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Bone Health And Coronary Heart Disease In Postmenopausal Women With Breast Cancer Treated With Tamoxifen: A Dissertation, Hongliu Ding Dec 2008

Bone Health And Coronary Heart Disease In Postmenopausal Women With Breast Cancer Treated With Tamoxifen: A Dissertation, Hongliu Ding

GSBS Dissertations and Theses

Breast cancer, osteoporosis, and coronary heart disease (CHD) are three major threats to women’s health. Postmenopausal women with breast cancer are also at high risk for osteoporosis and CHD. Adjuvant tamoxifen therapy is not only an effective treatment for breast cancer, but has been shown to have a beneficial effect on bone and the cardiovascular system. Although tamoxifen has been convincingly demonstrated to be able to preserve bone mineral density (BMD), an unexpected increase of risk of fractures in patients treated with tamoxifen has been reported. The findings of the association of tamoxifen and CHD from previous studies were ...


Ethanol Sensitivity And Tolerance Of Rat Neuronal Bk Channels: A Dissertation, Patricia M. Wynne Dec 2008

Ethanol Sensitivity And Tolerance Of Rat Neuronal Bk Channels: A Dissertation, Patricia M. Wynne

GSBS Dissertations and Theses

BK channels are well studied targets of acute ethanol action. They play a prominent role in neuronal excitability and have been shown to play a significant role in behavioral ethanol tolerance in invertebrates. The focus of my work centers on the effects of alcohol on the BK channel and comprises studies that examine how subcellular location affects acute ethanol sensitivity and how duration of acute alcohol exposure impacts the development of rapid tolerance. My results also provide potential mechanisms which underlie acute sensitivity and rapid tolerance.

I first explore BK channel sensitivity to ethanol in the three compartments (dendrite, cell ...


Chromatin Remodeling And Transcriptional Memory: A Dissertation, Sharmistha Kundu Dec 2008

Chromatin Remodeling And Transcriptional Memory: A Dissertation, Sharmistha Kundu

GSBS Dissertations and Theses

Transcriptional regulation of gene expression is critical for all unicellular and multicellular organisms. The ability to selectively induce or repress expression of only a few genes from the entire genome gives cells the ability to respond to changing environmental conditions, grow and proliferate. Multicellular organisms begin life as a single totipotent cell, which undergoes many cell divisions during embryonic and later postnatal development. During this process, the dividing cells of the embryo progressively lose their pluripotency and adopt restricted cell fates. Cell fate restriction leads different cell types to gain unique transcriptional profiles. This transcriptional profile or gene expression pattern ...


Adipocyte Insulin-Mediated Glucose Transport: The Role Of Myosin 1c, And A Method For In Vivo Investigation: A Dissertation, G. Nana Hagan Dec 2008

Adipocyte Insulin-Mediated Glucose Transport: The Role Of Myosin 1c, And A Method For In Vivo Investigation: A Dissertation, G. Nana Hagan

GSBS Dissertations and Theses

The importance of insulin delivery and action is best characterized in Type 2 Diabetes, a disease that is becoming a pandemic both nationally and globally. Obesity is a principal risk factor for Type 2 Diabetes, and adipocyte function abnormalities due to adipose hypertrophy and hyperplasia, have been linked to obesity. Numerous reports suggest that the intracellular and systemic consequences of adipocyte function abnormalities include adipocyte insulin resistance, enhanced production of free fatty acids, and production of inflammatory mediators. A hallmark of adipocyte insulin sensitivity is the stimulation of glucose transporter isoform 4 (GLUT4) trafficking events to promote glucose uptake. In ...


Vps45p As A Model System For Elucidation Of Sec1/Munc18 Protein Function: A Dissertation, Melonnie Lynn Marie Furgason Dec 2008

Vps45p As A Model System For Elucidation Of Sec1/Munc18 Protein Function: A Dissertation, Melonnie Lynn Marie Furgason

GSBS Dissertations and Theses

Vesicular trafficking, the movement of vesicles between organelles and the plasma membrane for secretion, consists of multiple highly regulated processes. Many protein families function as specificity and regulatory determinants to ensure correct vesicle targeting and timing of trafficking events. The SNARE proteins dock and fuse vesicles to their target membranes. Sec1/Munc18 (SM) proteins regulate membrane fusion through interactions with the SNAREs—SM proteins have been shown to act as both inhibitors and stimulators of SNARE assembly and membrane fusion. However, the details of these SM protein functions are not understood.

