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2014

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Articles 301 - 330 of 359

Full-Text Articles in Cell Biology

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 ...


A Chemical-Genetic Screen For Identifying Substrates Of The Er Kinase Perk, Nancy L. Maas Jan 2014

A Chemical-Genetic Screen For Identifying Substrates Of The Er Kinase Perk, Nancy L. Maas

Publicly Accessible Penn Dissertations

Cells constantly encounter changing environments that challenge the ability to adapt

and survive. Signal transduction networks enable cells to appropriately sense and respond

to these changes, and are often mediated through the activity of protein kinases. Protein

kinases are a class of enzyme responsible for regulating a broad spectrum of cellular

functions by transferring phosphate groups from ATP to substrate proteins, thereby

altering substrate activity and function. PERK is a resident kinase of the endoplasmic

reticulum, and is responsible for sensing perturbations in the protein folding capacity of

the ER. When the influx of unfolded, nascent proteins exceeds the folding ...


Ebna1-Specific T Cell Responses During Persistent Rhesus Lcv Infection And The Development Of A Novel Therapeutic Prototype Vaccine For Ebv-Associated Diseases, Rachel Mandy Leskowitz Jan 2014

Ebna1-Specific T Cell Responses During Persistent Rhesus Lcv Infection And The Development Of A Novel Therapeutic Prototype Vaccine For Ebv-Associated Diseases, Rachel Mandy Leskowitz

Publicly Accessible Penn Dissertations

The impact of EBV on human health is substantial, but vaccines that prevent primary EBV infections or treat EBV-associated diseases are not yet available. The Epstein-Barr nuclear antigen 1 (EBNA1) is an important target for vaccination because it is the only protein expressed in all forms of latency and in all EBV-associated malignancies. The overarching goal throughout this dissertation was to determine if EBNA1 is a suitable target for vaccine development. This was addressed in two ways. First, because an improved understanding of EBNA1-specific T cell responses benefits EBV vaccine development, we characterized responses against EBNA1 of the EBV-homologous rhesus ...


Opposing Actin Networks Modulate The Mechano-Activation Of The Integrin Lfa-1 During Immunological Synapse Formation, William Andrew Comrie Jan 2014

Opposing Actin Networks Modulate The Mechano-Activation Of The Integrin Lfa-1 During Immunological Synapse Formation, William Andrew Comrie

Publicly Accessible Penn Dissertations

Formation of a functional immune response requires the regulated transfer of information between T cells, and APCs, which leads to a variety of functional outcomes. In many cases this information transfer occurs at a regulated area of cell - cell contact termed the immunological synapse (IS). In T cells responding to APCs there is a robust accumulation of F-actin on the T cell side of the synapse. This F-actin response is characterized by robust polymerization at the periphery of the contact site followed by centripetal flow of the network towards the center of the IS. While it is well known that ...


Proliferation And Survival Mechanisms In Soft Tissue Sarcoma And Glioblastoma Tumors, Vera Mucaj Jan 2014

Proliferation And Survival Mechanisms In Soft Tissue Sarcoma And Glioblastoma Tumors, Vera Mucaj

Publicly Accessible Penn Dissertations

Soft tissue sarcomas and glioblastomas are two deadly tumors that are characterized by aggressive overproliferation, and regions of severe intratumoral nutrient and oxygen deprivation. The mechanisms by which tumors evade proliferation control signals and survive in a hostile microenvironment are active areas of investigation. This work describes two projects investigating loss of proliferation control in soft tissue sarcoma, as a result of Hippo pathway deregulation, and mechanisms of survival under stress in glioblastoma, as a result of decreased microRNA-124 (miR-124) levels. First, we demonstrate that the Hippo pathway is deregulated in soft tissue sarcoma patient samples, leading to overexpression of ...


Roles Of Tnfaip8 Protein In Cell Death, Listeriosis, And Colitis, Thomas Porturas Jan 2014

Roles Of Tnfaip8 Protein In Cell Death, Listeriosis, And Colitis, Thomas Porturas

Publicly Accessible Penn Dissertations

TNF-alpha-induced protein 8 (TNFAIP8 or TIPE) is a newly described regulator of cancer and infection. However, its precise roles and mechanisms of actions are not well understood. Here I report the generation of TNFAIP8 knockout mice and describe their increased responsiveness to colonic inflammation and resistance to lethal Listeria monocytogenes infection. TNFAIP8 knockout mice were generated by germ line gene targeting and were born without noticeable developmental abnormalities. Their major organs including those of the immune and digestive systems were macroscopically and microscopically normal. However, compared to wild type mice, TNFAIP8 knockout mice exhibited significant differences in the development of ...


