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Chronic Arsenic Exposure In Nanomolar Concentrations Accelerates Senescent Phenotypes In Vitro, Heather M. Sabo May 2017

Chronic Arsenic Exposure In Nanomolar Concentrations Accelerates Senescent Phenotypes In Vitro, Heather M. Sabo

Biological Sciences

Arsenic is recognized as an environmental carcinogen, in which over 100 million individuals worldwide experience chronic exposure through contaminated drinking water. Arsenic exposure is linked to several health conditions, such as cancer, diabetes, skin lesions, immune dysfunction, and cardiovascular disease. Here we test the hypothesis that toxicants, such as arsenic, accelerate the program of senescence. Human (IMR-90) primary diploid fibroblasts were chronically exposed to arsenic at nanomolar concentrations and the impact on the expression of senescent-associated mRNAs was evaluated. IMR-90 cells were exposed either to untreated media or exposed to 130nM and 330nM AsCl3 supplemented media. RNA samples were extracted …


Bhlhe40-As1 A Long-Noncoding Rna Regulates Dec1 On Breast Cancer Progression, Denisse Duran-Reyes May 2017

Bhlhe40-As1 A Long-Noncoding Rna Regulates Dec1 On Breast Cancer Progression, Denisse Duran-Reyes

Biological Sciences

Ductal Carcinoma in Situ (DCIS) is a precursor to breast cancer where abnormal cells have been found in the mammary duct but have not become invasive and spread into surrounding tissue. There has been an increase in early diagnosis of DCIS, but only around 40% of the cases ever progress to an invasive stage, and thus detection can lead to unnecessary surgeries. To identify which of these 40% progress, long noncoding RNAs were used. Through RNA sequencing of DCIS and invasive cells from real patient samples, BHLHE40 - AS1 was discovered, a long - noncoding R NA, to be highly …


Exploration Of The Interactions Between Amyloid-Beta Protein And Insulin In Various Ionic Conditions, Quade Goldenberg May 2017

Exploration Of The Interactions Between Amyloid-Beta Protein And Insulin In Various Ionic Conditions, Quade Goldenberg

Biological Sciences

Alzheimer’s disease (AD) is characterized by tau tangles and amyloid - β (Aβ) peptide aggregates amyloids in the brain, specifically in the hippocampus. Aβ plaques are known to form primarily in the extracellular space aroun d neuronal cells, interfering with synaptic transmission. The aggregation of Aβ in the hippocampus is associated with a decline in hippocampally - mediated cognitive abilities, which is a symptom of AD. AD has a strong correlation to type 2 diabetes mellitus (T2DM), which is defined by hyperinsulinemia and dysregulated glucose metabolism. It has been shown that insulin plays a role in both memory and learning …


Transcriptional Regulation Of Dksa P3 Promoter In Escherichia Coli, Chibuokem Ikwuazom May 2017

Transcriptional Regulation Of Dksa P3 Promoter In Escherichia Coli, Chibuokem Ikwuazom

Biological Sciences

DksA, a global gene regulator, binds to RNA po lymerase to regulate transcription initiation in Escherichia coli . It negatively regulates transcription of some genes, such as those for ribosomal RNAs and fis , and positively regulates transcription of other genes, including genes involved in amino acid biosynthesis. Little is known about how DksA itself is regulated. Current work in our lab has shown three major promoters, a σ 70 dependent P 1 promoter and two σ 38 (RpoS) - dependent promoters (P 2 and P 3 ), regulate the transcription of dksA . More is current ly known about …


Mulitmodal Molecular Mechanisms Control Germline Stem Cell Differentiation In Drosophila, Mohamad Nasrallah May 2017

Mulitmodal Molecular Mechanisms Control Germline Stem Cell Differentiation In Drosophila, Mohamad Nasrallah

Biological Sciences

Stem cells have the intrinsic ability to divide to form a stem cell daughter, while also retaining the ability to self - renew. These qualities are critical , as improper stem cell maintenance is implicit in aging and provokes diseases such as cancer. We previously revealed that during Drosophila oogenesis, transcriptional silencing mediated by polar granule component (pgc) alters the germ line cell cycle to promote germ line stem cell (GSC) differentiation. O ur work with pgc suggested that cell cycle regulation might be an important general mecha nism to facilitate division GSCs into daughter stem cells (or cystoblast, CBs), …


