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Molecular Biology

2010

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Articles 1 - 30 of 207

Full-Text Articles in Biochemistry, Biophysics, and Structural Biology

Characterization Of The Role Of Nicotine And Delta 9-Thc In Modulation Of Neuroinflammation, Jared Ehrhart Dec 2010

Characterization Of The Role Of Nicotine And Delta 9-Thc In Modulation Of Neuroinflammation, Jared Ehrhart

Graduate Theses and Dissertations

Neuroinflammation is a major driving force in the progression of neurodegenerative disorders. Nicotinic acetylcholine receptors, as well as cannabinoid CB2 receptors, have been shown to have strong anti-inflammatory properties when activated. These effects are shown, in vivo, to be a result of stimulation of α7 nAChRs and CB2 cannabinoid receptors. Microglia cells, an immune cell in the brain, are shown to express both of these receptor subtypes. The studies detailed herein, investigated the ability of two compounds, nicotine and Δ9-THC, in modulation of inflammatory processes. Stimulation of these receptors on microglia using nicotine and Δ9-THC blocked the activation of these ...


Nucleoside Modifications Suppress Rna Activation Of Cytoplasmic Rna Sensors, Bart R. Anderson Dec 2010

Nucleoside Modifications Suppress Rna Activation Of Cytoplasmic Rna Sensors, Bart R. Anderson

Publicly Accessible Penn Dissertations

Multiple innate defense pathways exist to recognize and defend against foreign nucleic acids. Unlike innate immune receptors that recognize structures specific for pathogens that are not shared by mammalian hosts — for example, toll-like receptor (TLR)4-lipopolysaccharide, TLR5-flagellin, NOD1 and 2-peptidoglycan — all nucleic acids are made from four components that are identical from bacteria to man. Nucleoside modifications are prevalent in nature but vary greatly in their distribution and frequency, and therefore could serve as patterns for recognition of pathogenic nucleic acids. The presence of modified nucleosides in RNA reduces the activation of RNA-sensing TLRs and retinoic acid inducible gene I ...


Characterization Of Thap10 And Thap11 As Transcriptional Repressors In Dna Damage And Colon Cancer Progression, James B. Parker Dec 2010

Characterization Of Thap10 And Thap11 As Transcriptional Repressors In Dna Damage And Colon Cancer Progression, James B. Parker

Publicly Accessible Penn Dissertations

The THAP (Thanatos associated protein) domain is an evolutionarily conserved zinc-finger motif highly similar to the sequence specific DNA binding domain of Drosophila P element transposase. Emerging data suggest THAP proteins may function in DNA and chromatin dependent processes, including transcription. However, the transcriptional regulatory function, mechanisms of action, and role of most THAP proteins in normal and aberrant cellular processes remain largely unknown.

In this thesis, we demonstrate that several human THAP proteins contain transcriptional repressor activity and specifically identify THAP10 and THAP11 as differentially expressed in human DNA damage and colon cancer progression, respectively. THAP10 and THAP11 repressed ...


Utilizing Genetically Engineered Mouse Models Of Pancreatic Cancer: Evaluating The Role Of Cathepsin B And The Efficacy Of Farnesyl Thiosalicylic Acid, Aarthi Gopinathan Dec 2010

Utilizing Genetically Engineered Mouse Models Of Pancreatic Cancer: Evaluating The Role Of Cathepsin B And The Efficacy Of Farnesyl Thiosalicylic Acid, Aarthi Gopinathan

Publicly Accessible Penn Dissertations

I have utilized genetically engineered mouse models of pancreatic cancer to identify a potential new therapeutic target, and to test the efficacy of a putative ras inhibitor. In the first part, I show that cathepsin B is upregulated during disease progression in the mouse pancreas, as is overall cathepsin activity. Loss of cathepsin B decreases preinvasive disease burden and imparts a significant survival benefit, with a consistent decrease in proliferation. In addition, lack of cathepsin B also decreases the burden of liver metastasis. Phospho-Erk localization appears to be affected by cathepsin B loss, which may account for the defect in ...


