Biology Commons^™

Intranuclear Strain Measured By Iterative Warping In Cells Under Mechanical And Osmotic Stress, Jonathan T Henderson

Open Access Dissertations

The nucleus is a membrane bound organelle and regulation center for gene expression in the cell. Mechanical forces transfer to the nucleus directly and indirectly through specific cellular cytoskeletal structures and pathways. There is increasing evidence that the transferred forces to the nucleus orchestrate gene expression activity. Methods to characterize nuclear mechanics typically study isolated cells or cells embedded in 3D gel matrices. Often report only aspect ratio and volume changes, measures that oversimplify the inherent complexity of internal strain patterns. This presents technical challenges to simultaneously observe small scale nuclear mechanics and gene expression levels inside the nuclei of …

Modulation Of Host Phosphatidylinositol Phosphates By Salmonella Effector Protein Sopb, Heather L. Piscatelli

Open Access Dissertations

Salmonella spp. are gram negative bacteria capable of infecting a number of eukaryotic hosts. In humans, Salmonella infection can range anywhere from acute gastroenteritis to typhoid fever which can oftentimes be fatal.Salmonella are facultative intracellular pathogens that have acquired the ability to enter non-phagocytic cells such as those lining the intestinal epithelium. Uptake into epithelial cells is mediated by the Salmonellapathogenicity island 1 (SPI1) encoded type III secretion system (T3SS), a needle-like complex composed of over 20 proteins that translocates effector proteins directly into the host cell cytosol. Salmonella possess a second type III secretion system encoded on …

Associated Behavioral, Genetic, And Gene Expression Variation With Alternative Life History Tactics In Salmonid Fishes, Ashley Chin-Baarstad

Open Access Dissertations

Individual differences in behavior can have potential fitness consequences and often reflect underlying genetic variation. My research focuses on three objectives related to individual level variation: 1) evaluating the innate behavioral variation within and between individuals, families, and progeny of different life-history types across time; 2) testing for differences in gene expression within the brain associated with this behavioral variation; and 3) using genetic polymorphisms to test for associations with ecotype, as well as population structure, in polymorphic populations. First, we evaluated the variation in a suite of ecologically relevant behaviors across time in juvenile progeny produced from crosses within …

Impact Of Mtr4 Structural Domains On Its Enzymatic Activities, In The Regulation Of Nuclear Rna Turnover, Li Yan

Dissertations (1934 -)

RNA processing and turnover plays an important role in RNA maturation, metabolism and quality control, which contribute to gene regulation and cell health. The TRAMP complex, composed of an RNA binding protein Air2p, a poly-A polymerase Trf4p, and a RNA helicase Mtr4p, assist nuclear exosome-dependent RNA processing and degradation in Saccharomyces cerevisiae, like tRNAiMet turnover, 5'ETS degradation and rRNA processing. Mtr4p structure reveals a novel protruding arch domain, which contains the recognizable KOW domain and a stalk domain. Except for the two conserved RecA-like helicase domains, the helicase core contains two other structural domains, a winged helix that connects arch …

Enhanced Expression Of Codon Optimized Mycobacterium Avium Subsp. Paratuberculosis Antigens In Lactobacillus Salivarius, Christopher D. Johnston, John P. Bannatine, Rodney Govender, Lorraine Endersen, Daniel Pletzer, Helge Weingart, Aidan Coffey, Jim O'Mahony, Roy D. Sleator

Department of Biological Sciences Publications

It is well documented that open reading frames containing high GC content show poor expression in A+T rich hosts. Specifically, G+C-rich codon usage is a limiting factor in heterologous expression of Mycobacterium avium subsp. paratuberculosis (MAP) proteins using Lactobacillus salivarius. However, re-engineering opening reading frames through synonymous substitutions can offset codon bias and greatly enhance MAP protein production in this host. In this report, we demonstrate that codon-usage manipulation of MAP2121c can enhance the heterologous expression of the major membrane protein (MMP), analogous to the form in which it is produced natively by MAP bacilli. When heterologously over-expressed, antigenic determinants …

