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Articles 1 - 18 of 18
Full-Text Articles in Life Sciences
Nkains: A Novel Family Of Membrane Proteins That Interact With The Na, K-Atpase And Affect Membrane Excitability, Svetlana Gorokhova
Nkains: A Novel Family Of Membrane Proteins That Interact With The Na, K-Atpase And Affect Membrane Excitability, Svetlana Gorokhova
Student Theses and Dissertations
A novel family of Na,K-ATPase interacting (NKAIN) proteins was cloned and characterized. These proteins are highly conserved across species and do not resemble any known proteins in the genome. Aside from the conserved transmembrane domains, NKAINs contain no known functional domains. Striking amino acid conservation in the first two transmembrane domains suggests that the function of these proteins is concentrated in the membrane bilayer. NKAINl, 2, 3 and a splice form of NKAIN4 are brain and testis specific; another splice form of NKAIN4 is expressed ubiquitously. In the central nervous system, NKAINs localize to neurons. The C-terminal tail of NKAIN …
Microarray Analysis Identifies Novel Cholesterol Regulated Genes, Including Pcsk9 Which Regulates Ldl Receptor Function And Ldl Cholesterol Levels, Kara Noelle Maxwell
Microarray Analysis Identifies Novel Cholesterol Regulated Genes, Including Pcsk9 Which Regulates Ldl Receptor Function And Ldl Cholesterol Levels, Kara Noelle Maxwell
Student Theses and Dissertations
Precise regulation of cholesterol levels is necessary for survival of individual cells and the normal functioning of multicellular organisms. Many of the genes important in these processes are regulated at a transcriptional level by the sterol regulatory element binding proteins (SREBPs) and liver X receptors (LXRs). This thesis describes the identification by microarray technology of novel genes in cholesterol metabolism and the characterization of two of these genes. Microarray analysis of the livers of mice fed a low versus high cholesterol diet identified 37 down-regulated and 32 up-regulated genes. Confirmation of these genes and analysis in transgenic and pharmacologically treated …
A Molecular Dissection Of The Ventromedial Hypothalamic Nucleus, Jeremy P. Segal
A Molecular Dissection Of The Ventromedial Hypothalamic Nucleus, Jeremy P. Segal
Student Theses and Dissertations
The ventromedial hypothalamic nucleus (VMH) plays an important role in the regulation of food intake, glucose metabolism, and body weight. However, in contrast to other hypothalamic nuclei that are also known to regulate energy homeostasis, there is a paucity of nucleus-specific marker genes for the VMH that can be used to label its constituent neurons. This represents a significant impediment to the application of molecular approaches for analyzing VMH circuitry and function. Thus, we conducted a microarray screen in order to identify VMH-specific genes that could be used to label populations of VMH neurons. Laser-capture microdissection was used to isolate …
Tmem27: A Cleaved And Shed Plasma Membrane Protein That Stimulates Pancreatic Beta Cell Proliferation, Pinar Akpinar
Tmem27: A Cleaved And Shed Plasma Membrane Protein That Stimulates Pancreatic Beta Cell Proliferation, Pinar Akpinar
Student Theses and Dissertations
The signals and the molecular mechanisms that regulate the replication of terminally differentiated β cells are unclear. In this thesis I report the identification of a gene encoding transmembrane protein 27 (TMEM27) in pancreatic β cells. Expression of Tmem27 is reduced in Tcf1–/– mice, which exhibit defects in proliferation, and is increased in islets of ob/ob, db/db and aP2- Srebp-1c transgenic mice with marked hypertrophy of the endocrine pancreas. Tmem27 is expressed in hormone positive cells at early stages of pancreas development and becomes restricted to pancreatic β cells in the mature pancreas. Biochemical characterization revealed that the Tmem27 exists …
The Role Of Drosophila Odorant Receptors In Odor Coding, Elane Fishilevich
The Role Of Drosophila Odorant Receptors In Odor Coding, Elane Fishilevich
Student Theses and Dissertations
Drosophila melanogaster is a powerful genetic model organism, and a promising model system in olfaction. At the onset of my thesis research, the expression patterns of fly’s 62 odorant receptors (ORs) were largely unknown. I set out to understand the rules of connectivity of olfactory sensory neurons and the resulting properties of olfactory circuit. Consequently, we assembled maps of the olfactory neuron projections in the fly brain and characterized the contribution of several ORs to olfactory-guided behavior. We compiled near-complete maps of OR-specific neuronal projections to the antennal lobe glomeruli of adult and larval fly brains. We analyzed expression profiles …
The Roles Of Daf-6 And Cell-Cell Interactions In Sensory Organ Morphogenesis, Elliot A. Perens
The Roles Of Daf-6 And Cell-Cell Interactions In Sensory Organ Morphogenesis, Elliot A. Perens
Student Theses and Dissertations
The development of multicellular organs depends on the regulation of cell shape, position, and orientation. The genetic regulation of these morphogenetic processes is poorly understood. As a model for organ morphogenesis, I studied the development of the Caenorhabditis elegans amphid sensory organ. Sensory organs in diverse species are often composed of neuronal sensory endings accommodated in a lumen formed by ensheathing epithelia or glia. The generation of this structure may require cell-autonomous factors that control lumen formation, as well as cell non-autonomous factors that coordinate the morphogenesis of the lumen with the resident neuronal processes. Understanding these processes would provide …