The Role Of Trim58 In Erythropoiesis, Christopher Stephen Thom Jan 2014

The Role Of Trim58 In Erythropoiesis, Christopher Stephen Thom

Publicly Accessible Penn Dissertations

Red blood cells (erythrocytes) deliver oxygen to all tissues of the body. Defects in red blood cell production (erythropoiesis) can cause disease. Mammalian erythropoiesis culminates in enucleation, an incompletely understood process that entails the physical separation of the nucleus and cytoplasm. The work in this thesis investigated the role of a previously uncharacterized protein named Trim58 in erythropoiesis.

Human genetic studies suggested that TRIM58 played an important role in erythroid development. In humans and mice, Trim58 expression was found to be restricted to red blood cell precursors during late stage maturation. In fact, murine Trim58 was upregulated just prior to ...


Hypoxia Inducible Factors In Cancer And Inflammation, Jessica Elizabeth Stewart Shay Jan 2014

Hypoxia Inducible Factors In Cancer And Inflammation, Jessica Elizabeth Stewart Shay

Publicly Accessible Penn Dissertations

Hypoxia-inducible factors (HIFs) mediate adaptation to low O2, or hypoxia, are important at every stage of tumor initiation, and impact the progression of a variety of diseases, including colorectal cancer. This body of work investigates the role of hypoxia and HIF-mediated signaling in both tumor cells and macrophages across the natural history of inflammation-induced cancers. First, the effect of HIF inhibition in tumor parenchyma and stroma in extant colitis-associated colon carcinomas (CAC) is investigated using acriflavine (ACF), a naturally occurring compound known to repress HIF transcriptional activity. Pharmacologic HIF inhibition represents a novel therapeutic strategy for cancer treatment and data ...


Identification Of Molecular Mechanisms Underlying The Development Of Barrett's Esophagus, Maria Eugenia Vega Jan 2014

Identification Of Molecular Mechanisms Underlying The Development Of Barrett's Esophagus, Maria Eugenia Vega

Publicly Accessible Penn Dissertations

Esophageal cancer is one of the deadliest cancers in the U.S and worldwide. Esophageal cancer is characterized by two subtypes: esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC). One of the major risk factors for the development of EAC is Barrett's esophagus (BE). BE is defined as incomplete intestinal metaplasia characterized by the presence of columnar and goblet cells in the formerly stratified squamous epithelium of the esophagus. Currently, the cell of origin for human BE has yet to identified. Using an innovative 3D organotypic culture system, we explored the role of inhibition of Notch signaling promotion ...


Microtubule Motors Drive Nuclear Dynamics And Positioning In Developing Skeletal Muscle Cells, Meredith Hayley Wilson Jan 2014

Microtubule Motors Drive Nuclear Dynamics And Positioning In Developing Skeletal Muscle Cells, Meredith Hayley Wilson

Publicly Accessible Penn Dissertations

Dynamic interactions with the cytoskeleton are essential to move and anchor nuclei during tissue development, and defects resulting in nuclear mispositioning are often associated with human disease, such as muscular dystrophy and myopathy. Skeletal muscle cells are large syncytia formed by fusion of myoblasts, and contain hundreds of nuclei positioned regularly along the length the cell. During muscle cell development, nuclear movement in myotubes requires microtubules, but the mechanisms involved have not been elucidated. Here, we find that nuclei actively translocate through myotubes. As they translocate, they also rotate in three-dimensions. These movements require an intact microtubule cytoskeleton, which forms ...


Mutual Reinforcement Between Telomere Capping And Canonical Wnt Pathway Activity In The Intestinal Stem Cell Niche, Ting-Lin Yang Jan 2014

Mutual Reinforcement Between Telomere Capping And Canonical Wnt Pathway Activity In The Intestinal Stem Cell Niche, Ting-Lin Yang

Publicly Accessible Penn Dissertations

Mice lacking telomerase (e.g. mTR-/-) for several generations develop dysfunctional telomeres and severe gastrointestinal pathology. Intestinal stem cell (ISC) abnormalities in late-generation mTR mice have been described, and we set out to characterize it in more detail. Expression profiling of mTR-/- crypts and an unbiased gene set enrichment analysis revealed broadly decreased expression of Wnt pathway genes in crypt epithelia and underlying stroma. We describe abnormalities in the Wnt-dependent intestinal stem cell (ISC) niche in these mice, including decreased expression of ISC marker genes Ascl2, Lgr5, and Sox9. The importance of these changes was revealed by rescue of crypt ...


