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2017

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How A Nutrient, Glutamine, Can Control Gene Programs In Cells, Jeff Hansen Aug 2017

How A Nutrient, Glutamine, Can Control Gene Programs In Cells, Jeff Hansen

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No abstract provided.

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Pharmacologic Or Genetic Targeting Of Glutamine Synthetase Skews Macrophages Toward An M1-Like Phenotype And Inhibits Tumor Metastasis., Erika M. Palmieri, Alessio Menga, Rosa Martín-Pérez, Annamaria Quinto, Carla Riera-Domingo, Giacoma De Tullio, D Craig Hooper, Wouter H. Lamers, Bart Ghesquière, Daniel W. Mcvicar, Attilio Guarini, Massimiliano Mazzone, Alessandra Castegna Aug 2017

Pharmacologic Or Genetic Targeting Of Glutamine Synthetase Skews Macrophages Toward An M1-Like Phenotype And Inhibits Tumor Metastasis., Erika M. Palmieri, Alessio Menga, Rosa Martín-Pérez, Annamaria Quinto, Carla Riera-Domingo, Giacoma De Tullio, D Craig Hooper, Wouter H. Lamers, Bart Ghesquière, Daniel W. Mcvicar, Attilio Guarini, Massimiliano Mazzone, Alessandra Castegna

Department of Cancer Biology Faculty Papers

Glutamine-synthetase (GS), the glutamine-synthesizing enzyme from glutamate, controls important events, including the release of inflammatory mediators, mammalian target of rapamycin (mTOR) activation, and autophagy. However, its role in macrophages remains elusive. We report that pharmacologic inhibition of GS skews M2-polarized macrophages toward the M1-like phenotype, characterized by reduced intracellular glutamine and increased succinate with enhanced glucose flux through glycolysis, which could be partly related to HIF1α activation. As a result of these metabolic changes and HIF1α accumulation, GS-inhibited macrophages display an increased capacity to induce T cell recruitment, reduced T cell suppressive potential, and an impaired ability to foster endothelial …

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Epigenetic Regulation Of Kpc1 Ubiquitin Ligase Affects The Nf-Κb Pathway In Melanoma., Yuuki Iida, Aaron Ciechanover, Diego M Marzese, Keisuke Hata, Matias Bustos, Shigeshi Ono, Jinhua Wang, Matthew P Salomon, Kevin Tran, Stella Lam, Sandy Hsu, Nellie Nelson, Yelena Kravtsova-Ivantsiv, Gordon B Mills, Michael A Davies, Dave S B Hoon Aug 2017

Epigenetic Regulation Of Kpc1 Ubiquitin Ligase Affects The Nf-Κb Pathway In Melanoma., Yuuki Iida, Aaron Ciechanover, Diego M Marzese, Keisuke Hata, Matias Bustos, Shigeshi Ono, Jinhua Wang, Matthew P Salomon, Kevin Tran, Stella Lam, Sandy Hsu, Nellie Nelson, Yelena Kravtsova-Ivantsiv, Gordon B Mills, Michael A Davies, Dave S B Hoon

Articles, Abstracts, and Reports

Purpose: Abnormal activation of the NF-κB pathway induces a more aggressive phenotype of cutaneous melanoma. Understanding the mechanisms involved in melanoma NF-κB activation may identify novel targets for this pathway. KPC1, an E3 ubiquitin ligase, is a regulator of the NF-κB pathway. The objective of this study was to investigate the mechanisms regulating KPC1 expression and its clinical impact in melanoma.Experimental Design: The clinical impact of KPC1 expression and its epigenetic regulation were assessed in large cohorts of clinically well-annotated melanoma tissues (tissue microarrays; n = 137, JWCI cohort; n = 40) and The Cancer Genome Atlas database (TCGA …

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The Effects Of Moringa Leaves On Hepatic Lipid Accumulation And Inflammation In A Guinea Pig Model Of Hepatic Steatosis, Manal Almatrafi Aug 2017

The Effects Of Moringa Leaves On Hepatic Lipid Accumulation And Inflammation In A Guinea Pig Model Of Hepatic Steatosis, Manal Almatrafi

