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GSBS Dissertations and Theses

2010

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Clinical Course Of Bipolar Disorder During The Menopausal Transition: Comparison With Reproductive Age And Post Menopausal Women: A Master's Thesis, Wendy K. Marsh Dec 2010

Clinical Course Of Bipolar Disorder During The Menopausal Transition: Comparison With Reproductive Age And Post Menopausal Women: A Master's Thesis, Wendy K. Marsh

GSBS Dissertations and Theses

Introduction: The late menopausal transition is a time of increased risk of depression in the general population. Nonetheless, mood course during the late menopausal transition in women with bipolar disorder in relatively unknown.

Methods: Mood state data in 519 reproductive age women (5989 clinic visits), 116 late menopausal transition (perimenopausal) women (2046 visits), and 133 postmenopausal women (1,437 visits) with bipolar disorder who were receiving optimized naturalistic treatment in the multisite STEP-BD study over an average of 19.8±15.5 months were analyzed for proportion of clinic visits with syndromal depression, mood elevation and euthymia between the three ...


Host Cell Attachment By Lyme Disease And Relapsing Fever Spirochetes: A Dissertation, Vivian M. Benoit Dec 2010

Host Cell Attachment By Lyme Disease And Relapsing Fever Spirochetes: A Dissertation, Vivian M. Benoit

GSBS Dissertations and Theses

Host cell attachment by pathogenic bacteria can play very different roles in the course of infection. The pathogenic spirochetes Borrelia hermsii and Borrelia burgdorferi sensu lato which cause relapsing fever and Lyme disease, respectively, are transmitted by the bite of infected ticks. After transmission, these spirochetes can cause systemic infection. Relapsing fever spirochetes remain largely in the bloodstream causing febrile episodes, while Lyme disease will often colonize a variety of tissues, such as the heart, joint and nervous system, resulting in a chronic multisystemic disorder. Borrelia species have the ability to bind to various cell types, a process which plays ...


Immunity, Pathogenesis, And Prevention Of Poxvirus Infections: A Dissertation, Mina O. Seedhom Dec 2010

Immunity, Pathogenesis, And Prevention Of Poxvirus Infections: A Dissertation, Mina O. Seedhom

GSBS Dissertations and Theses

Vaccinia virus (VAC) is the prototypical member of the orthopoxvirus genus of the poxvirus family and the virus used for smallpox vaccinations. The following describes the testing of VAC variants designed to have similar immuno-protective profiles with decreased pathogenicity, examines the immune response to VAC after lethal infection in wild type and lupus-prone mice, and describes a method that allows for the enumeration of VAC-specific CD8+ T in naïve and VAC-immune mice.

The first part describes work examining VAC Wyeth (VAC-Wy) variants engineered to be less pathogenic in vivo. VAC-Wy variants included genes that code for three immunomodulatory proteins, an ...


The C Terminus Of Activation Induced Cytidine Deaminase (Aid) Recruits Proteins Important For Class Switch Recombination To The Ig Locus: A Dissertation, Sanjay Ranjit Dec 2010

The C Terminus Of Activation Induced Cytidine Deaminase (Aid) Recruits Proteins Important For Class Switch Recombination To The Ig Locus: A Dissertation, Sanjay Ranjit

GSBS Dissertations and Theses

Activation-induced cytidine deaminase (AID) is a key protein required for both class switch recombination (CSR) and somatic hypermutation (SHM) of antibody genes. AID is induced in B cells during an immune response. Lack of AID or mutant form of AID causes immunodeficiency; e.g., various mutations in the C terminus of AID causes hyper IgM (HIGM2) syndrome in humans. The C terminal 10 amino acids of AID are required for CSR but not for SHM. During both CSR and SHM, AID deaminates dCs within Ig genes, converting them to dUs, which are then either replicated over, creating mutations, or excised ...


