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Articles 1 - 13 of 13

Full-Text Articles in Molecular Biology

Structural Basis For Ternary Complex Formation Between Tau, Hsp90, And Fkbp51, Alexander Steven Barrett Jan 2013

Structural Basis For Ternary Complex Formation Between Tau, Hsp90, And Fkbp51, Alexander Steven Barrett

Graduate Theses and Dissertations

The accumulation of the microtubule associated protein tau has been implicated in several neurological disorders; however, its interaction with chaperones along its normal degradation pathway remains largely uncharacterized at single residue resolution. In this study, nuclear magnetic resonance (NMR) spectroscopy was used to probe the interaction between tau, the molecular chaperone Hsp90, and the immunophilin FKBP51. Resonance intensity changes were observed for specific residues in the heteronuclear single quantum coherence (HSQC) spectra of 15N-labeled tau in the presence of Hsp90 and/or FKBP51. Analysis of the HSQC spectra identified the two hydrophobic hexapeptide motifs located at residues V275 - K280 and ...


Regulation Of The Tumor Suppresser P53 And Survivin By Ras And Ral Gtpases:Implications For Malignant Transformation, Awet G. Tecleab Jan 2013

Regulation Of The Tumor Suppresser P53 And Survivin By Ras And Ral Gtpases:Implications For Malignant Transformation, Awet G. Tecleab

Graduate Theses and Dissertations

Abstract

Although the critical role of the small GTPases Ras and Ral in oncogenesis has been well documented, much remains to be investigated about the molecular mechanism by which these GTPases regulate malignant transformation. The work under this thesis made two major contributions to this field. The first is the discovery that K-Ras, RalA and/or RalB are required for the maintenance of the high levels of the anti-apoptotic protein survivin in some human cancer cells, and the second is the demonstration that down regulation of K-Ras, RalA and/or RalB, but not Raf-1 or Akt1/2, stabilizes the tumor ...


Mass Spectrometry-Based Methods For The Detection And Characterization Of Protein-Tyrosine Nitration, Kent W. Seeley Jan 2013

Mass Spectrometry-Based Methods For The Detection And Characterization Of Protein-Tyrosine Nitration, Kent W. Seeley

Graduate Theses and Dissertations

Protein tyrosine nitration (PTN) is a posttranslational modification resulting from oxidative/nitrosative stress that has been implicated in a wide variety of disease states. Characterization of PTN is challenging due to several factors including its low abundance in a given proteome, preferential site modification, multiple target site proximity within unique peptide sequences, and analytical method and instrument limitations. Current analytical techniques are insufficiently sensitive to identify endogenous nitration sites without incorporation of either nitrotyrosine or target protein enrichment. However, enrichment proficiency can also be inadequate. Chemical derivatization of the nitro- moiety can be incomplete or result in undesirable byproduct formation ...


Epigenetic Modifiers To Augment The Immunogenicity Of Chronic Lymphocytic Leukemia, Jason A. Dubovsky Jan 2013

Epigenetic Modifiers To Augment The Immunogenicity Of Chronic Lymphocytic Leukemia, Jason A. Dubovsky

Graduate Theses and Dissertations

Cancer cells employ a litany of immunosuppressive and immunevasive strategies to avoid detection and elimination by the various arms of the innate and adaptive immune system. Many hematologic and solid tumors progressively develop a specialized microenvironment which promotes tissue restructuring inflammation while masking the immune signature of the tumor cells themselves. Chronic lymphocytic leukemia, a malignancy of mature B lymphocytes must constantly balance on the precipice of immune recognition. A mature antigen presenting cell themselves, CLL clonal growth is dependent on the very interactions which, if effective, could potentially lead to their demise. To circumvent this, CLL clones set up ...