Ku Can Contribute To Telomere Lengthening In Yeast At Multiple Positions In The Telomerase Rnp, David C. Zappulla, Karen J. Goodrich, Julian R. Arthur, Lisa A. Gurski, Elizabeth M. Denham, Anne E. Stellwagen, Thomas R. Cech Dec 2010

Ku Can Contribute To Telomere Lengthening In Yeast At Multiple Positions In The Telomerase Rnp, David C. Zappulla, Karen J. Goodrich, Julian R. Arthur, Lisa A. Gurski, Elizabeth M. Denham, Anne E. Stellwagen, Thomas R. Cech

Chemistry & Biochemistry Faculty Contributions (1986-2018)

Unlike ribonucleoprotein complexes that have a highly ordered overall architecture, such as the ribosome, yeast telomerase appears to be much more loosely constrained. Here, we investigate the importance of positioning of the Ku subunit within the 1157-nt yeast telomerase RNA (TLC1). Deletion of the 48-nt Ku-binding hairpin in TLC1 RNA (tlc1Δ48) reduces telomere length, survival of cells with gross chromosomal rearrangements, and de novo telomere addition at a broken chromosome end. To test the function of Ku at novel positions in the telomerase RNP, we reintroduced its binding site into tlc1Δ48 RNA at position 446 or 1029. We found that ...


Identification Of Regions Responsible For The Open Conformation Of S100a10 Using Chimaeric S100a11/S100a10 Proteins, Liliana Santamaria-Kisiel Dec 2010

Identification Of Regions Responsible For The Open Conformation Of S100a10 Using Chimaeric S100a11/S100a10 Proteins, Liliana Santamaria-Kisiel

Electronic Thesis and Dissertation Repository

S100A11 is a dimeric, EF-hand calcium-binding protein. Calcium binding to S100A11 results in a large conformational change that uncovers a broad hydrophobic surface used to interact with phospholipid-binding proteins (annexins A1 and A2), and facilitate membrane vesiculation events. In contrast to other S100 proteins, S100A10 is unable to bind calcium due to deletion and substitution of calcium-ligating residues. Despite this, calcium-free S100A10 assumes an “open” conformation that is very similar to S100A11 in its calcium-bound state (Ca2+-S100A11). To understand how S100A10 is able to adopt an open conformation in the absence of calcium, seven chimeric proteins were constructed where ...


The Role Of The Suppressor Of Hairy-Wing Insulator Protein In Chromatin Organization And Expression Of Transposable Elements In Drosophila Melanogaster, Heather Anne Wallace Dec 2010

The Role Of The Suppressor Of Hairy-Wing Insulator Protein In Chromatin Organization And Expression Of Transposable Elements In Drosophila Melanogaster, Heather Anne Wallace

Doctoral Dissertations

ABSTRACT Chromatin insulators are required for proper temporal and spatial expression of genes in metazoans. Insulators are thought to play an important role in the regulation of gene expression through the formation of higher-order chromatin structures. One of the best characterized insulators is the Drosophila gypsy insulator, which is located in the gypsy retrovirus. Several proteins are required for gypsy insulator function, including Su(Hw), Mod(mdg4), and CP190. In addition to the gypsy insulator, these proteins are located throughout the genome at sites which are thought to correspond to endogenous insulators. Analysis of the distribution of insulator proteins across ...


Applications Of Site-Specific Recombination Systems In Transgene Expression And Marker Gene Removal, Mehmet Aydin Akbudak Dec 2010

Applications Of Site-Specific Recombination Systems In Transgene Expression And Marker Gene Removal, Mehmet Aydin Akbudak

Theses and Dissertations

Site Specific Recombination systems, such as FLP-FRT and Cre-lox, have been successfully used for site-specific gene integration and marker-gene deletion in plant systems. They are very useful tools in the integration of single-copy full-length transgene cassettes into the genome because the transgene integration via conventional methods often generate multi-copy locus. Such complex locus containing direct and inverted repeats of full-length and truncated copies of the transgene cassette generate aberrant RNA resulting in gene silencing. Therefore, for stable gene expression, a single copy transgene locus is preferred. However, even single copy locus sometimes succumbs to gene silencing. Although the mechanism is ...