Axon Death Prevented: WldS And Other Neuroprotective Molecules: A Dissertation, Michelle A. Avery Dec 2010

Axon Death Prevented: WldS And Other Neuroprotective Molecules: A Dissertation, Michelle A. Avery

GSBS Dissertations and Theses

A common feature of many neuropathies is axon degeneration. While the reasons for degeneration differ greatly, the process of degeneration itself is similar in most cases. Axon degeneration after axotomy is termed ‘Wallerian degeneration,’ whereby injured axons rapidly fragment and disappear after a short period of latency (Waller, 1850). Wallerian degeneration was thought to be a passive process until the discovery of the Wallerian degeneration slow (Wlds) mouse mutant. In these mice, axons survive and function for weeks after nerve transection. Furthermore, when the full-length protein is inserted into mouse models of disease with an axon degeneration phenotype (such ...


Cd8+ T Cell Serotype-Cross-Reactivity Is A Predominant Feature Of Dengue Virus Infections In Humans: A Dissertation, Heather L. Friberg-Robertson Nov 2010

Cd8+ T Cell Serotype-Cross-Reactivity Is A Predominant Feature Of Dengue Virus Infections In Humans: A Dissertation, Heather L. Friberg-Robertson

GSBS Dissertations and Theses

The four serotypes of dengue virus (DENV 1-4) have a significant and growing impact on global health. Dengue disease encompasses a wide range of clinical symptoms, usually presenting as an uncomplicated febrile illness lasting 5-7 days; however, a small percentage of infections are associated with plasma leakage and bleeding tendency (called dengue hemorrhagic fever, DHF), which can result in shock. Epidemiological studies indicate that severe dengue disease most often occurs during secondary heterotypic DENV infection. Additionally, plasma leakage (the hallmark of DHF) coincides with defervescence and viral clearance, suggesting that severe disease arises from the immune response to infection rather ...


Mri Contrast Agent Studies Of Compartmental Differentiation, Dose-Dependence, And Tumor Characterization In The Brain: A Dissertation, Mohammed S. Shazeeb Nov 2010

Mri Contrast Agent Studies Of Compartmental Differentiation, Dose-Dependence, And Tumor Characterization In The Brain: A Dissertation, Mohammed S. Shazeeb

GSBS Dissertations and Theses

Magnetic resonance imaging (MRI) has increasingly become the preferred imaging modality in modern day research to study disease. MRI presents an imaging technique that is practically non-invasive and without any ionizing radiation. This dissertation presents the use of contrast agents in MRI studies to differentiate compartments, to study dose dependence of relaxation times, and to characterize tumors using signal amplifying enzymes in the brain.

Differentiating compartments in the brain can be useful in diffusion studies to detect stroke at an early stage. Diffusion-weighted NMR techniques have established that the apparent diffusion coefficient (ADC) of cerebral tissue water decreases during ischemia ...


A Mindfulness-Based Intervention For Treatment Of Anxiety In Icd Patients: Feasibility And Baseline Findings: A Dissertation, Elena Salmoirago Blotcher Nov 2010

A Mindfulness-Based Intervention For Treatment Of Anxiety In Icd Patients: Feasibility And Baseline Findings: A Dissertation, Elena Salmoirago Blotcher

GSBS Dissertations and Theses

Background. Primary and secondary prevention trials have shown that implantable cardioverter-defibrillators (ICD) reduce the risk of cardiac death, but concerns have been raised regarding the psychological well-being of ICD patients. Anxiety can affect a significant proportion of these patients, but there is limited information about prevalence and determinants of anxiety after the implementation of the more recent guidelines for ICD implantation. Several behavioral interventions have been effective in improving anxiety in these patients, however the efficacy of mindfulness-based interventions (MBI) has not been investigated in ICD patients, and there is limited information regarding the characteristics of pre-intervention, “dispositional” mindfulness in ...


