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Full-Text Articles in Cell Biology

Traf2 Phosphorylation Regulates Cd40 Signaling To Facilitate B-Cell Lymphoma Progression, Lauren Michelle Workman Dec 2014

Traf2 Phosphorylation Regulates Cd40 Signaling To Facilitate B-Cell Lymphoma Progression, Lauren Michelle Workman

Theses and Dissertations

CD40 is a TNF-Receptor (TNFR) superfamily member that functions to promote several facets of the humoral immune response--including B cell proliferation, differentiation, antibody isotype switching, and cytokine expression. TNFR superfamily members lack intrinsic kinase activity and must recruit members of the TNFR-associated factor (TRAF) family of adaptor proteins to connect the receptor to intracellular signaling pathways. CD40-mediated JNK and NF-κB activation is critical for an intact humoral immune response; however, the precise mechanisms governing the spatiotemporal activation of these pathways are not completely understood.

In this study we report that CD40 ligation results in the dual phosphorylation of TRAF2 on ...


The Role Of Neuronal Mtorc1 Signaling In The Regulation Of Physiological Processes, Kenjiro Muta Dec 2014

The Role Of Neuronal Mtorc1 Signaling In The Regulation Of Physiological Processes, Kenjiro Muta

Theses and Dissertations

The mammalian target of rapamycin complex 1 (mTORC1) is an evolutionary conserved serine/threonine kinase regulating diverse cellular functions, including cell growth, protein synthesis and sensing nutrients and energy status. Prior studies have identified the involvement of hypothalamic mTORC1 in the control of energy balance, renal sympathetic activation and blood pressure regulation.

Hypothalamic insulin receptor signaling through the phosphatidylinositol 3-kinase (PI3K) is known to regulate energy homeostasis and sympathetic nerve activity (SNA). We examined the role of hypothalamic mTORC1 in the anorectic and sympathetic effects of central insulin. mTORC1 inhibition by rapamycin or PI3K mutation resulted in blunted regional SNA ...


Molecular And Cellular Basis Of Hematopoietic Stem Cells Maintenance And Differentiation, Khanh Linh Duong Dec 2014

Molecular And Cellular Basis Of Hematopoietic Stem Cells Maintenance And Differentiation, Khanh Linh Duong

Theses and Dissertations

The blood system consists of two main lineages: myeloid and lymphoid. The myeloid system consists of cells that are part of the innate immune response while the lymphoid system consist of cells that are part of humoral response. These responses protect our bodies from foreign pathogens. Thus, malignancies in these systems often cause complications and mortality. Scientists world wide have been researching alternatives to treat hematologic disorders and have explored induced pluripotent stem cells (iPSCs) and the conversion of one cell type to another.

First, iPS cells were generated by overexpression of four transcription factors: Oct4, Sox2, Klf4 an cMyc ...


Manipulation Of The Innate Immune Response And Evasion Of Macrophage Host Defense Mechanisms By Francisella Tularensis, Matthew Eugene Long Dec 2014

Manipulation Of The Innate Immune Response And Evasion Of Macrophage Host Defense Mechanisms By Francisella Tularensis, Matthew Eugene Long

Theses and Dissertations

Tularemia is a potentially fatally illness caused by the facultative intracellular Gram-negative bacterium Francisella tularensis. Virulent strains of F. tularensis can cause a fatal disease after inhalation of a few as ten organisms. Due to the highly pathogenic features of Francisella, it has been designated as a Tier 1 select agent, meaning that its possession and handling is highly restricted. Macrophages are phagocytes that play a central role in the innate immune response to infection that can be used by certain pathogens, including Francisella, as a niche for bacterial replication and dissemination during infection. After infection of macrophages Francisella escapes ...


