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Full-Text Articles in Life Sciences

Site And Mechanism Of Leptin's Antisteatotic And Insulin Sensitizing Actions In Lipodystrophic Liver, Esra Asilmaz Jan 2004

Site And Mechanism Of Leptin's Antisteatotic And Insulin Sensitizing Actions In Lipodystrophic Liver, Esra Asilmaz

Student Theses and Dissertations

An adipocyte hormone which functions as the afferent signal in a negative feedback loop regulating energy balance, has profound effects on glucose and lipid metabolisms. Lipodystrophic humans and mice have a complete or partial absence of adipose tissue and a secondary reduction of leptin. This is associated with insulin resistance and hepatic steatosis, which are corrected by leptin administration. This thesis aimed to define the site of leptin action and understand the molecular basis of leptin's insulin sensitizing and antisteatotic effects in lipodystrophy. To determine the site of leptin action, we treated lipodystrophic aP2-nSREBP-lc mice with a low dose of …


Attenuated Salmonella Typhimurium Can Be Used To Transduce Human Dendritic Cells Towards Vaccination Against Hiv-1, Deborah Gurner Jan 2004

Attenuated Salmonella Typhimurium Can Be Used To Transduce Human Dendritic Cells Towards Vaccination Against Hiv-1, Deborah Gurner

Student Theses and Dissertations

The promise of D N A vaccination is limited in part by invasive, untargeted administration. We refined the strategy by incorporating attenuated bacteria to deliver plasmids directly to APCs. Initial studies involved human macrophages, which were infected with aroASalmonella typhimurium transformed with eukaryotic vectors encoding 8- galactosidase. Results of staining with x-gal demonstrated effective transfer of plasmids to the target cells, which expressed the reporter gene themselves. Similarly, immunocytochemical staining of macrophages infected with bacteria bearing a eukaryotic vector encoding HIV-1 env showed expression of the viral gene. Macrophages were also infected with bacteria harboring vectors encoding SIV env and …


Roles For The E3 Ligase Itch In Immune Response Modulation, Sukhvinder Kaur Sahota Jan 2004

Roles For The E3 Ligase Itch In Immune Response Modulation, Sukhvinder Kaur Sahota

Student Theses and Dissertations

Cloning of the inversion breakpoints in the agouti mutant strain a has implicated the E3 ligase Itch in the spontaneous inflammation that occurs in these mice. 1 RH Anaylsis of a mice suggests that the inflammatory disease is due to a dysregulated T helper type-2 immune response. In order to verify the importance of Itch inactivation in the spontaneous inflammation of a mice and to determine which cell type is responsible for the pathology, the Itch gene has been targeted for conditional deletion in mice using the Cre-loxP system. The results presented in this thesis provide the first direct evidence …


Molecular Basis Of Vertebrate Embryonic Migration, Paris A. Skourides Jan 2004

Molecular Basis Of Vertebrate Embryonic Migration, Paris A. Skourides

Student Theses and Dissertations

Embryology aims at understanding how a single fertilized cell develops into a complex multicellular organism. Initially the embryo is no more than a ball of cells where the three primordial layers, the ectoderm, mesoderm and the endoderm are one on top of the other. The three germ layers will go on to form all the tissues and organs of the embryo. For example, the ectoderm will give rise to epidermis and the nervous system; the mesoderm to muscles, the skeletal system, the dermis or inner layer of the skin, the circulatory, excretory, and reproductive systems; and, finally, the endoderm will …


Life Without Gpr7, The Neuropeptide W1 Receptor: Regulation Of Energy Homeostasis By Gpr7 And Its Endogenous Neuropeptide Ligands, Makoto Ishii Jan 2004

Life Without Gpr7, The Neuropeptide W1 Receptor: Regulation Of Energy Homeostasis By Gpr7 And Its Endogenous Neuropeptide Ligands, Makoto Ishii

Student Theses and Dissertations

Classic lesion experiments from the 1940s have established the hypothalamus as playing an essential role in controlling energy homeostasis. Gold-thioglucose (GTG) induces lesions in the ventromedial nucleus of the hypothalamus (VMH) resulting in hyperphagia and obesity. To identify genes involved in the hypothalamic regulation of energy homeostasis, we employed a screen to search for genes that were dysregulated in GTG induced obese mice. In this screen, GPR7, the endogenous G protein-coupled receptor (GPCR) for the recently identified ligands neuropeptide B (NPB) and neuropeptide W (NPW), was found to be specifically down-regulated after GTG treatment. The physiological role of GPR7 was …


