Molecular Biology Commons^™

Brain Energy Homeostasis And The Regulation Of N-Acetyl-Aspartate Metabolism In Development And Disease, Samantha Zaroff

Graduate School of Biomedical Sciences Theses and Dissertations

N-acetylaspartate (NAA) is a non-invasive clinical marker of neuronal metabolic integrity because of its strong proton magnetic resonance spectroscopy (H-MRS) peak and direct correlation with energetic integrity. Specifically, NAA is used to track the progression of neurodegenerative diseases due to the characteristic reduction of whole brain levels of NAA which occur simultaneously with reduced glucose utilization and mitochondrial dysfunction, but prior to the onset of disease specific pathology. However, NAA will also significantly increase simultaneously with energetic integrity during periods of recovery or remission in applicable disorders, such as traumatic brain injuries. Unfortunately, it remains enigmatic exactly why NAA is …

Type Ix Secretion System: Characterization Of An Effector Protein And An Insight Into The Role Of C-Terminal Domain Dimeration In Outer Membrane Translocation., Lahari Koneru

Electronic Theses and Dissertations

Porphyromonas gingivalis and Tannerella forsythia are two of the primary pathogens that are associated in the etiology and progression of chronic periodontitis. In T. forsythia, KLIKK proteases are the recently identified group of proteolytic enzymes that are secreted through Type IX secretion system (T9SS). Among, these KLIKK proteases a synergistic relationship was observed between karilysin and mirolysin in invading the host complement system for the survival of the bacteria. Since, karilysin has been already characterized, in this study we propose to study about mirolysin through structural, biochemical and biological characterization. The obtained results from the experiments has shown the …

Developing Algorithms For Quantifying The Super Resolution Microscopic Data: Applications To The Quantification Of Protein-Reorganization In Bacteria Responding To Treatment By Silver Ions, Sai Divya Challapalli

Graduate Theses and Dissertations

Histone-like nucleoid structuring proteins (HNS) play significant roles in shaping the chromosomal DNA, regulation of transcriptional networks in microbes, as well as bacterial responses to environmental changes such as temperature fluctuations. In this work, the intracellular organization of HNS proteins in E. coli bacteria was investigated utilizing super-resolution fluorescence microscopy, which surpasses conventional microscopy by 10–20 fold in spatial resolution. More importantly, the changes of the spatial distribution of HNS proteins in E. coli, by addition of silver ions into the growth medium were explored. To quantify the spatial distribution of HNS in bacteria and its changes, an automatic method …

Characterization Of Notch1 And Pi3k-Pten-Akt/Mtor Pathway Interaction In Head And Neck Squamous Cell Carcinoma, Kyriante' Henry

Dissertations and Theses (Open Access)

Head and neck squamous cell carcinoma (HNSCC) affects various mucosal sites of the upper aerodigestive tract, including the nasal and oral cavities, the nasopharynx, and the oropharynx. More than five hundred thousand new cases of HNSCC occurred in 2011 alone, with 50,000 reported cases in the United States. This trend made HNSCC the seventh most common non-skin cancer worldwide (Ferlay et al., 2015). Although significant epidemiological and pathological advancements have been made, survival rates have not improved much over the last 40 years, leaving a mortality rate that remains at approximately 50%. An unbiased drug screen demonstrated that HNSCC cell …

The Functions Of Setd5 And Mir-221 In Embryonic Stem Cell Differentiation, Tsai-Yu Chen

Dissertations and Theses (Open Access)

Embryonic stem cells (ESCs) are a widely used model system to study cellular differentiation because of their pluripotent characteristics, and ESC differentiation is an epigenetic process. In an effort to identify a new epigenetic factor that is required for ESC differentiation, the function of SETD5 in ESCs was studied for this thesis. Results show that SETD5 is essential for retinoic acid (RA)-induced differentiation of mouse ESCs and for RA-induced expression of critical developmental genes (e.g., Hoxa1 and Hoxa2) and neuron-related genes (e.g., Nestin and Pax6). SETD5 was upregulated during ESC differentiation. Additional results demonstrated that SETD5 bound to …

