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Full-Text Articles in Molecular Biology

Mechanisms And Molecular Biology Of Major Tumor Suppressors, Brienne E. Engel Sep 2014

Mechanisms And Molecular Biology Of Major Tumor Suppressors, Brienne E. Engel

Graduate Theses and Dissertations

This dissertation is devoted to the study of the molecular biology of major tumor suppressors, defined as those that prevent the cellular processes identified as the hallmarks of cancer. Specifically, the major tumor suppressors pRb and STK11 are explored in the context of osteosarcoma and lung cancer, respectively.

RB1 was the first tumor suppressor gene discovered. Over four decades of work have revealed that the Rb protein (pRb) is a master regulator of biological pathways influencing virtually every aspect of intrinsic cell fate including cell growth, cell-cycle checkpoints, differentiation, senescence, self-renewal, replication, genomic stability and apoptosis. While these many processes ...


Role And Regulation Of Snon/Skil And Plscr1 Located At 3q26.2 And 3q23, Respectively, In Ovarian Cancer Pathophysiology, Madhav Karthik Kodigepalli Sep 2014

Role And Regulation Of Snon/Skil And Plscr1 Located At 3q26.2 And 3q23, Respectively, In Ovarian Cancer Pathophysiology, Madhav Karthik Kodigepalli

Graduate Theses and Dissertations

Ovarian cancer is one of the most common causes of gynecological cancer related deaths in women. In 2014, the estimated number of deaths due to ovarian cancer is 14,270 with occurrence of over 22, 240 new cases (National Cancer Institute, http://seer.cancer.gov/statfacts/html/ovary.html). Despite improvement in treatment strategies, the 5-year survival rate is still below 50% mainly due to chemoresistance and relapse. Amplification of chromosomal region 3q26 is a common characteristic in various epithelial cancers including ovarian cancer. This region harbors various oncogenes including the TGFβ signaling mediators EVI1 and SnoN/SkiL, PKCι and ...


Eukaryotic Gene Expression Patterns Of Microorganisms In The Amazon River Plume Parallel The Biogeochemistry Of Plume Waters, Brian L. Zielinski Sep 2014

Eukaryotic Gene Expression Patterns Of Microorganisms In The Amazon River Plume Parallel The Biogeochemistry Of Plume Waters, Brian L. Zielinski

Graduate Theses and Dissertations

Unraveling the microbiological processes that occur as water travels from a river's mouth into the ocean is critical to understanding the role of river plumes in global biogeochemical cycles. Metranscriptomics, the gene expression of a whole community of organisms, was utilized to examine six stations along the Amazon River Plume (ARP) in 2010 to test thehypothesis that there were measurable differences in gene expression for key biogeochemical genes along the ARP. This body of work focuses on methods developed to identify which genes are biogeochemically important for a particular environment along extreme salinity, nutrient and community gradients in the ...


The Interrelationship Of Brca1 185delag, Interleukin-1Β, And Ovarian Oncogenesis, Kamisha Woolery Jun 2014

The Interrelationship Of Brca1 185delag, Interleukin-1Β, And Ovarian Oncogenesis, Kamisha Woolery

Graduate Theses and Dissertations

While the etiology of ovarian cancer (OC) is not completely understood, evidence suggests that chronic inflammation may promote malignant transformation. However, familial history remains the strongest risk factor for developing OC and is associated with germline BRCA1 mutations, such as the 185delAG mutation. Normal human ovarian surface epithelial cells expressing the 185delAG mutant, BRAT, exhibit molecular and pathological changes that may contribute to OC oncogenesis. In the current study, I sought to determine whether BRAT could promote an inflammatory phenotype by investigating BRAT's impact on the expression of the proinflammatory cytokine, Interleukin-1β (IL-1β). Using a culture model system of ...


Rna Detection Technology For Applications In Marine Science: Microbes To Fish, Robert Michael Ulrich Jun 2014

Rna Detection Technology For Applications In Marine Science: Microbes To Fish, Robert Michael Ulrich

Graduate Theses and Dissertations

The accurate identification of taxa from mixed assemblages using genetic analysis remains an important field of molecular biology research. The common principle behind the development of numerous documented genetic detection technologies is to exploit specific nucleotide sequences inherent to each taxon. This body of work focuses on practical applications of real-time nucleic acid sequence-based amplification (RT-NASBA) in marine science, and is presented in four case studies. Each study represents novel work in the genetic identification of respective taxa of interest using RT-NASBA. Two case studies documented the development of an assay targeting mitochondrial 16S rRNA to discern legally salable grouper ...