Novel Constitutively Active Point Mutations In The Nh2 Domain Of Cxcr2 Capture The Receptor In Different Activation States, Giljun Park Dec 2010

Novel Constitutively Active Point Mutations In The Nh2 Domain Of Cxcr2 Capture The Receptor In Different Activation States, Giljun Park

Doctoral Dissertations

Chemokines are structurally and functionally related 8-10 kDa proteins defined by four conserved cysteine residues. They consist of a superfamily of proinflammatory mediators that promote the recruitment of various kinds of leukocytes and other cell types through binding to their respective chemokine receptor, a member of the GPCR family. Abnormal control of this system results in various diseases including tumorigenesis and cancer metastasis. Deregulation can occur when constitutively active mutant (CAM) chemokine receptors are locked in the “on” position. This can lead to cellular transformation/tumorigenesis. A viral CAM receptor, ORF74, that can cause tumors in humans, also has homology ...


Genotype And Breed Trend Influences On Citric Acid And Coagulation Times Of Raw Milk, Melissa Looney Dec 2010

Genotype And Breed Trend Influences On Citric Acid And Coagulation Times Of Raw Milk, Melissa Looney

Dairy Science

The objective of the study was to determine if citric acid levels measured in milk was related to genetic variants identified in Holstein and Jersey cows. The data used were milk samples collected from both Holstein and Jersey cows at Cal Poly, San Luis Obispo. Citric acid levels and other constituents were measured using FTIR methods with the FOSS MilkoscanTM FT2 on each sample. Genotypes were obtained for the DGAT 1 locus using polymerase chain reaction and an enzymatic digestion using the MWO I restriction enzyme. Observations were obtained on 13 Holsteins and 12 Jersey cows. Results indicated that citric ...


Production, Purification And Crystallization Of Membrane Integrated Multimeric Bax, Adelbert Mark Villoso Dec 2010

Production, Purification And Crystallization Of Membrane Integrated Multimeric Bax, Adelbert Mark Villoso

UNLV Theses, Dissertations, Professional Papers, and Capstones

Apoptosis, or programmed cell death, is a vital process intimately involved in the embryonic development and homeostatic maintenance of all multicellular organisms. The committing step to apoptosis is regulated by a key protein, Bax, and its ability to integrate and form a pore structure at the outer mitochondrial membrane.


Unfortunately, the molecular details of apoptosis remain largely unclear due to the lack of structural data of integral membrane (IM) Bax. Experimental limitations of membrane protein production have slowed the pursuit of an IM-Bax structure simply because standard protocols for producing recombinant IM-Bax are inefficient in producing adequate quantities of IM-Bax ...


Transcriptional Regulation Of Shigella Virulence Plasmid-Encoded Genes By Virb And Crp, Christopher Thomas Hensley Dec 2010

Transcriptional Regulation Of Shigella Virulence Plasmid-Encoded Genes By Virb And Crp, Christopher Thomas Hensley

UNLV Theses, Dissertations, Professional Papers, and Capstones

Shigella flexneri is a species of Gram-negative intracellular pathogens that causes bacillary dysentery in humans. Shigella relies on the precise transcriptional regulation of virulence genes, encoded by a large virulence plasmid, for invasion and infection of human colonic epithelial cells. The transcription of most identified virulence genes are regulated through a cascade controlled by the primary regulator of virulence genes, VirF, and the global transcriptional regulator, VirB. Currently, few studies have addressed how individual Shigella virulence genes are precisely regulated for optimal expression during specific stages of pathogenesis and within the constraints of the regulatory cascade. This work addresses how ...


Elucidating Functional Roles For Myogenin In Adult Skeletal Muscle Metabolism, Exercise Capacity, And Regeneration, Jesse Flynn Dec 2010

Elucidating Functional Roles For Myogenin In Adult Skeletal Muscle Metabolism, Exercise Capacity, And Regeneration, Jesse Flynn

UT GSBS Dissertations and Theses (Open Access)

The four basic helix-loop-helix myogenic transcription factors, myogenin, Myf5, MRF4, and MyoD are critical for embryonic skeletal muscle development. Myogenin is necessary for the terminal differentiation of myoblasts into myofibers during embryogenesis, but little is known about the roles played by myogenin in adult skeletal muscle function and metabolism. Furthermore, while metabolism is a well-studied physiological process, how it is regulated at the transcriptional level remains poorly understood. In this study, my aim was to determine the function of myogenin in adult skeletal muscle metabolism, exercise capacity, and regeneration. To investigate this, I utilized a mouse strain harboring the Myogflox ...


