate Theses and Dissertations

Cancer is the second leading cause of death in the USA and it is expected to surpass heart diseases making it important to understand the underlying mechanisms of cancer. The efforts to target single signaling molecule showed little success in increasing the patient survival and it can be due to increased compensation for cell survival by alternative pathway activations. Hence comprehensive understanding of the alternative signaling pathways may help us treat cancer better. Chronic inflammation is attributed to increased risk of cancer and emerging studies show the growing importance of both canonical and non-canonical IκB kinases such as IKKα, IKKβ ...


Gene Expression Profiling And The Role Of Hsf1 In Ovarian Cancer In 3d Spheroid Models, Trillitye Paullin Nov 2016

Gene Expression Profiling And The Role Of Hsf1 In Ovarian Cancer In 3d Spheroid Models, Trillitye Paullin

Graduate Theses and Dissertations

Ovarian cancer is the most lethal gynecological cancer, with over 200,000 women diagnosed each year and over half of those cases leading to death. These poor statistics are related to a lack of early symptoms and inadequate screening techniques. This results in the cancer going undetected until later stages when the tumor has metastasized through a process that requires the epithelial to mesenchymal transition (EMT). In lieu of traditional monolayer cell culture, EMT and cancer progression in general is best characterized through the use of 3D spheroid models. In this study, we examine gene expression changes through microarray analysis ...


Quantitative Proteomic Investigation Of Disease Models Of Type 2 Diabetes, Mark Gabriel Athanason Nov 2016

Quantitative Proteomic Investigation Of Disease Models Of Type 2 Diabetes, Mark Gabriel Athanason

Graduate Theses and Dissertations

PANcreatic DERived factor (PANDER, FAM3B) is a member of a superfamily of FAM3 proteins that are uniquely structured and strongly expressed from the endocrine pancreas and co-secreted with insulin. Unique animal models available to our lab have indicated that PANDER can induce a selective hepatic insulin resistant (SHIR) phenotype whereby insulin signaling is blunted yet lipogenesis is increased. The complexity of the biological networks involved with this process warranted the logical approach of employing quantitative mass spectrometry based proteomic analysis using stable isotope labeling of amino acids in cell culture (SILAC) to identify the global proteome differences between the PANDER ...


Computational Modeling Of Allosteric Stimulation Of Nipah Virus Host Binding Protein, Priyanka Dutta Jul 2016

Computational Modeling Of Allosteric Stimulation Of Nipah Virus Host Binding Protein, Priyanka Dutta

Graduate Theses and Dissertations

Nipah belongs to the family of paramyxoviruses that cause numerous fatal diseases in humans and farm animals. There are no FDA approved drugs for Nipah or any of the paramyxoviruses. Designing antiviral therapies that are more resistant to viral mutations require understanding of molecular details underlying infection. This dissertation focuses on obtaining molecular insights into the very first step of infection by Nipah. Such details, in fact, remain unknown for all paramyxoviruses. Infection begins with the allosteric stimulation of Nipah virus host binding protein by host cell receptors. Understanding molecular details of this stimulation process have been challenging mainly because ...


Tunable Nano-Delivery System For Cancer Treatment: A New Approach For Targeted Localized Drug Delivery, Rana Falahat Jun 2016

Tunable Nano-Delivery System For Cancer Treatment: A New Approach For Targeted Localized Drug Delivery, Rana Falahat

Graduate Theses and Dissertations

Localized drug delivery systems have been widely studied as potential replacements for conventional chemotherapy with the capability of providing sustained and controlled drug release in specific targeted sites. They offer numerous benefits over conventional chemotherapy such as enhancing the stability of embedded drugs and preserving their anticancer activity, providing sustained and controlled drug release in the tumor site, reducing toxicity and diminishing subsequent side effects, minimizing the drug loss, averting the need for frequent administrations, and minimizing the cost of therapy.

The aim of this study is to develop a localized drug delivery system with niosomes embedded in a chitosan ...


Cmg Helicase Assembly And Activation: Regulation By C-Myc Through Chromatin Decondensation And Novel Therapeutic Avenues For Cancer Treatment, Victoria Bryant Jun 2016

Cmg Helicase Assembly And Activation: Regulation By C-Myc Through Chromatin Decondensation And Novel Therapeutic Avenues For Cancer Treatment, Victoria Bryant

Graduate Theses and Dissertations

The CMG (Cdc45, MCM, GINS) helicase is required for cellular proliferation and functions to unwind double-stranded DNA to allow the replication machinery to duplicate the genome. Cancer cells mismanage helicase activation through a variety of mechanisms, leading to the potential for the development of novel anti-cancer treatments. Mammalian cells load an excess of MCM complexes that act as reserves for new replication origins to be created when replication forks stall due to stress conditions, such as drug treatment. Targeting the helicase through inhibition of the MCM complex has sensitized cancer cells to drugs that inhibit DNA replication, such as aphidicolin ...