Novel Cell Cycle Proteins In Apicomplexan Parasites, Carrie Butler Jun 2014

Novel Cell Cycle Proteins In Apicomplexan Parasites, Carrie Butler

Graduate Theses and Dissertations

Apicomplexans are responsible for major human diseases such as toxoplasmosis caused by Toxoplasma gondii (T. gondii) and the deadliest form of malaria caused by Plasmodium falciparum (P. falciparum). The genomes of these pathogens are now sequenced ushering in a new era of drug development. A major hurdle to exploiting this genome resource is that a large number of the encoded genes are "hypotheticals" and have yet to be characterized. Hypothetical proteins comprise roughly half of the predicted gene complement of T. gondii and P. falciparum and represent the largest class of uniquely functioning proteins in these parasites.

Following the idea ...


Genetic Basis For The Virulence Of Enterohemorrhagic Escherichia Coli Strain Tw14359, Jason Kyle Morgan May 2014

Genetic Basis For The Virulence Of Enterohemorrhagic Escherichia Coli Strain Tw14359, Jason Kyle Morgan

Graduate Theses and Dissertations

Enterohemorrhagic Escherichia coli (EHEC) is a virulent pathotype of E. coli that is associated with major outbreaks of hemorrhagic colitis and the life-threatening kidney disease hemolytic uremic syndrome. For successful host colonization and attachment to the intestinal mucosa, EHEC requires the locus of enterocyte effacement (LEE) pathogenicity island, which encodes a type III secretion system (TTSS) responsible for secreting and translocating effector proteins into host colonocytes. Regulation of the LEE is primarily directed through the first operon, LEE1, encoding the locus encoded regulator (Ler), and occurs through the direct and indirect action of several regulators. The 2006 U.S. spinach ...


Novel Roles Of The Protein Tyrosine Phosphatase Shp2 In Non-Small Cell Lung Cancer, Valentina Schneeberger May 2014

Novel Roles Of The Protein Tyrosine Phosphatase Shp2 In Non-Small Cell Lung Cancer, Valentina Schneeberger

Graduate Theses and Dissertations

The gene PTPN11 was identified in the early 1990s, and encodes the non-transmembrane protein tyrosine phosphatase SHP2. SHP2 is expressed ubiquitously in cells, and plays an important role in cancer. Unlike most phosphatases, SHP2 positively regulates several signaling pathways including the Ras/MAPK and Src signaling pathways and acts as a proto-oncogene. SHP2 is also a cancer essential gene in certain types of carcinomas, and promotes growth, survival, and epithelial to mesenchymal transformation. Gain of function (GOF) SHP2 mutations are known leukemic oncogenes, and have been identified to a smaller extent in solid tumors as well. Currently, the roles of ...


Ube3a Role In Synaptic Plasticity And Neurodevelopmental Disorders.The Lessons From Angelman Syndrome., Irina Filonova May 2014

Ube3a Role In Synaptic Plasticity And Neurodevelopmental Disorders.The Lessons From Angelman Syndrome., Irina Filonova

Graduate Theses and Dissertations

Angelman Syndrome (AS) is a severe neurodevelopmental disorder that affects 1:12000 newborns. It is characterized by mental retardation, delayed major motor and cognitive milestones, seizures, absence of speech and excessive laughter. The majority of AS cases arise from deletions or mutations of UBE3A gene located on the chromosome 15q11-13. UBE3A codes for E3-ubiquitin ligase that target specific proteins for degradation. To date, a wide variety of Ube3a substrates has been identified. The accumulation of Ube3a-dependent proteins and their effect on the multitude of signal transduction pathways are` considered the main cause of the AS pathology. While the majority of ...


Molecular Evidence For Vector Implication Of Onchocerca Lupi In Los Angeles County, Ca, Shanna June Bolcen May 2014

Molecular Evidence For Vector Implication Of Onchocerca Lupi In Los Angeles County, Ca, Shanna June Bolcen

Graduate Theses and Dissertations

Onchocerca is a genus of roundworm most commonly associated with the human infection onchocerciasis, or river blindness. While typically a zoonotic infection of ungulate populations, canine cases (Onchocerca lupi) have been identified in the United States and Greece. In 2012, Los Angeles County, Veterinary Public Health Program identified 3 cases of Onchocerca spp. infections in domestic canines. Samples from the ensuing blackfly collections were sent to the Global Health Infectious Disease Research Unnasch Laboratory for parasite isolation and vector species identification. Species-specific primers were designed and optimized for O. lupi using a non- specific cytochrome oxidase (COI) gene target (689bp ...


