Physiological And Evolutionary Implications Of The Pattern Of Expression Of Oxygen-Binding Hemoproteins In Antarctic Notothenioid Fishes, Kimberly Borley
Electronic Theses and Dissertations
Antarctic icefish do not express hemoglobin (Hb). Icefishes possess cardiovascular modifications including increased densities of blood vessels, larger ventricles and increased blood volume compared to red-blooded relatives. In addition to delivering oxygen to tissues, Hb degrades nitric oxide (NO), a small signaling molecule. To investigate the mechanism driving development of icefish cardiovascular characteristics, I present and test the hypothesis that loss of Hb results in increased steady-state levels of NO, triggering downstream signaling pathways such as angiogenesis. I measured NO breakdown products, as a proxy for NO, and found that icefish have higher steady-state levels of NO metabolites in their ...
Protein Evolution Via Amino Acid And Codon Elimination, 2010 University of Copenhagen
Protein Evolution Via Amino Acid And Codon Elimination, Lise Goltermann, Marie Sofie Yoo Larsen, Ranat Banerjee, Andreas C. Joerger, Michael Ibba, Thomas Bentin
Biology, Chemistry, and Environmental Sciences Faculty Articles and Research
Global residue-specific amino acid mutagenesis can provide important biological insight and generate proteins with altered properties, but at the risk of protein misfolding. Further, targeted libraries are usually restricted to a handful of amino acids because there is an exponential correlation between the number of residues randomized and the size of the resulting ensemble. Using GFP as the model protein, we present a strategy, termed protein evolution via amino acid and codon elimination, through which simplified, native-like polypeptides encoded by a reduced genetic code were obtained via screening of reduced-size ensembles.
The strategy involves combining a ...
Determinants For Stop-Transfer And Post-Import Pathways For Protein Targeting To The Chloroplast Inner Envelope Membrane, 2010 University of Massachusetts - Amherst
Determinants For Stop-Transfer And Post-Import Pathways For Protein Targeting To The Chloroplast Inner Envelope Membrane, Antonio A. B. Viana, Ming Li, Danny Schnell
he inner envelope membrane (IEM) of the chloroplast plays key roles in controlling metabolite transport between the organelle and cytoplasm and is a major site of lipid and membrane synthesis within the organelle. IEM biogenesis requires the import and integration of nucleus-encoded membrane proteins. Previous reports have led to the conclusion that membrane proteins are inserted into the IEM during protein import from the cytoplasm via a stop-transfer mechanism or are completely imported into the stroma and then inserted into the IEM in a post-import mechanism. In this study, we examined the determinants for each pathway by comparing the targeting ...
Oxidation Of Methane By A Biological Dicopper Centre, 2010 Northwestern University
Oxidation Of Methane By A Biological Dicopper Centre, Ramakrishnan Balasubramanian, Stephen M. Smith, Swati Rawat, Liliya A. Yatsunyk, Timothy L. Stemmler, Amy C. Rosenzweig
Biochemistry and Molecular Biology Faculty Publications
Vast world reserves of methane gas are underutilized as a feedstock for the production of liquid fuels and chemicals owing to the lack of economical and sustainable strategies for the selective oxidation of methane to methanol1. Current processes to activate the strong C–H bond (104 kcal mol−1) in methane require high temperatures, are costly and inefficient, and produce waste2. In nature, methanotrophic bacteria perform this reaction under ambient conditions using metalloenzymes called methane monooxygenases (MMOs). MMOs thus provide the optimal model for an efficient, environmentally sound catalyst3. There are two types of MMO. Soluble MMO (sMMO),expressed by ...
How The Sequence Of A Gene Can Tune Its Translation, 2010 The Ohio State University
How The Sequence Of A Gene Can Tune Its Translation, Kurt Fredrick, Michael Ibba
Biology, Chemistry, and Environmental Sciences Faculty Articles and Research
Sixty-one codons specify 20 amino acids, offering cells many options for encoding a polypeptide sequence. Two new studies (Cannarrozzi et al., 2010, Tuller et al., 2010) now foster the idea that patterns of codon usage can control ribosome speed, fine-tuning translation to increase the efficiency of protein synthesis.
Ribosomal Rna Mutations That Inhibit The Activity Of Transfer-Messenger Rna Of Stalled Ribosomes, 2010 Brigham Young University - Provo
Ribosomal Rna Mutations That Inhibit The Activity Of Transfer-Messenger Rna Of Stalled Ribosomes, Jacob N. Crandall
Theses and Dissertations
In eubacteria, stalled ribosomes are rescued by a conserved quality-control mechanism involving transfer-messenger RNA (tmRNA) and its protein partner SmpB. Mimicking a tRNA, tmRNA enters stalled ribosomes, adds Ala to the nascent polypeptide, and serves as a template to encode a short peptide that tags the nascent protein for destruction. To further characterize the tagging process, we developed two genetic selections that link tmRNA activity to cell death. These negative selections can be used to identify inhibitors of tagging or to identify mutations in key residues essential for ribosome rescue. Little is known about which ribosomal elements are specifically required ...