Glyoxylate Metabolism In Mycobacterium Smegmatis, Lubomir Nikolaev Merkov
Glyoxylate Metabolism In Mycobacterium Smegmatis, Lubomir Nikolaev Merkov
Student Theses and Dissertations
Much has been learned about Mycobacterium tuberculosis, the causative agent of tuberculosis, “the great white plague,†since the bacterium was isolated and initially characterized by Robert Koch over a century ago. Over the last decade, new genetic tools for manipulation of the bacterium have been developed, its genome has been sequenced, and the search for new vaccines and drug targets has greatly intensified. Yet, surprisingly little is known about which mycobacterial genes are truly important for the organism’s ability to persist in the tissues of its human hosts. The metabolic pathways used by the tubercle bacillus to establish and maintain …
Role Of Laminin Gamma 1 In Cortical Development, Veronique Haegeli
Role Of Laminin Gamma 1 In Cortical Development, Veronique Haegeli
Student Theses and Dissertations
Laminins are a major component of basement membranes, including those in the central nervous system (CNS). To explore the role of laminin \l, a subunit common to all laminins found within the CNS, we developed a murine model in which laminin yl is conditionally disrupted in the nervous system. These mice show cortical developmental abnormalities including undulations in the embryonic cortical plate and resultant adult cortical layers and abnormal positioning of pyramidal neurons and interneurons. We have investigated the mechanisms underlying these abnormalities. Neuronal migration via the establishment of the radial glial scaffold and the Cajal-Retzius cell layer was affected …
Self-Renewal Requirements Of Human Embryonic Stem Cells And Their Engraftment Potential In Mouse Blastocysts, Daylon Jefferson James
Self-Renewal Requirements Of Human Embryonic Stem Cells And Their Engraftment Potential In Mouse Blastocysts, Daylon Jefferson James
Student Theses and Dissertations
Human embryonic stem cells (hESCs) are a unique population of cells derived from a 6 day old human embryo that can be maintained indefinitely in vitro and have the ability to differentiate to all adult cell types. In addition to their potential for cell based therapies in the treatment of disease and injury, the broad developmental capacity of hESCs offers potential for studying the origins of all human cell types. Embryonic stem cells were first derived from mouse embryos (mESCs), and years of work have demonstrated their utility to developmental research, but relatively little is known about human ESCs. The …
Immunologic Memory To Polysaccharide Antigens, Tetyana V. Obukhanych
Immunologic Memory To Polysaccharide Antigens, Tetyana V. Obukhanych
Student Theses and Dissertations
Immunologic memory is the ability of the immune system to generate an enhanced antibody response against previously encountered antigens. The clonal selection theory of acquired immunity attributes immunologic memory to the formation of an expanded compartment of quiescent antigen-specific memory B cells that are capable of rapid activation upon secondary antigen encounter. Whereas protein antigens are known to elicit memory B cells, it is not known whether polysaccharide antigens do. Here we report that polysaccharide antigens elicit memory B cells that are phenotypically distinct from those elicited by protein antigens. We show that antigen affinity of the B cell receptor …
Integration Of Light And Temperature In The Regulation Of Circadian Gene Expression In Drosophila, Catharine E. Boothroyd
Integration Of Light And Temperature In The Regulation Of Circadian Gene Expression In Drosophila, Catharine E. Boothroyd
Student Theses and Dissertations
Clocks are aligned to the environment via inputs from both daily light and temperature cycles. Previous molecular and behavioral studies in Drosophila have largely focused on light-dependent regulation of circadian clocks and their outputs. Although light is the strongest and best understood Zeitgeber for the circadian clock, temperature is also an important factor. This thesis aims to understand better the role of temperature on gene expression and behavior in the fly, as well as to examine how information from both light and temperature are integrated by the clock to regulate circadian gene expression. Genome-wide expression profiles of transcripts from wild-type, …
Control Of Chromosome Segregation By The Aurora B Complex, Srinath Cidambi Sampath
Control Of Chromosome Segregation By The Aurora B Complex, Srinath Cidambi Sampath
Student Theses and Dissertations
Chromosome segregation during cell division requires spindle assembly around M-phase chromatin. In cells lacking centrosomes, such as those found in female meiosis, chromosomes themselves nucleate and stabilize microtubules in order to promote accurate spindle formation. Here we present a description of the composition and function of the vertebrate chromosomal passenger complex (CPC), known to include Incenp, Survivin, and the kinase Aurora B. We report the identification of Dasra A and Dasra B as two new components of the vertebrate CPC, and demonstrate that the CPC is required for chromatin-dependent spindle formation in Xenopus egg extracts. The failure of microtubule stabilization …
Studies On The Histone Methyltransferase G9a, Srihari Cidambi Sampath