Robust Meta-Analysis Shows That Glioma Transcriptional Subtyping Complements Traditional Approaches, Sanghoon Lee, Stephen Piccolo, Kristina Allen-Brady

Faculty Publications

Background Gliomas traditionally have been sub-classified
based on histopathological observations. However, this ap-
proach is subject to inter-observer variability, and histopatho-
logical features may not reflect the biological mechanisms that
drive tumor growth. High-throughput transcriptional profiling
has shown promise in objectively and reproducibly identify-
ing glioma subtypes. Most prior studies have typically used
only modest sample sizes and have sometimes overlooked
important data-processing steps to ensure sample quality and
to evaluate the robustness of quantitative findings. The pur-
pose of our study was to define robust glioma subtypes by
applying rigorous preprocessing and validation steps to 1,952
microarray samples aggregated …

Serotonergic Signaling Pathways That Suppress Amyloid Beta In Mouse Models Of Ad, Jonathan Robert Fisher

All Theses and Dissertations (ETDs)

A diagnosis of Alzheimer's disease is one of the most devastating things one can hear. This terrible disease robs people of their ability to remember cherished events as their brains become riddled with beta amyloid plaques. Alzheimer's is especially terrifying because there currently are no effective treatments for slowing or stopping the disease. However, recent research has shown that plaque formation is correlated to concentrations of amyloid beta. This discovery suggests that limiting amyloid beta production could potentially halt the disease. One promising avenue for slowing amyloid beta production is serotonergic signaling.

This dissertation presents evidence for a direct sequence …

Electrophoresis Staining: A New Method Of Whole Mount Staining, Mitchell G. Ayers, Sarah Calve, Zhiyu Li

The Summer Undergraduate Research Fellowship (SURF) Symposium

Advances in tissue clearing techniques have allowed almost a ten-fold increase in the viewing depth of confocal microscopy. This allows for intact cellular structures to be rendered in 3D. However, viewing tissues to this depth is often limited to endogenous fluorescence as passive diffusion of antibodies via whole mount staining can take weeks. Our lab is developing a new method involving electrophoresis as a driving force that will promote active antibody binding deep into tissue, reducing the amount of time needed to stain for cellular structures. Due to the inherent charge within antibodies, they are able to be directionally forced …

Strategies To Sensitize Bladder Cancer Cells To Small Molecule Inhibitors Targeting The Pi3k Pathway, Giovanni Nitti

Dissertations and Theses (Open Access)

After many years of cancer research, it is well accepted by the scientific community that the future cure for this disease lies in a personalized therapeutic approach. Anticipating therapeutic outcome based on the genetic signature of a tumor has become the new paradigm. The PI3K pathway represents an ideal target for bladder cancer, as many of the key proteins of this pathway are altered or mutated in this particular type of cancer. Several small molecule inhibitors have been developed to target this pathway, but their efficacy has been shown to be heterogeneous among different cell lines and mostly cytostatic but …

Controlling Pseudomonas Aeruginosa Biofilms And Persister Cells By Manipulating Cell-Cell Signaling, Shuyuan Ma

Theses - ALL

Bacterial cells often form sessile biofilms that are up to 1,000 times more resistant to antimicrobial agents than free-living cells. Meanwhile, bacteria produce a small subpopulation of slow-growing or non-growing persister cells that exhibit high tolerance to antibiotics. Both biofilms and persister cells play important roles in the recalcitrance of chronic infections. Recent studies have shown that bacterial cell-to-cell communication, named quorum sensing (QS), is involved in the biofilm and persister formation.