Insights Into The Therapeutic Potential Of Salt Inducible Kinase 1: A Novel Mechanism Of Metabolic Control, Randi Fitzgibbon

Dissertations and Theses (Open Access)

Salt inducible kinase 1 (SIK1) has been considered a stress-inducible kinase since it was first cloned in 1999. Continued efforts since this time have been dedicated to characterizing the structure and function of SIK1. Such research has laid the ground work for our understanding of SIK1 action and regulation in tissue and stimuli dependent manners. The fundamental findings of this dissertation continue in this tradition and include investigations of SIK1 regulatory mechanisms in skeletal muscle cells, the cellular and physiological effects of SIK1 loss of function in vitro and in vivo, and intracellular metabolic and mitochondrial regulation by this …

Endocytic Trafficking Of The Amyloid Precursor Protein In Rat Cortical Neurons, Sahily Reyes

Dissertations and Theses (Open Access)

Amyloid-beta (Aβ) aggregation and deposition into extracellular plaques is a hallmark of the most common forms of dementia, including Alzheimer’s disease. The Aβ-containing plaques result from pathogenic cleavage of amyloid precursor protein (APP) by secretases resulting in intracellular production of Aβ peptides that are secreted and accumulate extracellularly. Despite considerable progress towards understanding APP processing and Aβ aggregation, the mechanisms underlying endosomal production of Aβ peptides and their secretion remain unclear. Using endosomes isolated from cultured primary neurons, we determined that the trafficking of APP from the endosomal membrane into internal vesicles of late endosome/multivesicular bodies (MVB) is dependent on …

Understanding Intracellular Redox Regulation In Methanogens: Characterization Of The Components And Targets Of The Nadph-Dependent Thioredoxin System From Methanosarcina Acetivorans, Addison Clark Mccarver

Graduate Theses and Dissertations

All cells have a reduced intracellular environment. In the presence of oxygen, the non-specific oxidation of intracellular components leads to the production of reactive oxygen species (ROS) within cells leading to oxidative stress. During oxidative stress labile cofactors (e.g. Fe-S clusters) are lost and deleterious disulfide bonds are formed within proteins. Intracellular redox maintenance systems are used to direct reducing equivalents towards the repair of oxidatively-damaged proteins. The thioredoxin system is the ubiquitous intracellular redox system, found in virtually all species. The canonical thioredoxin system is comprised of a NADPH-dependent thioredoxin reductase (TrxR) that functions to reduced thioredoxin (Trx). Although …

Cellular Mechanisms Of Ionoregulation In The Gill Of Japanese Medaka And Rainbow Trout, Rebecca Jo Bollinger

Graduate Theses and Dissertations

Euryhaline fishes are capable of adapting to a wide range of salinities such as freshwater, brackish water or seawater. Through the combined effort of the gill, kidney and intestine, they are able to osmoregulate to maintain a constant internal hydromineral balance. As the gill is in direct contact with the external environment, it is continuously working to maintain ion and acid/base balance, gas exchange and eliminate nitrogenous waste. Fish in freshwater are subjected to osmotic water gain and diffusional ion loss across the gill and experience the opposite in seawater. Therefore, the gill exhibits extreme plasticity when experiencing a change …

Role Of Cannabinoid Receptor Type 2 (Cb2) In Late Stage Atherosclerosis, Makenzie Fulmer

Electronic Theses and Dissertations

Atherosclerosis is a chronic inflammatory disorder of medium and large vessels. Immune signaling and dyslipidemia are two of several processes which influence lesion development in atherosclerosis. Cannabinoids, such as those found in marijuana, exert their effects through two cannabinoid receptors, CB1 and CB2. Recent studies using CB2 knockout mice and CB2-selective ligands have shed light on a protective role of CB2 in early stages of atherosclerosis. However, the role of CB2 in advanced stages of atherosclerosis remains unclear. To determine if CB2 plays a role in advanced atherosclerotic lesion composition and progression, we investigated the effects of systemic CB2 gene …