The Role Of Aim2 And Nlrp12 In The Innate Immune Response To Francisella Tularensis, Tyler Kent Ulland Dec 2014

The Role Of Aim2 And Nlrp12 In The Innate Immune Response To Francisella Tularensis, Tyler Kent Ulland

Theses and Dissertations

The innate immune response to pathogens by the host is dependent upon the interplay of both pathogen and host intrinsic factors. Nucleotide-binding domain leucine-rich repeat containing (NLR) and pyrin and HIN200 domain containing (PYHIN) proteins are intracellular sensors of damage-associated and pathogen-associated molecular patterns. The studies presented here focus on the PYHIN molecule, AIM2, and the NLR, NLRP12, and the importance of bacteria- and host-associated proteins in the coordination of the innate immune response to the Gram-negative pathogen Fracisella tularensis. We have found that several genes expressed by F. tularensis encode for proteins that, when disrupted, cause the bacteria to ...


Investigation Of Nuclear And Cytoplasmic Functions Of The Dlipin Protein Of Drosophila Melanogaster, Qiuyu Chen Dec 2014

Investigation Of Nuclear And Cytoplasmic Functions Of The Dlipin Protein Of Drosophila Melanogaster, Qiuyu Chen

Theses and Dissertations

Lipin family proteins are highly conserved proteins present in species ranging from mammals to yeast. Lipin 1, the first Lipin gene identified in fatty liver dystrophy (fld) mutant mice, encodes the bifunctional protein Lipin 1, which can serve as an Mg2+-dependent phosphatidic acid phosphatase (PAP) and transcriptional co-regulator. dLipin, the single Lipin ortholog of Drosophila melanogaster, is required in triglyceride synthesis and fat body development. To study the transcriptional co-regulator activity of dLipin, nuclear receptors were screened to find receptors that interact with dLipin. The genetic interaction data indicated that Drosophila hepatic nuclear receptor 4 (HNF4) was a promising ...


Genetic Analysis Of Ton2 Dependent Processes In Microtubule Organization In Arabidopsis Thaliana, Samantha Nicole Atkinson Oct 2014

Genetic Analysis Of Ton2 Dependent Processes In Microtubule Organization In Arabidopsis Thaliana, Samantha Nicole Atkinson

Theses and Dissertations

Microtubules carry out many functions within the cell. They're used during mitosis and meiosis to move chromosomes to opposite sides of the cell so that cell division can occur. They're also used as structural support for the cell and are involved in establishing the cell shape. Microtubules are also able to reorient from a longitudinal orientation to a transverse orientation in response to gibberellic acid and auxin (two hormones that are involved in cell elongation). The mechanism for how this reorientation occurs is unknown. The TONNEAU2 (TON2) protein is necessary for proper microtubule organization. We looked at how ...


Use Of Photobiomodulation In Osteoclast Formation: Possible Intervention For The Treatment Of Osteoporosis, Lisa Lauren Anderson-Antle Aug 2014

Use Of Photobiomodulation In Osteoclast Formation: Possible Intervention For The Treatment Of Osteoporosis, Lisa Lauren Anderson-Antle

Theses and Dissertations

After critically examining the literature to gain a robust understanding for the pathogenesis of bone loss, specifically osteoporosis, the development of a possible new intervention to prevent or treat osteoporosis was explored. The purpose of this dissertation was to pilot test a new protocol designed to answer the broad research question: Does Near-Infrared Light Emitting Diode (NIR-LED) treatment affect Receptor Activator of Nuclear Factor Kappa-B Ligand (RANKL) induced osteoclastogenesis in a cell culture model?

Osteoporosis is defined as a disease characterized by low bone mass and structural deterioration of bone tissue, leading to bone fragility and an increased susceptibility to ...


Development Of Peripheral Innervation In The Frog Xenopus Laevis, Mitali A. Gandhi Aug 2014

Development Of Peripheral Innervation In The Frog Xenopus Laevis, Mitali A. Gandhi

Theses and Dissertations

The skin in Xenopus laevis is innervated by two different sets of mechanosensory neurons at different times during development. Rohon Beard (RB) neurons start differentiating during gastrulation, innervate the embryonic skin and mediate sensory function during hatching. Dorsal Root Ganglion (DRG) neurons start differentiating after neural crest migration, innervate adult epidermal targets and mediate mechanosensory function during larval and adult stages and eventually replace RB neurons. The change in sensory neurons occurs during the transformation of skin, sensory structures, and behavior from their embryonic to their larval forms. We hypothesized that developmental changes in either the sensory end organs or ...


