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An Extra-Embryonic Wnt Signaling Event Controls Gastrulation In Mice: A Dissertation, Giovane G. Tortelote Nov 2012

An Extra-Embryonic Wnt Signaling Event Controls Gastrulation In Mice: A Dissertation, Giovane G. Tortelote

GSBS Dissertations and Theses

The formation of the anterior-posterior axis requires a symmetry-breaking event that starts gastrulation. Ultimately, the morphogenetic movements of gastrulation reshape the embryo to its final tri-dimensional form. In mouse embryos, the identity of the molecule that breaks the bilateral symmetry and sets in motion gastrulation remains elusive. The Wnt signaling pathway plays a pivotal role during axial specification and gastrulation in metazoans. Loss-of-function experiments have demonstrated a requirement of Wnt3 for gastrulation in mice. But because Wnt3 is expressed sequentially in two tissues, the visceral endoderm and the epiblast, its tissue specific requirements remain uncertain. Here, we report that embryos ...


Neuronal Nicotinic Acetylcholine Receptors: Molecular Targets For Alcoholism And Ethanol Reward: A Dissertation, Linzy M. Hendrickson Jan 2011

Neuronal Nicotinic Acetylcholine Receptors: Molecular Targets For Alcoholism And Ethanol Reward: A Dissertation, Linzy M. Hendrickson

GSBS Dissertations and Theses

While it is clear that most drugs of abuse act to increase extracellular dopamine levels in the nucleus accumbens (NAc), the molecular mechanisms mediating this process vary depending on the molecular target each drug acts on. The rewarding properties of most drugs of abuse including cocaine, amphetamine, and heroin have been well established for some time; however, the molecular mechanisms by which ethanol acts to mediate reward have not been fully elucidated. In this thesis, I have examined the role of nicotinic acetylcholine receptors (nAChRs), known molecular targets for nicotine addiction, in mediating the initial rewarding properties of alcohol. Using ...


Role Of The Cjun Nh2-Terminal Kinase (Jnk) In Cancer: A Dissertation, Cristina Arrigo Cellurale Jul 2010

Role Of The Cjun Nh2-Terminal Kinase (Jnk) In Cancer: A Dissertation, Cristina Arrigo Cellurale

GSBS Dissertations and Theses

cJun NH2-terminal kinase (JNK) is a member of the MAPK (mitogen- activated protein kinase) signaling family that responds to various extracellular stimuli, such as stress, growth factors, cytokines, or UV radiation. JNK activation can lead to cellular responses including gene expression, growth, survival, and apoptosis. JNK has been implicated in normal developmental processes, including tissue morphogenesis, as well as pathological processes, such as cellular transformation and cancer. JNK exists in three isoforms, and knockout mice have been generated for each isoform; the ubiquitously expressed Jnk1 and Jnk2 have been studied independently, however, the two isoforms are partially functionally ...


Development Of A Substrate With Photo-Modulatable Rigidity For Probing Spatial And Temporal Responses Of Cells To Mechanical Signals: A Dissertation, Margo Tilley Frey Jul 2008

Development Of A Substrate With Photo-Modulatable Rigidity For Probing Spatial And Temporal Responses Of Cells To Mechanical Signals: A Dissertation, Margo Tilley Frey

GSBS Dissertations and Theses

Topographical and mechanical properties of adhesive substrates provide important biological cues that affect cell spreading, migration, growth, and differentiation. The phenomenon has led to the increased use of topographically patterned and flexible substrates in studying cultured cells. However, these studies may be complicated by various limitations. For example, the effects of ligand distribution and porosity are affected by topographical features of 3D biological constructs. Similarly, many studies of mechanical cues are compounded with cellular deformation from external forces, or limited by comparative studies of separate cells on different substrates. Furthermore, understanding cell responses to mechanical input is dependent upon reliable ...


Innate Immunity In Type 2 Diabetes Pathogenesis: Role Of The Lipopolysaccharide Signaling Cascade: A Dissertation, James L. Young Jul 2008

Innate Immunity In Type 2 Diabetes Pathogenesis: Role Of The Lipopolysaccharide Signaling Cascade: A Dissertation, James L. Young

GSBS Dissertations and Theses

Once seen as a disease of wealthy nations, type 2 diabetes mellitus is now showing unprecedented growth throughout the world, fueling increases in microvascular and macrovascular complications. A compelling and growing body of evidence suggests that glucose intolerance and insulin resistance, hallmarks of the diabetic patient, may be driven by chronic inflammation. In particular, a predominance of visceral fat has been associated with enhanced inflammatory cytokine secretion that may contribute to enhanced risk of diabetes and comorbid cardiovascular disease in these individuals. As a function of its potency and wide environmental and biological distribution, we hypothesized that bacterial lipopolysaccharide (LPS ...


