Analysis Of The Role Of Two Autophagy Pathway Related Genes, Becn1 And Tsc1, In Murine Mammary Gland Development And Differentiation,
2014
University of Kentukcky
Analysis Of The Role Of Two Autophagy Pathway Related Genes, Becn1 And Tsc1, In Murine Mammary Gland Development And Differentiation, Amber N. Hale
Theses and Dissertations--Biology
The mammary gland is a dynamic organ that undergoes the majority of its development in the postnatal period in four stages; mature virgin, pregnancy, lactation, and involution. Every stage relies on tightly regulated cellular proliferation, programmed cell death, and tissue remodeling mechanisms. Misregulation of autophagy, an intracellular catabolic process to maintain energy stores, has long been associated with mammary tumorigenesis and other pathologies. We hypothesize that appropriate regulation and execution of autophagy are necessary for proper development of the mammary ductal tree and maintenance of the secretory epithelia during late pregnancy and lactation. To test this hypothesis we examined the …
Calpain 5: A Non-Classical Calpain Highly Expressed In The Cns And Localized To Mitochondria And Nuclear Pml Bodies,
2014
University of Kentucky
Calpain 5: A Non-Classical Calpain Highly Expressed In The Cns And Localized To Mitochondria And Nuclear Pml Bodies, Ranjana Singh
Theses and Dissertations--Neuroscience
Calpain 5 (CAPN5) is a non-classical member of the calpain family. It lacks the EF-hand motif characteristic of the classical calpains, calpain 1 and 2, but retains catalytic and Ca2+ binding non EF domains. Tra-3, an ortholog of CAPN5, is involved in necrotic cell death in C.elegans; although specific role of CAPN5 has not been investigated in the mammalian CNS. I compared relative mRNA levels of calpains in rat CNS, which revealed that CAPN5 is the second most highly expressed calpain. We examined relative levels of CAPN5 from late embryonic day 18 to postnatal day 90 and …
Mechanisms Of Cyclooxygenase-2-Dependent Human Aortic Smooth Muscle Cell Phenotypic Modulation,
2014
University of Kentucky
Mechanisms Of Cyclooxygenase-2-Dependent Human Aortic Smooth Muscle Cell Phenotypic Modulation, Oreoluwa O. Adedoyin
Theses and Dissertations--Pharmacy
Abdominal aortic aneurysm (AAA) is a disease of the aorta characterized by pathological remodeling and progressive weakening of the vessel resulting in the increased risk of rupture and sudden death. In a mouse model of the disease induced by chronic Angiotensin II (AngII) infusion, progression of AAAs is associated with reduced differentiation of smooth muscle cells (SMCs) at the site of lesion development. In the mouse model, the effectiveness of cyclooxygenase-2 (COX-2) inhibition for attenuating AAA progression is associated with maintenance of a differentiated SMC phenotype. However, the safety of COX-2 inhibitors is currently in question due to the increased …
Dephosphorylation Of Iqg1 By Cdc14 Temporally Regulates Actin Ring Formation,
2014
Missouri University of Science and Technology
Dephosphorylation Of Iqg1 By Cdc14 Temporally Regulates Actin Ring Formation, Daniel Patrick Miller
Masters Theses
"Cytokinesis is the final step in cell division when the cell separates the cytoplasm by contracting a ring composed of filamentous actin (F-actin) and type II myosin. Iqg1, an IQGAP family member, is an essential scaffolding protein in budding yeast (S. cerevisiae) required for actin recruitment to, and contraction of, the actomyosin ring. Actin is recruited by the calponin homology domain (CHD) in anaphase after Iqg1 is localized to the bud neck. Consensus sites for the cyclin-dependent kinase (CDK) Cdc28 were identified flanking the CHD. This led us to the hypothesis that phosphorylation of Iqg1 by Cdc28 negatively regulates actin …
Functional Genomic And Proteomic Analysis Of Highly Drug Resistant Chronic Myeloid Leukemia,
2014
University of Texas at El Paso
Functional Genomic And Proteomic Analysis Of Highly Drug Resistant Chronic Myeloid Leukemia, Derrick Matthew Oaxaca
Open Access Theses & Dissertations
Chronic Myeloid Leukemia (CML) has served as a model for how cancer can be selectively targeted with advanced forms of chemotherapies known as kinase inhibitors. Such new therapies have significantly altered the field of oncology and have led to monumental increases in both survival rates and quality of life for cancer patients. However, approximately one-third of CML patients will go on to develop drug resistance against major kinase inhibitors. Along with this, other cancers are showing increased incidences of drug resistance. Understanding how these cancers, such as CML, overcome drug sensitivity is of major importance within the clinic. To predict …