Constructing a model of SM protein function has been ...


Effect Of Kcne1 And Kcne3 Accessory Subunits On Kcnq1 Potassium Channel Function: A Dissertation, Jessica Marie Rocheleau Dec 2008

Effect Of Kcne1 And Kcne3 Accessory Subunits On Kcnq1 Potassium Channel Function: A Dissertation, Jessica Marie Rocheleau

GSBS Dissertations and Theses

The KCNE1 and KCNE3 type I transmembrane-spanning β-subunits assemble with the KCNQ1 voltage-gated K+ channel to afford membrane-embedded complexes with dramatically different properties. Assembly with KCNE1 produces the very slowly activating and deactivating IKs current that shapes the repolarization phase of cardiac action potentials. Genetic mutations in KCNQ1 or KCNE1 that reduce IKs current cause long QT syndrome and predispose affected individuals to potentially fatal cardiac arrhythmias. In contrast, complexes formed between KCNQ1 and KCNE3 produce rapidly activating and mostly voltage-independent currents, properties that are essential for function in K+ recycling and Clsecretion in gastrointestinal epithelia.

This ...


Pirna Function And Biogenesis In The Drosophila Female Germline: A Dissertation, Carla Andrea Klattenhoff Nov 2008

Pirna Function And Biogenesis In The Drosophila Female Germline: A Dissertation, Carla Andrea Klattenhoff

GSBS Dissertations and Theses

The studies presented in this thesis addressed mainly two aspects of Piwi-interacting RNA (piRNA) biology in the Drosophilagermline.

We investigated the role of the piRNA pathway in embryonic axis specification. piRNAs mediate silencing of retrotransposons and the Stellate locus. Mutations in the Drosophila piRNA pathway genes armitage and aubergine disrupt embryonic axis specification, triggering defects in microtubule polarization and asymmetric localization of mRNA and protein determinants in the developing oocyte. Mutations in the ATR/Chk2 DNA damage signal transduction pathway dramatically suppress these axis specification defects, but do not restore retrotransposon or Stellatesilencing. Furthermore, piRNA pathway mutations lead ...


Role Of Tnf In Heterologous Immunity Between Lymphocytic Choriomeningitis Virus And Vaccinia Virus: A Dissertation, Siwei Nie Nov 2008

Role Of Tnf In Heterologous Immunity Between Lymphocytic Choriomeningitis Virus And Vaccinia Virus: A Dissertation, Siwei Nie

GSBS Dissertations and Theses

Prior immunity to a related or unrelated pathogen greatly influences the host’s immune response to a subsequent infection and can cause a dramatic difference in disease course, a phenomenon known as heterologous immunity. Heterologous immunity can influence protective immunity, immunopathology and/or immune deviation of cytokine-producing T cell subsets. Examples of heterologous immunity have been well documented in mouse models, as well as during human infections. For example, prior immunity to lymphocytic choriomeningitis virus (LCMV) provides partial protection against vaccinia virus (VV), as LCMV-immune mice show reduced VV titers and increased survival upon lethal dose VV infection. Heterologous protection ...


Regulation Of Reactive Nitrogen Species (Rns) Metabolism And Resistance Mechanisms In Haemophilus Influenzae: A Dissertation, Jane Colleen Harrington Nov 2008

Regulation Of Reactive Nitrogen Species (Rns) Metabolism And Resistance Mechanisms In Haemophilus Influenzae: A Dissertation, Jane Colleen Harrington

GSBS Dissertations and Theses

Haemophilus influenzae encounters niches within the human host that are predicted to differ in availability of oxygen and reactive nitrogen species (RNS: nitrite and nitric oxide), which influence the environmental redox state. Previously reported data has indicated that an altered redox condition could serve as a signal recognized by H. influenzae to optimize its survival within host microenvironments. To elucidate the role of redox signaling in virulence, we examined regulation by the FNR homolog of H. influenzae, whose counterpart in E. coli has been reported to be a direct oxygen sensor and a regulator of genes responsible for RNS metabolism ...