Dynamics On Multiple Timescales In The Rna-Directed Rna Polymerase From The Cystovirus Φ6, 2010 CUNY City College
Dynamics On Multiple Timescales In The Rna-Directed Rna Polymerase From The Cystovirus Φ6, Zhen Ren, Hsin Wang, Ranajeet Ghose
Publications and Research
The de novoinitiating RNA-directed RNA polymerase (RdRP), P2, forms the central machinery in the infection cycle of the bacteriophage ϕ6 by performing the dual tasks of replication and transcription of the double-stranded RNA genome in the host cell. By measurement and quantitative analysis of multiple-quantum spin-relaxation data for the δ1 positions of Ile residues that are distributed over the 3D-fold of P2, we find that the enzyme is dynamic both on the fast (ps–ns) and slow (µs–ms) timescales. The characteristics of several motional modes including those that coincide with the catalytic timescale (500–800/s) are altered ...
Aspergillus Fumigatus Stimulates The Nlrp3 Inflammasome Through A Pathway Requiring Ros Production And The Syk Tyrosine Kinase, 2010 University of California, Merced
Aspergillus Fumigatus Stimulates The Nlrp3 Inflammasome Through A Pathway Requiring Ros Production And The Syk Tyrosine Kinase, Najwane Saïd-Sadier, Eduardo V. Padilla, Gordon Langsley, David M. Ojcius
Dugoni School of Dentistry Faculty Articles
Invasive aspergillosis (IA) is a life-threatening disease that occurs in immunodepressed patients when infected with Aspergillus fumigatus. This fungus is the second most-common causative agent of fungal disease after Candida albicans. Nevertheless, much remains to be learned about the mechanisms by which A. fulmigatus activates the innate immune system. We investigated the inflammatory response to conidia and hyphae of A. fumigatus and specifically, their capacity to trigger activation of an inflammasome. Our results show that in contrast to conidia, hyphal fragments induce NLRP3 inflammasome assembly, caspase-1 activation and IL-1β release from a human monocyte cell line. The ability of Aspergillus ...
The Genomics Education Partnership: Successful Integration Of Research Into Laboratory Classes At A Diverse Group Of Undergraduate Institutions, 2010 Washington University in St. Louis
The Genomics Education Partnership: Successful Integration Of Research Into Laboratory Classes At A Diverse Group Of Undergraduate Institutions, Christopher D. Shaffer, Consuelo Alvarez, Cheryl Bailey, Daron Barnard, Satish Bhalla, Chitra Chandrasekaran, Vidya Chandrasekaran, Hui-Min Chung, Douglas R. Dorer, Chunguang Du, Todd T. Eckdahl, Jeff L. Poet, Donald Frohlich, Anya L. Goodman, Yuying Gossner, Charles Hauser, Laura L.M. Hoopes, Diana Johnson, Christopher J. Jones, Marian Kaehler, Nighat Kokan, Olga R. Kopp, Gary A. Kuleck, Gerard Mcneil, Robert Moss, Jennifer L. Myka, Alexis Nagengast, Robert Morris, Paul J. Overvoorde, Elizabeth Shoop, Susan Parrish, Kelynne Reed, E. Gloria Regisford, Dennis Revie, Anne G. Rosenwald, Ken Saville, Stephanie Schroeder, Mary Shaw, Gary Skuse, Christopher Smith, Mary Smith, Eric P. Spana, Mary Spratt, Joyce Stamm, Jeff S. Thompson, Matthew Wawersik, Barbara A. Wilson, Jim Youngblom, Wilson Leung, Jeremy Buhler, Elaine R. Mardis, David Lopatto, Sarah C.R. Elgin
Biochemistry -- Faculty Publications
Genomics is not only essential for students to understand biology but also provides unprecedented opportunities for undergraduate research. The goal of the Genomics Education Partnership (GEP), a collaboration between a growing number of colleges and universities around the country and the Department of Biology and Genome Center of Washington University in St. Louis, is to provide such research opportunities. Using a versatile curriculum that has been adapted to many different class settings, GEP undergraduates undertake projects to bring draft-quality genomic sequence up to high quality and/or participate in the annotation of these sequences. GEP undergraduates have improved more than ...