Cxcr2 Macromolecular Complex In Pancreatic Cancer: A Potential Therapeutic Target In Tumor Growth,
2014
Wayne State University
Cxcr2 Macromolecular Complex In Pancreatic Cancer: A Potential Therapeutic Target In Tumor Growth, Shuo Wang
Wayne State University Dissertations
The signaling mediated by the chemokine receptor CXC chemokine receptor 2 (CXCR2) plays an important role in promoting the progression of many cancers, including pancreatic cancer, one of the most lethal human malignancies. CXCR2 possesses a consensus PSD-95/DlgA/ZO-1 (PDZ) motif at its carboxyl termini, which might interact with potential PDZ scaffold/adaptor proteins. We have previously reported that CXCR2 PDZ motif-mediated protein interaction is an important regulator for neutrophil functions. Here, using a series of biochemical assays, we demonstrate that CXCR2 is physically coupled to its downstream effector phospholipase C-β3 (PLC-β3) that is mediated by PDZ scaffold protein Na(+)/H(+) exchange regulatory …
Combating Resistance To Epidermal Growth Factor Recpetor Inhibitors In Triple Negative Breast Cancer,
2014
Wayne State University
Combating Resistance To Epidermal Growth Factor Recpetor Inhibitors In Triple Negative Breast Cancer, Julie Marie Madden
Wayne State University Dissertations
Triple negative breast cancer (TNBC) patients suffer from a highly malignant and aggressive cancer that lacks an effective targeted therapeutic. Although many TNBCs, both in vitro and in vivo, have increased expression of epidermal growth factor receptor (EGFR), EGFR targeted inhibitors, such as gefitinib (GEF), have yet to demonstrate efficacy. Using mass spectrometry to identify pathways that remain activated in the presence of GEF, we found that components of the mTOR signaling pathway remain phosphorylated. While inhibiting mTOR with temsirolimus (TEM) decreased mTOR signaling, EGFR signaling pathways remained activated and the TNBC cell lines continued to proliferate. However, dual treatment …
Regulation Of Inositol Biosynthesis And Cellular Consequences Of Inositol Depletion: Implications For The Mechanism Of Action Of Valproate,
2014
Wayne State University
Regulation Of Inositol Biosynthesis And Cellular Consequences Of Inositol Depletion: Implications For The Mechanism Of Action Of Valproate, Rania M. Deranieh
Wayne State University Dissertations
Inositol is a six-carbon cyclitol that is ubiquitous in biological systems. It is a precursor for the synthesis of numerous biologically important compounds, including inositol phosphates and phosphoinositides that are essential for cell function and viability. Inositol compounds play a role in membrane formation, gene regulation, signaling, regulation of ion channels, and membrane trafficking. Furthermore, inositol regulates hundreds of genes, including those involved in the biosynthesis of inositol and phospholipids. While transcriptional regulation of inositol biosynthesis has been extensively studied and well characterized, regulation of inositol biosynthesis at the enzymatic level has not been addressed. The current study shows that …
Junctional Sarcoplasmic Reticulum Protein Processing And Trafficking In Cardiac Tissue And Primary Cultured Cardiomyocytes,
2014
Wayne State University
Junctional Sarcoplasmic Reticulum Protein Processing And Trafficking In Cardiac Tissue And Primary Cultured Cardiomyocytes, Naama Sleiman
Wayne State University Dissertations
Junctional SR is an important and unique ER subdomain in the adult myocyte that releases Ca2+ through the actions of an exclusive set of resident proteins. Cardiac calsequestrin (CSQ2) undergoes two co-translational modifications: N-linked glycosylation on 316Asn, and phosphorylation by protein kinase CK2 on a cluster of 3 serines in its tail. In the heart, CSQ2 molecules undergo extensive mannose trimming by ER mannosidase(s), a posttranslational process that often regulates protein breakdown. To investigate CSQ2 protein processing in cardiomyopathy models, studies were performed to test whether CSQ2 glycan structures would be altered in heart tissue from mongrel dogs induced into …
The Interactions Between Jak/Stat Signaling Ligands In Drosophila Melanogaster,
2014