Sirt1 Regulation Of The Heat Shock Response In An Hsf1-Dependent Manner And The Impact Of Caloric Restriction, Rachel Rene Raynes Jan 2013

Sirt1 Regulation Of The Heat Shock Response In An Hsf1-Dependent Manner And The Impact Of Caloric Restriction, Rachel Rene Raynes

Graduate Theses and Dissertations

The heat shock response (HSR) is the cell's molecular reaction to protein damaging stress and is critical in the management of denatured proteins. Activation of HSF1, the master transcriptional regulator of the HSR, results in the induction of molecular chaperones called heat shock proteins (HSPs). Transcription of hsp genes is promoted by the hyperphosphorylation of HSF1, while the attenuation of the HSR is regulated by a dual mechanism involving negative feedback inhibition from HSPs and acetylation at a critical lysine residue within the DNA binding domain of HSF1, which results in a loss of affinity for DNA. SIRT1 is ...


Hybrid Breeding In Perennial Grasses Based On Self-Incompatibility And Self-Fertility, Andrea Sofia Arias Aguirre Jan 2013

Hybrid Breeding In Perennial Grasses Based On Self-Incompatibility And Self-Fertility, Andrea Sofia Arias Aguirre

Graduate Theses and Dissertations

For a long time, petroleum-based fuels have been used to provide energy, but limited supplies along with environmental effects of fossil fuels created the need of alternative and clean energy sources. Grasses in general have a low lignin content compared to woody species which is desirable for ethanol production. Furthermore, other features such as: low water and nutrient requirements, and a high rate of carbon fixation that make grasses desirable for biomass production. Perennial grasses have also environmental advantages such as reduced soil organic matter and tillage requirements compared with annual species. Perennial ryegrass has been increasingly used in Europe ...


Specificity Of The Cocaine Aptamer And Its Application In Measurement Of Cocaine And Metabolites In Homogeneous Samples For Forensic Analysis, Ashish Sachan Jan 2013

Specificity Of The Cocaine Aptamer And Its Application In Measurement Of Cocaine And Metabolites In Homogeneous Samples For Forensic Analysis, Ashish Sachan

Graduate Theses and Dissertations

Detection and quantification of molecules has an enormous importance and potential in the field of scientific development and basic discovery research. Advances in colorimetric techniques, fluorescent labeled probes and biosensor based technologies have resulted in the specific detection and precise quantification of analytes. The effective development of a particular detection method needs optimization in terms of overall speed, efficiency, and accuracy of the sensing system. Current biosensor approaches often rely on cumbersome procedural steps and reagent requirements. Along with the complexity of the assay, the size of the analytical instrument is a deterrent factor for on-site applications. To overcome such ...


Proteolytic Processing Of The Amyloid Precursor Protein During Apoptosis And Cell Cycle: Implications For Alzheimer's Disease, Tina N. Fiorelli Jan 2013

Proteolytic Processing Of The Amyloid Precursor Protein During Apoptosis And Cell Cycle: Implications For Alzheimer's Disease, Tina N. Fiorelli

Graduate Theses and Dissertations

Alzheimer's disease is characterized by the presence of amyloid plaques, made up primarily of Aϐ peptides, and neurofibrillary tangles, containing hyperphosphorylated tau. Aϐ is generated by sequential proteolysis of the amyloid precursor protein (APP) by beta and gamma secretases. The leading hypothesis of Alzheimer's disease pathogenesis is the amyloid cascade hypothesis, which suggests that amyloid is central to the disease process. However, tau pathology correlates more closely with cognitive dysfunction and follows a predictable anatomical course through the brain. We hypothesize that if Aϐ is upstream of tau pathology and tau pathology follows this predictable course through the ...


The Panicum Mosaic Virus-Like 3' Cap-Independent Translation Element: A Translation Enhancer That Functions In Mammalian Systems, Mariko Sada Peterson Jan 2013

The Panicum Mosaic Virus-Like 3' Cap-Independent Translation Element: A Translation Enhancer That Functions In Mammalian Systems, Mariko Sada Peterson

Graduate Theses and Dissertations

In canonical eukaryotic translation initiation, the recognition of mRNA by the translation machinery is facilitated through the binding of the 5' m7G cap structure to eukaryotic initiation factor 4E (eIF4E). This recognition is necessary for efficient translation of the message to occur. In contrast, some viruses lack the 5' cap structure but have alternative mechanisms to initiate translation and express the viral proteins necessary for replication. The positive-strand RNA plant viruses of the panico-, carmo-, umbra-, (1-3) and aureusviruses (4) contain an RNA structure in their 3' UTRs that binds eIF4E (2) and through communication with the 5' UTR, are ...