Mechanism Of N-Methylation By The Trna M1g37 Methyltransferase Trm5., Thomas Christian, Georges Lahoud, Cuiping Liu, Katherine Hoffmann, John J Perona, Ya-Ming Hou Dec 2010

Mechanism Of N-Methylation By The Trna M1g37 Methyltransferase Trm5., Thomas Christian, Georges Lahoud, Cuiping Liu, Katherine Hoffmann, John J Perona, Ya-Ming Hou

Department of Biochemistry and Molecular Biology Faculty Papers

Trm5 is a eukaryal and archaeal tRNA methyltransferase that catalyzes methyl transfer from S-adenosylmethionine (AdoMet) to the N(1) position of G37 directly 3' to the anticodon. While the biological role of m(1)G37 in enhancing translational fidelity is well established, the catalytic mechanism of Trm5 has remained obscure. To address the mechanism of Trm5 and more broadly the mechanism of N-methylation to nucleobases, we examined the pH-activity profile of an archaeal Trm5 enzyme, and performed structure-guided mutational analysis. The data reveal a marked dependence of enzyme-catalyzed methyl transfer on hydrogen ion equilibria: the single-turnover rate constant for methylation ...


Spidroin N-Terminal Domain: A Ph Sensor In The Spider Silk Assembly Process, William Gaines Dec 2010

Spidroin N-Terminal Domain: A Ph Sensor In The Spider Silk Assembly Process, William Gaines

All Dissertations

Spider silks are protein-based fibers with remarkable mechanical qualities. Perhaps even more impressive is the spinning process in which the spider silk proteins (spidroins) are assembled from a highly soluble storage state into a well-ordered and insoluble fiber. Indeed, the ordered arrangement of spidroins, which is endowed by the spinning process, is the basis of fiber strength. However, the forces driving fiber assembly and the mechanisms by which spidroins respond those forces are only poorly understood. Spidroins have a tripartite domain architecture consisting of a large and repetitive central domain flanked by small, non-repetitive N- and C-terminal domains. Both terminal ...


Controlling The Activity Of The Tec Kinase Itk By Mutation Of The Phenylalanine Gatekeeper Residue, Raji E. Joseph, Amy H. Andreotti Dec 2010

Controlling The Activity Of The Tec Kinase Itk By Mutation Of The Phenylalanine Gatekeeper Residue, Raji E. Joseph, Amy H. Andreotti

Biochemistry, Biophysics and Molecular Biology Publications

The regulatory spine is a set of conserved residues that are assembled and disassembled upon activation and inactivation of kinases. We recently identified the regulatory spine within the immunologically important Tec family kinases and have shown that in addition to the core spine residues within the kinase domain itself, contributions from the SH2−kinase linker region result in an extended spine structure for this kinase family. Disruption of the regulatory spine, either by mutation or by removal of the amino-terminal SH2−kinase linker region or by mutation of core spine residues, leads to inactivation of the Tec kinases. With a ...


Development Of A Genetic Modification System In Clostridium Scatologenes Atcc 25775 For Generation Of Mutants, Prasanna Tamarapu Parthasarathy Dec 2010

Development Of A Genetic Modification System In Clostridium Scatologenes Atcc 25775 For Generation Of Mutants, Prasanna Tamarapu Parthasarathy

Masters Theses & Specialist Projects

3-Methyl indole (3-MI) is a malodorant in food and animal waste and Clostridium scatologenes ATCC 25775 is the model organism for the study of 3-MI production. 3-MI is an anaerobic degradation product of L-tryptophan and can cause pulmonary disorders and death in cattle and goats. To elucidate the 3-MI biosynthesis pathway and the underlying genes, it is necessary to develop a system to allow genetic modification in Clostridium scatologenes ATCC 25775. Bacteriophages and transposons are useful tools to achieve this goal. Isolation of Clostridium scatologenes ATCC 25775 bacteriophage was attempted by prophage induction and enrichments using environmental sources. To induce ...


Dynamic Remodeling Of The Stressed Heart: Role Of Protein Degradation Pathways, Deborah Vela Dec 2010

Dynamic Remodeling Of The Stressed Heart: Role Of Protein Degradation Pathways, Deborah Vela

UT GSBS Dissertations and Theses (Open Access)

The heart is a remarkable organ. In order to maintain its function, it remodels in response to a variety of environmental stresses, including pressure overload, volume overload, mechanical or pharmacological unloading and hormonal or metabolic disturbances. All these responses are linked to the inherent capacity of the heart to rebuild itself. Particularly, cardiac pressure overload activates signaling pathways of both protein synthesis and degradation. While much is known about regulators of protein synthesis, little is known about regulators of protein degradation in hypertrophy. The ubiquitin-proteasome system (UPS) selectively degrades unused and abnormal intracellular proteins. I speculated that the UPS may ...


