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Full-Text Articles in Molecular Biology

Examination Of Microsporidia Spore Adherence And Host Cell Infection In Vitro., Timothy Robert Southern May 2007

Examination Of Microsporidia Spore Adherence And Host Cell Infection In Vitro., Timothy Robert Southern

Electronic Theses and Dissertations

Microsporidia are obligate intracellular pathogens that cause severe disease in immunocompromised humans. While albendazole is the treatment of choice, no therapy exists that effectively treats all forms or causes of human microsporidiosis. Recent studies show that the microsporidian Encephalitozoon intestinalis binds glycosaminoglycans (GAGs) associated with the host cell surface, and that the divalent cations manganese (Mn2+) and magnesium (Mg2+) augment spore adherence to host cells by activating a constituent on the spore surface. These studies also illustrate a direct relationship between spore adherence and host cell infection; inhibition of spore adherence leads to reduced host cell …


Notch Regulation Of Human Breat Cancer Progression: Contrasting Roles For Notch Signaling, Christine F. O'Neill May 2007

Notch Regulation Of Human Breat Cancer Progression: Contrasting Roles For Notch Signaling, Christine F. O'Neill

Electronic Theses and Dissertations

Notch signaling is associated with activation of either oncogenic or tumor suppressor activities. The human mammary adenocarcinoma cell line, MDA-MB-231, was characterized in vitro and in xenografts in vivo to test the hypothesis that activation of Notch signaling regulates mammary tumor phenotype. Notch 1, Notch2, and Notch4 signaling was compared by stable expression of their constitutively active intracellular domains (ICD). Notch4 activation led to enhanced tumorigenicity, in addition to increased cell proliferation and survival in vitro, whereas the activation of Notch 1 or Notch2 decreased cell proliferation and survival, in which Notch2 increased apoptosis. Stably transfected cell lines were …


Identification Of Genes Encoding Acyl-Coa Reductases And Aldehyde Reductases In Mycobacterial Genome By Characterization Of The Reductases Expressed In E. Coli, Harminder Singh Jan 2007

Identification Of Genes Encoding Acyl-Coa Reductases And Aldehyde Reductases In Mycobacterial Genome By Characterization Of The Reductases Expressed In E. Coli, Harminder Singh

Electronic Theses and Dissertations

Mycobacterium tuberculosis has been long known to produce wax esters. However, the enzymes involved in their biosynthesis have not been identified. Here we report the identification of Rv3391 and Rv1543 as genes that encode fatty acyl-CoA reductases and Rv1544 as one that encodes an aldehyde reductase. When expressed in E.coli, the products of Rv3391 and Rv1543 catalyzed reduction of fatty acyl-CoA to fatty alcohol with the corresponding aldehyde as an intermediate with an optimal pH of 7.0. Both enzymes showed a strong preference for NADPH over NADH as a reductant. Apparent Km for NADPH was 38 [micro]M for Rv3391 product …


The Effects Of Trivalent Arsenicals And Thioredoxin Reductase Inhibitors On Selenium Metabolism In Lung Cell Culture Models, Sarah Ryann Talbot Jan 2007

The Effects Of Trivalent Arsenicals And Thioredoxin Reductase Inhibitors On Selenium Metabolism In Lung Cell Culture Models, Sarah Ryann Talbot

Electronic Theses and Dissertations

Arsenic exposure, through various routes, is associated with the development of cancer of the skin, lung, liver, kidney, and bladder. Treatment of cells in culture with trivalent arsenicals has been shown to increase reactive oxygen species (ROS). In particular, monomethylarsonous acid (MMAIII), a trivalent metabolite of arsenite, is highly cytotoxic and possibly carcinogenic. Three trivalent arsenicals; arsenite, arsenic trioxide (ATO), and MMAIII, are also known inhibitors of the selenoprotein thioredoxin reductase (TrxR). Selenium, an essential micronutrient in mammals, is needed in the form of selenocysteine for activity of this enzyme and other selenoproteins. TrxR is part of a key component …


Physical Characteristics Of An Individual: The Identification Of Biomarkers For Biological Age Determination, Michelle Alvarez Jan 2007

Physical Characteristics Of An Individual: The Identification Of Biomarkers For Biological Age Determination, Michelle Alvarez