In this study, we investigated the effects of quorum sensing signals N-(3-oxododecanoyl)-homoserine lactone (3-oxo-C12-HSL) and N-butyryl homoserine lactone (C4-HSL) on isolated Pseudomonas aeruginosa PAO1 and PDO300 persister cells. …

Identification And Characterization Of Msab Gene Involved In Biofilm Formation And Virulence In Staphylococcus Aureus, Amelsaad Elbarasi

Master's Theses

Staphylococcus aureus is an important human pathogen that causes a wide variety of life-threatening infections ranging from minor skin and oral infections to severe infections, such as bacteremia, pneumonia, osteomyelitis, or endocarditis due to the presence and secretion of a large number of virulence factors that are controlled by global virulence regulators in complex networks. Furthermore, S. aureus infections have become a threat to public health because of their high potential to form biofilm, and their ability to resist a wide range of antibiotics has exacerbated further. Therefore, understanding the regulatory networks and developing a drug targeting these networks has …

Role Of Msaa Gene In Regulation Of The Msaabcr Operon And Biofilm Development In Staphylococcus Aureus, Ahmed Alzuway

Master's Theses

Staphylococcus aureus is an important human pathogen that causes wide variety of diseases ranging from chronic biofilm associated infection to acute life threatening infection such as bacteremia, pneumonia, osteomyelitis, or endocarditis, despite the progress with antibiotics used in the treatment of bacterial infections. Furthermore, increased use of prosthetic and indwelling devices in modern medical practices has led to increased infections due to S. aureus. Treating S. aureus infections have become difficult owing to its ability to resist most of the antibiotics; this problem is further exacerbated by ability of MRSA strains to form biofilms. Emergence of community-acquired methicillin resistance …

Metagenomic Identification Of A Novel Salt Tolerance Gene From The Human Gut Microbiome Which Encodes A Membrane Protein With Homology To A Brp/Blh-Family Beta-Carotene 15,15'-Monooxygenase, Eamonn P. Culligan, Roy D. Sleator, Julian R. Marchesi, Colin Hill

Department of Biological Sciences Publications

The human gut microbiome consists of at least 3 million non-redundant genes, 150 times that of the core human genome. Herein, we report the identification and characterisation of a novel stress tolerance gene from the human gut metagenome. The locus, assigned brpA, encodes a membrane protein with homology to a brp/blh-family β-carotene monooxygenase. Cloning and heterologous expression of brpA in Escherichia coli confers a significant salt tolerance phenotype. Furthermore, when cultured in the presence of exogenous β-carotene, cell pellets adopt a red/orange pigmentation indicating the incorporation of carotenoids in the cell membrane.

Key Residues Of Human Cytoplasmic Protein Tyrosine Phosphatase-A And -B For Substrate Binding And Specificity, Byunghyun Park

Open Access Theses

Reversible tyrosine phosphorylation plays an important role in signaling pathways that are essential for regulating cellular growth, differentiation and metabolism. Moreover, several human diseases such as diabetes, obesity and cancers are associated with the deregulation of protein tyrosine phosphatases (PTPs). Several studies provide evidence that PTPs not only contribute to cellular differentiation, but over-expression of these molecules also leads to transformation of non-transfomed cells as well. Based on these results, designing specific PTP inhibitors may ultimately function as potential therapeutic agents to treat various diseases including cancer, diabetes, and autoimmune diseases. EphA2 is a receptor tyrosine kinase which is hypo-phosphorylated …

Manipulating The Tumor Microenvironment For Therapeutic Benefit, Kate M. Bailey

USF Tampa Graduate Theses and Dissertations

The physical tumor microenvironment contributes significantly to carcinogenesis, cancer progression and metastatic dissemination. Two main components of the tumor microenvironment, hypoxia and acidosis, are present in nearly every solid tumor and act as powerful selection forces against the tumor. Hypoxia and acidosis promote tumor heterogeneity and contribute to chemotherapy and radiotherapy resistance. This dissertation interrogates methods to target the tumor microenvironment including two novel studies describing mechanisms of buffer therapy resistance and targeting tumor hypoxia with vasodilators to enhance the efficacy of a hypoxia activated prodrug, TH-302.

