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Essential Roles Of The Meis Family Proteins During Segmentation Of The Zebrafish Hindbrain : A Dissertation, Seong-Kyu Choe Dec 2003

Essential Roles Of The Meis Family Proteins During Segmentation Of The Zebrafish Hindbrain : A Dissertation, Seong-Kyu Choe

GSBS Dissertations and Theses

Hindbrain patterning requires many factors involved in early segmentation and later segment identity of the specific domains of the hindbrain. Hox proteins and their cofactors are of great importance during segmentation of the hindbrain, because segmentation and/or segment identity are lost when any of them are lost. Previously, we have reported that Meis proteins synergize with Pbx, another Hox cofactor, and Hox proteins expressed in the hindbrain. To further investigate Meis function during hindbrain development, we utilized a Meis dominant-negative molecule, ΔCPbx4, and expressed it in zebrafish embryos. We find that ΔCPbx4 affects gene expression and neuronal differentiation especially ...


Function Of The Zinc-Finger Repressor Nlz In The Developing Zebrafish Hindbrain: A Dissertation, Alexander Peter Runko Oct 2003

Function Of The Zinc-Finger Repressor Nlz In The Developing Zebrafish Hindbrain: A Dissertation, Alexander Peter Runko

GSBS Dissertations and Theses

Generation of the primitive neuroectoderm into specialized brain subdivisions, such as the hindbrain primordium, involves the regulated coordination of complex morphogenetic and molecular mechanisms. These processes are evident in the segregation of the zebrafish hindbrain into seven distinct lineage-restricted compartments, termed rhombomeres (r), which are established by the interplay of several spatially-restricted expressed genes. These include transcription factors, members of specific signaling pathways and specialized molecules that mediate cell adhesion and identity. Despite their extensive characterization, it is evident that other genes are involved to mediate the proper specification and segregation of individual rhombomeres. One candidate that likely fits this ...


Regulation Of Zebrafish Hindbrain Development By Fibroblast Growth Factor And Retinoic Acid: A Dissertation, Nicole Marie Roy Oct 2003

Regulation Of Zebrafish Hindbrain Development By Fibroblast Growth Factor And Retinoic Acid: A Dissertation, Nicole Marie Roy

GSBS Dissertations and Theses

Fibroblast growth factor (Fgf) and Retinoic acid (RA) are known to be involved in patterning the posterior embryo. Work has shown that Fgf can convert anterior tissue into posterior fates and that embryos deficient in Fgf signaling lack posterior trunk and tail structures. Likewise, studies performed on RA have shown that overexpression of RA posteriorizes anterior tissue, while disrupting RA signaling yields a loss of posterior fates. While it appears these signals are necessary for posterior development, the role Fgf and RA play in development of the hindbrain is still enigmatic. A detailed study of the requirements for Fgf and ...


Poly(Adp)-Ribose Polymerase Activity In The Eukaryotic Mono-Adp-Ribosyl Transferase, Art2: A Dissertation, Alan R. Morrison Sep 2003

Poly(Adp)-Ribose Polymerase Activity In The Eukaryotic Mono-Adp-Ribosyl Transferase, Art2: A Dissertation, Alan R. Morrison

GSBS Dissertations and Theses

The glycophosphatidylinositol(GPI)-linked membrane protein ART2 is an antigenic determinant for T lymphocytes that regulate the expression of diabetes in the BB/W rat model. Though little is understood of the physiologic role of ART2 on T lymphocytes, ART2 is a member of the mono-ADP-ribosyl transferase subgroup ofthe ADP-ribosyl transferase (ART) protein family. The ART protein family, which traditionally has been divided into mono-ADP-ribosyl transferases (mono-ARTs), poly(ADP)-ribose polymerases (PARPs), and ADP-ribosyl cyclases, influences various aspects of cellular physiology including: apoptosis, DNA damage repair, chromatin remodeling, telomere replication, cellular transport, immune regulation, neuronal function, and bacterial virulence. A ...


Conserved Nucleosome Remodeling/Histone Deacetylase Complex And Germ/Soma Distinction In C. Elegans: A Dissertation, Yingdee Unhavaithaya Aug 2003

Conserved Nucleosome Remodeling/Histone Deacetylase Complex And Germ/Soma Distinction In C. Elegans: A Dissertation, Yingdee Unhavaithaya

GSBS Dissertations and Theses

A rapid cascade of regulatory events defines the differentiated fates of embryonic cells, however, once established, these differentiated fates and the underlying transcriptional programs can be remarkably stable. Here, we describe two proteins, MEP-1, a novel protein, and LET-418/Mi-2, both of which are required for the maintenance of somatic differentiation in C. elegans. MEP-1 was identified as an interactor of PIE-1, a germ-specific protein required for germ cell specification, while LET-418 is a protein homologous to Mi-2, a core component of the nuc1eosome remodeling/histone deacetylase (NuRD) complex. In animals lacking MEP-1 and LET-418, germline-specific genes become derepressed in ...