The Role Of Janus-Kinase-3 In Cd4+ T Cell Proliferation And Differentiation: A Dissertation, Min Shi Oct 2008

The Role Of Janus-Kinase-3 In Cd4+ T Cell Proliferation And Differentiation: A Dissertation, Min Shi

GSBS Dissertations and Theses

Jak3, a member of the Janus family of tyrosine kinases, is essential for signaling via the receptors for IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21. These Jak3-dependent cytokines primarily activate STAT5 and are critical for lymphoid generation and differentiation. Using naïve CD4+ T cells from Jak3-deficient mice and wild type CD4+ T cells treated with a pharmacological inhibitor of Jak3, we report that Jak3-dependent cytokine signals are not required for the proliferation of naïve CD4+ T cells. This is illustrated by the similar percentage of divided cells, comparable cell divisions, intact cell cycle progression and unaffected regulation of cell cycle ...


Dna Damage-Induced Apoptosis In The Presence And Absence Of The Tumor Suppressor P53: A Dissertation, Laura Michelle Mcnamee Oct 2008

Dna Damage-Induced Apoptosis In The Presence And Absence Of The Tumor Suppressor P53: A Dissertation, Laura Michelle Mcnamee

GSBS Dissertations and Theses

A key regulator of DNA damage-induced apoptosis is the tumor suppressor gene, p53. p53 is a transcription factor that upregulates genes involved in cell cycle arrest, apoptosis, and senescence. How p53 decides to activate one of these responses in response to DNA damage is largely unanswered. Many have hypothesized it is due to interaction with various signaling pathways and post-translational modification. The p53 tumor suppressor can be modified by SUMO-1 in mammalian cells, but the functional consequences of this modification are unclear. Conjugation to SUMO is a reversible post-translational modification that regulates several transcription factors involved in cell proliferation, differentiation ...


Modulation Of Voltage-Gated N-Type Calcium Channels By G Protein-Coupled Receptors Involves Lipids And Proteins: A Dissertation, Tora Mitra Ganguli Oct 2008

Modulation Of Voltage-Gated N-Type Calcium Channels By G Protein-Coupled Receptors Involves Lipids And Proteins: A Dissertation, Tora Mitra Ganguli

GSBS Dissertations and Theses

Pain signaling involves transmission of nociceptive stimuli in the spinal cord where a critical balance between excitatory and inhibitory inputs determines the response to noxious stimuli. The neuropeptide, substance P (SP), mediates transmission of pain in part by binding to the tachykinin receptor (NK-1R) in the dorsal horn (DH) of the spinal cord. One of SP’s downstream effects is to modulate N-type Ca2+(N-) channels. While phospholipid breakdown is a part of the inflammatory process that accompanies tissue damage, the role of this metabolic pathway has not been completely described with respect to N-channel modulation during pain signaling ...


The Molecular Mechanisms Underlying The Polarized Distribution Of Drosophila Dscam In Neurons: A Dissertation, Shun-Jen Yang Oct 2008

The Molecular Mechanisms Underlying The Polarized Distribution Of Drosophila Dscam In Neurons: A Dissertation, Shun-Jen Yang

GSBS Dissertations and Theses

Neurons exhibit highly polarized structures, including two morphologically and functionally distinct domains, axons and dendrites. Dendrites and axons receive versus send information, and proper execution of each requires different sets of molecules. Differential distribution of membrane proteins in distinct neuronal compartments plays essential roles in neuronal functions. The major goal of my doctoral thesis was to study the molecular mechanisms that govern the differential distribution of membrane proteins in neurons, using the Drosophilalarval mushroom body (MB) as a model system.

My work was initiated by an observation of differential distribution of distinct Dscam isoforms in neurons. Dscam stands for ...


Structural And Functional Studies Of The Kcnq1-Kcne K+ Channel Complex: A Dissertation, Steven D. Gage Sep 2008

Structural And Functional Studies Of The Kcnq1-Kcne K+ Channel Complex: A Dissertation, Steven D. Gage

GSBS Dissertations and Theses

KCNQ1 is a homotetrameric voltage-gated potassium channel expressed in cardiomyocytes and epithelial tissues. However, currents arising from KCNQ1 have never been physiologically observed. KCNQ1 is able to provide the diverse potassium conductances required by these distinct cell types through coassembly with and modulation by type I transmembrane β-subunits of the KCNE gene family.