In the first study, mechanisms of buffer therapy resistance were identified and detailed. …

Fty720 (Fingolimod) Provides Insight Into The Molecular Mechanisms Of Multiple Sclerosis, Madelyn Elizabeth Crawford

Pursuit - The Journal of Undergraduate Research at The University of Tennessee

Multiple sclerosis (MS) is a neurodegenerative disorder caused by a prolonged immune- mediated inflammatory response that targets myelin. Nearly all of the drugs approved for the treatment of MS are general immunosuppressants or only function in symptom management. The oral medication fingolimod, however, is reported to have direct therapeutic effects on cells of the central nervous system in addition to immunomodulatory functions. Fingolimod is known to interact with sphingosine-1-phosphate (S1P) receptors, and the most widely- accepted theory for its mechanism of action is functional antagonism of the receptor. This review examines significant neuromodulatory effects achieved by functional antagonism of the …

Vitamin A Deficiency Causes Ovulation Abnormalities In Mice, Rebecca Ursin

DePaul Discoveries

Retinoic acid (RA) is an active metabolite of vitamin A (VA) and is involved in tissue organization, patterning, and growth. RA has been shown to regulate male reproduction, however information on its role in ovary development is limited. To investigate the functions of RA in the ovary, we examined its role in ovary development and ovulation using an in vivo dietary VA-deprivation animal model. Our preliminary results have shown that VA deficiency causes a variety of ovarian pathologies, including reduced numbers of total follicles and corpus lutea, formation of hemorrhagic and atretic follicles, and formation of bursa and follicular cysts. …

Identification Of Novel Small Rnas And Characterization Of The 6s Rna Of Coxiella Burnetii, Indu Warrier, Linda D. Hicks, James M. Battisti, Rahul Raghavan, Michael F. Minnick

Biology Faculty Publications and Presentations

Coxiella burnetii, an obligate intracellular bacterial pathogen that causes Q fever, undergoes a biphasic developmental cycle that alternates between a metabolically-active large cell variant (LCV) and a dormant small cell variant (SCV). As such, the bacterium undoubtedly employs complex modes of regulating its lifecycle, metabolism and pathogenesis. Small RNAs (sRNAs) have been shown to play important regulatory roles in controlling metabolism and virulence in several pathogenic bacteria. We hypothesize that sRNAs are involved in regulating growth and development of C. burnetii and its infection of host cells. To address the hypothesis and identify potential sRNAs, we subjected total RNA isolated …

Branching Into Rnai: Synthesis, Characterization And Biology Of Branch And Hyperbranch Sirnas, Anthony Muriithi Maina

Seton Hall University Dissertations and Theses (ETDs)

The cancer epidemic continues to afflict millions of humans world-wide each year and despite a renewed hope with the development of new and improved forms of therapy, a cure for cancer remains an elusive goal. This is partly related to the rise of resilient forms of tumors that have evolved with resistance towards conventional chemotherapy and radiation treatments. Moreover, these non-specific therapeutic regimens are highly toxic, leading to severe immunosuppressive effects which poisons the body and compromises the road towards remission. In an effort to mitigate these limitations, cancer-targeting approaches are currently experiencing a renaissance in the translation of new …

Phenotypic Variation In The Model Organism, Danio Rerio, Rachel D. Champaigne, Kim H. Brown

Student Research Symposium

Model organisms are used to study evolutionary conserved traits. Zebrafish (Danio rerio) are used a model organism because of their highly fecundity, external fertilization, and robust nature, making them highly adaptable to environmental and genetic variation. In an effort to limit data variation that lies outside of topic interest, phenotypic measures of variation must be performed, understood, and taken into consideration for future studies. A common measurement of phenotypic variation in fish is in the maximum (Ucrit) swimming speeds. Inter and intra-strain variation in zebrafish Ucrit swimming speeds will be observed in a swim tunnel. Baseline values will …