Intraspecific Variation In Two Cosmopolitan Myxomycetes, Didymium Squamulosum And Didymium Difforme (Physarales: Didymiaceae), Katherine Elizabeth Winsett Dec 2010

Intraspecific Variation In Two Cosmopolitan Myxomycetes, Didymium Squamulosum And Didymium Difforme (Physarales: Didymiaceae), Katherine Elizabeth Winsett

Theses and Dissertations

The myxomycetes (plasmodial slime molds or myxogastrids) are one of three groups considered to be true slime molds (class Eumycetozoa sensu Olive 1975). Two vegetative states--amoebae and plasmodia--along with a spore-producing fruiting body characterize the life cycle of the myxomycetes. These organisms are associated with decaying plant material and are found in all terrestrial habitats worldwide. A number of species are considered cosmopolitan, being found worldwide, where they are associated with a diversity of microhabitats and substrates. A review of the literature, including molecular investigations in all three groups of slime molds, is presented, and this is followed by four ...


Structural And Functional Analysis Of Toc75, Ashita Mukul Dave Dec 2010

Structural And Functional Analysis Of Toc75, Ashita Mukul Dave

Masters Theses

The majority of chloroplast proteins are nuclear-encoded and post-translationally imported into the chloroplast. These newly imported proteins are translocated from the cytosolic compartment to the stroma by the Translocons of the Outer/Inner membranes of Chloroplast (TOC/TIC). In order to understand protein transport across the chloroplast outer membrane, it is crucial to investigate the structure and function of these complexes. The TOC complex is composed of the beta-barrel channel protein Toc75 and the GTPase receptors Toc34 and Toc159.

Toc75 is a member of the OMP85 (Outer Member Protein, 85 kDa) superfamily. Other proteins of the OMP85 superfamily also exist ...


Study Of The Structure And Function Of Cxc Chemokine Receptor 2, Hae Ryong Kwon Dec 2010

Study Of The Structure And Function Of Cxc Chemokine Receptor 2, Hae Ryong Kwon

Masters Theses

It has been shown that the amino terminus and second extracellular loop (EC2) of CXCR2 are crucial for ligand binding and receptor activation. The lack of an ionic lock motif in the third intracellular loop of CXCR2 focuses an investigation of the mechanism by which these two extracellular regions contribute to receptor recognition and activation.

The first objective of this investigation was to predict the structure of CXCR2 based on known structures of crystallized GPCRs. Rhodopsin, β2-adrenergic receptor, CXCR4 were used for homology modeling of CXCR2 structure. Highly conserved motifs found in sequence alignments of the template GPCRs were helpful ...


Human Decomposition Ecology At The University Of Tennessee Anthropology Research Facility, Franklin Edward Damann Dec 2010

Human Decomposition Ecology At The University Of Tennessee Anthropology Research Facility, Franklin Edward Damann

Doctoral Dissertations

The University of Tennessee Anthropology Research Facility (ARF) is well known for its unique history as a site of human decomposition research in a natural environment. It has been integral to our understanding of the processes of human decomposition. Over the last 30 years 1,089 bodies have decomposed at this 1.28 acre facility, producing a density of 850 corpses per acre of land. This project evaluated the abiotic and biotic characteristics of the soil exposed to various levels of human decomposition in order to determine the effect on the physicochemical properties and the indigenous bacterial communities.

Specifically, 75 ...


Molecular Targets Of Apigenin In Colorectal Cancer Cells: Involvement Of P21, Nag-1 And P53., Yi Zhong, C Krisanapun, Seong-Ho Lee, T Nualsanit, C Sams, P Peungvicha, Seung Baek Nov 2010

Molecular Targets Of Apigenin In Colorectal Cancer Cells: Involvement Of P21, Nag-1 And P53., Yi Zhong, C Krisanapun, Seong-Ho Lee, T Nualsanit, C Sams, P Peungvicha, Seung Baek

Seung J Baek

Persuasive epidemiological and experimental evidence suggests that dietary flavonoids have anti-cancer activity. Since conventional therapeutic and surgical approaches have not been able to fully control the incidence and outcome of most cancer types, including colorectal neoplasia, there is an urgent need to develop alternative approaches for the management of cancer. We sought to develop the best flavonoids for the inhibition of cell growth, and apigenin (flavone) proved the most promising compound in colorectal cancer cell growth arrest. Subsequently, we found that pro-apoptotic proteins (NAG-1 and p53) and cell cycle inhibitor (p21) were induced in the presence of apigenin, and kinase ...