Controllable And Sequential Activation Of Cancer Nanotherapy For Enhanced Synergistic Effec, Vincent E. Lamantia May 2017

Controllable And Sequential Activation Of Cancer Nanotherapy For Enhanced Synergistic Effec, Vincent E. Lamantia

Biological Sciences

The treatment of numerous disease states has become increasingly more complex and challenging, even as we come out with new pharmacological and technological advancements. It is well known that cancer is not one disease, but many diseases that progress and present new challenges with each patient. With this we present a novel design which uses biorthogonal chemistry and magnetic nanoparticles (MNP’s) to create a drug delivery system with the capability to deliver two drugs that are released at two different time points under the direction of a single trigger. This innovative combination of multiple advancements will allow for the treatment …


Wheezing & Food Allergies In Infants Delivered Via Cesarean Section : The Upstate Kids Study, Temilayo Elizabeth Adeyeye Jan 2017

Wheezing & Food Allergies In Infants Delivered Via Cesarean Section : The Upstate Kids Study, Temilayo Elizabeth Adeyeye

Legacy Theses & Dissertations (2009 - 2024)

This dissertation sought to assess the effect of cesarean delivery (CD) on the risk of developing wheezing or food allergies in early childhood; and whether breastfeeding mediates the association between CD and the outcomes. We also aimed to highlight the differences in immunoglobulin concentrations by mode of delivery (MOD) in newborn dried blood spots (DBS), and the subsequent development of wheezing and food allergies in infants during the first three years of life. Data from the Upstate KIDS cohort was analyzed. Modified Poisson regression was used to compare the risks for wheezing and food allergies by MOD. We used a …


Lncrna Ak001796 Is Essential For The Survival Of Aggressive Breast Cancer Cells, Sumayya Adib Al-Chalabi Jan 2017

Lncrna Ak001796 Is Essential For The Survival Of Aggressive Breast Cancer Cells, Sumayya Adib Al-Chalabi

Legacy Theses & Dissertations (2009 - 2024)

Abstract:


Mass Spectrometric Analysis And Machine Learning Enable Microorganism Classification Based On Rna Posttranscriptional Modifications, Colin Christopher Aldrich Jan 2017

Mass Spectrometric Analysis And Machine Learning Enable Microorganism Classification Based On Rna Posttranscriptional Modifications, Colin Christopher Aldrich

Legacy Theses & Dissertations (2009 - 2024)

RNA post-transcriptional modifications (PTMs) are dynamic features that can be up- or down-regulated by the health and metabolic state of a cell. These covalent modifications are installed and removed on RNA nucleosides by enzymes controlled by the activation and deactivation of specific genes. The goal of this research was to demonstrate that RNA PTMs can serve as a unique feature for the classification/identification of microorganisms. We utilized a scheme based on electrospray ionization mass spectrometry (ESI-MS) to obtain global PTM profiles from total RNA extracted from various microorganisms in optimal growth conditions as well as Salmonella typhimurium (S. typhimurium) spiked …


Structural Characterization Of The Interactions Of Nicotinamide And Analogs With Human Sirt6 By Saturation Transfer Difference (Std) Nmr And Site Directed Mutagenesis, Beatriz Elena Bolivar-Vega Jan 2017

Structural Characterization Of The Interactions Of Nicotinamide And Analogs With Human Sirt6 By Saturation Transfer Difference (Std) Nmr And Site Directed Mutagenesis, Beatriz Elena Bolivar-Vega

Legacy Theses & Dissertations (2009 - 2024)

The allosteric regulation of SIRT6 by nicotinamide (NAM), along with the growing evidence of this enzyme's key role in the immune response, prompted the mechanistic study of SIRT6 inhibition by pyrazinamide (PZA) and analogs. In our current study, PZA, an analog of NAM, was revealed to have a modest modulatory effect on SIRT6, an enzyme that regulates the NF-κB signaling pathway at the transcriptional level (a relevant pathway to inflammation). Similarly, the analogs of PZA, 5-Cl PZA, 5-MeO PZA, and POA exhibited a modulatory effect against SIRT6 in our in vitro studies, enabling identification of a potential new target for …