Th17 Cell-Associated Response To Borrelia Burgdorferi Outer Surface Protein A, Megan Elizabeth Johnson Aug 2014

Th17 Cell-Associated Response To Borrelia Burgdorferi Outer Surface Protein A, Megan Elizabeth Johnson

Theses and Dissertations

Arthritis is a common symptom of Lyme disease, a debilitating condition resulting from infection with Borrelia burgdorferi. A protein found on the surface of B. burgdorferi, outer surface protein A (OspA), is known to elicit an inflammatory immune response involving T helper cells. T helper 17 (Th17) cells are associated with the inflammatory cytokines interleukin-17 (IL-17) and interleukin-23 (IL-23) and have been implicated in the development of Lyme arthritis. The objective of this thesis is to provide further characterization of the immune response to B. burgdorferi OspA. The central hypothesis of this thesis is: Vaccination with OspA will predispose mice ...


Zebrafish As A Model For Determining The Mechanisms Causing Deafness In Myh9-Related Disease, Luke David Spychalla Aug 2014

Zebrafish As A Model For Determining The Mechanisms Causing Deafness In Myh9-Related Disease, Luke David Spychalla

Theses and Dissertations

Approximately 1 in 500 infants are diagnosed with hearing loss, and about half of these cases can be traced to genetic defects. Several hundred genes have been implicated in deafness, including MYH9, which codes for the conventional motor protein non-muscle myosin IIA (NMIIA). Mutations in MYH9 lead to syndromic MYH9-related diseases, which include deafness as a variable symptom, as well as non-syndromic autosomal deafness DFNA17. Despite its identification as a deafness gene, the functions of MYH9 in ear development and hearing remain unknown. To study this role, we will use zebrafish as a model. Zebrafish offer significant advantages including established ...


Construction Of 3d Biomimetic Tissue Niches For Directing Pancreatic Lineage Differentiation Of Human Embryonic Stem Cells, Weiwei Wang Aug 2014

Construction Of 3d Biomimetic Tissue Niches For Directing Pancreatic Lineage Differentiation Of Human Embryonic Stem Cells, Weiwei Wang

Theses and Dissertations

The potential of human embryonic stem cells (hESCs) to differentiate into insulin producing beta cells offers great hope for cell-based therapy for diabetes treatment. However, in vitro pancreatic differentiation of hESCs remains challenging. In the past decade, most protocols for differentiating pancreatic cells have been focused on the use of signaling molecule cocktails on 2D substrates. Studies on embryonic development biology strongly suggest that extracellular matrix (ECM) plays a critical role on hESCs behavior. In this work, we first established a 3D collagen scaffold culture system for hESCs differentiating into definitive endoderm (DE), which is the first and most important ...


Impedance Biosensors For The Rapid Detection Of Viral And Bacterial Pathogens Using Avian Influenza Virus Subtypes H5n1 And H7n2 And Escherichia Coli O157:H7 As Model Targets, Jacob David Lum Aug 2014

Impedance Biosensors For The Rapid Detection Of Viral And Bacterial Pathogens Using Avian Influenza Virus Subtypes H5n1 And H7n2 And Escherichia Coli O157:H7 As Model Targets, Jacob David Lum

Theses and Dissertations

This research investigated impedance biosensors for the rapid detection of viral and bacterial pathogens using avian influenza virus (AIV) subtypes H5N1 and H7N2 and Escherichia coli O157:H7 as the model targets, which were chosen due to their impact on the agricultural and food industries. For the detection of AIV H7N2, a single stranded DNA aptamer was selected using systematic evolution of ligands by exponential enrichment (SELEX). The selected aptamer and a previously selected aptamer against AIV H5N1 were used in a microfluidics chip with an embedded interdigitated array microelectrode to fabricate an impedance biosensor for specific detection of AIV ...