Chondrocyte Adhesion To Rgd-Bonded Alginate: Effect On Mechanotransduction And Matrix Metabolism: A Dissertation, Nicholas G. Genes Aug 2003

Chondrocyte Adhesion To Rgd-Bonded Alginate: Effect On Mechanotransduction And Matrix Metabolism: A Dissertation, Nicholas G. Genes

GSBS Dissertations and Theses

The mechanism of mechanotransduction in chondrocyte matrix metabolism is not well understood, in part because of the density of cartilage and in part because of limitations in in vitroculture systems. Using alginate covalently modified to include the integrin adhesion ligand R-G-D (arginine-glycine-aspartate) represents a unique approach to studying mechanotransduction in that it allows for exploration of the role of integrin adhesion in mediating changes to chondrocyte behavior.

The hypothesis of this research was that chondrocytes will form a cytoskeletal adhesion to RGD-alginate mediated integrins, that this attachment will enable chondrocyte sensation of mechanical signals, and this signaling will alter ...


The Function Of The Tyrosine Kinase, Itk, In Cd4+ T Cell Differentiation And Death: A Dissertation, Andrew Todd Miller Jul 2003

The Function Of The Tyrosine Kinase, Itk, In Cd4+ T Cell Differentiation And Death: A Dissertation, Andrew Todd Miller

GSBS Dissertations and Theses

The Tec family tyrosine kinase, Itk, plays an important role in signal transduction following T cell receptor engagement. Several prior studies have established the importance of Itk in immune system processes, such as T cell development and T cell activation. Additional biochemical studies have found that Itk specifically functions within a multi-molecular signalosome complex, which ultimately functions to provide a platform by which Itk can phosphorylate and activate PLC-γ1, a crucial step in T cell activation. To further study how Itk regulates distinct immune outcomes via T cell effector processes within the peripheral immune system, and to further understand how ...


The Molecular Mechanisms Of T Cell Clonal Anergy: A Dissertation, John E. Harris Jun 2003

The Molecular Mechanisms Of T Cell Clonal Anergy: A Dissertation, John E. Harris

GSBS Dissertations and Theses

A side effect of generating an immune system for defense against invading pathogens is the potential to develop destructive cells that recognize self-tissues. Typically, through the "education" of developing immune cells, the organism inactivates potentially self-destructive cells, resulting in what is called self-tolerance. I proposed to explore the molecular mechanisms responsible for the induction and maintenance of tolerance. Our lab has developed a model of induced immune tolerance to skin and islet allografts utilizing a donor-specific transfusion of spleen cells and a brief course of anti-CD40L antibody. Because the difficulty in isolation of tolerant T cells from this system is ...


Cholesterol And Phospholipid Modulation Of Bk[Subscript Ca] Channel Activity And Ethanol Sensitivity: A Dissertation, John J. Crowley Jun 2003

Cholesterol And Phospholipid Modulation Of Bk[Subscript Ca] Channel Activity And Ethanol Sensitivity: A Dissertation, John J. Crowley

GSBS Dissertations and Theses

The large conductance Ca++-activated K+ channel (BKCa) regulates neuronal excitability through the efflux of K+, in response to membrane depolarization and increases in intracellular Ca++. The activity of the BKCa channel is increased by acute exposure to ethanol (EtOH), which is thought to underlie, in part, the influence of the drug on peptide hormone release from neurohypophysial nerve terminals (Dopico et al., 1996, 1998). Moreover, chronic EtOH exposure attenuates acute drug action on hormone release, and reduces the sensitivity of BKCa channels to acute EtOH exposure (Knott et al., 2002). The factors regulating EtOH action on ...


Mhc Class I Antigen Presentation Is Regulated By The Sumo-Conjugating Enzyme Ubc9: A Dissertation, Yuelei Shen Jun 2003

Mhc Class I Antigen Presentation Is Regulated By The Sumo-Conjugating Enzyme Ubc9: A Dissertation, Yuelei Shen

GSBS Dissertations and Theses

CD8 T cells recognize complexes of MHC class I and peptide on the surface of target cells. MHC class I antigen presentation is a long pathway, in which proteins are degraded by proteasomes to generating oligopeptides, which may be further trimmed by aminopeptidases in the cytosol. Peptides are transported into the ER, where they may be further trimmed by ER lumenal aminopeptidases and bind to newly-synthesized MHC class I complexes. Proteins degraded by the proteasome are generally tagged with ubiquitin by a combination of ubiquitin-conjugating enzymes and ubiquitin ligases. UBC9 is one ubiquitin conjugating enzyme, which does not conjugate ubiquitin ...