T Cells Bearing A Chimeric Antigen Receptor Against The Tumor Vasculature Destroy The Tumor Endothelium And Result In Tumor Regression, Stephen Santoro Jan 2014

T Cells Bearing A Chimeric Antigen Receptor Against The Tumor Vasculature Destroy The Tumor Endothelium And Result In Tumor Regression, Stephen Santoro

Publicly Accessible Penn Dissertations

Aberrant blood vessels enable tumor growth, provide a barrier to immune infiltration, and serve as a source of pro-tumorigenic signals. Targeting tumor blood vessels for destruction, or tumor vascular disruption therapy, can therefore provide significant therapeutic benefit. Here I describe the development of two chimeric antigen receptors (CAR)s against the tumor vasculature, targeting either tumor endothelial marker 1 (TEM1) or prostate-specific membrane antigen (PSMA). CAR T cells incorporating scFv78, an scFv isolated against TEM1, were able to recognize immobilized plate-bound TEM1 protein, but were unable to recognize TEM1 on the surface of endothelial cell targets. In contrast, anti-PSMA CAR ...


Computational Modeling Of Allosteric Regulation In The Hsp90 Chaperones: A Statistical Ensemble Analysis Of Protein Structure Networks And Allosteric Communications, Kristin Blacklock, Gennady M. Verkhivker Jan 2014

Computational Modeling Of Allosteric Regulation In The Hsp90 Chaperones: A Statistical Ensemble Analysis Of Protein Structure Networks And Allosteric Communications, Kristin Blacklock, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

A fundamental role of the Hsp90 chaperone in regulating functional activity of diverse protein clients is essential for the integrity of signaling networks. In this work we have combined biophysical simulations of the Hsp90 crystal structures with the protein structure network analysis to characterize the statistical ensemble of allosteric interaction networks and communication pathways in the Hsp90 chaperones. We have found that principal structurally stable communities could be preserved during dynamic changes in the conformational ensemble. The dominant contribution of the inter-domain rigidity to the interaction networks has emerged as a common factor responsible for the thermodynamic stability of the ...


Rapid Method Of Processing Sperm For Nucleic Acid Extraction In Clinical Research, Matthew K. De Gannes Jan 2014

Rapid Method Of Processing Sperm For Nucleic Acid Extraction In Clinical Research, Matthew K. De Gannes

Masters Theses

Background: Sperm contain highly compact nuclei, inhibiting DNA extraction using traditional techniques. Current methods extracting sperm DNA involve lengthy lysis and no means of stabilizing DNA, hindering clinical research.

Objective: We sought to optimize an efficient method of extracting high quality human sperm DNA.

Methods: Sperm from three volunteers were isolated using PureCeption. We tested 1) proteinase K with DNA/RNA Shield, 2) DTT and TCEP as reducing agents, 3) QIAshredder homogenization, and 4) stability of sperm DNA fresh (baseline) or after 4 weeks of storage at 4OC in DNA/RNA Shield using modified Quick-gDNA MiniPrep. DNA was ...


Clinical Features And Outcome Of Sporadic Colorectal Carcinoma In Young Patients: A Cross-Sectional Analysis From A Developing Country, Muhammad Nauman Zahir, Eisha Mahpara Azhar, Sobia Rafiq, Kulsoom Ghias, Munira Shabbir-Moosajee Jan 2014

Clinical Features And Outcome Of Sporadic Colorectal Carcinoma In Young Patients: A Cross-Sectional Analysis From A Developing Country, Muhammad Nauman Zahir, Eisha Mahpara Azhar, Sobia Rafiq, Kulsoom Ghias, Munira Shabbir-Moosajee

Department of Biological & Biomedical Sciences

Background: Early onset colorectal carcinoma (CRC) is rare and has been hypothesized to be a biologically and clinically distinct entity personifying aggressive disease and worse survival.
Methods: Data for 131 patients was collected by retrospective chart review. Cox proportional hazard model was used to compute prevalence ratios and 95% confidence intervals.
Results: Early onset sporadic CRC accounted for 32% of all CRC treated in the specified time period. The mean age was 33.3 ± 7.9 years and the male to female ratio was 2 : 1. Colon and rectal cancers accounted for 55% and 45% of patients, respectively. 96% of ...