Regulation Of Protein Trafficking By Ral Gtpases And Exocyst In Epithelial Cells, Yu-Tsan Liu Jul 2014

Regulation Of Protein Trafficking By Ral Gtpases And Exocyst In Epithelial Cells, Yu-Tsan Liu

Theses and Dissertations

In polarized epithelial cells, vectorial protein trafficking is important for transporting specific membrane proteins to generate distinct apical and basolateral membrane protein compositions. The Exocyst is a conserved hetero-octameric protein complex, which regulates different aspects of protein trafficking, including tethering of the Golgi-derived vesicles to target membranes. Two of the Exocyst subunits, Sec5 and Exo84, competitively bind to the small GTPases, RalA and RalB, in a GTP-dependent manner. Although Ral GTPases have been proposed to mediate assembly of Exocyst holocomplexes, we hypothesize that they actually serve to allosterically regulate Exocyst functions by promoting association or disassociation of additional factors. Previous ...


Prostaglandin Signaling Temporally Regulates Actin Cytoskeletal Remodeling During Drosophila Oogenesis, Andrew James Spracklen Jul 2014

Prostaglandin Signaling Temporally Regulates Actin Cytoskeletal Remodeling During Drosophila Oogenesis, Andrew James Spracklen

Theses and Dissertations

Prostaglandins (PGs) are small, lipid signaling molecules produced downstream of cyclooxygenase (COX) enzymes. PG signaling regulates many processes including pain, inflammation, fertility, cardiovascular function and disease, and cancer. One mechanism by which PG signaling exerts its function is by regulating the dynamics of the actin cytoskeleton; however, the exact mechanisms remain largely undefined.

Drosophila oogenesis provides an ideal system to determine how PG signaling regulates the actin cytoskeleton. Drosophila follicles, or eggs, pass through 14 well- characterized, morphologically defined stages of development. Each developing follicle is comprised of 16 interconnected germline-derived cells (15 nurse cells and 1 oocyte) that are ...


Intrinsic And Extrinsic Regulation Of Dna Methylation During Malignant Transformation, Bo-Kuan Wu Jul 2014

Intrinsic And Extrinsic Regulation Of Dna Methylation During Malignant Transformation, Bo-Kuan Wu

Theses and Dissertations

Cytosine methylation of CpG dinucleotides is an epigenetic modification that cells use to regulate gene expression, largely to promote transcriptional silencing. Focal hypermethylation of tumor suppressor genes (TSGs) accompanied by genomic hypomethylation are epigenetic hallmarks of malignancy. DNA methyltransferase 1 (DNMT1) is the principle vertebrate enzyme responsible for maintenance of DNA methylation and its dysregulation has been found to lead to aberrant methylation in cancer. In addition, recent findings demonstrated that the ten-eleven translocation 1 (TET1) protein functions as a 5-methylcytosine dioxygenase that converts 5-methylcytosine (5mC) bases to 5-hydroxymethylcytosine (5hmC) to mediate active DNA demethylation. Emerging evidence suggests that TET1 ...


Use Of Zebrafish To Test Candidate Genes And Mutations Associated With Structural Birth Defects, Primarily In Cleft Lip And Palate, Tiffany Lynn Smith May 2014

Use Of Zebrafish To Test Candidate Genes And Mutations Associated With Structural Birth Defects, Primarily In Cleft Lip And Palate, Tiffany Lynn Smith

Theses and Dissertations

Cleft lip and/or palate (CL/P) is a group of congenital birth defect caused by the failure of the lip and/or palate to properly fuse during facial development. This defect occurs in approximately 1:700 live births and is the most second most common developmental defect. Twin studies and evaluation of family history reveals that risk for CL/P is influenced by genetics. However, to date less than half of the heritable risk for CL/P has been ascribed to specific genes.

To identify new genes involved in CL/P, our colleagues, Dr. Manak and Dr. Murray, screened ...