In Vitro And In Vivo Antioxidant Capacity Of Synthetic And Natural Polyphenolic Compounds Identified From Strawberry And Fruit Juices, Marvin Abountiolas Mar 2016

In Vitro And In Vivo Antioxidant Capacity Of Synthetic And Natural Polyphenolic Compounds Identified From Strawberry And Fruit Juices, Marvin Abountiolas

Graduate Theses and Dissertations

Strawberries can be considered a functional food because their consumption has been associated with several health benefits. They are important sources of bioactive compounds, such as vitamins and polyphenolic compounds, with recognized antioxidant capacity (AOC). However, strawberry overall quality and bioactive content are greatly affected by environmental conditions during pre- and post-harvest and, little is known about the stability of its bioactive compounds, specifically ascorbic acid (AA) and polyphenolics compounds. Furthermore, additional research that addresses the impact of polyphenolic compounds on in vitro and in vivo models is needed to understand the mechanisms behind their potential health benefits. Therefore, the ...


Mir494 Reduces Renal Cancer Cell Survival Coinciding With Increased Lipid Droplets And Mitochondrial Changes, Punashi Dutta, Edward Haller, Arielle Sharp, Meera Nanjundan Jan 2016

Mir494 Reduces Renal Cancer Cell Survival Coinciding With Increased Lipid Droplets And Mitochondrial Changes, Punashi Dutta, Edward Haller, Arielle Sharp, Meera Nanjundan

Cell Biology, Microbiology, and Molecular Biology Faculty Publications

Background: miRNAs can regulate cellular survival in various cancer cell types. Recent evidence implicates the formation of lipid droplets as a hallmark event during apoptotic cell death response. It is presently unknown whether MIR494, located at 14q32 which is deleted in renal cancers, reduces cell survival in renal cancer cells and if this process is accompanied by changes in the number of lipid droplets.

Methods: 769-P renal carcinoma cells were utilized for this study. Control or MIR494 mimic was expressed in these cells following which cell viability (via crystal violet) and apoptotic cell numbers (via Annexin V/PI staining) were ...


Direct Analysis In Real Time (Dart) Of An Organothiophosphate At Ultrahigh Resolution By Fourier Transform Ion Cyclotron Resonance Mass Spectrometry And Tandem Mass Spectrometry, Laszlo Prokai, Stanley M. Stevens Jr. Jan 2016

Direct Analysis In Real Time (Dart) Of An Organothiophosphate At Ultrahigh Resolution By Fourier Transform Ion Cyclotron Resonance Mass Spectrometry And Tandem Mass Spectrometry, Laszlo Prokai, Stanley M. Stevens Jr.

Cell Biology, Microbiology, and Molecular Biology Faculty Publications

Direct analysis in real time (DART) is a recently developed ambient ionization technique for mass spectrometry to enable rapid and sensitive analyses with little or no sample preparation. After swab-based field sampling, the organothiophosphate malathion was analyzed using DART-Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry (MS) and tandem mass spectrometry (MS/MS). Mass resolution was documented to be over 800,000 in full-scan MS mode and over 1,000,000 for an MS/MS product ion produced by collision-induced dissociation of the protonated analyte. Mass measurement accuracy below 1 ppm was obtained for all DART-generated ions that belonged to ...


Effect Of Hydroxychloroquine And Characterization Of Autophagy In A Mouse Model Of Endometriosis, A. Ruiz, S. Rockfield, N. Taran, E. Haller, Robert Engelman, I Flores, P Panina-Bordignon, Meera Nanjundan Jan 2016

Effect Of Hydroxychloroquine And Characterization Of Autophagy In A Mouse Model Of Endometriosis, A. Ruiz, S. Rockfield, N. Taran, E. Haller, Robert Engelman, I Flores, P Panina-Bordignon, Meera Nanjundan

Cell Biology, Microbiology, and Molecular Biology Faculty Publications

In endometriosis, the increased survival potential of shed endometrial cells (which normally undergo anoikis) is suggested to promote lesion development. One mechanism that may alter anoikis is autophagy. Using an autophagic flux inhibitor hydroxychloroquine (HCQ), we identified that it reduces the in vitro survival capacity of human endometriotic and endometrial T-HESC cells. We also identified that HCQ could decrease lesion numbers and disrupt lesion histopathology, as well as increase the levels of peritoneal macrophages and the IP-10 (10 kDa interferon-γ-induced protein) chemokine in a mouse model of endometriosis. We noted that RNA levels of a subset of autophagic ...