A "Default Option" While Online Grocery Shopping To Enhance Nutrition Within A Food Insecure Population, Jaime Ashley Coffino Jan 2017

A "Default Option" While Online Grocery Shopping To Enhance Nutrition Within A Food Insecure Population, Jaime Ashley Coffino

Legacy Theses & Dissertations (2009 - 2024)

There is a need for sustainable interventions that improve diet-related health within the food insecure community. We examined if use of a “default” prefilled online grocery shopping cart, compared to nutrition education, would result in the purchase of healthier food items. Fifty participants (M age = 46.4 ± 12.46 years; M body mass index = 28.59 ± 6.48 kg/m2; 74.0% male) were randomized to: (1) read a brochure containing nutrition information (n = 23) or (2) be presented with a “default” prefilled online shopping cart containing groceries that meet nutritional guidelines to which they could freely make changes before completing …


Development And Characterization Of Novel Anti-Bat Monoclonal Antibodies For Studying Bat Immunity, Cailyn Cowan Jan 2017

Development And Characterization Of Novel Anti-Bat Monoclonal Antibodies For Studying Bat Immunity, Cailyn Cowan

Legacy Theses & Dissertations (2009 - 2024)

Abstract


Harnessing Electrocorticographic Signals For Neuroscience And Neurosurgery, Adriana De Pesters Jan 2017

Harnessing Electrocorticographic Signals For Neuroscience And Neurosurgery, Adriana De Pesters

Legacy Theses & Dissertations (2009 - 2024)

Daily human activities, such as speaking, driving or listening to music, are produced by activations of neurons in the brain. Where, when and how these activations occur has been the subject of intense debate for the last decades. Traditional techniques to image the human brain, such as functional magnetic resonance imaging (fMRI) or electroencephalography (EEG), only provide limited information regarding where and when these activations take place. For that reason, critical information is currently missing regarding how neurons from different parts of the brain interact and coordinate their activity to implement behavior. This information is critical to understand human behavior …


Study Of Biologically Important Macromolecules By Nuclear Magnetic Resonance, Christopher Michael Demott Jan 2017

Study Of Biologically Important Macromolecules By Nuclear Magnetic Resonance, Christopher Michael Demott

Legacy Theses & Dissertations (2009 - 2024)

Intrinsically disordered proteins or unstructured segments within proteins play an important role in cellular physiology and pathology. A combination of peptide aptamers selected by using the yeast-two-hybrid scheme, and in-cell NMR identified high affinity binders to a transiently structured intrinsically disordered proteins (IDP). This method was validated using the prokaryotic ubiquitin-like protein, Pup, of the Mycobacterium proteasome. We discover two peptide aptamers that bind to opposite sites of a transient helix in Pup, an intrinsically disordered protein, that have vastly different effects on the survival of Mycobacterium bovis BCG.


Grazing And The Coupling Of Vascular Plant And Soil Microbial Diversity In Agricultural Landscapes Of Eastern New York, Caroline Belle Girard-Cartier Jan 2017

Grazing And The Coupling Of Vascular Plant And Soil Microbial Diversity In Agricultural Landscapes Of Eastern New York, Caroline Belle Girard-Cartier

Legacy Theses & Dissertations (2009 - 2024)

ABSTRACT


Biomarkers And Metabolic Mechanisms Of Tobacco Smoke-Induced Lung Disease, Matthew Alan Hartog Jan 2017

Biomarkers And Metabolic Mechanisms Of Tobacco Smoke-Induced Lung Disease, Matthew Alan Hartog

Legacy Theses & Dissertations (2009 - 2024)