Oncomorphic Tp53 Mutations In Advanced Serous Ovarian Carcinomas, Pavla Brachova May 2014

Oncomorphic Tp53 Mutations In Advanced Serous Ovarian Carcinomas, Pavla Brachova

Theses and Dissertations

The tumor suppressor gene TP53 sits at the crux of response to cellular stresses. This is the most frequently inactivated gene in human tumors, being the target of somatic mutations. The protein product of TP53 is p53, and plays a crucial role in anti-proliferative signals through the induction of apoptosis, senescence, and cell-cycle arrest when activated by stresses such as genotoxic chemotherapeutic drugs. Therefore, the status of TP53 mutation in a tumor has profound implications for the tumorigenic potential as well as the response to anti-cancer therapies. Indeed, numerous studies have shown a predictive and prognostic value of TP53 mutations ...


Neutrophil Priming And Host Inflammation: The Roles Of Nox2 And Toll-Like Receptors, Laura Christine Whitmore May 2014

Neutrophil Priming And Host Inflammation: The Roles Of Nox2 And Toll-Like Receptors, Laura Christine Whitmore

Theses and Dissertations

Neutrophils, essential innate immune cells, recognize danger signals through receptors on their surface. Upon receptor ligation, neutrophils may undergo priming, a process involving limited reactive oxygen species (ROS) generation and partial degranulation. Priming facilitates neutrophil migration and prepares the cell for an enhanced response to a secondary stimulus, including a spike in ROS generation by NADPH oxidase 2 (NOX2). It is well established that NOX2-derived oxidants are involved in pathogen killing and that off-target effects can cause host tissue damage; however, several lines of recent evidence also support an anti-inflammatory function for NOX2 oxidants. First, patients with chronic granulomatous disease ...


Characterization Of Mir-888 Expression And Regulation In Endometrial Cancer, Adriann Marie Hovey May 2014

Characterization Of Mir-888 Expression And Regulation In Endometrial Cancer, Adriann Marie Hovey

Theses and Dissertations

Endometrial cancer is the fourth most common cancer in women and the most common gynecological malignancy. While patient outcome has improved for the majority of cancers, the outlook for endometrial cancer has steadily decreased. In order to address this problem, we must better understand the different mechanisms involved in endometrial cancer development and progression. To this end, we quantified expression of 667 miRNAs in four endometrioid adenocarcinoma and four serous adenocarcinoma using Taqman Low Density Arrays (TLDAs). miR-888 was one of the most highly overexpressed miRNAs in both endometrial cancer subtypes. Analysis of miR-888 expression across multiple cancer types using ...


Investigation Of Rice Bran Derived Anti-Cancer Pentapeptide For Mechanistic Potency In Breast Cancer Cell Models, Ruiqi Li May 2014

Investigation Of Rice Bran Derived Anti-Cancer Pentapeptide For Mechanistic Potency In Breast Cancer Cell Models, Ruiqi Li

Theses and Dissertations

Bioactive peptides derived from food sources with anti-proliferative properties against cancer have drawn more attention in recent years. A pentapeptide derived from rice bran has shown anti-proliferative propertiesagainst human breast cancer cells. The objective of this study was to investigate the mechanistic action of the pentapeptide-induced apoptosis in breast cancer cell models (MCF-7 and MDA-MB-231). The growth inhibition activity of the pentapeptide was

evaluated by MTS[3-(4,5-dimethylthiazol-2-yl)-5-(3- arboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt] assayand trypan blue assay in a dose- and time-dependent manner.

The apoptotic properties of pentapeptide-induced apoptosis on cancerous breast cells were evaluated by ...


The Effect Of Lactic Acid On Mast Cell Function, Andrew J. Spence Jan 2014

The Effect Of Lactic Acid On Mast Cell Function, Andrew J. Spence

Theses and Dissertations

This study shows for the first time the effect that L-(+)-lactic acid has on mast cell activation. Lactic acid is a byproduct of anaerobic glycolysis and is associated with inflammatory environments such as wounds, tumors and, asthma. In this study, pre-treatment with lactic acid altered cytokine production by bone marrow-derived mast cells (BMMC). Specifically, lactic acid enhanced cytokine secretion following IgE cross-linking, but decreased IL-33 mediated cytokine production. These effects were altered by genetic background, since C57BL/6 mast cells demonstrated the aforementioned result, but lactic acid had no effect on IgE-mediated cytokine production in 129/SvJ mast cells ...