Converging Pathways In The Regulation Of Longevity And Metabolism In Caenorhabditis Elegans: A Dissertation, Sri Devi Narasimhan Nov 2010

Converging Pathways In The Regulation Of Longevity And Metabolism In Caenorhabditis Elegans: A Dissertation, Sri Devi Narasimhan

GSBS Dissertations and Theses

The lifespan of an organism is determined by a complex array of genetic, environmental and nutritional factors. Yet single gene manipulations have been shown to significantly extend lifespan in several model organisms. Of all the genes that have been studied thus far, components of the insulin/IGF-1 signaling (IIS) pathway have emerged as the most robust regulators of longevity. In addition, IIS also regulates development, energy metabolism and the response to stress in a conserved manner. In Caenorhabditis elegans, signaling through this pathway is initiated by activation of the insulin/IGF-1 receptor tyrosine kinase DAF-2, which then activates a PI3-kinase ...


Beyond Toll-Like Receptor 9: Interactions Between Plasmacytoid Dendritic Cells And Aspergillus Fumigatus: A Dissertation, Zaida G. Ramirez-Ortiz Oct 2010

Beyond Toll-Like Receptor 9: Interactions Between Plasmacytoid Dendritic Cells And Aspergillus Fumigatus: A Dissertation, Zaida G. Ramirez-Ortiz

GSBS Dissertations and Theses

The opportunistic fungus, Aspergillus fumigatus, is a leading cause of morbidity and mortality among the immunocompromised population. Experimental and clinical findings have established that phagocytic defenses are critical in the recognition and clearance of A. fumigatus. Previous studies found that Toll-like receptors (TLRs), specifically TLR2 and TLR4, were essential in the detection of the mold. Furthermore, one study found that mice deficient in TLR9 lived longer than their wild-type counterparts following challenge with A. fumigatus. We sought to determine the role of TLR9 during A. fumigatus infection. Our results show that A. fumigatus contains unmethylated CpG DNA, the natural ligand ...


Drosophila Pirna Function In Genome Maintenance, Telomere Protection And Genome Evolution: A Dissertation, Jaspreet S. Khurana Oct 2010

Drosophila Pirna Function In Genome Maintenance, Telomere Protection And Genome Evolution: A Dissertation, Jaspreet S. Khurana

GSBS Dissertations and Theses

Upon fertilization, the early embryo sustains most of the cellular processes using the maternally deposited reserves in the egg itself until the zygotic gene expression takes charge. Among the plethora of essential components provided by the mother are small non-coding RNAs called PIWI-interacting RNAs (piRNAs), which provide immunity to the zygote against transposon challenge. In this thesis, I have presented three different functions of piRNAs in Drosophila melanogaster- in maintenance of genomic integrity, telomere protection and their role as an adaptive immune system against genomic parasites.

In Chapter 2, I have described the phenotypic effects of the loss of piRNA ...


Regulation Of Cellular And Hiv-1 Gene Expression By Positive Transcription Elongation Factor B: A Dissertation, Siobhan O'Brien Oct 2010

Regulation Of Cellular And Hiv-1 Gene Expression By Positive Transcription Elongation Factor B: A Dissertation, Siobhan O'Brien

GSBS Dissertations and Theses


RNA polymerase II-mediated transcription of HIV-1 genes depends on positive transcription elongation factor b (P-TEFb), the complex of cyclin T1 and CDK9. Recent evidence suggests that regulation of transcription by P-TEFb involves chromatin binding and modifying factors. To determine how P-TEFb may connect chromatin remodeling to transcription, we investigated the relationship between P-TEFb and histone H1. We show that P-TEFb interacts with H1 and that H1 phosphorylation in cell culture correlates with P-TEFb activity. Importantly, P-TEFb also directs H1 phosphorylation during Tat transactivation and wild type HIV-1 infection. Our results also show that P-TEFb phosphorylates histone H1.1 at a ...