Doctoral Dissertations

Moringa leaves (ML), have been recognized for their protective effects against chronic disease. To evaluate the protective effects of ML on hepatic steatosis and systemic inflammation, we used the guinea pig model. Male Hartley guinea pigs were assigned (n=8/group) to consume either a control diet (0 g Moringa), Low Moringa (LM) (10 %) or High Moringa (HM) (15%) diets, which were supplemented with 0.25% dietary cholesterol to induce hepatic steatosis. After 6 weeks, blood, liver, and adipose tissue were collected for determination of plasma lipids and lipoproteins, tissue cholesterol concentrations, inflammatory cytokines and expression of genes regulating hepatic cholesterol and …

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Perceptions Of Registered Nurses On The Choice Of Geriatric Nursing As A Specialty Area Of Practice: A Case Study, Cirila Daaco Negad Aug 2017

Perceptions Of Registered Nurses On The Choice Of Geriatric Nursing As A Specialty Area Of Practice: A Case Study, Cirila Daaco Negad

CUP Ed.D. Dissertations

The progressive growth of geriatric facilities as valuable element of the health system signified for increased services from health care workers particularly Registered Nurses (RNs). A major health care concern could be perceived due to the inadequate number of RNs providing care to elderly patients. Most studies centered on insufficiency of RNs in hospital settings while only few focused on geriatric facilities. In response to this gap, my study concentrated on perceptions of Registered Nurses on the demand for more RNs working with elderly patients in geriatric facilities with specialization in geriatric nursing. My study was a qualitative, descriptive, case …

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How A Nutrient, Glutamine, Can Control Gene Programs In Cells, Jeff Hansen Aug 2017

How A Nutrient, Glutamine, Can Control Gene Programs In Cells, Jeff Hansen

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No abstract provided.

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Selective Inhibitors Of Human Mpges-1 From Structure-Based Computational Screening, Ziyuan Zhou, Yaxia Yuan, Shuo Zhou, Kai Ding, Fang Zheng, Chang-Guo Zhan Aug 2017

Selective Inhibitors Of Human Mpges-1 From Structure-Based Computational Screening, Ziyuan Zhou, Yaxia Yuan, Shuo Zhou, Kai Ding, Fang Zheng, Chang-Guo Zhan

Molecular Modeling and Biopharmaceutical Center Faculty Publications

Human mPGES-1 is recognized as a promising target for next generation of anti-inflammatory drugs. Although various mPGES-1 inhibitors have been reported in literature, few have entered clinical trials and none has been proven clinically useful so far. It is highly desired for developing the next generation of therapeutics for inflammation-related diseases to design and discover novel inhibitors of mPGES-1 with new scaffolds. Here, we report the identification of a series of new, potent and selective inhibitors of human mPGES-1 with diverse scaffolds through combined computational and experimental studies. The computationally modeled binding structures of these new inhibitors with mPGES-1 provide …

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Reproductive And Metabolic State Differences In Olfactory Responses To Amino Acids In A Mouth Brooding African Cichlid Fish, Alexandre A. Nikonov, Julie M. Butler, Karen E. Field, John Caprio, Karen P. Maruska Aug 2017

Reproductive And Metabolic State Differences In Olfactory Responses To Amino Acids In A Mouth Brooding African Cichlid Fish, Alexandre A. Nikonov, Julie M. Butler, Karen E. Field, John Caprio, Karen P. Maruska

Faculty Publications

© 2017. Published by The Company of Biologists Ltd | Journal of Experimental Biology. Olfaction mediates many crucial life-history behaviors such as prey detection, predator avoidance, migration and reproduction. Olfactory function can also be modulated by an animal's internal physiological and metabolic states. While this is relatively well studied in mammals, little is known about how internal state impacts olfaction in fishes, the largest and most diverse group of vertebrates. Here we apply electroolfactograms (EOGs) in the African cichlid fish Astatotilapia burtoni to test the hypothesis that olfactory responses to food-related cues (i.e. L-amino acids; alanine and arginine) vary with …