The overall goal of the research conducted in this dissertation is to determine the role of cytochrome (CYP) P450-mediated xenobiotic bioactivation in the development of tobacco smoke-induced lung toxicity. The central hypothesis of this work is that CYP-mediated bioactivation of specific tobacco smoke constituents is an important contributor to the generation of tobacco smoke-induced lung inflammation and injury. The specific aims are 1) to demonstrate that CYP-mediated metabolism contributes to the onset of lung inflammation following tobacco smoke inhalation; 2) to demonstrate that specific tobacco smoke constituents undergo CYP-mediated bioactivation in vivo; 3) to demonstrate that CYP-mediated bioactivation of tobacco …


A Tale Of Two Regulators : Characterization Of The Novel Transcription Factor Abmr And The Small Non-Coding Rna Mcr11 In Mycobacterium Tuberculosis, Roxanne Candice Girardin Jan 2017

A Tale Of Two Regulators : Characterization Of The Novel Transcription Factor Abmr And The Small Non-Coding Rna Mcr11 In Mycobacterium Tuberculosis, Roxanne Candice Girardin

Legacy Theses & Dissertations (2009 - 2024)

Genes of unknown function make up nearly one third of Mtb’s genome (Cole,


Elucidating The Transcriptional Regulation Underlying Neural Induction, Sarah E. Hirsch Jan 2017

Elucidating The Transcriptional Regulation Underlying Neural Induction, Sarah E. Hirsch

Legacy Theses & Dissertations (2009 - 2024)

The brain is one of the most complicated structures in the human body and its development is also elusive. Great strides have been made in expounding some of the complex mechanisms of neural development, which allows for the creation of innovative, less invasive, and more effective treatments for neurodevelopmental and neurodegenerative disorders. The advent of stem cell technology has brought therapy development for these disorders closer to a reality, as stem cells provide a platform to model early stages of human neural development. This is of great importance, as only through studying neurodevelopment will the various transcriptional and molecular components …


Novel Approaches To Mitigating Bacterial Biofilm Formation And Intercellular Communication, Stephen Kasper Jan 2017

Novel Approaches To Mitigating Bacterial Biofilm Formation And Intercellular Communication, Stephen Kasper

Legacy Theses & Dissertations (2009 - 2024)

Long thought of as solitary single-cell organisms, it is now widely accepted that bacteria can act and cooperate as social organisms. Phenomena such as biofilm formation and quorum sensing (QS) are two intimately intertwined cooperative behaviors that significantly contribute to the pathogenesis of many bacteria. Biofilms are surface associated communities of bacteria encased in a secreted extracellular matrix, which provides several advantages over an individualized lifestyle, such as increased protection from antimicrobial agents as well as enhanced opportunity for the exchange of genetic material. Bacterial QS is a system of population-based communication through the production, sensing, and response to chemical …


Influence Of The Pre-Initiation Complex On Mediator Recruitment In Saccharomyces Cerevisiae, Elisabeth Rose Knoll Jan 2017

Influence Of The Pre-Initiation Complex On Mediator Recruitment In Saccharomyces Cerevisiae, Elisabeth Rose Knoll

Legacy Theses & Dissertations (2009 - 2024)

The Mediator complex plays a central, highly conserved role in eukaryotic transcription by RNA Polymerase II (Pol II) by stimulating the cooperative assembly of a pre-initiation complex (PIC) and recruitment of Pol II for gene activation. Mediator recruitment has generally been ascribed to sequence-specific activators engaging subunits from the tail module which in turn function to recruit the middle and head for complete assembly at the UAS. Mediator subunits of the middle and head then bridge the enhancer to connect with the PIC at the core promoter. It is reported that Mediator recruitment at the UAS preferentially occurs at SAGA-dependent, …


Organ-Specific Contribution Of P450 Enzymes To Bioactivation And Acute Respiratory Tract Toxicity Of Naphthalene, Nataliia Kovalchuk Jan 2017

Organ-Specific Contribution Of P450 Enzymes To Bioactivation And Acute Respiratory Tract Toxicity Of Naphthalene, Nataliia Kovalchuk

Legacy Theses & Dissertations (2009 - 2024)