Sigma Factor N: A Novel Regulator Of Acid Resistance And Locus Of Enterocyte Effacement In Escherichia Coli O157:H7, Avishek Mitra May 2014

Sigma Factor N: A Novel Regulator Of Acid Resistance And Locus Of Enterocyte Effacement In Escherichia Coli O157:H7, Avishek Mitra

Graduate Theses and Dissertations

In enterohemorrhagic E. coli (EHEC) sigma factor N (σN) regulates glutamate-dependent acid resistance (GDAR) and the locus of enterocyte effacement (LEE), discrete genetic systems required for transmission and virulence of this intestinal pathogen. Regulation of these systems requires nitrogen regulatory protein C, NtrC, and is a consequence of NtrC/σN-dependent reduction in the activity of sigma factor S (σS). This study elucidates pathway components and stimuli for σN-directed regulation of GDAR and the LEE in EHEC. Deletion of fliZ, the product of which reduces σS activity, phenocopies rpoNN) and ntrC null ...


Potential Targeted Therapeutic Strategies For Overcoming Resistance In Braf Wild Type Melanoma, Vito William Rebecca May 2014

Potential Targeted Therapeutic Strategies For Overcoming Resistance In Braf Wild Type Melanoma, Vito William Rebecca

Graduate Theses and Dissertations

Melanoma manifests itself from the malignant transformation of melanocytes and represents the deadliest form of skin cancer, being responsible for the disproportionate majority of all skin cancer deaths. The 2002 discovery that 50% of all melanoma patients possess activating BRAF mutations ignited a significant paradigm shift in the way the melanoma field approached research and how patients were treated [1]. The era of targeted therapy had begun and with it came successful targeted BRAF inhibitor therapy regimens, which have accomplished improved clinical benefit (response rate, progression free survival, and overall survival) compared with treatment with chemotherapy in three phase III ...


Pathogenic Mechanisms And Signaling Pathways In Plasmodium Falciparum, Jennifer L. Sedillo May 2014

Pathogenic Mechanisms And Signaling Pathways In Plasmodium Falciparum, Jennifer L. Sedillo

Graduate Theses and Dissertations

Plasmodium falciparum is a human intracellular parasite that is the causative agent of a deadly form of malaria. This species alone is responsible for 200 million cases of malaria annually resulting in over 1 million deaths worldwide. The excessive mortality due to P. falciparum infection is due to its ability to cause severe pathogenesis through hyperparasitemia and cytoadherence defined as the ability of infected red blood cells to adhere to host vasculature. Cytoadherence is mediated through the export of parasite proteins to the surface of the infected red blood cell (RBC). Exported proteins have been identified but the pathway for ...


Exploration Of Mutations In Erythroid 5-Aminolevulinate Synthase That Lead To Increased Porphyrin Synthesis, Erica Jean Fratz May 2014

Exploration Of Mutations In Erythroid 5-Aminolevulinate Synthase That Lead To Increased Porphyrin Synthesis, Erica Jean Fratz

Graduate Theses and Dissertations

5-Aminolevulinate synthase (ALAS; EC 2.3.1.37) is a pyridoxal 5'-phosphate (PLP)-dependent enzyme that catalyzes the first committed step of heme biosynthesis in animals, the condensation of glycine and succinyl-CoA yielding 5-aminolevuliante (ALA), CoA, and CO2. Murine erythroid-specific ALAS (mALAS2) variants that cause high levels of PPIX accumulation provide a new means of targeted, and potentially enhanced, photosensitization. Transfection of HeLa cells with expression plasmids for mALAS2 variants, specifically for those with mutated mitochondrial presequences and a mutation in the active site loop, caused significant cellular accumulation of PPIX, particularly in the membrane. Light treatment of HeLa ...


Immature Myeloid Cells Promote Tumor Formation Via Non-Suppressive Mechanism, Myrna Lillian Ortiz May 2014

Immature Myeloid Cells Promote Tumor Formation Via Non-Suppressive Mechanism, Myrna Lillian Ortiz

Graduate Theses and Dissertations

ABSTRACT

Although there is ample evidence linking chronic inflammation with cancer, the cellular mechanisms involved in early events leading to tumor development remain unclear. Myeloid cells are an intricate part of inflammation. They consist of mature cells represented by macrophages, dendritic cells and granulocytes and a population of Immature Myeloid Cells (IMC), which in healthy individuals are cells in transition to mature cells. There is a substantial expansion of IMC in cancer and many other pathological conditions which is associated with pathologic activation of these cells. As a result, these cells acquire the ability to suppress immune responses and are ...