Computational Protein Design: Advances In The Design And Redesign Of Biomolecular Nanostructures, 2010 University of Pennsylvania
Computational Protein Design: Advances In The Design And Redesign Of Biomolecular Nanostructures, Jeffery G. Saven
Departmental Papers (Chemistry)
Computational protein design facilitates the continued development of methods for the design of biomolecular structure, sequence and function. Recent applications include the design of novel protein sequences and structures, proteins incorporating nonbiological components, protein assemblies, soluble variants of membrane proteins, and proteins that modulate membrane function.
Characterization Of Glycation Sites On Human Serum Albumin Using Mass Spectrometry, 2010 University of Nebraska-Lincoln
Characterization Of Glycation Sites On Human Serum Albumin Using Mass Spectrometry, Omar S. Barnaby
Student Research Projects, Dissertations, and Theses - Chemistry Department
The modification of proteins by reducing sugars is a process that occurs naturally in the body. This process, which is known as glycation, has been linked to many of the chronic complications encountered during diabetes. Glycation has also been linked to changes in the binding of human serum albumin (HSA) to several drugs and small solutes in the body. While these effects are known, there is little information that explains why these changes in binding occur. The goal of this project was to obtain qualitative and quantitative information about glycation that occurs on HSA. The first section of this dissertation ...
Conformational Change And Topological Stability Of Proteins, 2010 Old Dominion University
Conformational Change And Topological Stability Of Proteins, Jeffrey Andrew Tibbitt
Chemistry & Biochemistry Theses & Dissertations
The conformation and topology of a protein changes when stabilizing forces are absent, but the mechanisms by which these changes occur remains elusive. This dissertation aims to broaden the understandings. On the conformational level, the M20 loop conformers of E. coli dihydrofolate reductase are interrogated to identify factors responsible for their stability as well as to determine how one conformer might change into another. Molecular dynamics is used to simulate the open, closed and occluded conformers (observed in X-ray crystal structures) under a series of different single ligand conditions. Analysis shows that all open conformers move to a similar new ...
A Comparison Of Three Computer-Based Methods Used To Determine Emg Signal Amplitude, 2010 University of Texas of the Permian Basin
A Comparison Of Three Computer-Based Methods Used To Determine Emg Signal Amplitude, Doug Renshaw
No abstract provided.
Systematic Discovery Of Regulatory Motifs In Fusarium Graminearum By Comparing Four Fusarium Genomes, 2010 University of Massachusetts - Amherst
Systematic Discovery Of Regulatory Motifs In Fusarium Graminearum By Comparing Four Fusarium Genomes, Lokesh Kumar, Andrew Breakspear, Corby Kistler, Li-Jun Ma, Xiaohui Xie
Fusarium graminearum (Fg), a major fungal pathogen of cultivated cereals, is responsible for billions of dollars in agriculture losses. There is a growing interest in understanding the transcriptional regulation of this organism, especially the regulation of genes underlying its pathogenicity. The generation of whole genome sequence assemblies for Fg and three closely related Fusarium species provides a unique opportunity for such a study.
Applying comparative genomics approaches, we developed a computational pipeline to systematically discover evolutionarily conserved regulatory motifs in the promoter, downstream and the intronic regions of Fg genes, based on the multiple alignments of sequenced Fusarium ...
Computational Design And Elaboration Of A De Novo Heterotetrameric Α-Helical Protein That Selectively Binds An Emissive Abiological (Porphinato)Zinc Chromophore, H Christopher Fry, Andreas Lehmann, Jeffery G. Saven, William F. Degrado, Michael J. Therien
Departmental Papers (Chemistry)
The first example of a computationally de novo designed protein that binds an emissive abiological chromophore is presented, in which a sophisticated level of cofactor discrimination is pre-engineered. This heterotetrameric, C(2)-symmetric bundle, A(His):B(Thr), uniquely binds (5,15-di[(4-carboxymethyleneoxy)phenyl]porphinato)zinc [(DPP)Zn] via histidine coordination and complementary noncovalent interactions. The A(2)B(2) heterotetrameric protein reflects ligand-directed elements of both positive and negative design, including hydrogen bonds to second-shell ligands. Experimental support for the appropriate formulation of [(DPP)Zn:A(His):B(Thr)](2) is provided by UV/visible and circular dichroism spectroscopies ...