University of Kentucky
The Interactions Between Jak/Stat Signaling Ligands In Drosophila Melanogaster, Qian Chen
Theses and Dissertations--Biology
The development of multi-cellular organisms requires extensive cell-cell communication to coordinate cell functions. However, only a handful of signaling pathways have emerged to mediate all the intercellular communications; therefore, each of them is under an array of regulations to achieve signaling specificity and diversity. One such signaling pathway is the Janus Kinase/ Signal Transducer and Activator of Transcription (JAK/STAT) pathway, which is the primary signaling cascade responding to a variety of cytokines and growth factors in mammals and involved in many developmental processes. This signaling pathway is highly conserved between mammals and Drosophila, …
Sphingosine 1-Phosphate Receptor Signaling In Mesenchymal Stromal Cells,
2014
Medical University of South Carolina
Sphingosine 1-Phosphate Receptor Signaling In Mesenchymal Stromal Cells, Sarah Tucker Marrison
MUSC Theses and Dissertations
Mesenchymal stromal cells (MSCs) are a multipotent cell population acquired most prominently from bone marrow with the capacity to differentiate into osteoblasts, chondrocytes, adipocytes, cardiomyoctes, fibroblasts and other cell types. The immunoprivileged nature of these cells combined with their ability to home to sites of injury enhances therapeutic interest in this stem cell population. Phase I‐III clinical trials are being conducted evaluating the therapeutic potential of MSCs in graft vs. host disease, following acute myocardial infarction, multiple sclerosis, and bone and cartilage diseases. Sphingosine 1‐phosphate (S1P) is a biologically active sphingolipid impacting proliferation, apoptosis, inflammation, and angiogenesis. Interactions with 5 …
Structure-Function Analysis Of Zapc, An Ftsz-Ring Stabilizer, In Escherichia Coli Cytokinesis,
2014
CUNY City College
Structure-Function Analysis Of Zapc, An Ftsz-Ring Stabilizer, In Escherichia Coli Cytokinesis, Lukasz Tchorzewski
Dissertations and Theses
In Escherichia coli, cell division is defined by the polymerization and constriction of a cytokinetic ring (Z ring) formed by FtsZ, a tubulin-like GTPase, at midcell. Division also involves the formation of a multi-protein complex at midcell known as the divisome. Several divisome proteins promote the assembly/disassembly processes of FtsZ, thereby exercising spatiotemporal control over division. Among FtsZ regulatory proteins are the FtsZ ringassociated proteins (Zap), which either directly or indirectly stabilize the Z-ring by increasing lateral interactions amongst FtsZ protofilaments in the Z-ring. ZapA-D are recruited during early cytokinesis and have overlapping functions in stabilizing FtsZ at midcell, but …
Isolation And Characterization Of Multipotent Lung Stem Cells From P53 Mutant Mice Models,
2014
Virginia Commonwealth University
Isolation And Characterization Of Multipotent Lung Stem Cells From P53 Mutant Mice Models, Venkat Sundar Gadepalli
Theses and Dissertations
Recent advances in understanding lung biology have shown evidence for the existence of resident lung stem cells. Independent studies in identifying and characterizing these somatic lung stem cells have shown the potential role of these cells in lung repair and regeneration. Understanding the functional characteristics of these tissue resident stem/progenitor cells has gained much importance with increasing evidence of cancer stem cells, cells in a tumor tissue with stem cell characteristics. Lung cancer is most commonly characterized by loss of p53 function which results in uncontrolled cell divisions. Incidence of p53 point mutations is highest in lung cancer, with a …
A Potential Mechanism For Extracellular Matrix Induction Of Breast Cancer Cell Normality,
2014
Old Dominion University
A Potential Mechanism For Extracellular Matrix Induction Of Breast Cancer Cell Normality, Robert D. Bruno, Gilbert H. Smith
School of Medical Diagnostics & Translational Sciences Publications
Extracellular matrix proteins from embryonic mesenchyme have a normalizing effect on cancer cells in vitro and slow tumor growth in vivo. This concept is suggestive of a new method for controlling the growth and spread of existing cancer cells in situ and indicates the possibility that extracellular proteins and/or embryonic mesenchymal fibroblasts may represent a fertile subject for study of new anti-cancer treatments.