Transcriptome Analysis Of Sea Lamprey Embryogenesis, Zakary Ilya Yermolenko

Seton Hall University Dissertations and Theses (ETDs)

The sea lamprey (Petromyzon marinus) has survived throughout evolution for hundreds of millions of years. It is considered an invasive species to the Great Lakes that has caused dramatic changes in the ecosystem for fish communities resulting in the collapse of a fishing industry that was previously valued at billions of dollars. Successful management of the sea lamprey is essential to a sustainable fishing industry and biodiversity. Therefore sea lamprey embryos were studied at various stages of development by growing them in a simulated habitat. RNAs from adult female ovaries and embryos at different time points during embryogenesis …

Progesterone Signaling In Mouse Oocyte Development Via The Pgrmc1 And Pgrmc2 Receptors And The Pairbp1 Protein, Amanda M. Catchings

Renée Crown University Honors Thesis Projects - All

There are thought to be many different causes that can lead to the development of infertility in females. Many of the causes for this condition present themselves before birth, which can predetermine a woman’s fertility capability before she is even born. The complex process of germ cell development possesses possibilities for error and malfunction that can have permanent, lasting effects on a developing fetus. The process of oocyte development is initiated when primordial germ cells migrate to the embryotic gonad and begin dividing mitotically. As mitosis proceeds, the process of cytokinesis does not go to completion, which maintains the cells …

Defining The Sites Of Interaction Of The Fancd2, Fance, And Fancl Proteins, Joseph Mcclanaghan

Senior Honors Projects

Fanconi anemia (FA) is a rare genetic disease characterized by congenital defects, bone marrow failure and increased cancer susceptibility. FA is caused by mutations in any one of 16 genes. These genes encode for proteins that function in the FA-BRCA pathway to repair damaged DNA. Because of its important r­­­ole in DNA repair, this pathway is considered a major cellular tumor suppressor pathway, i.e. is critical for the prevention of cancer. Underscoring this fact, several of the FA genes - including BRCA2, BRIP1, PALB2, and RAD51C - are bona fide breast and ovarian cancer susceptibility genes.

My …

Natural And Exogenous Genome Editing In Wiskott-Aldrich Syndrome Patient Cells, Tamara J. Laskowski

Dissertations and Theses (Open Access)

Wiskott-Aldrich syndrome (WAS) is an X-linked primary immunodeficiency disease characterized by thrombocytopenia, recurrent infections and increased autoimmunity. This disease is caused by mutations in the WAS gene (WAS) which encodes for the WAS protein (WASp), exclusively expressed in hematopoietic cells and required for proper platelet production and lymphoid cell function. Approximately 11% of patients with WAS exhibit a phenomenon called Somatic Revertant Mosaicism which is characterized by the presence of lymphocytes which naturally revert back to normal phenotype by restoring WASp expression. To date, the mechanisms of this naturally-occurring gene therapy remains poorly understood, and the full extent …

The Effect Of Repeated Mild Traumatic Brain Injury On Ventricular Volume And Microglial Activation, Lillian Rose Talbot

Honors Scholar Theses

As the leading cause of death and disability in individuals under the age of 45-years-old, Traumatic Brain Injury (TBI) is a public health crisis that demands the attention of the scientific and medical community [28]. The majority of all TBIs that occur in the United States each year are a non-deadly yet detrimental form of closed brain injury known as mild TBI (mTBI) or concussion [6]. Athletes, young people and military personnel all face a high risk of acquiring mTBI as a result of their environments. In our study we have chosen to model repeated mTBI (rmTBI) in the mouse …

Characterization Of Ftsa-Ftsn Interaction During Escherichia Coli Cell Division, [email protected] K. Busiek

Dissertations and Theses (Open Access)