Molecular Regulation Of Il-2 Inducible T-Cell Kinase (Itk) And The Tec Kinases: A Combined Experimental And Computational Study, With Emphasis On The N-Terminal Pleckstrin Homology Domain, Scott Edward Boyken Jan 2013

Molecular Regulation Of Il-2 Inducible T-Cell Kinase (Itk) And The Tec Kinases: A Combined Experimental And Computational Study, With Emphasis On The N-Terminal Pleckstrin Homology Domain, Scott Edward Boyken

Graduate Theses and Dissertations

This dissertation investigates the complex regulation of IL-2 inducible T-cell kinase (Itk) and its related Tec family kinase members, using a combination of experimental and computational approaches. Tec kinases are expressed primarily in hematopoietic cells and regulate key signaling events in lymphocyte activation, differentiation, and development. Itk functions in immune response, fine-tuning signaling downstream of the T-cell Receptor (TCR), and is a putative drug target for allergies and autoimmune disease. Btk, a Tec kinase found in B-cells, carries out a similar role to that of Itk, only downstream of B-cell Receptor (BCR) signaling. The chapters of this dissertation focus on ...


Investigating Higher-Order Chromatin Structure And Saga Cooperativity Using Existing And Modified In Vitro Chromatin Systems, Divya Sinha Jan 2013

Investigating Higher-Order Chromatin Structure And Saga Cooperativity Using Existing And Modified In Vitro Chromatin Systems, Divya Sinha

Graduate Theses and Dissertations

The organization of genomic DNA with histones and other proteins ensures the proper storage, utilization and segregation of DNA's encoded information in a healthy eukaryotic cell. These components comprise chromatin, and knowledge of its structure, mechanisms of its formation, and the dynamic changes it undergoes is essential to gain insights into chromatin's role in controlling gene regulation and the defects associated with misregulation. Here we describe our efforts to understand the different aspects of chromatin by using existing and modified in vitro chromatin model systems.

To better understand histone-histone interactions involved in the formation of higher-order chromatin structure ...


Investigation Of The Arabidopsis Nonhost Resistance Mechanism Against The Soybean Pathogen, Phytophthora Sojae, Rishi Sumit Jan 2013

Investigation Of The Arabidopsis Nonhost Resistance Mechanism Against The Soybean Pathogen, Phytophthora Sojae, Rishi Sumit

Graduate Theses and Dissertations

Nonhost resistance (NHR) provides immunity to all members of a plant species against all isolates of a microorganism that is pathogenic to other plant species. Three Arabidopsis thaliana PEN (penetration deficient) genes, PEN1, 2 and 3 have been shown to provide prehaustorial NHR against the barley pathogen Blumeria graminis f. sp. hordei. Arabidopsis pen1-1 mutant is penetrated by the hemibiotrophic oomycete pathogen, Phytophthora sojae that causes root and stem rot disease in soybean. The P. sojae susceptible (pss) 1 mutant is infected by both P. sojae and the hemibiotrophic fungal pathogen, Fusarium virguliforme that causes sudden death syndrome in soybean ...


The Effects Of Heat Stress In Redox Balance And Inflammatory Signaling In Porcine Skeletal Muscle, Sandra Isabel Rosado Montilla Jan 2013

The Effects Of Heat Stress In Redox Balance And Inflammatory Signaling In Porcine Skeletal Muscle, Sandra Isabel Rosado Montilla

Graduate Theses and Dissertations

Heat stress (HS) is a major concern for human health as well as for the swine industry. In 2012, HS resulted in the largest number of weather related human fatalities in the US. Animal production is also compromised as HS leads to poor sow performance, decreased carcass value and increased veterinary costs. However, the molecular effects of HS on skeletal muscle are still unclear. This study aimed to determine the extent to which HS disrupted redox balance and initiated an inflammatory response in oxidative and glycolytic porcine skeletal muscle. Moreover, we quantified the contribution of reduced feed intake to the ...