Acute Modulation Of Endothelial Cell Glucose Transport: A Dissertation, Anthony J. Cura Oct 2010

Acute Modulation Of Endothelial Cell Glucose Transport: A Dissertation, Anthony J. Cura

GSBS Dissertations and Theses

Studies have demonstrated that under conditions of chronic metabolic stress, GLUT1-mediated sugar transport is upregulated at the blood-brain barrier by a number of mechanisms. Although acute metabolic stress has also been shown to increase GLUT1-mediated transport, the mechanisms underlying this regulation remain unclear. This work attempts to explain how GLUT1-mediated sugar uptake is increased during acute metabolic stress, as well as explore the factors involved in this modulation of sugar transport in blood-brain barrier endothelial cells. Glucose depletion, KCN and FCCP were applied to brain microvascular endothelial cell line bEnd.3 in order to induce acute metabolic stress by ATP ...


Generating Nucleosomal Asymmetry In Saccharomyces Cerevisiae: A Masters Thesis, Yuanyuan Chen Oct 2010

Generating Nucleosomal Asymmetry In Saccharomyces Cerevisiae: A Masters Thesis, Yuanyuan Chen

GSBS Dissertations and Theses

There are two copies of each core histone in a nucleosome, however, it is unclear whether post-translational modifications on each molecule function redundantly or if symmetrical modifications are required to properly regulate gene expression. We tried to address this question by breaking nucleosomal symmetry and measuring its impact on gene expression. Our strategy includes re-engineering specific residues at the H3-H3 interface, generating pairs of mutant proteins, which were predicted by computational methods to form obligate heterodimers. Using S. cerevisiae as a model system, we tested the viability of strains with mutant histones, and analyzed the interaction between by co-immunoprecipitation from ...


Energy Metabolism And The Induction Of The Unfolded Protein Response: A Dissertation, Alison M. Burkart Sep 2010

Energy Metabolism And The Induction Of The Unfolded Protein Response: A Dissertation, Alison M. Burkart

GSBS Dissertations and Theses

White adipose plays a major role in the regulation of whole body metabolism through the storage and hydrolysis of triglycerides and by secretion of adipokines. The function of endocrine cells is highly dependent on the unfolded protein response (UPR), a homeostatic signaling mechanism that balances the protein folding capacity of the endoplasmic reticulum (ER) with the cell's secretory protein load. Here we demonstrate that the adipocyte UPR pathway is necessary for its secretory functions, and can thus play a crucial role in the control of whole body energy homeostasis. ER protein folding capacity is dependent both on the number ...


A Glia-Mediated Feedback Mechanism For The Termination Of Drosophila Visual Response: A Dissertation, Peiyi Guo Sep 2010

A Glia-Mediated Feedback Mechanism For The Termination Of Drosophila Visual Response: A Dissertation, Peiyi Guo

GSBS Dissertations and Theses

High temporal resolution of vision relies on the rapid kinetics of the photoresponse in the light-sensing photoreceptor neurons. It is well known that the rapid recovery of photoreceptor membrane potential at the end of light stimulation depends on timely deactivation of the visual transduction cascade within photoreceptors. Whether any extrinsic factor contributes to the termination speed of the photoresponse is unknown.

In this thesis, using Drosophilaas a model system, I show that a feedback circuit mediated by both neurons and glia in the visual neuropile lamina is required for rapid repolarization of the photoreceptor at the end of the ...


Mitochondrial Dysfunction And Akt Isoform-Specific Regulation In 3t3-L1 Adipocytes: A Dissertation, Xiarong Shi Sep 2010

Mitochondrial Dysfunction And Akt Isoform-Specific Regulation In 3t3-L1 Adipocytes: A Dissertation, Xiarong Shi

GSBS Dissertations and Theses

Excess food consumption and/or lack of exercise have dramatically contributed to the prevalence of overweight (BMI≥25) and obesity (BMI≥30) in modern society. The obesity epidemic has been linked to the rise in type 2 diabetes. In recent years, evidence has pointed to a close association between mitochondrial dysfunction in white adipose tissue (WAT) and insulin resistance, a key feature of type 2 diabetes. In order to dissect the cause and effect relationship between WAT mitochondrial dysfunction and insulin resistance, we established an in vitro cell line system to investigate this issue. We artificially introduced mitochondrial dysfunction in ...