KCNQ1-KCNE K+ channels play important physiological roles. In cardiac tissues the association of KCNQ1 with KCNE1 gives rise to IKs, the slow delayed outwardly rectifying potassium current. IKs is in part responsible for repolarizing heart muscle, and is therefore crucial in maintaining normal heart rhymicity ...


Checkpoint Regulation Of S-Phase Transcription: A Dissertation, Chaitali Dutta Sep 2008

Checkpoint Regulation Of S-Phase Transcription: A Dissertation, Chaitali Dutta

GSBS Dissertations and Theses

The DNA replication checkpoint transcriptionally up-regulates genes that allow cells to adapt to and survive replication stress. Our results show that, in the fission yeast Schizosaccharomyces pombe, the replication checkpoint regulates the entire G1/S transcriptional program by directly regulating MBF (aka DSC1), the G1/S transcription factor. Instead of initiating a checkpoint-specific transcriptional program, the replication checkpoint targets MBF to maintain the normal G1/S transcriptional program during replication stress. We propose a mechanism for this regulation, based on in vitrophosphorylation of the Cdc10 subunit of MBF by the Cds1 replication-checkpoint kinase. Substitution of two potential phosphorylation sites ...


Roles For Histones H4 Serine 1 Phosphorylation In Dna Double Strand Break Repair And Chromatin Compaction: A Dissertation, Melissa Anne Foley Aug 2008

Roles For Histones H4 Serine 1 Phosphorylation In Dna Double Strand Break Repair And Chromatin Compaction: A Dissertation, Melissa Anne Foley

GSBS Dissertations and Theses

The study of DNA templated events is not complete without considering the chromatin environment. Histone modifications help to regulate gene expression, chromatin compaction and DNA replication. Because DNA damage repair must occur within the context of chromatin, many remodeling enzymes and histone modifications work in concert to enable access to the DNA and aid in restoration of chromatin after repair is complete. CK2 has recently been identified as a histone modifying enzyme. In this study we identify CK2 as a histone H3 tail kinase in vitro, identify the phospho-acceptor site in vitro, and characterize the modification in vivo in S ...


Chemical-Biological Investigation Of Kcnq1/Kcne K+ Channel Complexes: A Dissertation, Trevor J. Morin Aug 2008

Chemical-Biological Investigation Of Kcnq1/Kcne K+ Channel Complexes: A Dissertation, Trevor J. Morin

GSBS Dissertations and Theses

KCNE β-subunits modulate KCNQ1 (Q1) voltage-gate K+channels providing the current diversity required for Q1 channels to function in a wide variety of cell types and tissues. In the present thesis, the stoichiometry of KCNE1 (E1) β-subunits in functioning Q1 channels is investigated, along with the formation of heteromeric channel complexes, complexes containing 2 different KCNE β-subunits. The chemical approaches used to answer these questions were then expanded to generate a novel labeling reagent.

To determine the stoichiometry of the Q1/E1 complex, I devised an iterative subunit counting approach that relies on a chemically releasable K+channel blocking reagent ...


Toll-Like Receptors: Target Of Hepatitis C Virus: A Dissertation, Serena Soyoung Yunmee Chang Aug 2008

Toll-Like Receptors: Target Of Hepatitis C Virus: A Dissertation, Serena Soyoung Yunmee Chang

GSBS Dissertations and Theses

Hepatitis C Virus (HCV) is the primary cause of liver transplantation due to its chronic nature in up to eighty percent of infected cases. Around 3 percent of the world’s population is infected with HCV. Treatment for HCV is a combined Ribavirin and interferon-α (IFN-α) therapy effective in only fifty to eighty percent of patients depending on HCV genotype. The growing health concern with this disease is the lack of a cure despite liver transplantation. HCV targets hepatocytes, liver cells, but is not cytolytic. HCV has been shown to induce end stage liver disease through sustained inflammation from the ...


Glut1 Structure Function; Context, Ligand Cooperativity, And Mutagenesis Studies: A Dissertation, Trista K. Robichaud Jul 2008

Glut1 Structure Function; Context, Ligand Cooperativity, And Mutagenesis Studies: A Dissertation, Trista K. Robichaud

GSBS Dissertations and Theses

Carrier mediated nutrient import is vital for cell and tissue homeostasis. Structural insights of carrier mediated transport, particularly the human glucose transporter GLUT1, are essential for understanding the mechanisms of human metabolic disease, and provide model systems for cellular processes as a whole.