Mechanistic Analysis Of Chromatin Remodeling Enzymes: A Dissertation, Mariela Jaskelioff May 2003

Mechanistic Analysis Of Chromatin Remodeling Enzymes: A Dissertation, Mariela Jaskelioff

GSBS Dissertations and Theses

The inherently repressive nature of chromatin presents a sizeable barrier for all nuclear processes in which access to DNA is required. Therefore, eukaryotic organisms ranging from yeast to humans rely on a battery of enzymes that disrupt the chromatin structure as a means of regulating DNA transactions.

These enzymes can be divided into two broad classes: those that covalently modify histone proteins, and those that actively disrupt nucleosomal structure using the free energy derived from ATP hydrolysis. The latter group, huge, multisubunit ATP-dependent chromatin remodeling factors, are emerging as a common theme in all nuclear processes in which access to ...


Actin Pedestal Formation On Mammalian Cells By Enteropathogenic Escherichia Coli: A Dissertation, Kenneth Geno Campellone May 2003

Actin Pedestal Formation On Mammalian Cells By Enteropathogenic Escherichia Coli: A Dissertation, Kenneth Geno Campellone

GSBS Dissertations and Theses

Enteropathogenic Escherichia coli (EPEC) and enterohemorrhagic E. coli O157:H7 (EHEC) form characteristic lesions on infected mammalian cells called actin pedestals. Each of these two pathogens injects its own translocated intimin receptor (Tir) molecule into the plasma membranes of host cells. Interaction of translocated Tir with the bacterial outer membrane protein intimin is required to trigger the assembly of actin into focused pedestals beneath bound bacteria. Despite similarities between the Tir molecules and the host components that associate with pedestals, recent work indicates that EPEC and EHEC Tir are not functionally interchangeable. For EPEC, Tir-mediated binding of Nck, a host ...


Cd40-Cd154 Blockade Facilitates Induction Of Allogeneic Hematopoietic Chimerism And Transplantation Tolerance: A Dissertation, Edward Seung May 2003

Cd40-Cd154 Blockade Facilitates Induction Of Allogeneic Hematopoietic Chimerism And Transplantation Tolerance: A Dissertation, Edward Seung

GSBS Dissertations and Theses

Allogeneic hematopoietic chimerism leading to central tolerance has significant therapeutic potential. Establishment of hematopoietic chimerism created by stem cell transplantation has been shown to prevent and cure a number of autoimmune diseases and induce the most robust and long-lasting form of transplantation tolerance known. However, the realization of the vast clinical potential of hematopoietic chimerism for induction of transplantation tolerance has been impeded by the toxicity of the host conditioning regimen and the development of graft-versus-host disease (GVHD). This thesis describes the development of stem cell transplantation protocols that 1) reduce the host conditioning regimen; and 2) abrogate the development ...


Mechanics Of Fibroblast Migration: A Dissertation, Steven Munevar May 2003

Mechanics Of Fibroblast Migration: A Dissertation, Steven Munevar

GSBS Dissertations and Theses

Cell migration involves complex mechanical interactions between cells or between cells and the underlying substrate. Using a newly developed technique, "traction force microscopy", I have been able to visualize the dynamic characteristics of mechanical forces exerted by migrating fibroblasts such as magnitude, direction, and shear. For NIH 3T3 fibroblasts, I found that the lamellipodium provides nearly all of the force necessary for cell migration. A high shear zone separates the lamellipodium from the remainder of the cell body, suggesting that they are mechanically distinct entities. The timing of the tractions at the leading edge, as well as the spatial distribution ...


Peptidyltransfer Reaction Catalyzed By The Ribosome And The Ribozyme: A Dissertation, Lele Sun May 2003

Peptidyltransfer Reaction Catalyzed By The Ribosome And The Ribozyme: A Dissertation, Lele Sun

GSBS Dissertations and Theses

The "RNA world" hypothesis makes two predictions that RNA should have been able both to catalyze RNA replication and to direct protein synthesis. The evolution of RNA-catalyzed protein synthesis should be critical in the transition from the RNA world to the modem biological systems. Peptide bond formation is a fundamental step in modem protein biosynthesis. Although many evidence suggests that the ribosome is a ribozyme, peptide bond formation has not been achieved with ribosomal RNAs only. The goal of this thesis is to investigate whether RNA could catalyze peptide bond formation and how RNA catalyzes peptide bond formation. Two systems ...