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Analysis Of Dl-ρ¡-Tocopherol As Antioxidant On Malondialdehyde Level In Pediatric Patients With ρ¢-Thalassemia Major, Levana Rismayanti, Yulistiani Yulistiani, Mia Ratwita Andarsini, Mariyatul Qibtiyah Aug 2017

Analysis Of Dl-ρ¡-Tocopherol As Antioxidant On Malondialdehyde Level In Pediatric Patients With ρ¢-Thalassemia Major, Levana Rismayanti, Yulistiani Yulistiani, Mia Ratwita Andarsini, Mariyatul Qibtiyah

Folia Medica Indonesiana

Thalassemia is a hereditary form of anemia that affects the synthesis of hemoglobin. The management of therapy in patients with b-thalassemia major which patients should receive continuous blood transfusions and increased iron absorption from the digestive tract causes excess iron in the body. This will lead to an increase of free iron level that triggers Radical Oxygen Species (ROS). Increased level of ROS can initiate lipid peroxidation which used as an indicator of oxidative stress in cells and tissues and produce reactive carbonyl, mainly malondialdehyde (MDA). Thus, MDA measurement is widely used as an indicator of lipid peroxidation. On the …

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Temperature-Modulated Expression Of Allometric Respiration Strategies Supports A Metabolic Scaling Rule, Chet F. Rakocinski, Kelsey Burns Gillam Aug 2017

Temperature-Modulated Expression Of Allometric Respiration Strategies Supports A Metabolic Scaling Rule, Chet F. Rakocinski, Kelsey Burns Gillam

Faculty Publications

A model based on the mass-specific oxygen consumption rate of the tolerant polychaete, Capitella telata, related meaningfully to a novel metabolic scaling rule as applied to the infaunal size spectrum. Depending on temperature, C. telataexpressed divergent oxyregulating or oxyconforming strategies relative to oxygen availability. A non-linear response surface fitted to the allometric exponents of a family of VO2 curves for 12 treatment combinations of DO saturation and temperature was used to project oxygen consumption rates across the infaunal size spectrum. Plasticity in respiration strategies was evident, based on four simulated dynamic 32 d oxygen-temperature exposure scenarios and …

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Brain Enriched Micrornas Open The Neurogenic Potential Of Adult Human Fibroblasts, Daniel Gene Abernathy Aug 2017

Brain Enriched Micrornas Open The Neurogenic Potential Of Adult Human Fibroblasts, Daniel Gene Abernathy

Arts & Sciences Graduate Student Theses and Dissertations

The seemingly limitless capacities of mammals to sense, respond, and manipulate their environments stems from their structurally and functionally diverse nervous systems. Establishing these complex behaviors requires the integration of many biological phenomena including, morphogenetic gradients, cell-cell signaling, transcriptional networks, cell migration and epigenetic gene regulation. As mammalian development progresses, these pathways coordinate the production of highly specialized neuronal and glial cells, that connect and communicate with another in an even more complex manner. While evolution has shaped a multitude of pathways to produce numerous favorable traits, it has also created an intricate system vulnerable to disease. The loss of …

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The Effect Of Dietary Fat On Obesity, Gene Expression, And Dna Methylation In Two Generations Of Mice, Madeline Rose Keleher Aug 2017

The Effect Of Dietary Fat On Obesity, Gene Expression, And Dna Methylation In Two Generations Of Mice, Madeline Rose Keleher

Arts & Sciences Graduate Student Theses and Dissertations

As obesity rates continue rising nationally and globally, it is crucial to understand how a high-fat diet disrupts the regulation of the genome and leads to adverse health effects. Uncovering the underlying gene expression and DNA methylation changes induced by an individual’s high-fat diet and a maternal high-fat diet can pinpoint new targets for epigenetic therapies and reveal the physiological and behavioral changes in obesity. The goal of this dissertation is to gain deeper insight into the DNA methylation and gene expression changes that occur in response to a high-fat diet.I studied the response to dietary fat within two generations …

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Antiviral Nucleoside Inhibitors Of Leishmania Rna Virus 1: Discovery And Mechanism, John Isaac Robinson Aug 2017