Naphthalene (NA) is an omnipresent air pollutant and respiratory toxicant and a possible human lung carcinogen. NA induces cytotoxicity in airways following bioactivation by CYP (P450) enzymes. The overall goal of this study was to examine the relative contributions of hepatic and pulmonary CYPs to bioactivation, disposition and NA-induced pneumotoxicity in vivo. Substantial differences in the expression and enzymatic activity of P450s occur in various organs in human populations, which could modify susceptibility to NA-induced airway damage. The central hypothesis for this study was that NA has the potential to cause lung toxicity in humans and that the metabolism of …


Investigating The Role Of Epitranscriptomics In Viral Immunity, Kaycie S. Lawson Jan 2017

Investigating The Role Of Epitranscriptomics In Viral Immunity, Kaycie S. Lawson

Legacy Theses & Dissertations (2009 - 2024)

The characterization of host-virus relationships is essential for understanding the process of viral replication and driving the development of effective viral targeting strategies. In this work, I tested the hypothesis that ribonucleic acid (RNA) post-transcriptional modifications (PTMs) may play a significant role in defining host-virus interactions. The model system consisted of a yeast strain capable of harboring the endogenous L-A virus, which allowed me to evaluate the possible involvement of PTMs in the process of cellular immunity to virus-borne toxicity. A mass spectrometry-based platform was utilized to compare the global PTM profile of wild-type yeast with those of the same …


Further Development Of Raman Spectroscopy For Body Fluid Investigation : Forensic Identification, Limit Of Detection, And Donor Characterization, Claire K. Muro Jan 2017

Further Development Of Raman Spectroscopy For Body Fluid Investigation : Forensic Identification, Limit Of Detection, And Donor Characterization, Claire K. Muro

Legacy Theses & Dissertations (2009 - 2024)

The challenges to forensic body fluid analysis have placed limitations on the type of information that investigators can acquire and how that information can be collected. In recent years, Raman spectroscopy has proven itself useful for characterizing body fluids. In 2008, a large-scale investigation was undertaken to explore the use of Raman spectroscopy as a means of identifying body fluids. This work resulted in multidimensional Raman spectroscopic signatures for the five main body fluids: semen, peripheral blood, saliva, vaginal fluid, and sweat. These studies were incredibly successful and created the foundation for years of continued research. Accordingly, the studies included …


Understanding The Genotoxicity Of Silver Nanoparticles And The Chemoprevention Of Pomegranate Extract, Sameera Nallanthighal Jan 2017

Understanding The Genotoxicity Of Silver Nanoparticles And The Chemoprevention Of Pomegranate Extract, Sameera Nallanthighal

Legacy Theses & Dissertations (2009 - 2024)

The use of silver nanoparticles (AgNPs) in a wide variety of consumer products (i.e. toothpastes, food containers, dietary supplements and garments) for their antimicrobial properties can lead to potential oral exposure in humans. To enhance their stability, AgNPs are coated with capping agents such as citrate and polyvinylpyrrolidone (PVP). Despite the lack of significant general toxicity based on hematology, blood chemistry and histology evaluations, the potential genotoxic effects of AgNPs cannot be ruled out and have to be addressed. Studies examining the genotoxic risks of AgNPs are needed because genotoxicity is a strong indicator of cancer risk. Here we examined …


Analysis Of Candidate Genes For Seizure Susceptibility In Epileptogenesis, Brittany O'Brien Jan 2017

Analysis Of Candidate Genes For Seizure Susceptibility In Epileptogenesis, Brittany O'Brien

Legacy Theses & Dissertations (2009 - 2024)

The occurrence of recurrent spontaneous seizures is the hallmark of epilepsy. The key to understanding how a normal brain can develop epilepsy through a process known as epileptogenesis is identifying susceptibility factors. Previously, various strains of inbred mice from the hybrid mouse diversity panel were subjected to multiple seizures via the repeated flurothyl model (RFM) for epileptogenesis. The results demonstrated differences in kindling among the inbred strains; specifically two main trends in the generalized seizure threshold (GST) data were kindling-sensitive and kindling-resistant strains. In addition, genome wide association studies done from these mice demonstrated a quantitative trait locus (QTL) on …