The Humanized Mouse Model: The Study Of The Human Alloimmune Response: A Dissertation, Marie A. King May 2008

The Humanized Mouse Model: The Study Of The Human Alloimmune Response: A Dissertation, Marie A. King

GSBS Dissertations and Theses

The transplantation of allogeneic cells and tissues for the treatment of human disease has been a life-saving procedure for many thousands of patients worldwide. However, to date, neither solid organ transplantation nor bone marrow transplantation have reached their full clinical potential. Significant limitations to the advancement of clinical transplantation stem from our current inability to prevent the rejection of allogeneic tissues by the immune system of the host. Similarly, in patients that receive allogeneic bone marrow transplants, we cannot permanently prevent the engrafted immune system from mounting a response against the patient. This problem, termed graft versus host disease is ...


Regulation Of Contractility By Adenosine A1 And A2a Receptors In The Murine Heart: Role Of Protein Phosphatase 2a: A Dissertation, Eugene I. Tikh Jun 2006

Regulation Of Contractility By Adenosine A1 And A2a Receptors In The Murine Heart: Role Of Protein Phosphatase 2a: A Dissertation, Eugene I. Tikh

GSBS Dissertations and Theses

Adenosine is a nucleoside that plays an important role in the regulation of contractility in the heart. Adenosine receptors are G-protein coupled and those implicated in regulation of contractility are presumed to act via modulating the activity of adenylyl cyclase and cAMP content of cardiomyocytes. Adenosine A1 receptors (A1R) reduce the contractile response of the myocardium to β-adrenergic stimulation. This is known as anti adrenergic action. The A2A adenosine receptor (A2AR) has the opposite effect of increasing contractile responsiveness of the myocardium. The A2AR also appears to attenuate the effects of A ...


Mechanisms Of Tal1 Induced Leukemia In Mice: A Dissertation, Jennifer Elinor O'Neil Jan 2004

Mechanisms Of Tal1 Induced Leukemia In Mice: A Dissertation, Jennifer Elinor O'Neil

GSBS Dissertations and Theses

Activation of the basic helix-loop-helix (bHLH) gene TAL1 is the most common genetic event seen in both childhood and adult T cell acute lymphoblastic leukemia (T-ALL). Despite recent success in treating T-ALL patients, TAL1 patients do not respond well to current therapies. In hopes of leading the way to better therapies for these patients, we have sought to determine the mechanism(s) of Tal1 induced leukemia in mice. By generating a DNA-binding mutant Tal1 transgenic mouse we have determined that the DNA binding activity of Tal1 is not required to induce leukemia. We have also shown that Tal1 expression in ...


The Genetic Basis Of Resistance To Transplantation Tolerance Induced By Costimulation Blockade In Nod Mice: A Dissertation, Todd Pearson Mar 2003

The Genetic Basis Of Resistance To Transplantation Tolerance Induced By Costimulation Blockade In Nod Mice: A Dissertation, Todd Pearson

GSBS Dissertations and Theses

The NOD mouse is a widely studied model of type 1 diabetes. The loss of self-tolerance leading to autoimmune diabetes in NOD mice involves at least 27 genetic loci. Curing type I diabetes in mice and humans by islet transplantation requires overcoming both allorejection and recurrent autoimmunity. This has been achieved with systemic immunosuppression, but tolerance induction would be preferable. In addition to their genetic defects in self-tolerance, NOD mice resist peripheral transplantation tolerance induced by costimulation blockade using donor-specific transfusion and anti-CDl54 antibody. Failure has been attributed to the underlying autoimmunity, assuming that autoimmunity and resistance to transplantation tolerance ...