The Role Of The Novel Lupus Antigen, Acheron, In Moderating Life And Death Decisions, Ankur Sheel Jan 2014

The Role Of The Novel Lupus Antigen, Acheron, In Moderating Life And Death Decisions, Ankur Sheel

Masters Theses

Programmed cell death (PCD) is a major regulatory mechanism employed during development and homeostasis. The term PCD was coined to describe the death of the intersegmental muscles (ISMs) of moths at the end of metamorphosis. The timing of ISM death in the Tobacco Hawkmoth, Manduca sexta, is regulated by a fall in the titer of the steroid molting hormone 20-hydroxyecdysone (20E) late on day 17of pupal-adult development. This triggers the release of the peptide hormone, Eclosion Hormone (EH), which mediates its effects via the secondary messenger cGMP. It has been previously demonstrated that ISM death requires de novo gene expression ...


Degradation Of The Oncoprotein Mdmx In Neurodegenerative States: Evidence For A Pro-Survival Role Of Mdmx In Neurons, Daniel James Colacurcio Jan 2014

Degradation Of The Oncoprotein Mdmx In Neurodegenerative States: Evidence For A Pro-Survival Role Of Mdmx In Neurons, Daniel James Colacurcio

Publicly Accessible Penn Dissertations

Neurodegenerative diseases, such as Alzheimer Disease (AD) and HIV–associated neurocognitive disorder (HAND) represent a tremendous burden to healthcare and a devastating impact on society. A common feature of neurodegenerative diseases is progressive dysfunction and death of neurons in key regions of the brain. Observations of dysregulated cell cycle proteins in the brains of patients, along with research in animal models and cultured cells, suggest that aberrant functions of cell cycle proteins contribute to neuronal death and progression of neurodegenerative diseases.

The p53 tumor suppressor is a key component in cell cycle signaling and cell death. p53 maintains multiple functions ...


Distinct Patterns Of Ccr5 Versus Alternative Coreceptor Dependence In Non-Natural Host Versus Natural Host Simmian Immunodeficiency Virus Infection, Sarah Tc Elliott Jan 2014

Distinct Patterns Of Ccr5 Versus Alternative Coreceptor Dependence In Non-Natural Host Versus Natural Host Simmian Immunodeficiency Virus Infection, Sarah Tc Elliott

Publicly Accessible Penn Dissertations

Natural host sooty mangabeys infected with simian immunodeficiency viruses (SIV) exhibit high plasma viral loads without widespread CD4+ T cell loss. By contrast, non-natural host rhesus macaques experimentally infected with related SIV exhibit high viral loads but display subsequent CD4+ T cell loss and progression to AIDS, analogous to the effects of HIV-1 infection in humans. Several mechanisms have been proposed to explain these discrepant outcomes, including infection of distinct target cells in vivo. Cell targeting is substantially determined at the level of viral entry. Prior work demonstrated that sooty mangabey infection occurs in the absence of functional coreceptor CCR5 ...


Mechanochemical Control Of Stem Cell Biology In Development And Disease: Experimental And Theoretical Models, Polimyr Caesar Dave Pelisco Dingal Jan 2014

Mechanochemical Control Of Stem Cell Biology In Development And Disease: Experimental And Theoretical Models, Polimyr Caesar Dave Pelisco Dingal

Publicly Accessible Penn Dissertations

Whether a stem cell remains or egresses away from its physiological niche is a function of mechanical and soluble factors in a time-dependent manner, which implicates a `memory' of prior mechanochemical conditioning. Virtually every organ in the body contains resident stem or progenitor cells that contribute to organ homeostasis or repair. The wound healing process in higher vertebrate animals is spatiotemporally complex and usually leads to scarring. Limitations for the use of stem cells as regenerative therapy include the lack of expansion capabilities in vitro as well as materials issues that complicate traditional biochemical protocols. A minimal `scar in a ...