Excision Dynamics Of Vibrio Pathogenicity Island-2 From Vibrio Cholerae: Role Of A Recombination Directionality Factor Vefa, Salvador Almagro-Moreno, Michael G. Napolitano, E. Fidelma Boyd Nov 2010

Excision Dynamics Of Vibrio Pathogenicity Island-2 From Vibrio Cholerae: Role Of A Recombination Directionality Factor Vefa, Salvador Almagro-Moreno, Michael G. Napolitano, E. Fidelma Boyd

Open Dartmouth: Faculty Open Access Scholarship

Vibrio Pathogenicity Island-2 (VPI-2) is a 57 kb region present in choleragenic V. cholerae isolates that is required for growth on sialic acid as a sole carbon source. V. cholerae non-O1/O139 pathogenic strains also contain VPI-2, which in addition to sialic acid catabolism genes also encodes a type 3 secretion system in these strains. VPI-2 integrates into chromosome 1 at a tRNA-serine site and encodes an integrase intV2 (VC1758) that belongs to the tyrosine recombinase family. ntV2 is required for VPI-2 excision from chromosome 1, which occurs at very low levels, and formation of a non-replicative circular intermediate.


Molecular Basis For Drug Resistance In Hiv-1 Protease, Akbar Ali, Rajintha M. Bandaranayake, Yufeng Cai, Nancy M. King, Madhavi Kolli, Seema Mittal, Jennifer E. Foulkes-Murzycki, Madhavi N. L. Nalam, Ellen A. Nalivaika, Aysegul Ozen, Moses Prabu-Jeyabalan, Kelly Thayer, Celia A. Schiffer Nov 2010

Molecular Basis For Drug Resistance In Hiv-1 Protease, Akbar Ali, Rajintha M. Bandaranayake, Yufeng Cai, Nancy M. King, Madhavi Kolli, Seema Mittal, Jennifer E. Foulkes-Murzycki, Madhavi N. L. Nalam, Ellen A. Nalivaika, Aysegul Ozen, Moses Prabu-Jeyabalan, Kelly Thayer, Celia A. Schiffer

Biochemistry and Molecular Pharmacology Publications and Presentations

HIV-1 protease is one of the major antiviral targets in the treatment of patients infected with HIV-1. The nine FDA approved HIV-1 protease inhibitors were developed with extensive use of structure-based drug design, thus the atomic details of how the inhibitors bind are well characterized. From this structural understanding the molecular basis for drug resistance in HIV-1 protease can be elucidated. Selected mutations in response to therapy and diversity between clades in HIV-1 protease have altered the shape of the active site, potentially altered the dynamics and even altered the sequence of the cleavage sites in the Gag polyprotein. All ...


Resonance Assignments And Secondary Structure Predictions Of The As(Iii) Metallochaperone Arsd In Solution, Jun Ye, Yanan He, Jack Skalicky, Barry P. Rosen, Timothy L. Stemmler Nov 2010

Resonance Assignments And Secondary Structure Predictions Of The As(Iii) Metallochaperone Arsd In Solution, Jun Ye, Yanan He, Jack Skalicky, Barry P. Rosen, Timothy L. Stemmler

Biochemistry and Molecular Biology Faculty Publications

ArsD is a metallochaperone that delivers As(III) to the ArsA ATPase, the catalytic subunit of the ArsAB pump encoded by the arsRDABC operon of Escherichia coli plasmid R773. Conserved ArsD cysteine residues (Cys12, Cys13 and Cys18) construct the As(III) binding site of the protein, however a global structural understanding of this arsenic binding remains unclear. We have obtained NMR assignments for ArsD as a starting point for probing structural changes on the protein that occur in response to metalloid binding and upon formation of a complex with ArsA. The predicted solution structure of ArsD is in agreement with ...