Division of a bacterial cell into two equal daughter cells requires precise assembly and constriction of the division machinery, or divisome. The Escherichia coli divisome includes nearly a dozen essential cell division proteins that assemble at midcell between segregating sister chromosomes. FtsZ, a homolog of eukaryotic tubulin, is the first essential cell division protein to localize at midcell where it polymerizes into a ring-shaped scaffold (Z ring). Establishment of the Z ring is required for recruitment of downstream cell division proteins including FtsA, a cytoplasmic protein that tethers the Z ring to the inner membrane. Following localization of FtsA and …

P53 Maintains Hepatic Cell Identity During Liver Regeneration, Zeynep Hande Coban Akdemir

Dissertations and Theses (Open Access)

p53 MAINTAINS HEPATIC CELL IDENTITY DURING LIVER REGENERATION

Zeynep Hande Coban Akdemir, B.S.,M.A.

Advisory Professor: Michelle Craig Barton, Ph.D.

p53 is a tumor suppressor that has been well studied in tumor-derived, cultured cells. However, its functions in normal proliferating cells and tissues are generally overlooked. We propose that p53 functions during the G1-S transition can be studied in normal, differentiated cells during surgery-induced liver regeneration. Two-thirds partial hepatectomy (PH) of mouse liver offers a unique model to compare p53 functions in regenerating versus sham (control) cells. My hypothesis is that intersection of global expression analyses (microarray and RNA sequencing) and …

Regulation Of Mammary Gland Development And Tumorigenesis By 14-3-3 Zeta, Sumaiyah Rehman

Dissertations and Theses (Open Access)

Signaling pathways that play critical roles in organ development are often aberrantly regulated during cancer initiation and progression. 14-3-3z is overexpressed in more than 40% of breast cancers and is associated with poor patient prognosis. Therefore, the function of 14-3-3z in cancer and normal mammary gland development was investigated utilizing multiple in vivo and in vitro approaches. 14-3-3z is a chaperone protein that interacts with a multitude of oncogenes and tumor suppressor genes, thereby functioning as a critical node in multiple oncogenic signaling networks. Mammary gland-specific 14-3-3z transgenic mouse models showed that 14-3-3z overexpression was sufficient to induce mammary tumorigenesis. …

Chemical Induced Hypoxia Differentially Affects Gene Expression In Human Neuronal Cells, Natasha V. Pavlichko

Seton Hall University Dissertations and Theses (ETDs)

Previously, our laboratory used desferoxamine (DFO), to generate hypoxic conditions (a low oxygen condition) which decreased human neuronal cell viability, but some cells still survived. These surviving neurons showed no morphological changes when compared to the non-treated group. However, the alteration of several intracellular events were detected, such as an increase of hypoxia inducible factor 1 (HIF-1) mRNA levels, a decrease of human mu opioid receptor (hMOR) message, and no change of human delta opioid receptor (hDOR) receptor message. Western blot analysis showed the Janus kinase (JAK)/ Signal Transducers and Activators of Transcription (STAT) pathway was activated and an increase …

The Grass Shrimp, Palaemonetes, Pugio: Hypoxic Influences On Embryonic Development, Christensen C. Javier

UNLV Theses, Dissertations, Professional Papers, and Capstones

Grass shrimp,Palaemonetes pugio, can survive in brackish waters and estuarine ecosystems despite the frequent oscillations and fluctuations in salinity, temperature and oxygen. AdultP. pugiohave the ability to osmoregulate (Romney and Reiber 2011), change cardiac parameters to tolerate temperatures (not yet published, Mika and Reiber) and oxyregulate (Guadagnoli and Reiber 2013). Manipulation of cardiac parameters allows for these methods of regulation. However, cardiac contraction and internal convection of oxygen do not occur until later stages of embryonic development. Studies focused on these morphological and physiological advantages may provide further understanding of the regulatory mechanisms within grass shrimp embryos, larvae and adults. …