Electronic Theses and Dissertations

It is now a matter of routine for the forensic scientist to obtain the genetic profile of an individual from DNA recovered from a biological stain deposited at a crime scene. Potential contributors of the stain must either be known to investigators (i.e. a developed suspect) or the questioned profile must be searched against a database of DNA profiles such as those maintained in the CODIS National DNA database. However, in those instances where there is no developed suspect and no match is obtained after interrogation of appropriate DNA databases, the DNA profile per se presently provides no meaningful information …


Correlation Of Rpob Gene Mutation With Clinical Rifabutin And Rifampicin Resistance For Treatment Of Crohn's Disease, Daniel Beckler Jan 2007

Correlation Of Rpob Gene Mutation With Clinical Rifabutin And Rifampicin Resistance For Treatment Of Crohn's Disease, Daniel Beckler

Electronic Theses and Dissertations

Emerging rise in microbial drug resistance and the slow-growing characteristic of some intracellular pathogens such as MAP (Mycobacterium avium subspecies paratuberculosis) strongly urges the need for an effective approach for unconventional drug susceptibility testing. We designed a molecular-based PCR method for the evaluation of rifabutin (RFB) and rifampicin (RIF) resistance based on probable determinant regions within the rpoB gene of MAP, including the 81 bp variable site located between nucleotides 1363 and 1443. The minimum inhibitory concentration (MIC) for RIF was also determined against 10 MAP isolates in attempt to seek correlation with rpoB sequences. We determined that MAP strain …


Mechanism Of Action And Regulation Of Membrane Serine Protease Prostasin In The Prostate And Prostate Cancer, Mengqian Chen Jan 2007

Mechanism Of Action And Regulation Of Membrane Serine Protease Prostasin In The Prostate And Prostate Cancer, Mengqian Chen

Electronic Theses and Dissertations

The glycosylphosphatidylinositol (GPI)-anchored serine protease prostasin (PRSS8) is expressed at the apical membrane surface of epithelial cells and acts as a suppressor of tumor invasion when re-expressed in highly invasive human prostate and breast cancer cell lines. To better understand the molecular mechanisms underlying the anti-invasion phenotype associated with prostasin re-expression in prostate cancer cells, we expressed wild-type human prostasin or a serine active-site mutant prostasin in the PC-3 human prostate carcinoma cells. Molecular changes were measured at the mRNA and the protein levels. The expression of several invasion-promoting molecules is regulated by prostasin re-expression, mediated by a protein-level down-regulation …


A Member Of The Novel Fikk Family Of Plasmodium Falciparum Putative Protein Kinases Exhibits Diacylglycerol Kinase Activity And Is Exported To The Host Erythrocyte, David Floyd Curtis Jan 2007

A Member Of The Novel Fikk Family Of Plasmodium Falciparum Putative Protein Kinases Exhibits Diacylglycerol Kinase Activity And Is Exported To The Host Erythrocyte, David Floyd Curtis

Electronic Theses and Dissertations

Plasmodium falciparum is one of four species known to cause malaria in humans and is the species that is associated with the most virulent form of the disease. Malaria causes nearly two million deaths each year, many of these occurring among children in under-developed countries of the world. One reason for this is the prevalence of drug resistant strains of malaria that mitigate the efficacy of existing drugs. Hence, the identification of a new generation of pharmacological agents for malaria is extremely urgent. The recent identification of a group of novel protein kinases within the Plasmodium falciparum genome has provided …


The Generation And Scavenging Of Radicals Via Cerium And Nanoceria, Eric Glenn Heckert Jan 2007

The Generation And Scavenging Of Radicals Via Cerium And Nanoceria, Eric Glenn Heckert

Electronic Theses and Dissertations

Cerium is the most abundant of the rare earth metals, found on average at a level of 66 parts per million in the earth's crust. The unique redox properties of cerium and cerium oxide nanoparticles have led to its use in a wide variety of industrial and commercial uses such as oxygen sensors, fertilizers and as a catalyst to remove toxic gases in automobile exhaust. The use of cerium has also garnered interest in the nanotechnology field. Nanoceria has been generated in its oxide form as nanoparticles and nanorods. Recently, nanoceria has been shown to protect against oxidative stress in …


Mechanisms Promoting Phosphorylation Of The Nf2 Tumor Suppressor And Its Effects On Schwann Cell Development, Courtney Lynn Thaxton Jan 2007

Mechanisms Promoting Phosphorylation Of The Nf2 Tumor Suppressor And Its Effects On Schwann Cell Development, Courtney Lynn Thaxton