Regulation Of Early T Cell Activation By Tnf Superfamily Members Tnf And Fasl: A Dissertation, Bhavana Priyadharshini Sep 2010

Regulation Of Early T Cell Activation By Tnf Superfamily Members Tnf And Fasl: A Dissertation, Bhavana Priyadharshini

GSBS Dissertations and Theses

The instructive signals received by T cells during the programming stages of activation will determine the fate of effector and memory populations generated during an immune response. Members of the tumor necrosis factor (TNF) superfamily play an essential role in influencing numerous aspects of T cell adaptive immune responses including cell activation, differentiation, proliferation, survival, and apoptosis. My thesis dissertation describes the involvement of two such members of the TNF superfamily, TNF and FasL, and their influence on the fate of T cells early during responses to viral infections and to the induction of transplantation tolerance.

TNF is a pleiotropic ...


Elucidating The Transcriptional Network Underlying Expression Of A Neuronal Nicotinic Receptor Gene: A Dissertation, Michael D. Scofield Sep 2010

Elucidating The Transcriptional Network Underlying Expression Of A Neuronal Nicotinic Receptor Gene: A Dissertation, Michael D. Scofield

GSBS Dissertations and Theses

Neuronal nicotinic acetylcholine receptors (nAChRs) are involved in a plethora of fundamental biological processes ranging from muscle contraction to the formation of memories. The studies described in this work focus on the transcriptional regulation of the CHRNB4 gene, which encodes the ß4 subunit of neuronal nAChRs. We previously identified a regulatory sequence (5´– CCACCCCT –3´), or “CA box”, critical for CHRNB4 promoter activity in vitro. Here I report transcription factor interaction at the CA box along with an in vivo analysis of CA box transcriptional activity. My data indicate that Sp1, Sp3, Sox10 and c-Jun interact with the CHRNB4 CA ...


Magnetic Resonance Imaging Of Neural And Pulmonary Vascular Function: A Dissertation, Ronn P. Walvick Sep 2010

Magnetic Resonance Imaging Of Neural And Pulmonary Vascular Function: A Dissertation, Ronn P. Walvick

GSBS Dissertations and Theses

Magnetic resonance imaging (MRI) has emerged as the imaging modality of choice in a wide variety experimental and clinical applications. In this dissertation, I will describe novel MRI techniques for the characterization of neural and pulmonary vascular function in preclinical models of disease.

In the first part of this dissertation, experimental results will be presented comparing the identification of ischemic lesions in experimental stroke using dynamic susceptibility contrast (DSC) and a well validated arterial spin labeling (ASL). We show that DSC measurements of an index of cerebral blood flow are sensitive to ischemia, treatment, and stroke subregions. Further, we derived ...


Structural And Functional Studies Of Proteins Involved In Antigen Processing: A Dissertation, Tina T. Nguyen Aug 2010

Structural And Functional Studies Of Proteins Involved In Antigen Processing: A Dissertation, Tina T. Nguyen

GSBS Dissertations and Theses

This thesis is comprised of studies of proteins involved in class I and class II major histocompatibility complex (MHC) antigen procressing. In class I MHC processing, structural and functional studies were conducted of an aminopeptidase, ERAP1, that mediates the final step in antigen processing to understand how it is particularly suitable for cleavage of antigenic peptides for class I MHC presentation. In the class II MHC antigen presentation pathway, structural studies were conducted to characterize a fluorogenic peptide that can be used to understand peptide loading events in vivo and in real time. Also structural studies of class II MHC ...