Involvement Of Cdp/Cux In The Regulation Of Histone H4 Gene Expression, Proliferation And Differentiation: A Dissertation, Mai X. Luong May 2003

Involvement Of Cdp/Cux In The Regulation Of Histone H4 Gene Expression, Proliferation And Differentiation: A Dissertation, Mai X. Luong

GSBS Dissertations and Theses

Proliferation and differentiation are essential processes for the growth and development of higher eukaryotic organisms. Regulation of gene expression is essential for control of cell division and differentiation. Normal eukaryotic cells have a limited proliferative capacity, and ultimately undergo cellular senescence and apoptosis. Terminal differentiation of cells is associated with loss of proliferative capacity and acquisition of specialized functions. Proliferation and differentiation are processes required for the creation and maintenance of diverse tissues both during embryonic development and postnatal life. The cell cycle is the process by which cells reproduce, and requires duplication and segregation of hereditary material. Loss of ...


T Cell Immunity And Hiv-1 Replication In Vertically-Infected Infants And Children: A Dissertation, Zachary Aaron Scott May 2003

T Cell Immunity And Hiv-1 Replication In Vertically-Infected Infants And Children: A Dissertation, Zachary Aaron Scott

GSBS Dissertations and Theses

Virus-specific cellular immune responses have been shown to be important in the control of viral replication in several animal and human virus models. Cells of both the CD8+ and CD4+T cell lineages have been shown to play protective roles during viral infections by exerting effector functions that can kill infected host cells or inhibit the production and spread of infectious virions. The continued spread of HIV-1 infection throughout the world, as well as the lack of a prophylactic HIV-1 vaccine have generated much interest in HIV-specific cellular immune responses. Recent technical advances have yielded a tremendous increase in our ...


Role Of C-Jun Nh-Terminal Kinase In Bcr/Abl Induced Cell Transformation: A Dissertation, Patricia M. Hess Apr 2003

Role Of C-Jun Nh-Terminal Kinase In Bcr/Abl Induced Cell Transformation: A Dissertation, Patricia M. Hess

GSBS Dissertations and Theses

The c-Jun NH2-terminal kinase (JNK) group of kinases include ten members that are created by alternative splicing of transcripts derived from Jnk1, Jnk2 and Jnk3 genes. The JNK1 and JNK2 protein kinases are ubiquitously expressed while JNK3 is expressed in a limited number of tissues. The JNK signaling pathway is implicated in multiple physiological processes including cell transformation. There is growing evidence that JNK signaling is involved in oncogenesis. Nevertheless, the role that JNK plays in malignant transformation is still unclear. The aim of this thesis is to examine the role of JNK in malignant transformation. For this ...


Intranuclear Trafficking Of Runx/Aml/Cbfa/Pebp2 Transcription Factors In Living Cells: A Dissertation, Kimberly Stacy Harrington Mar 2003

Intranuclear Trafficking Of Runx/Aml/Cbfa/Pebp2 Transcription Factors In Living Cells: A Dissertation, Kimberly Stacy Harrington

GSBS Dissertations and Theses

The family of runt related transcription factors (RUNX/Cbfa/AML/PEBP2) are essential for cellular differentiation and fetal development. RUNX factors are distributed throughout the nucleus in punctate foci that are associated with the nuclear matrix/scaffold and generally correspond with sites of active transcription. Truncations of RUNX proteins that eliminate the C-terminus including a 31-amino acid segment designated the nuclear matrix targeting signal (NMTS) lose nuclear matrix association and result in lethal hematopoietic (RUNX1) and skeletal (RUNX2) phenotypes in mice. These findings suggest that the targeting of RUNX factors to subnuclear foci may mediate the formation of multimeric regulatory ...


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 ...


Hiv-1 Gene Expression: Transcriptional Regulation And Rna Interference Studies: A Dissertation, Ya-Lin Chiu Jan 2003

Hiv-1 Gene Expression: Transcriptional Regulation And Rna Interference Studies: A Dissertation, Ya-Lin Chiu

GSBS Dissertations and Theses

Gene expression of human immunodeficiency virus type-1 (HIV-1), which causes Acquired Immunodeficiency Syndrome (AIDS), is regulated at the transcriptional level, where negative factors can block elongation that is overcome by HIV Tat protein and P-TEFb. P-TEFb, a positive elongation transcription factor with two subunits, CDK9 and Cyclin T1 (CycT1), catalyzes Tat-dependent phosphorylation of Ser-5 in the Pol II C-terminal domain (CTD), allowing production of longer mRNAs. Ser-5 phosphorylation enables the CTD to recruit mammalian mRNA capping enzyme (Mce1) and stimulate its guanylyltransferase activity. This dissertation demonstrates that stable binding of Mce1 and cap methyltransferase to template-engaged Pol II depends on ...