Climate Change, Spruce Root Phenology, And Allocation Of Carbon Below- And Above-Ground, Marie Louise Orton Jan 2017

Climate Change, Spruce Root Phenology, And Allocation Of Carbon Below- And Above-Ground, Marie Louise Orton

Legacy Theses & Dissertations (2009 - 2024)

Tree ring analysis has relied on a close relationship between climate and photosynthetically-derived stem enlargement. Lengthening growing seasons associated with climate warming have been predicted to enhance carbon sequestration as wood in trees, but this


Detecting And Analyzing Trna Modification Systems And Homologs Using In Silico And Colorectal Cancer Models, Khadijah Onanuga Jan 2017

Detecting And Analyzing Trna Modification Systems And Homologs Using In Silico And Colorectal Cancer Models, Khadijah Onanuga

Legacy Theses & Dissertations (2009 - 2024)

tRNA modifications can be considered epitranscriptomic signaling components that regulate translation and play integral roles in stress response pathways. As such, tRNA modification enzymes have roles in cancer etiology and potential utility as biomarkers of pathological states. For my thesis project I have used computational and wet bench approaches to study tRNA modification systems. Chapter two of my thesis deals with tRNA modification detection, as current methods are costly, time consuming, and require RNA fragmentation. I present a single-molecule-based approach for RNA modification detection, which involves in slico studies using a 5-layered graphene nanopore. Our simulations using a 1.5 nm …


Discovering Small Molecule Inhibitors Targeted To Ligand-Stimulated Rage-Diaph1 Signaling Transduction, Jinhong Pan Jan 2017

Discovering Small Molecule Inhibitors Targeted To Ligand-Stimulated Rage-Diaph1 Signaling Transduction, Jinhong Pan

Legacy Theses & Dissertations (2009 - 2024)

The receptor of advanced glycation end product (RAGE) is a multiligand receptor of the immunoglobulin superfamily of cell surface molecules, which plays an important role in immune responses. Full-length RAGE includes three extracellular immunoglobulin domains, a transmembrane domain and an intracellular domain. It is a pattern recognition receptor that can bind diverse ligands. NMR spectroscopy and x-ray crystallization studies of the extracellular domains of RAGE indicate that RAGE ligands bind by distinct charge- and hydrophobicity-dependent mechanisms. It is found that calgranulin binding to the C1C2 domain or AGEs binding to the V domain activates extracellular signaling, which triggers interactions of …


Effects Of Antibiotic Treatment On The Expression Of Hepatic And Intestinal Cytochrome P450, Bruno Pereira De Carvalho Jan 2017

Effects Of Antibiotic Treatment On The Expression Of Hepatic And Intestinal Cytochrome P450, Bruno Pereira De Carvalho

Legacy Theses & Dissertations (2009 - 2024)

Expression of metabolic enzymes Cytochrome P450 (CYP) is highly affected by drugs, diseases, age and gender. The Intestinal microflora has been suggested to play a role in regulating CYP expression and antibiotic treatments would lead to changes in level and composition of microbiota in mouse gut. This study aims to analyze CYP expression changes in the liver and small intestine resulted from the reduction of intestinal microflora by antibiotics. Impacts on bile acid signaling were also analyzed for a better comprehension of the mechanisms involved in this modulation. Female C57BL/6J mice (9- to 13-week old) were treated with ampicillin (AMP) …


Structural And Functional Characterization Of An Unusual Camp Responsive Transcription Factor, Cmr, In Tb Complex Mycobacteria, Sridevi Ranganathan Jan 2017

Structural And Functional Characterization Of An Unusual Camp Responsive Transcription Factor, Cmr, In Tb Complex Mycobacteria, Sridevi Ranganathan

Legacy Theses & Dissertations (2009 - 2024)

Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis in humans, is an intracellular pathogen that infects millions of people every year. Mtb can survive inside the host for extended periods of time by sensing and adapting to the host environmental stressors. Transcriptional gene regulation plays a critical role in this adaptation. This dissertation focuses on understanding the structural and functional aspects of one such transcriptional regulatory unit, Cmr (Rv1675c), in Mtb.