Electronic Theses and Dissertations

Neurofibromatosis type 2 is an autosomal dominant disease characterized by the formation of schwannomas and other peripheral neuropathies. The nf2 gene encodes the protein Schwannomin, or merlin. Schwannomin (Sch) is a membrane-cytoskeletal linking protein that suppresses cell proliferation at high cell density and modulates cell shape. Sch's tumor suppressive activity is regulated by its localization, conformation, and phosphorylation at serine 518 (S518). Sch's localization is dependent on binding the scaffold protein, paxillin. Phosphorylation of Sch at S518 regulates its conformation and tumor suppressor function. In a negative feedback loop, unphosphorylated Sch restricts cell proliferation downstream of Rac and p21-activated kinase …


Glutamate Excitotoxicity In Epilepsy And Ischemia, Mangala Meenakshi Soundarapandian Jan 2007

Glutamate Excitotoxicity In Epilepsy And Ischemia, Mangala Meenakshi Soundarapandian

Electronic Theses and Dissertations

'Excitotoxicity' represents the excitatory amino acid mediated degeneration of neurons. Glutamate is the major excitatory neurotransmitter in the brain. Glutamate excitotoxicity has been implicated in a number of neurodegenerative disorders like Stroke, Epilepsy, Alzheimer's disease and traumatic brain injury. This neurotoxicity is summed up by the 'glutamate hypothesis' which describes the cause of neuronal cell death as an excessive release of glutamate causing over excitation of the glutamate receptors and subsequent increase in influx of calcium leading to cell death. An effort to counteract this neurotoxicity has lead to the development of glutamate receptor antagonists that can effectively serve as …


Lim Kinase 1 Modulates Expression Of Matrix Metalloproteinases And Associates With Gamma-Tubulin: Dual Role In Invasion And Mito, Tenekua Tapia Jan 2007

Lim Kinase 1 Modulates Expression Of Matrix Metalloproteinases And Associates With Gamma-Tubulin: Dual Role In Invasion And Mito, Tenekua Tapia

Electronic Theses and Dissertations

LIM kinase 1 (LIMK1) is a unique dual specificity serine/threonine kinase containing two N-terminal LIM domains in tandem, a PDZ domain and a C-terminal catalytic domain. LIMK1 is involved in modulation of actin cytoskeleton through inactivating phosphorylation of the ADF (actin depolymerization factor) family protein cofilin. Recent studies have shown that LIMK1 is upregulated in breast and prostate cancer cells and tissues, promotes metastasis in animals and induces acquisition of an invasive phenotype when ectopically expressed in benign prostate epithelial (BPH) cells. Furthermore, overexpression of LIMK1 was associated with altered sub cellular localization of the membrane type 1 matrix metalloprotease …


Helical Packing Regulates Structural Transitions In Bax, Nuska Tschammer Jan 2007

Helical Packing Regulates Structural Transitions In Bax, Nuska Tschammer

Electronic Theses and Dissertations

Apoptosis is essential for development and the maintenance of cellular homeostasis and is frequently dysregulated in disease states. Proteins of the BCL-2 family are key modulators of this process and are thus ideal therapeutic targets. In response to diverse apoptotic stimuli, the pro-apoptotic member of BCL-2 family, BAX, redistributes from the cytosol to the mitochondria or endoplasmic reticulum and primes cells for death. The structural changes that enable this lethal protein to transition from a cytosolic form to a membrane-bound form remain poorly understood. Elucidating this process is a necessary step in the development of BAX as a novel therapeutic …


Retrocyclin Rc-101 Overcomes Cationic Mutations On The Heptad Repeat 2 Of Hiv-1 Gp41, Christopher Fuhrman Jan 2007

Retrocyclin Rc-101 Overcomes Cationic Mutations On The Heptad Repeat 2 Of Hiv-1 Gp41, Christopher Fuhrman

Electronic Theses and Dissertations

Retrocyclin RC-101, a θ-defensin with lectin-like properties, potently inhibits infection by many HIV-1 subtypes by binding to the heptad repeat (HR)-2 region of gp41 and preventing six-helix bundle formation. In the present study, we used in silico computational exploration to identify residues of HR2 that interacted with RC-101 and then analyzed the HIV-1 Sequence Database at LANL for residue variations in the HR1 and HR2 segments that could plausibly impart in vivo resistance. Docking RC-101 to gp41 peptides in silico confirmed its strong preference for HR2 over HR1, and implicated residues crucial for its ability to bind HR2. We mutagenized …