Antiviral Nucleoside Inhibitors Of Leishmania Rna Virus 1: Discovery And Mechanism, John Isaac Robinson

Arts & Sciences Graduate Student Theses and Dissertations

Some Leishmania parasites in the Viannia sub-genus are persistently infected with Leishmania RNA virus 1 (LRV1), a single-segmented double-stranded RNA virus belonging to the family Totiviridae. Infected parasites cause greater pathology and reach higher populations in mouse models of Leishmania infection. In human disease, LRV1+ parasites are correlated with increased frequency of treatment failure and relapse. Efficient methods to detect LRV1 and eliminate it from parasites are required to better understand the role of LRV1 in Leishmania infection. We optimized multiple techniques to measure LRV1 levels in parasites, most notably using flow cytometry to measure the amount of viral capsid …

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Robust Algorithms For Detecting Hidden Structure In Biological Data, Roman Sloutsky Aug 2017

Robust Algorithms For Detecting Hidden Structure In Biological Data, Roman Sloutsky

Arts & Sciences Graduate Student Theses and Dissertations

Biological data, such as molecular abundance measurements and proteinsequences, harbor complex hidden structure that reflects its underlyingbiological mechanisms. For example, high-throughput abundance measurementsprovide a snapshot the global state of a living cell, while homologousprotein sequences encode the residue-level logic of the proteins' functionand provide a snapshot of the evolutionary trajectory of the protein family.In this work I describe algorithmic approaches and analysis software Ideveloped for uncovering hidden structure in both kinds of data.Clustering is an unsurpervised machine learning technique commonly usedto map the structure of data collected in high-throughput experiments,such as quantification of gene expression by DNA microarrays orshort-read sequencing. …

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Mechanisms And Regulation Of Resection In Dna Damage Response, Sharad C. Paudyal Aug 2017

Mechanisms And Regulation Of Resection In Dna Damage Response, Sharad C. Paudyal

Arts & Sciences Graduate Student Theses and Dissertations

Deoxyribonucleic acid (DNA) encodes genetic information essential for cell survival and function. However, it is constantly under assault from endogenous and exogenous damaging agents that not only threaten our own survival but also affect the faithful transmission of genetic information to our offspring. Double-strand breaks (DSBs) are one of the most hazardous forms of DNA damage, which if unrepaired or improperly repaired could lead to plethora of systemic human diseases including cancer. To deal with this problem, cells have evolved with a mechanism called DNA damage response (DDR) to detect, signal, and repair the breaks by inducing multiple cellular events. …

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Mri In Cancer: Improving Methodology For Measuring Vascular Properties And Assessing Radiation Treatment Effects In Brain, Chong Duan Aug 2017

Mri In Cancer: Improving Methodology For Measuring Vascular Properties And Assessing Radiation Treatment Effects In Brain, Chong Duan

Arts & Sciences Graduate Student Theses and Dissertations

Tumors cannot survive, progress and metastasize without recruiting new blood vessels. Vascular properties, including perfusion and permeability, provide valuable information for characterizing cancers and assessing therapeutic outcomes. Dynamic contrast-enhanced (DCE) MRI is a non-invasive imaging technique that affords quantitative parameters describing the underlying vascular structure of tissue. To date, the clinical application of DCE-MRI has been hampered by the lack of standardized and validated quantitative modeling approaches for data analysis.From a therapeutic perspective, radiation therapy is a central component of the standard treatment for patients with cancer. Besides killing cancer cells, radiation also induces parenchymal and stromal changes in normal …

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Effects Of Nucleosome Structure On Dna Photoproduct Formation And Deamination, Kesai Wang Aug 2017

Effects Of Nucleosome Structure On Dna Photoproduct Formation And Deamination, Kesai Wang

Arts & Sciences Graduate Student Theses and Dissertations

Cyclobutane pyrimidine dimers (CPDs) are DNA photoproducts linked to skin cancer, whose mutagenicity depends in part on their frequency of formation and deamination. Nucleosomes modulate CPD formation, favoring outside facing sites, and disfavoring inward facing sites. A similar pattern of CPD formation in protein-free DNA loops suggest that DNA bending causes the modulation of photoproduct formation in nucleosomes. To systematically study the cause and effect of nucleosome structure on CPD formation and deamination, we had developed a circular permutation synthesis strategy for positioning a target sequence at different superhelix locations (SHLs) across a nucleosome in which the DNA has been …