The Role Of The Swi/Snf Component Ini1 In Mammalian Development And Tumorigenesis: A Dissertation, Cynthia J. Guidi Feb 2003

The Role Of The Swi/Snf Component Ini1 In Mammalian Development And Tumorigenesis: A Dissertation, Cynthia J. Guidi

GSBS Dissertations and Theses

In vivo DNA is compacted tightly, via its association with histones and non-histone proteins, into higher-order chromatin structure. In this state, the DNA is refractory to the cellular factors that require access to DNA. The repressive nature of chromatin is alleviated in part by the action enzymes that modify chromatin structure. There are two major groups of chromatin modifying enzymes: those that post-translationally modify histones by the addition of small chemical moieties and those that utilize the energy derived from ATP hydrolysis to physically disrupt chromatin structure. The SWI/SNF enzyme belongs to this latter group.

The SWI/SNF complex ...


In Vitro And In Vivo Studies Of Murine Polytropic Retrovirus Infections: A Dissertation, Scott A. Loiler Sep 2000

In Vitro And In Vivo Studies Of Murine Polytropic Retrovirus Infections: A Dissertation, Scott A. Loiler

GSBS Dissertations and Theses

Murine leukemia viruses (MuLV) are retroviruses that play important roles in the study of oncogenes, integration, transcriptional regulation and gene therapy. Mink cell focus-inducing (MCF) viruses are polytropic MuLVs that by definition infect cells from a wide variety of species. Their ability to infect human cells and their utility as gene therapy vectors were not well characterized. To address this issue, primary and immortalized human cells were tested for their ability to be infected by MCF packaged defective vectors as well as replication competent MCF virus. A new packaging cell line, called MPAC, was created to package defective retroviral vectors ...


Analysis Of Low Zone Tolerance In Normal And B Cell-Deficient Mice, Allison Michelle Baird Apr 1996

Analysis Of Low Zone Tolerance In Normal And B Cell-Deficient Mice, Allison Michelle Baird

GSBS Dissertations and Theses

This thesis investigates the role of B cells as antigen-specific antigen-presenting cells (APC) in self tolerance to low concentrations of soluble self proteins and in acquired tolerance to low doses of soluble foreign protein antigens. Experiments were performed in normal and B cell-deficient animals, and tolerance induction was measured by T cell proliferation assays. T cell proliferation was reduced in B cell-deficient mice, indicating that B cells may be involved in efficient activation of naive T cells in response to protein antigen both in vivo and in vitro. To study acquired tolerance induced by low doses of soluble foreign protein ...


Regulation Of Transcription Of Mouse Immunoglobulin Germ-Line Γ1 Rna: Structural Characterization Of Germ-Line Γ1 Rna And Molecular Analysis Of The Promoter: A Dissertation, Minzhen Xu May 1991

Regulation Of Transcription Of Mouse Immunoglobulin Germ-Line Γ1 Rna: Structural Characterization Of Germ-Line Γ1 Rna And Molecular Analysis Of The Promoter: A Dissertation, Minzhen Xu

GSBS Dissertations and Theses

The antibody class switch is achieved by DNA recombination between the sequences called switch (S) regions located 5' to immunoglobulin (Ig) heavy chain constant (CH) region genes. This process can be induced in cultured B cells by polyclonal stimulation and switching can be directed to specific antibody classes by certain lymphokines. These stimuli may regulate the accessibility of CH genes and their S regions to a recombinase as indicated by hypomethylation and transcriptional activity. For example, RNAs transcribed from specific unrearranged (germ-line) CH genes are induced prior to switching under conditions that promote subsequent switching to these ...


Myc And E1a Oncogenes Alter The Response Of Pc12 Cells To Nerve Growth Factor And Block Differentiation: A Thesis, Susan C. Schiavi Aug 1988

Myc And E1a Oncogenes Alter The Response Of Pc12 Cells To Nerve Growth Factor And Block Differentiation: A Thesis, Susan C. Schiavi

GSBS Dissertations and Theses

PC12 rat pheochromocytoma cells respond to nerve growth factor (NGF) by neuronal differentiation and partial growth arrest. Mouse c-myc and adenovirus E1A genes were introduced into PC12 cells to study the influence of these nuclear oncogenes on neuronal differentiation. Expression of myc and E1A blocked morphological differentiation and caused NGF to stimulate rather than inhibit cell proliferation. NGF binding to cell surface receptors, activation of ribosomal S6 kinase, and ornithine decarboxylase induction were similar in myc and E1A expressing clones compared with wild-type PC12 cells, suggesting that changes in the cellular response to NGF were at a post-receptor level. The ...