A Forward Genetic Screen Identifies Factors Associated With Fever Pathogenesis In Plasmodium Falciparum, Phaedra J. Thomas Sep 2015

A Forward Genetic Screen Identifies Factors Associated With Fever Pathogenesis In Plasmodium Falciparum, Phaedra J. Thomas

Graduate Theses and Dissertations

Infectious diseases that spread from person-to-person and continent-to-continent are a cause for concern for any health entity. One such disease is malaria, a mosquito-borne infection instigated by the protozoan parasite, Plasmodium falciparum. Hundreds of millions of people are affected annually and it is responsible for nearly 1 million deaths. It is the most fatal species causing malaria and proliferates in human red blood cells with a life cycle occurring every 48 hours. At this time, the parasite’s late stage form or schizont bursts from the erythrocyte releasing immune-inducing particles and infective forms (merozoites) into the bloodstream. The merozoites go ...


A Functional Chlorophyll Biosynthesis Pathway Identified In The Kleptoplastic Sea Slug, Elysia Chlorotica, Julie A. Schwartz Feb 2015

A Functional Chlorophyll Biosynthesis Pathway Identified In The Kleptoplastic Sea Slug, Elysia Chlorotica, Julie A. Schwartz

Graduate Theses and Dissertations

The sacoglossan sea slug, Elysia chlorotica, feeds upon and sequesters plastids from the heterokont alga, Vaucheria litorea, and maintains the metabolically active organelles for up to nine months under starvation conditions while utilizing the photosynthate to survive and reproduce. The photosynthetic pigment, chlorophyll a (Chla), is found in all oxygenic photosynthetic organisms and is responsible for capturing photons of light and converting them into chemical energy. Chlorophyll and its associated proteins involved in the light capturing process are subject to photo oxidative damage and must be continually replaced for ongoing photosynthesis to continue; however, genes encoding these proteins are present ...


High-Throughput Screening Of Age-Related Changes In Caenorhabditis Elegans, Neil Copes Jan 2015

High-Throughput Screening Of Age-Related Changes In Caenorhabditis Elegans, Neil Copes

Graduate Theses and Dissertations

This project was developed to identify novel methods for high-throughput culturing and screening of C. elegans to investigate age-related metabolic changes and to survey the proteomic and metabolomic factors associated with age-related changes. To accomplish these goals we developed a novel way to grow C. elegans in liquid culture in 96-well microplates for several weeks without suffering significant fluid loss due to evaporation and without needing to shake or unseal the plates for aeration. We also developed methods for assaying the total volume of live C. elegans in microplate cultures using a fluorescence microplate reader and for performing RNAi experiments ...


The Effects Of Supplemented Metabolites On Lifespan And Stress Response Pathways In Caenorhabditis Elegans, Clare B. Edwards Jan 2015

The Effects Of Supplemented Metabolites On Lifespan And Stress Response Pathways In Caenorhabditis Elegans, Clare B. Edwards

Graduate Theses and Dissertations

Understanding how metabolites contribute to anaplerosis, antioxidant effects, and hormetic pathways during aging is fundamental to creating supplements and dietary habits that may decrease age-associated disease and decline, thus improving the quality of life in old age. In order to uncover metabolic pathways that delay aging, the effects of large sets of metabolites associated with mitochondrial function on lifespan were investigated.

Malate, the tricarboxylic acid (TCA) cycle metabolite, increased lifespan and thermotolerance in C. elegans. Addition of fumarate and succinate also extended lifespan and all three metabolites activated nuclear translocation of the cytoprotective DAF-16/FOXO transcription factor and protected from ...


Functional Analysis Of The Ovarian Cancer Susceptibility Locus At 9p22.2 Reveals A Transcription Regulatory Network Mediated By Bnc2 In Ovarian Cells, Melissa Buckley Jan 2015

Functional Analysis Of The Ovarian Cancer Susceptibility Locus At 9p22.2 Reveals A Transcription Regulatory Network Mediated By Bnc2 In Ovarian Cells, Melissa Buckley

Graduate Theses and Dissertations

GWAS have identified several chromosomal loci associated with ovarian cancer risk. However, the mechanism underlying these associations remains elusive. We identify candidate functional Single Nucleotide Polymorphisms (SNPs) at the 9p22.2 ovarian cancer susceptibility locus, several of which map to transcriptional regulatory elements active in ovarian cells identified by FAIRE-seq (Formaldehyde assisted isolation of regulatory elements followed by sequencing) and ChIP-seq (Chromatin Immunoprecipitation followed by sequencing) in relevant cell types. Reporter and electrophoretic mobility shift assays (EMSA) determined the extent to which candidate SNPs had allele specific effects. Chromosome conformation capture (3C) reveals a physical association between Basonuclin 2 (BNC2 ...