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The Solid & The Shifting: Darwinian Time, Evolutionary Form And The Greek Ideal 
In The Early Works Of Virginia Woolf, Joseph Monroe Kreutziger Aug 2017

The Solid & The Shifting: Darwinian Time, Evolutionary Form And The Greek Ideal 
In The Early Works Of Virginia Woolf, Joseph Monroe Kreutziger

Arts & Sciences Graduate Student Theses and Dissertations

ABSTRACT OF THE DISSERTATION“The Solid & the Shifting”: Evolutionary Form, Darwinian Time, and the Greek Ideal in the Early Works of Virginia WoolfByJoseph KreutzigerDoctor of Philosophy in English and American LiteratureWashington University in St. Louis, 2017Professors Melanie Micir, Robert Milder, Steven Meyer, Vincent Sherry, Zoe Stamatopoulou_____________________________________________________________________
“Now is life very solid or very shifting?” Virginia Woolf asks in her diary of 1931, a question she claims haunts her in its contradictions. This dynamism between the solid and the shifting aspects of life and temporality is fundamental to an analysis of Woolf’s writing process. It resonates throughout the narratives of her …

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The Developmental Interplay Of Personality And Relationship Quality In Young Adulthood, Kelci Harris Aug 2017

The Developmental Interplay Of Personality And Relationship Quality In Young Adulthood, Kelci Harris

Arts & Sciences Graduate Student Theses and Dissertations

I used the framework of the personality-relationship transaction to examine the co-development of personality and relationship quality during college in three different relationship contexts: an aggregate of friends, romantic partner dyads, and friend dyads. I treat the personality-relationship transaction as a dyadic process, rather than an ego-centric one, by including friends’ and romantic partners’ reports of personality and relationship quality. I created a multivariate latent growth curve model version of the Actor Partner Interdependence Model to test how personality and relationship quality co-developed. Initial correlations between personality and relationship quality reflect what is seen in previous work; self-reported extraversion, agreeableness, …

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Intimate Partner Violence Among South Asian Women In The United States: Prevalence And Help-Seeking Behaviors, Vithya Murugan Aug 2017

Intimate Partner Violence Among South Asian Women In The United States: Prevalence And Help-Seeking Behaviors, Vithya Murugan

Arts & Sciences Graduate Student Theses and Dissertations

Data suggests that over 35% of women in the United States have experienced rape, physical violence, and/or stalking by an intimate partner in their lifetime and have reported significant short and long-term impacts, such as post-traumatic stress disorder symptoms and injury (Breiding et al., 2011). Ethnic/minority women are especially vulnerable to IPV with rates ranging from 44% for African American women to 46% for American Indian/Alaska Native women (Breiding et al., 2011).Although South Asians are some of the most recent immigrants, they are one of the fastest growing ethnic groups in the United States, with a current population of 3.4 …

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Mass Spectrometry-Based Structural Proteomics: Methodology And Application Of Fast Photochemical Oxidation Of Proteins (Fpop), Ben Niu Aug 2017

Mass Spectrometry-Based Structural Proteomics: Methodology And Application Of Fast Photochemical Oxidation Of Proteins (Fpop), Ben Niu

Arts & Sciences Graduate Student Theses and Dissertations

The dissertation will be solely focused on using mass spectrometry to characterize protein high order structures (HOS), it emphasizes the use of hydroxyl radical footprinting (FPOP) coupled to bottom-up MS approach. A detailed background information about FPOP, and the corresponding method developments as well as applications will be covered.The first chapter will be a comprehensive review regarding the FPOP. Following this, chapter 2, 3, and 4 will be focused on the method developments. Chapter 2 describes an isotope dilution GC-MS method to quantitate OH radicals in FPOP; chapter 3 describes the incorporation of Leu-enkephalin as reporter peptide for a more …