Evaluation Of Immunogene Therapy Using A Plasmid Encoding Il-15 Delivered By Electroporation In A 3d Tumor Model And A Mouse Melanoma Model, Bernadette Marrero Nov 2010

Evaluation Of Immunogene Therapy Using A Plasmid Encoding Il-15 Delivered By Electroporation In A 3d Tumor Model And A Mouse Melanoma Model, Bernadette Marrero

Graduate Theses and Dissertations

Melanoma is an aggressive disease with few effective treatment options. Non-toxic, anti-tumor therapies and prophylactic approaches are currently being investigated to identify treatment options that will control and remove late-stage melanoma.

The overall goal of this project was to establish an effective delivery method for a plasmid encoding human interleukin (phIL-15) into mouse melanoma cells (B16.F10) using the gene transfer technique electroporation (EP)1. The EP delivery phIL-15 was optimized using an in vitro 3D tumor model. The purpose was to translate these IL-15 delivery conditions into an in vivo mouse melanoma model to study IL-15 signal transduction and ...


Virulence Of An Emerging Respiratory Pathogen, Genus Pandoraea, In Vivo And Its Interactions With Lung Epithelial Cells, Gillian Herbert, Anne Costello, Lydia Fabunmi, Kirsten Schaffer, Kevin Kavanagh, Emma M. Caraher, Máire Callaghan, Siobhan Mcclean Nov 2010

Virulence Of An Emerging Respiratory Pathogen, Genus Pandoraea, In Vivo And Its Interactions With Lung Epithelial Cells, Gillian Herbert, Anne Costello, Lydia Fabunmi, Kirsten Schaffer, Kevin Kavanagh, Emma M. Caraher, Máire Callaghan, Siobhan Mcclean

Articles

Pandoraea species have emerged as opportunistic pathogens among cystic fibrosis (CF) and non-CF patients. Pandoraea pulmonicola is the predominant Pandoraea species among Irish CF patients. The objective of this study was to investigate the pathogenicity and potential mechanisms of virulence of Irish P. pulmonicola isolates and strains from other Pandoraea species. Three patients from whom the P. pulmonicola isolates were isolated have since died. The in vivo virulence of these and other Pandoraea strains was examined by determining the ability to kill Galleria mellonella larvae. The P. pulmonicola strains generally were the most virulent of the species tested, with three ...


Identification Of An Allosteric Signaling Network Within Tec Family Kinases, Raji E. Joseph, Qian Xie, Amy H. Andreotti Oct 2010

Identification Of An Allosteric Signaling Network Within Tec Family Kinases, Raji E. Joseph, Qian Xie, Amy H. Andreotti

Biochemistry, Biophysics and Molecular Biology Publications

The Tec family kinases are tyrosine kinases that function primarily in hematopoietic cells. The catalytic activity of the Tec kinases is positively influenced by the regulatory domains outside of the kinase domain. The current lack of a full-length Tec kinase structure leaves a void in our understanding of how these positive regulatory signals are transmitted to the kinase domain. Recently, a conserved structure within kinases, the ‘regulatory spine’, has been identified that assembles and disassembles as a kinase switches between its active and inactive states. Here we define the residues that comprise the regulatory spine within Tec kinases. Compared to ...


Tetrahymena Telomerase Protein P65 Induces Conformational Changes Throughout Telomerase Rna (Ter) And Rescues Telomerase Reverse Transcriptase And Ter Assembly Mutants▿†, Andrea J. Berman, Anne R. Gooding, Thomas R. Cech Oct 2010

Tetrahymena Telomerase Protein P65 Induces Conformational Changes Throughout Telomerase Rna (Ter) And Rescues Telomerase Reverse Transcriptase And Ter Assembly Mutants▿†, Andrea J. Berman, Anne R. Gooding, Thomas R. Cech

Chemistry & Biochemistry Faculty Contributions (1986-2018)

The biogenesis of the Tetrahymena telomerase ribonucleoprotein particle (RNP) is enhanced by p65, a La family protein. Single-molecule and biochemical studies have uncovered a hierarchical assembly of the RNP, wherein the binding of p65 to stems I and IV of telomerase RNA (TER) causes a conformational change that facilitates the subsequent binding of telomerase reverse transcriptase (TERT) to TER. We used purified p65 and variants of TERT and TER to investigate the conformational rearrangements that occur during RNP assembly. Nuclease protection assays and mutational analysis revealed that p65 interacts with and stimulates conformational changes in regions of TER beyond stem ...