Determination Of The Effects Of Different Maillard Reaction Products On The Taxonomic Composition Of The Gut Microbiota, Nesreen Hamdan Aljahdali

Graduate Theses and Dissertations

The Maillard Reaction (MR) is a non-enzymatic chemical reaction which results in linkage between the amino group of amino acids and the carbonyl group of reduced sugars. This reaction generates Maillard reaction products (MRPs) which are not present naturally in foods, and are responsible for a range of colors, odors, flavors, and other sensory properties. Conflicting reports of MRPs impacts on human health are probably due to the fact that bioconversion of these digestible molecules by the gut microbiota has been marginally taken into account. This study aimed to determine the effects of different MRPs on rodent’s gut microbiota through16S …

Detection Of Survival And Proliferation Of Sulfate Reducers Under Simulated Martian Atmospheric And Soil Conditions, Sergio Mosquera Mora

Graduate Theses and Dissertations

Numerous studies have tried to determine the survivability and proliferation of microorganisms under simulated Martian conditions. Furthermore, most of them have been focused on the ability of these microbes to cope with high brines’ salt (NaCl) concentrations inherent of the Martian surface. However, there are not studies related to the ability of bacteria to survive on subsurface environments that have increasing concentrations of sulfate compounds. For this research, a group of microorganisms known as sulfate-reducing bacteria or simply sulfate reducers were chosen due to their ability to use sulfate compounds as terminal electron acceptors to produce metabolic energy, their tolerance …

Piglet Gut Microbiota Responses To Exposure To Outdoor Simulated Environment And Formula Feeding, Nguyen Vo

Graduate Theses and Dissertations

Several lines of evidence suggest that early-life gut microbiota composition is a crucial determinant of the susceptibility to diseases later in life. Understanding the evolution of early-life gut microbiota and critical factors that can modify this microbial community will espouse the prevention or reversion of health risk originating from dysbiosis of the gut microbiota in the early stage. In this research, we hypothesized that alterations in the environment (simulation of rural conditions by soil exposure) and feeding mode (breastmilk versus formula milk) will have significant impacts on the establishment of the gut microbiota in early life. At first, in literature …

Software For Sequence Analysis Of Variants In Functional Screening Libraries And Personalized Genome Files, Jacklyn Michelle Newsome

UNLV Theses, Dissertations, Professional Papers, and Capstones

Detailed knowledge of protein function is critical for both the study of protein interactions and the development of drugs which target specific proteins. Currently, there are few techniques that directly examine protein function. The techniques that are available are time consuming and can only address one variant of a protein at a time. Our laboratory has designed 3 high throughput protein function screens. We hypothesize that these will address this shortfall.

The first screen is the Chimeric Minimotif Decoy (CMD) Assay. For this screen, we constructed red fluorescent proteins with one or more C-terminal minimotifs. Minimotifs are short, contiguous amino …

Complete Sequencing And Comparative Analysis Of The Genomes Of The First Magnetotactic Gammaproteobacteria Isolated In Pure Culture: Strains Bw-2 And Ss-5, Corey Geurink

UNLV Theses, Dissertations, Professional Papers, and Capstones

The genomes of the first two discovered magnetotactic bacteria (MTB) belonging to the ammaproteobacteria, strains BW-2 and SS-51, were sequenced, sealed, annotated and compared to MTB of other phylogenetic groups. Cells of both strains are rod-shaped and biomineralize cuboctahedral and elongated octahedral crystals of magnetite, respectively, that are enveloped in a protein-embedded, lipid-bilayer membrane referred to as the magnetosome membrane or vesicle. The crystals and their associated membranes are known as magnetosomes. Magnetosome crystals consist of either magnetite (Fe3O4) or greigite (Fe3S4) and, because of their specific mineral compositions, crystal morphologies and sizes, the biomineralization processes involved in magnetosome formation …

Role Of Incompatibility Group 1 (Inci1) Plasmid-Encoded Factors On Salmonella Enterica Antimicrobial Resistance And Virulence, Pravin Raghunath Kaldhone