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Exploring Host-Virus Interactions In Caenorhabditis Nematodes, Kevin Chen Aug 2017

Exploring Host-Virus Interactions In Caenorhabditis Nematodes, Kevin Chen

Arts & Sciences Graduate Student Theses and Dissertations

Caenorhabditis elegans is a powerful model organism that has elucidated many biological questions in the fields of genetics, development, and neurobiology. In addition, C. elegans has been used in the past decade to investigate host-pathogen interactions with bacteria and fungi. The recent identification of nematode viruses that naturally infect C. elegans and Caenorhabditis briggsae provides a unique opportunity to define host-virus interactions in these model hosts.This dissertation first explored the transcriptional response of C. elegans and C. briggsae to virus infection by RNA-seq. I identified a total of 320 differentially expressed genes (DEGs) in C. elegans following Orsay virus infection. …

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Specificity Determination By Paralogous Winged Helix-Turn-Helix Transcription Factors, Adam Joyce Aug 2017

Specificity Determination By Paralogous Winged Helix-Turn-Helix Transcription Factors, Adam Joyce

Arts & Sciences Graduate Student Theses and Dissertations

Transcription factors (TFs) localize to regulatory regions throughout the genome, where they exert physical or enzymatic control over the transcriptional machinery and regulate expression of target genes. Despite the substantial diversity of TFs found across all kingdoms of life, most belong to a relatively small number of structural families characterized by homologous DNA-binding domains (DBDs). In homologous DBDs, highly-conserved DNA-contacting residues define a characteristic ‘recognition potential’, or the limited sequence space containing high-affinity binding sites. Specificity-determining residues (SDRs) alter DNA binding preferences to further delineate this sequence space between homologous TFs, enabling functional divergence through the recognition of distinct genomic …

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Nuclear Export Factor 3 Regulates The Localization Of Small Nucleolar Rnas, Melissa Wanling Li Aug 2017

Nuclear Export Factor 3 Regulates The Localization Of Small Nucleolar Rnas, Melissa Wanling Li

Arts & Sciences Graduate Student Theses and Dissertations

Metabolic diseases, such as obesity and diabetes, are associated with excess levels of lipids, which can lead to organelle dysfunction, cell death and eventually organ dysfunction. This process, termed lipotoxicity, is still not completely understood. In a genetic screen used to identify genes critical for lipotoxicity, the Schaffer lab has identified small nucleolar RNAs (snoRNAs) within the ribosomal protein L13a (Rpl13a) locus that mediate the cellular response to lipotoxic and general metabolic stress. These snoRNAs are non-canonical in that they accumulate in the cytosol after metabolic stresses like lipotoxicity and oxidative stress, suggesting that cells have specific mechanisms for regulating …

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Investigation Of The Contribution Of Type 1 Pili In Enterotoxigenic Escherichia Coli (Etec) Pathogen-Host Interactions, Alaullah Sheikh Aug 2017

Investigation Of The Contribution Of Type 1 Pili In Enterotoxigenic Escherichia Coli (Etec) Pathogen-Host Interactions, Alaullah Sheikh

Arts & Sciences Graduate Student Theses and Dissertations

Enterotoxigenic Escherichia coli (ETEC) are one of the leading causes of death due to diarrhea in children living in developing countries. ETEC are also the leading cause of diarrhea in travelers to developing countries lacking sanitation and safe drinking water. Unfortunately, there is no broadly protective vaccine available against these important pathogens. In order to cause infection, ETEC colonize the intestinal epithelium and secrete toxins, including heat-labile toxin (LT) and/or heat-stable toxin (ST). Efficient delivery of these toxins to the cognate receptors on target intestinal cells requires direct ETEC-host interactions. Earlier studies demonstrated that ETEC facilitate interactions with host by …

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Dna Replication Challenges: Telomeres And R Loops, Shankar Parajuli Aug 2017