Studies On The Histone Methyltransferase G9a, Srihari Cidambi Sampath
Student Theses and Dissertations
The size and complexity of eukaryotic genomes require that specific mechanisms exist for ensuring both the stability as well as the accessibility of DNA. One such mechanism is the association of DNA with histones to form chromatin, the physiological substrate of gene expression. An important means by which histones impact transcriptional activity is through site-specific enzymatic modification of the amino terminal histone “tailsâ€, which can alter the spectrum of chromatin-associated proteins and hence transcriptional states. Among the known modifications of histones, lysine methylation has been proposed to represent a relatively stable mark which might mediate stable activation or repression, depending …
The Dual Role Of Oca-B In B Cell Development And Signaling, Rachael Siegel
The Dual Role Of Oca-B In B Cell Development And Signaling, Rachael Siegel
Student Theses and Dissertations
OCA-B (Oct coactivator from B cells) is a B-cell specific coactivator of transcription that acts in conjunction with the ubiquitously expressed activator, OCT-1 or the B cell-restricted OCT-2. OCT-1 or OCT-2 can bind an upstream octamer element with the consensus sequence 5'- ATGCAAAT-3' in target gene promoters and enhancers. At the octamer element, the OCT-1/2-OCA-B complex is able to regulate gene expression via interaction with the basal transcription machinery. OCA-B was originally identified as a nuclear transcriptional coactivator and then shown to be essential for antigen-driven immune responses, including secondary isotype expression, germinal center formation and BCRdependent proliferation. These defects …
Dendritic Cells Mediate The Dual Effects Of Ifn Alpha/Beta In Hcv Immunity, Randy Longman
Dendritic Cells Mediate The Dual Effects Of Ifn Alpha/Beta In Hcv Immunity, Randy Longman
Student Theses and Dissertations
Hepatitis C virus (HCV) infects an estimated 170 million people and is responsible for considerable morbidity and mortality worldwide. Successful resolution of infection is achieved naturally in approximately 30% of infected individuals and correlates with a strong T cell response. Furthermore, treatment with interferon (IFN)a achieves sustained virologic response in approximately 50% of chronically infected individuals. Conventional dendritic cells (cDCs), as the most potent antigen presenting cells, and plasmacytoid DCs (pDCs), as the principal IFNa/|3 producing cells, serve as potential targets for both immune evasion and therapeutic strategies. In order to evaluate the effects of HCV on DC function, we …
Exploring The Biophysical Properties Of Domains Within Multi-Domain Proteins, Vasant Muralidharan
Exploring The Biophysical Properties Of Domains Within Multi-Domain Proteins, Vasant Muralidharan
Student Theses and Dissertations
The past few decades, considerable progress has been made in understanding the biophysical properties of proteins using small modular domains such as SH3 domains. However, there is a surprising lack of knowledge regarding how these properties are affected when the domain is placed back within its full-length multi-domain protein. Using a combination of expressed protein ligation (EPL) and in vivo amino acid replacement of tryptophans with tryptophan (Trp) analogues, we have developed an integrated approach that allows the domain-specific incorporation of optical probes into large recombinant proteins. The Src homology 3 (SH3) domain from the c-Crk-l adaptor protein has been …
Structural Analysis Of An Rna Polymerase Sigma Factor And Its Anti-Sigma: Sigma28/Flgm, Margareta K. SöRenson
Structural Analysis Of An Rna Polymerase Sigma Factor And Its Anti-Sigma: Sigma28/Flgm, Margareta K. SöRenson
Student Theses and Dissertations
Eubacterial sigma (o) factors are required during the initiation of transcription, where they play key roles in promoter recognition, melting, and transcriptional regulation, sigma is a dissociable subunit of RNA polymerase (RNAP), and sequence-specifically recognizes promoters, but only after associating with RNAP to form the holoenzyme. In the holoenzyme, the major sigma domains (sigma2, sigma3, and sigma4) are spread across the surface, with the promoter binding surfaces solvent exposed and appropriately positioned for simultaneous recognition of the -10 and -35 promoter elements. A -30 residue linker connecting sigma3 and sigma4 is unfolded and threads through the interior of the enzyme. …
Telomere Structure And Shortening In Telomerase-Deficient Trypanosoma Brucei: Implications For Anitgenic Variation, Oliver Dreesen
Telomere Structure And Shortening In Telomerase-Deficient Trypanosoma Brucei: Implications For Anitgenic Variation, Oliver Dreesen
Student Theses and Dissertations
A variety of parasites persist in their host through sequential expression of variant surface antigens. Intriguingly, the genes encoding these antigens are frequently found adjacent to the telomeres. Telomeres are nucleoprotein complexes consisting of tandem DNA repeats and proteins that bind to them. Their function is to protect chromosome ends from the DNA repair machinery that would otherwise recognize them as double-stranded breaks. With the help of the ribonucleoprotein telomerase they compensate for the gradual sequence loss that would otherwise arise from the inability of conventional DNA polymerases to replicate chromosome ends. In Trypanosoma brucei, the causative agent of African …