Graduate Theses and Dissertations

Foodborne illnesses are a leading cause of infectious diseases in the world. Among enteric organisms Salmonella is a key pathogen. It’s high prevalence in poultry and other food-animal sources make it imperative to study. Salmonella has the ability to modify its genetic content with help of mobile genetic elements such as plasmids. Incompatibiltiy group 1 (IncI1) plasmids are commonly reported in Salmonella. This study evaluates role on IncI1 plasmids in antimicrobial resistance and virulence in Salmonella. Genetic determinants of resistance and virulence are noted among our IncI1-containing Salmonella isolates. These genetic elements are also transferable and reported to carry respective …

Robust Expression Of Tumor Suppressor Mirna's Let-7 And Mir-195 Detected In Plasma Of Saudi Female Breast Cancer Patients., Amal Qattan, Haya Intabli, Wafa Alkhayal, Chafica Eltabache, Taher Tweigieri, Suad Bin Amer

Biochemistry and Molecular Medicine Faculty Publications

Background

Female breast cancer is frequently diagnosed at a later stage and the leading cause of cancer deaths world-wide. Levels of cell-free circulating microRNAs (miRNAs) can potentially be used as biomarkers to measure disease progression in breast cancer patients in a non-invasive way and are therefore of high clinical value.

Methods

Using quantitative RT-PCR, circulating miRNAs were measured in blood samples collected from disease-free individuals (n = 34), triple-negative breast tumours (TNBC) (n = 36) and luminal tumours (n = 57). In addition to intergroup comparisons, plasma miRNA expression levels of all groups were analyzed against RNASeq …

Role Of Heat Shock Transcription Factor 1 In Ovarian Cancer Epithelial-Mesenchymal Transition And Drug Sensitivity, Chase David Powell

USF Tampa Graduate Theses and Dissertations

The heat shock response (HSR) is a robust cellular reaction to mitigate protein damage from heat and other challenges to the proteome. This protective molecular program in humans is controlled by heat shock transcription factor 1 (HSF1). Activation of HSF1 leads to the induction of an array of cytoprotective genes, many of which code for chaperones. These chaperones, known as heat shock proteins (HSPs), are responsible for maintaining the functional integrity of the proteome. HSPs achieve this by promoting proper folding and assembly of nascent proteins, refolding denatured proteins, and processing for degradation proteins and aggregates which cannot be returned …

The Role Of Sgs1 And Exo1 In The Maintenance Of Genome Stability., Lillian Campos-Doerfler

USF Tampa Graduate Theses and Dissertations

Genome instability is a hallmark of human cancers. Patients with Bloom’s syndrome, a rare chromosome breakage syndrome caused by inactivation of the RecQ helicase BLM, result in phenotypes associated with accelerated aging and develop cancer at a very young age. Patients with Bloom’s syndrome exhibit hyper-recombination, but the role of BLM and increased genomic instability is not fully characterized. Sgs1, the only member of the RecQ family of DNA helicases in Saccharomyces cerevisiae, is known to act both in early and late stages of homology-dependent repair of DNA damage. Exo1, a 5′–3′ exonuclease, first discovered to play a role …

Endonucleolytic Cleavage In The Expansion Segment 7 Of 25s Rrna Is An Early Marker Of Low-Level Oxidative Stress In Yeast, Daniel Shedlovskiy, Jessica A Zinskie, Ethan Gardner, Dimitri G Pestov, Natalia Shcherbik

Rowan-Virtua School of Osteopathic Medicine Departmental Research

The ability to detect and respond to oxidative stress is crucial to the survival of living organisms. In cells, sensing of increased levels of reactive oxygen species (ROS) activates many defensive mechanisms that limit or repair damage to cell components. The ROS-signaling responses necessary for cell survival under oxidative stress conditions remain incompletely understood, especially for the translational machinery. Here, we found that drug treatments or a genetic deficiency in the thioredoxin system that increase levels of endogenous hydrogen peroxide in the yeast Saccharomyces cerevisiae promote site-specific endonucleolytic cleavage in 25S ribosomal RNA (rRNA) adjacent to the c loop of …