Rna Detection Technology For Applications In Marine Science: Microbes To Fish, Robert Michael Ulrich Jun 2014

Rna Detection Technology For Applications In Marine Science: Microbes To Fish, Robert Michael Ulrich

Graduate Theses and Dissertations

The accurate identification of taxa from mixed assemblages using genetic analysis remains an important field of molecular biology research. The common principle behind the development of numerous documented genetic detection technologies is to exploit specific nucleotide sequences inherent to each taxon. This body of work focuses on practical applications of real-time nucleic acid sequence-based amplification (RT-NASBA) in marine science, and is presented in four case studies. Each study represents novel work in the genetic identification of respective taxa of interest using RT-NASBA. Two case studies documented the development of an assay targeting mitochondrial 16S rRNA to discern legally salable grouper ...


Transcriptional Control Of Toxoplasma Development, Joshua Byran Radke Mar 2014

Transcriptional Control Of Toxoplasma Development, Joshua Byran Radke

Graduate Theses and Dissertations

Toxoplasma gondii is an obligate intracellular protozoan parasite of animals and man. The asexual life cycle of Toxoplasma involves three very distinct, but tightly coordinated developmental stages. In nature, the sporozoite (contained within an oocyst) and bradyzoite (contained within a tissue cyst) initiate infection of the intermediate host, followed by rapid differentiation into the actively replicating tachyzoite. When countered by an effective host response, the tachyzoite differentiates back into the latent bradyzoite and this unique ability of Toxoplasma to interconvert between the replicating tachyzoite and the latent bradyzoite within a single host is the cause of life long infection. The ...


Structure, Dynamics, And Evolution Of The Intrinsically Disordered P53 Transactivation Domain, Wade Michael Borcherds Jan 2013

Structure, Dynamics, And Evolution Of The Intrinsically Disordered P53 Transactivation Domain, Wade Michael Borcherds

Graduate Theses and Dissertations

in numerous disease states, including cancers and neurodegenerative diseases. All proteins are dynamic in nature, occupying a range of conformational flexibilities. This inherent flexibility is required for their function, with ordered proteins and IDPs representing the least flexible, and most flexible, respectively. As such IDPs possess little to no stable tertiary or secondary structure, they instead form broad ensembles of heterogeneous structures, which fluctuate over multiple time scales. Although IDPs often lack stable secondary structure they can assume a more stable structure in the presence of their binding partners in a coupled folding binding reaction.

The phenomenon of the dynamic ...


Matrix Metalloproteinase Genes Are Transcriptionally Regulated By E2f Transcription Factors: A Link Between Cell Cycle Control And Metastatic Progression, Jacqueline Lea Johnson Jan 2012

Matrix Metalloproteinase Genes Are Transcriptionally Regulated By E2f Transcription Factors: A Link Between Cell Cycle Control And Metastatic Progression, Jacqueline Lea Johnson

Graduate Theses and Dissertations

The RbµE2F transcriptional regulatory pathway plays a critical role in the cell cycle. Rb is inactivated through multiple waves of phosphorylation, mediated mainly by cyclin D and cyclin E associated kinases. Once Rb is inactivated, cells can enter Sµphase. Collectively, three Rb family members and ten E2F proteins coordinate every additional stage of the cell cycle, from quiescence to mitosis. However the RbµE2F pathway is frequently altered in cancer. Aside from cell proliferation, the RbµE2F pathway regulates other essential cellular processes including apoptosis, cell differentiation, angiogenesis and DNA damage repair pathways, but its role in invasion and cancer progression is ...


Stable Carbon Isotope Discrimination By Rubisco Enzymes Relevant To The Global Carbon Cycle, Amanda J. Boller Jan 2012

Stable Carbon Isotope Discrimination By Rubisco Enzymes Relevant To The Global Carbon Cycle, Amanda J. Boller

Graduate Theses and Dissertations

Five different forms of ribulose 1,5-bisphosphate carboxylase/oxygenase (RubisCO; IA, IB, IC, ID, II), the carboxylase of the Calvin-Benson-Bassham cycle (CBB), are utilized by plants, algae and autotrophic bacteria for carbon fixation. Discrimination against 13C by RubisCO is a major factor dictating the stable carbon isotopic composition (δ13C = {[13C/12C sample/13C/12C standard] - 1} X 1000) of biomass. To date, isotope discrimination, expressed as ε values (={[12k/13k] - 1} X 1000; 12k and 13k = rates of 1 ...