Dna Replication Challenges: Telomeres And R Loops, Shankar Parajuli

Arts & Sciences Graduate Student Theses and Dissertations

Faithful DNA replication and repair are essential for maintaining genome stability and preventing various diseases including cancer. Both processes are executed by numerous redundant mechanisms to ensure that these processes are uninterrupted even when a primary mechanism fails. Despite this, they are not immune to challenges and failures leading to DNA damage and genome instability. These problems are more evident at the difficult-to-replicate regions of the genome such as the telomeres that cap and protect linear chromosome ends. Additionally, topological structures such as RNA:DNA hybrids, commonly referred to as R loops, can also present severe challenges to the DNA replication …

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Characterization And Function Of Islet Antigen Presenting Cells During Nod Diabetes, Stephen Thomas Ferris Aug 2017

Characterization And Function Of Islet Antigen Presenting Cells During Nod Diabetes, Stephen Thomas Ferris

Arts & Sciences Graduate Student Theses and Dissertations

Here we characterized the initial antigen presenting cells (APCs) within the islet of Langerhans to ascertain their identity and functional role as it pertains to autoimmune diabetes. The activation of the adaptive immune system is induced by the innate immune system, and more specifically APCs. Therefore, it is crucial to identify the APCs that are initiating T1D in order to elucidate the break in tolerance and intervene in order to inhibit progression. We have found that there is a resident macrophage that is present in all strains of mice. This islet macrophage has a distinct transcriptional profile that is unique …

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Synthesis, Characterization, And Biological Activity Of Spherical Nucleic Acid (Sna) Constructs For Cancer Therapy And Imaging, Colin Calabrese Aug 2017

Synthesis, Characterization, And Biological Activity Of Spherical Nucleic Acid (Sna) Constructs For Cancer Therapy And Imaging, Colin Calabrese

Arts & Sciences Graduate Student Theses and Dissertations

This dissertation focuses on the development of biocompatible oligonucleotide-based nanomaterials, known as spherical nucleic acids (SNAs), as therapeutic and diagnostic agents for intracellular gene regulation and in vivo cancer imaging by positron emission tomography (PET). SNAs consist of a nanoparticle core functionalized with a dense shell of oligonucleotides such as deoxyribonucleic acid (DNA). Detailed synthetic procedures and characterization of novel SNAs with purpose-built biocompatible core materials are described. The SNAs exhibit comparable chemical, physical and biological properties regardless of core composition. The functionalities of the SNAs were further tailored by deliberate design and chemical modification of their oligonucleotide sequences. The …

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Expansion Of Microbial Virology By Impetus Of The Reduction Of Viral Dark Matter, Siddharth Ravindran Krishnamurthy Aug 2017

Expansion Of Microbial Virology By Impetus Of The Reduction Of Viral Dark Matter, Siddharth Ravindran Krishnamurthy

Arts & Sciences Graduate Student Theses and Dissertations

Modern metagenomic methods have rapidly accelerated the rate of viral discovery. Currently, to discover a novel virus, deep sequencing reads must align to a known reference virus. While alignment is effective at identifying closely related viruses, highly divergent viruses can often share no discernable sequence alignment with known viruses. Therefore, the accurate classification of viral dark matter – metagenomic sequences that originate from viruses but do not align to any reference virus sequences – is one of the major obstacles in not only discovering novel viruses, but also by extension, comprehensively defining the virome. As viral dark matter results fundamentally …

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The Role Of Vip Scn Neurons In Circadian Physiology And Behavior, Cristina Mazuski Aug 2017

The Role Of Vip Scn Neurons In Circadian Physiology And Behavior, Cristina Mazuski

Arts & Sciences Graduate Student Theses and Dissertations

Located in the ventral hypothalamus, the suprachiasmatic nucleus (SCN) is necessary for entraining daily rhythms in physiology and behavior to environmental cues. Though the 20,000 neurons of the SCN uniformly express GABA, they differ greatly in neuropeptide content. One anatomically and functionally distinct class of neuropeptidergic SCN neurons is vasoactive intestinal polypeptide (VIP). Expressed by approximately 10% of SCN neurons, VIP is necessary for synchronizing single-cell SCN rhythms to produce coherent output and sufficient for entrainment. However, little is known about the firing activity of these neurons releases VIP and results in circadian entrainment. We utilized multielectrode array technology and …

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