GLUT1 function and expression is characterized by a complexity unexplained by the current hypotheses for carrier-mediated sugar transport (9). It is possible that the operational properties of GLUT1 are determined by host cell environment. A glucose transport-null strain of Saccharomyces cerevisiae(RE700A) was transfected with the p426 GPD yeast expression vector containing DNA encoding the wild-type human ...


Role Of Map4k4 Signaling In Adipocyte And Macrophage Derived Inflammation: A Dissertation, Gregory J. Tesz Jul 2008

Role Of Map4k4 Signaling In Adipocyte And Macrophage Derived Inflammation: A Dissertation, Gregory J. Tesz

GSBS Dissertations and Theses

Human obesity is increasing globally at an impressive rate. The rise in obesity has led to an increase in diseases associated with obesity, such as type 2 diabetes. A major prerequisite for this disease is the development of insulin resistance in the muscle and adipose tissues. Interestingly, experiments in rodent models suggest that adipocytes and macrophages can profoundly influence the development of insulin resistance. Accordingly, the number of adipose tissue macrophages increases substantially during the development of obesity. Numerous research models have demonstrated that macrophages promote insulin resistance by secreting cytokines, like TNFα, which impair whole body insulin sensitivity and ...


Analysis Of Protein Arginine Methyltransferase Function During Myogenic Gene Transcription: A Dissertation, Caroline S. Dacwag Jul 2008

Analysis Of Protein Arginine Methyltransferase Function During Myogenic Gene Transcription: A Dissertation, Caroline S. Dacwag

GSBS Dissertations and Theses

Skeletal muscle differentiation requires synergy between tissue-specific transcription factors, chromatin remodeling enzymes and the general transcription machinery. Here we demonstrate that two distinct protein arginine methyltransferases are required to complete the differentiation program. Prmt5 is a type II methyltransferase, symmetrically dimethylates histones H3 and H4 and has been shown to play a role in transcriptional repression. An additional member of the Prmt family, Carm1 is a type I methyltransferase, and asymmetrically methylates histone H3 and its substrate proteins. MyoD regulates the activation of the early class of skeletal muscle genes, which includes myogenin. Prmt5 was bound to and dimethylates H3R8 ...


Role Of Endoplasmic Reticulum Stress Response Signaling In T Cells: A Dissertation, Steven C. Pino Jul 2008

Role Of Endoplasmic Reticulum Stress Response Signaling In T Cells: A Dissertation, Steven C. Pino

GSBS Dissertations and Theses

T cells play a central role in cellular-mediated immunity and must become activated to participate as effector cells in the immune response. The activation process is highly intricate and involves stimulation of a number of downstream signaling pathways enabling T cells to proliferate and produce cytokines that are vital for proper effector function. This increase in protein production and protein folding activity adds to the normal physiological strain on cellular machinery. One cellular compartment that has generated a mechanism to mitigate the stress induced by increased protein production is the endoplasmic reticulum (ER).

In general, an increase in cellular production ...


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 ...


Role Of Disulfide Bond Rearrangement In Newcastle Disease Virus Entry: A Dissertation, Surbhi Jain Jun 2008

Role Of Disulfide Bond Rearrangement In Newcastle Disease Virus Entry: A Dissertation, Surbhi Jain

GSBS Dissertations and Theses

Newcastle disease virus (NDV), an avian paramyxovirus, enters the host cell by fusion of viral and host cell membranes. The fusion of two membranes is mediated by the viral fusion (F) protein. The F protein, like other class I fusion proteins, is thought to undergo major conformational changes during the fusion process. The exact mechanism that leads to major refolding of F protein is not clear. Recently, it has been proposed that disulfide bond reduction in the fusion protein of some viruses may be involved in the conformational changes in fusion proteins. In some viruses, the reduction of disulfide bonds ...