Mechanical Flow Restoration In Acute Ischemic Stroke: A Model System Of Cerebrovascular Occlusion: A Dissertation, Juyu Chueh Aug 2010

Mechanical Flow Restoration In Acute Ischemic Stroke: A Model System Of Cerebrovascular Occlusion: A Dissertation, Juyu Chueh

GSBS Dissertations and Theses

Stroke is the third most common cause of death and a leading cause of disability in the United States. The existing treatments of acute ischemic stroke (AIS) involve pharmaceutical thrombolytic therapy and/or mechanical thrombectomy. The Food and Drug Administration (FDA)-approved recombinant tissue plasminogen activator (tPA) administration for treatment of stroke is efficacious, but has a short treatment time window and is associated with a risk of symptomatic hemorrhage. Other than tPA, the Mechanical Embolus Removal in Cerebral Ischemia (MERCI) retriever system and the Penumbra Aspiration system are both approved by the FDA for retrieval of thromboemboli in AIS ...


Dissecting The Role Of Innate Pattern Recognition Receptors And Interferon Regulatory Factor-5 In The Immune Response To Human Metapneumovirus And Other Pathogens: A Dissertation, Zhaozhao Jiang Aug 2010

Dissecting The Role Of Innate Pattern Recognition Receptors And Interferon Regulatory Factor-5 In The Immune Response To Human Metapneumovirus And Other Pathogens: A Dissertation, Zhaozhao Jiang

GSBS Dissertations and Theses

The Innate immune system is the first line of defense against invading microbial pathogens. It is a fast-acting and non-antigen-specific defense system, which employs germline encoded surveillance systems capable of responding to a broad-spectrum of pathogens. The innate immune system involves a variety of immune cells, which express different profiles of surveillance or detection receptors. Upon sensing pathogens, these receptors trigger cell signalling to turn on transcription of inflammatory cytokines, chemokines, anti-microbial peptides and type I Interferons. These effectors have direct effects on the control of pathogen load and also activate the adaptive immune system, which is ultimately required to ...


Elucidation Of The Multi-Faceted Roles Of The Sin (Septation Initiation Network); Understanding How The Sin Promotes Cytokinesis And Inhibits Interphase Growth In The Fission Yeast Schizosaccharomyces Pombe: A Dissertation, Samriddha Ray Aug 2010

Elucidation Of The Multi-Faceted Roles Of The Sin (Septation Initiation Network); Understanding How The Sin Promotes Cytokinesis And Inhibits Interphase Growth In The Fission Yeast Schizosaccharomyces Pombe: A Dissertation, Samriddha Ray

GSBS Dissertations and Theses

Cytokinesis is the cytoplasmic division of one cell into two independent daughter cells. Precise regulation of cytokinesis during cell cycle is essential for healthy and rapid multiplication of any organism. Schizosaccharomyces pombe has emerged as an excellent model system to study eukaryotic cell division regulation. This rod shaped organism grows by bipolar elongation in interphase when its actin cytoskeleton is concentrated at the cell ends (poles). However, growth stops in mitosis and the actin cytoskeleton is rearranged to facilitate assembly of the contractile actomyosin ring at the cell middle. Although several studies have focused on the separate processes of growth ...


Maternally Derived Anti-Dengue Antibodies And Risk Of Dhf In Infants: A Case-Control Study, Steven Hatch Aug 2010

Maternally Derived Anti-Dengue Antibodies And Risk Of Dhf In Infants: A Case-Control Study, Steven Hatch

GSBS Dissertations and Theses

This study proposes to directly test the hypothesis that antibody-dependent enhancement (ADE) is the critical factor in the development of dengue hemorrhagic fever (DHF) in infants. DHF occurs in two distinct clinical settings: a) in children and adults with secondary DENV infection, and b) in infants with primary DENV infection born to mothers with prior DENV infection. The ADE hypothesis proposes that pre-existing serotype-cross-reactive non-neutralizing anti-DENV antibodies bind the heterotypic DENV during secondary infection and enhance its uptake into immune cells, leading to increased viral load and DHF. This model suggests that DHF in DENV-infected infants is caused by the ...