Transcriptional Control Of Toxoplasma Development, Joshua Byran Radke May 2014

Transcriptional Control Of Toxoplasma Development, Joshua Byran Radke

Graduate Theses and Dissertations

Toxoplasma gondii is an obligate intracellular protozoan parasite of animals and man. The asexual life cycle of Toxoplasma involves three very distinct, but tightly coordinated developmental stages. In nature, the sporozoite (contained within an oocyst) and bradyzoite (contained within a tissue cyst) initiate infection of the intermediate host, followed by rapid differentiation into the actively replicating tachyzoite. When countered by an effective host response, the tachyzoite differentiates back into the latent bradyzoite and this unique ability of Toxoplasma to interconvert between the replicating tachyzoite and the latent bradyzoite within a single host is the cause of life long infection. The ...


Structure-Based Design Of Novel Inhibitors And Ultra High Resolution Analysis Of Ctx-M Beta-Lactamase, Derek Allen Nichols May 2014

Structure-Based Design Of Novel Inhibitors And Ultra High Resolution Analysis Of Ctx-M Beta-Lactamase, Derek Allen Nichols

Graduate Theses and Dissertations

The emergence of CTX-M class-A extended-spectrum β-lactamases, which confer resistance to second and third-generation cephalosporins, poses a serious health threat to the public. CTX-M β-lactamases use a catalytic serine to hydrolyze the β-lactam ring. Specifically, the hydrolysis reaction catalyzed by CTX-M β-lactamase proceeds through a pre-covalent complex, a high-energy tetrahedral acylation intermediate, a low-energy acyl-enzyme complex, a high-energy tetrahedral deacylation intermediate after attack via a catalytic water, and lastly, the hydrolyzed β-lactam ring product which is released from the enzyme complex. The crystallographic structure of CTX-M at sub-angstrom resolution has enabled us to study enzyme catalysis as well as perform ...


Identification And Characterization Of A Novel Structural Protein Of Porcine Reproductive And Respiratory Syndrome Virus, The Replicase Nonstructural Protein 2, Matthew Allan Kappes Jan 2014

Identification And Characterization Of A Novel Structural Protein Of Porcine Reproductive And Respiratory Syndrome Virus, The Replicase Nonstructural Protein 2, Matthew Allan Kappes

Graduate Theses and Dissertations

Porcine reproductive and respiratory syndrome virus (PRRSV) is a rapidly mutating pathogen eliciting respiratory and reproductive disease of high economic consequence. The PRRSV non-structural protein 2 (nsp2) is a large multifunctional protein encoded by the most genetically diverse region of the genome - the selective pressure potentiating mutation within this region is unknown. Here we report the identification of a unique function of nsp2 as a structural component of the PRRSV virion; the first PRRSV structural protein identified which is not expressed from a sub-genomic RNA or regulated via the discontinuous transcription pathway. Through the use of a set of custom ...


A Single Molecular Study Of The Regulation Of Snare-Mediated Membrane Fusion, Jaekyun Song Jan 2014

A Single Molecular Study Of The Regulation Of Snare-Mediated Membrane Fusion, Jaekyun Song

Graduate Theses and Dissertations

The presynaptic membrane fusion is mediated by a protein set called SNARE (Soluble NSF Attachment protein REceptor) proteins. SNARE proteins form a ternary SNARE-complex that comprises minimal machinery for membrane fusion; the complex consists of three SNARE proteins: Syntaxin 1, SNAP-25 and Vamp 2, also called Synaptobrevin 2. The SNARE complex is a four-helix coiled coil with four SNARE motifs; two come from SNARE-25 and one each from Syntaxin 1 and Vamp 2. It is believed that a regulatory protein Complexin binds tightly to the SNARE complex and stabilizes the complex, preventing it from driving toward fusion. However, the detailed ...


Mobile Mrna: A Long Distance Signaling System In Potato, Tian Lin Jan 2014

Mobile Mrna: A Long Distance Signaling System In Potato, Tian Lin

Graduate Theses and Dissertations

Mobile mRNA is one of the most important long-distance signals in plant vascular system. They play important roles in responding to environmental cues, such as photoperiod. There are numerous studies on mobile mRNAs in plants and thousand of mRNAs have been detected in phloem sap. One of the BEL1-like genes, designated StBEL5, has transcripts that move long distance from leaf to stolon tips and enhance tuberization. However, not many mobile mRNAs have been characterized. The mechanism of the long-distance movement of mRNAs is not clear. In this dissertation, we conducted research on different levels to characterize known mobile mRNA and ...