Tracing Beta Strands Using Strandtwister From Cryo-Em Density Maps At Medium Resolutions,
2014
Old Dominion University
Tracing Beta Strands Using Strandtwister From Cryo-Em Density Maps At Medium Resolutions, Dong Si, Jing He
Computer Science Faculty Publications
Major secondary structure elements such as α helices and β sheets can be computationally detected from cryoelectron microscopy (cryo-EM) density maps with medium resolutions of 5–10 A˚ . However, a critical piece of information for modeling atomic structures is missing, because there are no tools to detect β strands from cryo-EM maps at medium resolutions. We propose a method, StrandTwister, to detect the traces of β strands through the analysis of twist, an intrinsic nature of a β sheet. StrandTwister has been tested using 100 β sheets simulated at 10 A˚ resolution and 39 β sheets computationally detected from cryo-EM …
A Structure-Function Analysis Of The Arabidopsis Chloroplast Import Protein Attic20,
2014
Wilfrid Laurier University
A Structure-Function Analysis Of The Arabidopsis Chloroplast Import Protein Attic20, James H. Campbell
Theses and Dissertations (Comprehensive)
Arabidopsis thaliana protein Tic20 (atTic20) is a member of the translocon at the inner envelope membrane of chloroplasts. Evidence to date suggests it is part of the main preprotein conducting aperture in the complex, but its exact role is still debated. To help characterize its role, a protocol optimizing yield and purity of recombinantly expressed atTic20 was developed, and a series of experiments was performed to examine its secondary structure and its ability to interact with chloroplast transit peptides. The attempt to increase protein yield was successful, with growth at 20oC in the auto-inducing media ZYP-5052 showing the …
Characterizing Dsrna Production In Virus-Infected Fish Cells,
2014
Wilfrid Laurier University
Characterizing Dsrna Production In Virus-Infected Fish Cells, Amal Brek Aloufi
Theses and Dissertations (Comprehensive)
Viral dsRNA is produced by almost all viruses sometime during their replicative cycle. These viral nucleic acids are potent inducers of both innate and adaptive immune responses, and are therefore considered important immuno-modulators. Previous studies have shown that viruses produce dsRNA when replicating in mammalian cells; however, to date no one has demonstrated viral dsRNA production in virus infected fish cells. Therefore, the goal of this study is to investigate dsRNA production by fish viruses in fish cells, verifying production and performing initial characterization of the dsRNA molecules being produced. Three different rainbow trout cell lines were used in this …
The Establishment Of A Fibroblastic Cell Line From Yellow Perch (Perca Flavescens) And Its Potential Applications In Toxicology,
2014
Wilfrid Laurier University
The Establishment Of A Fibroblastic Cell Line From Yellow Perch (Perca Flavescens) And Its Potential Applications In Toxicology, Katelin W. Spiteri
Theses and Dissertations (Comprehensive)
This thesis describes the establishment, characterization and potential toxicological applications of YPF5, a yellow perch cell line. YPF5 is a fibroblastic cell line derived from the caudal fin of yellow perch. This cell line has been maintained for over 2 years. Cultures have been passaged over 60 times, and successfully cryopreserved and thawed. YPF5 is grown at room temperature in Leibovitz-15 (L-15) media, supplemented with 10% fetal bovine serum and 3% penicillin-streptomycin. The origin of YPF5 has been confirmed as Perca flavescens through “DNA Barcoding” and reaffirmed through Karyotyping (2n = 48) as per literature reported karyology for percidae including …
The Innate Antiviral Effects Of Extracellular Viral Dsrna In Rainbow Trout Cells,
2014
Wilfrid Laurier University
The Innate Antiviral Effects Of Extracellular Viral Dsrna In Rainbow Trout Cells, Sarah J. Poynter
Theses and Dissertations (Comprehensive)
Viral double-stranded RNA (dsRNA) molecules are a potent pathogen-associated molecular pattern and play a crucial role in the innate immune response. During a viral infection, extracellular and intracellular dsRNA can initiate pathways resulting in the production of type I interferons (IFNs) and interferon-stimulated genes (ISGs). The accumulation of ISGs within a cell results in a protective antiviral state. This study used both commercially available dsRNA (poly I:C) and in vitro transcribed dsRNA molecules, based on the viral hemorrhagic septicemia virus (VHSV) genome sequence, as stimuli to investigate the effects of these molecules on the innate immune response in rainbow trout …
Partitioning The Fitness Components Of Rna Populations Evolving In Vitro,
2013
Portland State University
Partitioning The Fitness Components Of Rna Populations Evolving In Vitro, Carolina Diaz Arenas, Niles Lehman
Chemistry Faculty Publications and Presentations
All individuals in an evolving population compete for resources, and their performance is measured by a fitness metric. The performance of the individuals is relative to their abilities and to the biotic surroundings – the conditions under which they are competing – and involves many components. Molecules evolving in a test tube can also face complex environments and dynamics, and their fitnessmeasurements should reflect the complexity of various contributing factors as well. Here, the fitnesses of a set of ligase ribozymes evolved by the continuous in vitroevolution system were measured. During these evolution cycles there are three different catalytic …