Using Microscopy To Examine Mechanisms Of Cell Division, Lily Copenagle Jan 2004

Using Microscopy To Examine Mechanisms Of Cell Division, Lily Copenagle

Student Theses and Dissertations

The accurate segregation of chromosomes during cell division requires the assembly of a microtubule-based mitotic spindle. In the research presented here, I examined two aspects of mitotic spindle morphogenesis. First, I looked at how chromosomes attach to microtubules in mitosis. The capture of microtubule plus-ends by kinetochores (the site of chromosome-microtubule attachment) has been described previously. However, recent data suggests that another mechanism must also contribute to this essential process. Here, with the aid of real-time confocal microscopy, I present direct evidence for an additional chromosome-spindle attachment mechanism in which the minus-ends of microtubules attached to chromosomes are captured by …


Differential Screening In Immunodeficient Mice Reveals Bacterial Enzymes With Unexpected Roles In Host-Pathogen Interactions, Katherine B. Hisert Jan 2004

Differential Screening In Immunodeficient Mice Reveals Bacterial Enzymes With Unexpected Roles In Host-Pathogen Interactions, Katherine B. Hisert

Student Theses and Dissertations

Over centuries of co-existence with their hosts, microbes that are exclusively vertebrate pathogens have evolved mechanisms for manipulation of host cells and evasion of the immune system. Some pathogens dodge the immune response by altering the functions of and hiding within the very cells that should be consuming and digesting them: macrophages. The aim of these studies was to explore the dynamic interactions the host with two microbes that opt to live within the macrophage phagosome: Mycobacterium tuberculosis (Mtb) and Salmonella typhimurium. In order to identify bacterial genes that provide protection against specific host immune pathways, we have developed the …


Resonant Detection Of Nano To Microscopic Objects Using Whispering Gallery Modes, Frank Vollmer Jan 2004

Resonant Detection Of Nano To Microscopic Objects Using Whispering Gallery Modes, Frank Vollmer

Student Theses and Dissertations

A micron sized glass sphere is able to confine light to its interior volume. The trapped light describes an orbital trajectory circumnavigating just below the microsphere surface. Whenever the light ray tries to escape it is sent back on its circular path by total internal reflection. The light orbit closes in on itself several thousand times and thus creates an optical resonance. The unprecedented narrow linewidth of such a microsphere resonance (Q factors of up to 3 x 10 ) allows precise measurement of its frequency. Dielectric microspheres of very high Q are thus the ideal choice for a resonant …


Functional Analyses Of Htel2 And Trf2 Deltab: Insights Into The Role Of A New Dna Damage Pathway And Homologous Recombination In Mammalian Telomere Function, Richard Chih-Chien Wang Jan 2004

Functional Analyses Of Htel2 And Trf2 Deltab: Insights Into The Role Of A New Dna Damage Pathway And Homologous Recombination In Mammalian Telomere Function, Richard Chih-Chien Wang

Student Theses and Dissertations

Tel2 influences telomere length in S. cerevisiae and DNA-damage signaling in C. elegans. We found that endogenous human Tel2 (hTel2) localized in a diffuse, granular patter to the nuclei of human cells where it was enriched in PML nuclear bodies, but telomeres. Surprisingly, hTel2 also localized to centrosomes. Although hTe!2 did not detectably interact with telomeric proteins or telomeric chromatin, the overexpression untagged hTel2 resulted in the slow elongation of telomeres in HTC75 and SK-HEP-1 cells. Furthermore, hTel2 overexpression suppressed the accumulation of cells in G2 after ionizing radiation. The depletion of hTel2 in HeLa cells by RNA interference resulted …


A Novel Subfamily Of Three Star-Related Lipid Transfer Proteins That Are Differentially-Regulated And Function In Intracellular Cholesterol Metabolism, Raymond E. Soccio Jan 2004

A Novel Subfamily Of Three Star-Related Lipid Transfer Proteins That Are Differentially-Regulated And Function In Intracellular Cholesterol Metabolism, Raymond E. Soccio

Student Theses and Dissertations

thesis describes the discovery, cloning, and initial characterization of StarD4, sterol-regulated gene encoding a StAR-related lipid transfer (START) protein, and its close homologues, StarD5 and StarD6. StarD4 was identified using cDNA microarrays, as liver StarD4 expression decreased three-fold in mice fed a high cholesterol diet. StarD4 also sterol-regulated in cultured cells, and a functional sterol regulatory element (SRE) identified in its promoter. StarD4 was preferentially activated in mouse liver by SREBP-rather than SREBP-1, supporting a role in cholesterol rather than fatty acid metabolism. X-ray crystal structure of StarD4 was solved, revealing a hydrophobic lipid binding cavity described for other START …