Aphid Small Rnas And Viruses, Diveena Vijayendran Jan 2014

Aphid Small Rnas And Viruses, Diveena Vijayendran

Graduate Theses and Dissertations

Aphids are important agricultural pests with about 250 species known to cause damage by feeding on plant phloem and transmitting plant viruses. Current management relies primarily on the application of chemical insecticides, which can be deleterious to the environment, and the use of aphid resistant cultivars hampered by the presence of resistant aphid biotypes. We aim to develop novel biotechnology based approaches to better manage pestiferous aphids. To this end, we (i) identified and characterized aphid viruses, and (ii) analyzed a class of small RNA, microRNAs specific to aphids. We used transcriptome and small RNA sequencing datasets to identify viruses ...


Development Of An In Vitro Model And Fluorescent Protein Expression System For The Study Of Highly Abortigenic Campylobacter Jejuni, Moria Ann Borys Jan 2014

Development Of An In Vitro Model And Fluorescent Protein Expression System For The Study Of Highly Abortigenic Campylobacter Jejuni, Moria Ann Borys

Graduate Theses and Dissertations

Campylobacter spp. are a leading cause of sheep abortions worldwide; Campylobacter fetus ssp. fetus has historically been the major culprit. Increasingly, however, C. jejuni has been isolated from cases of sheep abortion, and it has now replaced C. fetus ssp. fetus as the predominant cause of Campylobacter-related ovine abortion in the United States. Emergence of a single tetracycline resistant clone (clone SA) has been implicated as the primary reason for this shift. Virulence factors for clone SA have still not been completely elucidated, and it is not known how this bacterium reaches the uterine and placental tissue from the ...


Modification Of The Bt Toxin Cry4aa For Improved Toxin Processing In The Gut Of The Pea Aphid (Acyrthosiphon Pisum), Michael Allen Rausch Jan 2014

Modification Of The Bt Toxin Cry4aa For Improved Toxin Processing In The Gut Of The Pea Aphid (Acyrthosiphon Pisum), Michael Allen Rausch

Graduate Theses and Dissertations

Aphids are sap-sucking insects (order: Hemiptera) that cause extensive damage to a wide range of agricultural crops. Our goal is to produce a "designer" toxin based on naturally occurring insecticidal crystalline (Cry) toxins produced by the soil-dwelling bacterium Bacillus thuringiensis for use against the pea aphid, Acyrthosiphon pisum. On the basis that activation of the Cry4Aa protoxin could be a rate-limiting factor contributing to the relatively low aphicidal activity of this toxin, we introduced cathepsin L and cathepsin B cleavage sites into Cry4Aa for rapid activation and generation of the active toxin in the aphid gut environment. Incubation of modified ...


Epigenetic Interplay Between Histone H3k9me2 And Jil-1 Mediated Histone H3s10ph, Chao Wang Jan 2014

Epigenetic Interplay Between Histone H3k9me2 And Jil-1 Mediated Histone H3s10ph, Chao Wang

Graduate Theses and Dissertations

In Drosophila, JIL-1 Kinase specifically localizes to euchromatic interband regions of polytene chromosomes and is responsible for histone H3S10 phosphorylation at interphase. Previous genetic interaction assays have demonstrated that the JIL-1 protein can counterbalance the effect of the major heterochromatin components Su(var)3-7 on position-effect variegation (PEV). In this study, we show that the haplo-enhancer effect of JIL-1 has the ability to counterbalance the haplo-suppressor effect of two other major heterochromatin components, Su(var)3-9 and Su(var)2-5, on position-effect variegation, providing evidence that a finely tuned balance between the levels of JIL-1 and the major heterochromatin components ...


Studies Of Integrins' Lateral Dynamics At A Single Particle Level, Dipak Mainali Jan 2014

Studies Of Integrins' Lateral Dynamics At A Single Particle Level, Dipak Mainali

Graduate Theses and Dissertations

One of the important factors in controlling the dynamics, structure, and functioning of the cell membrane is the lateral diffusion of membrane proteins and lipids. Integrins are one of the ubiquitous transmembrane proteins that are vital for numerous cellular functions. Integrins' lateral mobility and rearrangement is essential for integrins primary function of cell-extracellular matrix adhesion, cell-cell adhesion, and signaling. Lateral movement allows integrins to associate with extracellular ligand and other cytoplasmic and membrane proteins to incite biological activity such as signaling and downstream effects. This thesis describes the role of both downstream and upstream effectors, such as extracellular ligand, selected ...