Epigenetic Regulation Of Progenitor Cell Commitment By Hdac3, Mudit Gupta Jan 2014

Epigenetic Regulation Of Progenitor Cell Commitment By Hdac3, Mudit Gupta

Publicly Accessible Penn Dissertations

Tissue-specific progenitor cells emerge during development to expand and differentiate into the multiple cell lineages that populate the embryo. Appropriate differentiation of these precursor cells requires coordinated expression of numerous lineage-specific genes and repression of alternative fate programs. Epigenetic regulators are enzymes capable of activating or silencing large genomic domains by altering histone modifications, DNA methylation status and chromatin organization. Although differentiating progenitor cells undergo epigenetic changes and epigenetic factors are required for appropriate cell behavior, the precise mechanism of how these proteins influence cell fate remains unclear. In this dissertation, I examine the role of histone deacetylase 3 in ...


Recirculation Of Innate Lymphocyte Subsets In The Skin, Skye Geherin Jan 2014

Recirculation Of Innate Lymphocyte Subsets In The Skin, Skye Geherin

Publicly Accessible Penn Dissertations

The trafficking of innate-like lymphocytes, such as γδ T cells and B-1 B cells, has garnered comparatively little attention from the immunological community relative to conventional T and B cells. However, recent studies have shown that innate-like cell subsets are critical for immune regulation and host defense. In this study, we use a classic ovine lymph cannulation model to describe the phenotype and function of γδ T cells migrating through the skin. We find that γδ T cells traveling in the skin-draining afferent lymph are IFN-γ- and/or IL-17-producing effector cells that express high levels of the skin- and inflammation-seeking ...


Role Of Cytoskeletal Remodeling In T Cell Receptor Signaling And Integrin Activation At The Immunological Synapse, Alexander Babich Jan 2014

Role Of Cytoskeletal Remodeling In T Cell Receptor Signaling And Integrin Activation At The Immunological Synapse, Alexander Babich

Publicly Accessible Penn Dissertations

The efficiency of an immune response critically depends on the ability of T cells to respond to antigens. Upon encountering cognate antigenic peptides on the surface of antigen-presenting cells, T cells form a specialized interface, termed the immunological synapse (IS), which serves as the site of information transfer between the cells. This contact zone is characterized by the enrichment of signaling receptors, kinases and adaptor proteins, and is the site of extensive cytoskeletal remodeling. The versatile nature and spatio-temporal regulation of signaling cascades at the IS has long been recognized but the exact mechanisms that coordinate these processes remain poorly ...


Epithelial Cell Shape Changes During Lung Branching Morphogenesis: The Role Of Wnt/Fzd2 Signaling In Directing New Branch Formation, Rachel S. Kadzik Jan 2014

Epithelial Cell Shape Changes During Lung Branching Morphogenesis: The Role Of Wnt/Fzd2 Signaling In Directing New Branch Formation, Rachel S. Kadzik

Publicly Accessible Penn Dissertations

Formation of the intricately branched mammalian lung requires precise coordination between the epithelium and mesenchyme over the course of development. This coordination is mediated by molecular signaling between the two tissue compartments. How these signaling pathways coordinate changes in cellular and tissue morphology to give rise to the highly ramified branched network of the lung is not well understood. In this work, I show that signaling through Frizzled 2 (Fzd2) is required for promoting changes in epithelial cell shape that lead to tissue-level changes needed for branching morphogenesis in the lung. Through analysis of both fixed lungs and live imaging ...


Membrane Forces And Key Protein Determinants Of Hematopoietic Cell Function: Lamins And Myosin-Ii In Hematopoiesis And Cd47 In Immunotherapy Of Cancer, Kyle Spinler Jan 2014

Membrane Forces And Key Protein Determinants Of Hematopoietic Cell Function: Lamins And Myosin-Ii In Hematopoiesis And Cd47 In Immunotherapy Of Cancer, Kyle Spinler

Publicly Accessible Penn Dissertations

Hematopoiesis in human bone marrow generates every second about 105 – 106 anucleated platelets and red blood cells as well as nucleated white blood cells that are capable of infiltrating distant tissues. The thesis begins in the marrow with a description of (1) nuclear membrane ‘lamina’ physicochemical properties that influence marrow-to-circulation trafficking, and proceeds to detail (2) the physicochemical roles of membrane cortex ‘myosin’ in key marrow processes of motility and division as well as platelet biogenesis and disease. The thesis finishes with (3) studies of macrophages in peripheral tissues far from the marrow and aspects of how such ...