C. Elegans Metabolic Gene Regulatory Networks: A Dissertation, H. Efsun Arda Jul 2010

C. Elegans Metabolic Gene Regulatory Networks: A Dissertation, H. Efsun Arda

GSBS Dissertations and Theses

In multicellular organisms, determining when and where genes will be expressed is critical for their development and physiology. Transcription factors (TFs) are major specifiers of differential gene expression. By establishing physical contacts with the regulatory elements of their target genes, TFs often determine whether the target genes will be expressed or not. These physical and/or regulatory TF-DNA interactions can be modeled into gene regulatory networks (GRNs), which provide a systems-level view of differential gene expression. Thus far, much of the GRN delineation efforts focused on metazoan development, whereas the organization of GRNs that pertain to systems physiology remains mostly ...


Role Of Cpeb In Senescence And Inflammation: A Dissertation, Maria Ivshina Jul 2010

Role Of Cpeb In Senescence And Inflammation: A Dissertation, Maria Ivshina

GSBS Dissertations and Theses

Cytoplasmic polyadenylation element-binding protein (CPEB) is a sequence-specific RNA-binding protein that promotes polyadenylation-induced translation. While a CPEB knockout (KO) mouse is sterile but overtly normal, embryo fibroblasts derived from this mouse (MEFs) do not enter senescence in culture as do wild-type MEFs, but instead are immortal. Exogenous CPEB restores senescence in the KO MEFs and also induces precocious senescence in wild-type MEFs. CPEB cannot stimulate senescence in MEFs lacking the tumor suppressors p53, p19ARF, or p16INK4A; however, the mRNAs encoding these proteins are unlikely targets of CPEB since their expression is the same in wild-type and KO MEFs ...


Novel Complement Blocking Antibodies Against Serogroup B N. Meningitidis: A Dissertation, Tathagat Dutta Ray Jul 2010

Novel Complement Blocking Antibodies Against Serogroup B N. Meningitidis: A Dissertation, Tathagat Dutta Ray

GSBS Dissertations and Theses

N. meningitidis is a common commensal of the human upper respiratory tract and a leading cause of bacterial meningitis and septicemia worldwide. The classical pathway of complement (C) is essential for both naturally acquired and vaccine induced immunity against N. meningitidis. Qualitative and/or quantitative differences in anti-meningococcal antibodies (Abs) in serum is one reason for variations in C-dependent bactericidal Ab activity among individuals. I showed that IgG isolated from select individuals could block killing of group B meningococci by Abs that were otherwise bactericidal. Ligand overlay immunoblots revealed that these blocking IgG Abs were directed against a meningococcal antigen ...


Post-Transcriptional Control Of Human Cellular Senescence: A Dissertation, David M. Burns Jul 2010

Post-Transcriptional Control Of Human Cellular Senescence: A Dissertation, David M. Burns

GSBS Dissertations and Theses

The central dogma of biology asserts that DNA is transcribed into RNA and RNA is translated into protein. However, this overtly simplistic assertion fails to portray the highly orchestrated and regulated mechanisms of transcription and translation. During the process of transcription, RNA provides the template for translation and protein synthesis as well as the structural and sequence specificity of many RNA and protein-based machines. While only 1-5% of the genome will escape the nucleus to be translated as mRNAs, complex, parallel, highly-conserved mechanisms have evolved to regulate specific mRNAs. Trans-acting factors bind cis-elements in both the 5" and 3" untranslated ...


Endocytosis, Phagocytosis, And Innate Immune Responses: A Dissertation, Christine A. St. Pierre Jul 2010

Endocytosis, Phagocytosis, And Innate Immune Responses: A Dissertation, Christine A. St. Pierre

GSBS Dissertations and Theses

In this dissertation, the roles of endocytosis and phagocytosis pathways in a variety of clinically relevant scenarios were examined. These scenarios include antibody-mediated internalization of cell surface proteins, titanium wear-particle uptake in failed joint replacements, and polymeric microparticle uptake and immune responses for drug delivery or adjuvant use.

The use of antibodies specific for cell surface proteins has become a popular method to deliver therapeutics to target cells. As such, it is imperative to fully understand the ability of antibodies to mediate internalization and endosomal trafficking of the surface protein that it recognizes, so that drug delivery can be optimized ...