The Role Of Tec Family Kinases In Innate T Cell Development And Function: A Dissertation, Martin Felices Jun 2008

The Role Of Tec Family Kinases In Innate T Cell Development And Function: A Dissertation, Martin Felices

GSBS Dissertations and Theses

The Tec family kinases Itk and Rlk have been previously shown to have an important role in signaling downstream of the T cell receptor [TCR]. Almost all of the work done in the past on these two kinases looked at their role in conventional αβ T cells, specifically CD4+ T cells. These studies demonstrated functions for Itk [primarily] and Rlk in T cell development, activation, and differentiation. However, despite the wealth of knowledge on conventional CD4+ T cells, prior to the work presented here little to no studies addressed the role of Tec family kinases on CD8+ or innate T ...


Small Rna Sorting In Drosophila Produces Chemically Distinct Functional Rna-Protein Complexes: A Dissertation, Michael D. Horwich Jun 2008

Small Rna Sorting In Drosophila Produces Chemically Distinct Functional Rna-Protein Complexes: A Dissertation, Michael D. Horwich

GSBS Dissertations and Theses

Small interfering RNAs (siRNAs), microRNAs (miRNAs), and piRNAs (piRNA) are conserved classes of small single-stranded ~21-30 nucleotide (nt) RNA guides that repress eukaryotic gene expression using distinct RNA Induced Silencing Complexes (RISCs). At its core, RISC is composed of a single-stranded small RNA guide bound to a member of the Argonaute protein family, which together bind and repress complementary target RNA. miRNAs target protein coding mRNAs—a function essential for normal development and broadly involved in pathways of human disease; small interfering RNAs (siRNA) defend against viruses, but can also be engineered to direct experimental or therapeutic gene silencing; piwi ...


Notch-1 And Igf-1 As Survivin Regulatory Pathways In Cancer: A Dissertation, Connie Wing-Ching Lee Jun 2008

Notch-1 And Igf-1 As Survivin Regulatory Pathways In Cancer: A Dissertation, Connie Wing-Ching Lee

GSBS Dissertations and Theses

The 21st century brought about a dramatic increase in knowledge about genetic and molecular profiles of cancer. This information has validated the complexity of tumor cells and increased awareness of “nodal proteins”, but has yet to advance the development of rational targeted cancer therapeutics. Nodal proteins are critical cellular proteins that collect biological inputs and distribute the information across diverse biological processes. Survivin acts as a nodal protein by interfacing the multiple signals involved in mitosis and apoptosis and functionally integrate proliferation, cell death, and cellular homeostasis. By characterizing survivin as a target of both Type 1 Insulin-like Growth ...


Analysis Of Cpeb Family Protein Member Cpeb4 Function In Mammalian Neurons: A Dissertation, Ming-Chung Kan Jun 2008

Analysis Of Cpeb Family Protein Member Cpeb4 Function In Mammalian Neurons: A Dissertation, Ming-Chung Kan

GSBS Dissertations and Theses

Local protein synthesis is required for long-term memory formation in the brain. One protein family, Cytoplasmic Polyadenylation Element binding Protein (CPEB) that regulates protein synthesis is found to be important for long-term memory formation possibly through regulating local protein synthesis in neurons. The well-studied member of this family, CPEB1, mediates both translational repression and activation of its target mRNAs by regulating mRNA polyadenylation. Mouse with CPEB1 KO shows defect in memory extinction but not long-term memory formation. Three more CPEB1 homologs (CPEB2-4) are identified in mammalian system. To test if CPEB2-4 may have redundant role in replacing CPEB1 in mediating ...


A Study Of Cell Polarity And Fate Specification In Early C. Elegans Embryos: A Dissertation, Soyoung Kim May 2008

A Study Of Cell Polarity And Fate Specification In Early C. Elegans Embryos: A Dissertation, Soyoung Kim

GSBS Dissertations and Theses

Asymmetric cell divisions constitute a basic foundation of animal development, providing a mechanism for placing specific cell types at defined positions in a developing organism. In a 4-cell stage embryo in Caenorhabditis elegansthe EMS cell divides asymmetrically to specify intestinal cells, which requires a polarizing signal from the neighboring P2 cell. Here we describe how the extracellular signal from P2 is transmitted from the membrane to the nucleus during asymmetric EMS cell division, and present the identification of additional components in the pathways that accomplish this signaling.

P2/EMS signaling involves multiple inputs, which impinge on the Wnt, MAPK-like ...