Md-2-Mediated Ionic Interactions Between Lipid A And Tlr4 Are Essential For Receptor Activation, 2010 University of Massachusetts Medical School
Md-2-Mediated Ionic Interactions Between Lipid A And Tlr4 Are Essential For Receptor Activation, Jianmin Meng, Egil Lien, Douglas T. Golenbock
Infectious Diseases and Immunology Publications
Lipopolysaccharide (LPS) activates innate immune responses through TLR4.MD-2. LPS binds to the MD-2 hydrophobic pocket and bridges the dimerization of two TLR4.MD-2 complexes to activate intracellular signaling. However, exactly how lipid A, the endotoxic moiety of LPS, activates myeloid lineage cells remains unknown. Lipid IV(A), a tetra-acylated lipid A precursor, has been used widely as a model for lipid A activation. For unknown reasons, lipid IV(A) activates proinflammatory responses in rodent cells but inhibits the activity of LPS in human cells. Using stable TLR4-expressing cell lines and purified monomeric MD-2, as well as MD-2-deficient bone marrow-derived ...
Genetic And Molecular Characterization Of A Cryptochrome From The Filamentous Fungus Neurospora Crassa, Allan C. Froehlich, Chen-Hui Chen, William J. Belden, Cornelia Madeti
In plants and animals, cryptochromes function as either photoreceptors or circadian clock components. We have examined the cryptochrome from the filamentous fungus Neurospora crassa and demonstrate that Neurospora cry encodes a DASH-type cryptochrome that appears capable of binding flavin adenine dinucleotide (FAD) and methenyltetrahydrofolate (MTHF). The cry transcript and CRY protein levels are strongly induced by blue light in a wc-1-dependent manner, and cry transcript is circadianly regulated, with a peak abundance opposite in phase to frq. Neither deletion nor overexpression of cry appears to perturb the free-running circadian clock. However, cry disruption knockout mutants show a small phase delay ...
Antimicrobial And Antioxidant Activities Of Essential Oil And Methanol Extract Of Jasminum Sambac From Djibouti, 2010 University of Djibouti
Antimicrobial And Antioxidant Activities Of Essential Oil And Methanol Extract Of Jasminum Sambac From Djibouti, Fatou Abdoul-Latif, Prosper Edou, François Eba, Nabil Mohamed, Adwa Ali, Samatar Djama, Louis-Clément Obame, Mamoudou Hama Dicko
Pr. Mamoudou H. DICKO, PhD
The essential oil of jasminum sambac from Djibouti was subjected to screening for their possible antioxidant activity by two complementary test systems, namely DPPH free radical scavenging and beta-carotene-linoleic acid assays. Butylated hydroxytoluene (BHT) was used as positive control in both test systems. In the DPPH test system, the IC50 value of essential oil and methanol extract were respectively 7.43 and 2.30 μg/ml. In the beta-carotene-linoleic acid system, oxidation was effectively inhibited by Jasminum sambac, the RAA value of essential oil and methanol extract were respectively 96.6 and 93.9%. When compared to BHT, the essential ...
Role Of Members Of The Phosducin Gene Family In Protein Translation And Folding, 2010 Brigham Young University - Provo
Role Of Members Of The Phosducin Gene Family In Protein Translation And Folding, Nana Sono-Koree
Theses and Dissertations
G proteins regulate various physiological processes by way of transducing a wide variety of signals ranging from hormonal to sensory stimuli. Malfunctions in G protein signaling lead to numerous diseases. G protein signaling begins with binding of a ligand to a G protein-coupled receptor resulting in a conformational change that leads to the exchange of a GDP for a GTP on G α. The GTP bound α subunit dissociates for its stable Gβγ dimer partner. G α-GTP and Gβγ control the activity of effector enzymes and ion channels that ultimately orchestrate the cellular response to stimulus. Current reports have shown ...
The Asymmetric Phase-Transfer Catalyzed Alkylation Of Imidazolyl Ketones And Aryl Acetates And Their Applications To Total Synthesis, 2010 Brigham Young University - Provo
The Asymmetric Phase-Transfer Catalyzed Alkylation Of Imidazolyl Ketones And Aryl Acetates And Their Applications To Total Synthesis, Michael Andrew Christiansen
Theses and Dissertations
Phase-transfer catalysts derived from the cinchona alkaloids cinchonine and cinchonidine are widely used in the asymmetric alkylation of substrates bearing moieties that resonance stabilize their enolates. The investigation of α-oxygenated esters revealed decreased α-proton acidity, indicating the oxygen's overall destabilizing effect on enolates by electron-pair repulsion. Alkylation of α-oxygenated aryl ketones with various alkyl halides proved successful with a cinchonidine catalyst, giving products with high yield and enantioselectivity. The resulting compounds were converted to esters through modified Baeyer-Villiger oxidation. Alkylation with indolyl electrophiles gave products that underwent decomposition under Baeyer-Villiger conditions. Alternative N-methylimidazolyl ketones were explored. Alkylated imidazolyl ketones ...