Regulation Of Zygotic Transcription And Cell Cycle Checkpoints In Early Embryogenesis, Xiang Maomao Zhang Jan 2014

Regulation Of Zygotic Transcription And Cell Cycle Checkpoints In Early Embryogenesis, Xiang Maomao Zhang

Publicly Accessible Penn Dissertations

For many organisms, the first goal of embryogenesis is to accumulate a large cell population to accommodate gastrulation. To achieve this quickly, embryos employ specialized cell cycles called cleavages that consist of continuous rounds of DNA replication and division. Cell proliferation occurs rapidly because cleavage cycles lack the gap phases and cell cycle checkpoints found in canonical cell cycles. Further, the genetic materials required to sustain cleavage cycles are preloaded during oogenesis, aiding efficient cell cycle progression. After a constant, organism-specific number of cleavages, many metazoan embryos undergo the mid-blastula transition (MBT), which initiates extensive cell cycle remodeling. Cell cycles ...


The Role Of The Exocyst In Membrane Deformation, Cell Migration And Exocytosis, Yuting Zhao Jan 2014

The Role Of The Exocyst In Membrane Deformation, Cell Migration And Exocytosis, Yuting Zhao

Publicly Accessible Penn Dissertations

Dynamic shape changes of the plasma membrane are fundamental to many processes ranging from morphogenesis and cell migration to phagocytosis and viral propagation. In this study, I showed that Exo70, a component of the exocyst complex, induces tubular membrane invaginations towards the lumen of synthetic vesicles in vitro and generates actin-free protrusions on the surface of cells. Analyses using Exo70 mutants suggest that Exo70 generates negative membrane curvature through an oligomerization-based mechanism. The membrane-deformation function of Exo70 is likely to be independent of the other exocyst subunits. Exo70 thus represents a novel membrane-deforming protein for plasma membrane remodeling. Directional cell ...


Mitochondrial Dynamics: Exploring A Novel Target Against Myocardial Ischemia-Reperfusion Injury, Yi Dong Jan 2014

Mitochondrial Dynamics: Exploring A Novel Target Against Myocardial Ischemia-Reperfusion Injury, Yi Dong

Wayne State University Dissertations

Mitochondrial fusion and fission, collectively termed mitochondrial dynamics, are among the core mechanisms responsible for maintaining mitochondrial health and functional integrity. Dynamin-related protein 1 (DRP1) is a key regulator of mitochondrial fission. Recent studies suggest that i) mitochondrial dynamics, particularly, mitochondrial fission, serves as a mediator of cell fate in the setting of ischemia-reperfusion (IR) injury, and, ii) inhibition of DRP1 and mitochondrial fission provides cardioprotection against IR injury. However, the precise role of DRP1 translocation to mitochondria in the pathogenesis of myocardial ischemia-reperfusion injury has not been established.

Using an established model of hypoxia-reoxygenation (HR) in cultured HL-1 cardiomyocytes ...


Structure-Function Analysis Of Zapc, An Ftsz-Ring Stabilizer, In Escherichia Coli Cytokinesis, Lukasz Tchorzewski Jan 2014

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 ...


Isolation And Characterization Of Multipotent Lung Stem Cells From P53 Mutant Mice Models, Venkat Sundar Gadepalli Jan 2014

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 ...


Microenvironment Regulation Of Matrix Metalloproteinase Activity In Pancreatic Cancer Cells, Amanda Michelle Haage Jan 2014

Microenvironment Regulation Of Matrix Metalloproteinase Activity In Pancreatic Cancer Cells, Amanda Michelle Haage

Graduate Theses and Dissertations

Currently there are no reliable treatment options for cancer metastasis. The complex cascade of events leading to metastasis reveals a multitude of therapeutic targets, but few of these targets are extensively involved in as many steps as the matrix metalloproteinases (MMPs). The MMP family is the major extracellular matrix (ECM) remodeling enzymes utilized by normal and cancerous cell alike. A therapeutic technique aimed at MMPs has been the subject of much research, but remains elusive due to two major concerns: 1) MMPs are post-translationally activated, usually by other MMPs, resulting in convoluted catalytic networks where activity does not equate expression ...