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Articles 9811 - 9840 of 13714

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

Biophysical Characterization Of Tryptophan Locales, Mg²+ Binding And Protein Folding In Gα Subunits, Matthew Najor Jan 2013

Biophysical Characterization Of Tryptophan Locales, Mg²+ Binding And Protein Folding In Gα Subunits, Matthew Najor

Dissertations

The objective of this study is to understand the structure of guanine nucleotide - binding (G) proteins using a variety of spectroscopic tools. G proteins are membrane-bound proteins consisting of α, β, and γ subunits required for the transduction of extracellular signals to various intracellular effectors. Activation of G protein coupled receptors by neurotransmitters or hormones result in a conformational change of a G protein that is triggered by the exchange of guanosine 5'- diphosphate (GDP) bound to the  subunit for guanosine 5'- triphosphate (GTP) and concomitant dissociation of the  dimer.

Wild type (WT) Giα1 has three tryptophan …


Hiv-1 Frameshift Efficiency Is Primarily Determined By The Stability Of Base Pairs Positioned At The Mrna Entrance Channel Of The Ribosome, Kathryn Mouzakis Jan 2013

Hiv-1 Frameshift Efficiency Is Primarily Determined By The Stability Of Base Pairs Positioned At The Mrna Entrance Channel Of The Ribosome, Kathryn Mouzakis

Chemistry and Biochemistry Faculty Works

The human immunodeficiency virus (HIV) requires a programmed -1 ribosomal frameshift for Pol gene expression. The HIV frameshift site consists of a heptanucleotide slippery sequence (UUUUUUA) followed by a spacer region and a downstream RNA stem-loop structure. Here we investigate the role of the RNA structure in promoting the -1 frameshift. The stem-loop was systematically altered to decouple the contributions of local and overall thermodynamic stability towards frameshift efficiency. No correlation between overall stability and frameshift efficiency is observed. In contrast, there is a strong correlation between frameshift efficiency and the local thermodynamic stability of the first 3-4 bp in …


Critical Events In Human Metapneumovirus Infection: From Entry To Egress, Brent A. Hackett Jan 2013

Critical Events In Human Metapneumovirus Infection: From Entry To Egress, Brent A. Hackett

Theses and Dissertations--Molecular and Cellular Biochemistry

Human metapneumovirus (HMPV) is a respiratory pathogen in Paramyxovirus family that demonstrates extremely high morbidity in the population, with most individuals having been infected by the age of five. Despite the prevalence of this negative-sense RNA virus in the population for decades, it was only identified in 2001. As such, there is currently no specific treatment for HMPV and the potentially severe consequences of infection for elderly and immunocompromised individuals and particularly infants make development of antivirals targeting HMPV of high significance. HMPV constitutes a quarter of all respiratory hospitalizations among infants, placing it second only to RSV, in addition …


Fabrication Of Responsive Polymer Brushes For Patterned Cell Growth And Detachment, Ashley B. Sutherland Jan 2013

Fabrication Of Responsive Polymer Brushes For Patterned Cell Growth And Detachment, Ashley B. Sutherland

Browse all Theses and Dissertations

Patterned polymer brushes are used in biological applications to enhance cell function and to achieve selective cell growth. These patterned surfaces have a variety of applications, including cell sheet harvesting and tissue engineering. This work describes creation of chemical, topological, and responsive patterns on glass by sequential surface-initiated polymerization of poly(N-isopropylacrylamide)-co-(2-hydroxyethyl methacrylate) (pNIPAM-co-HEMA) and subsequent use of UV lithography to pattern the surface with pNIPAM. The cell adhesion peptide, RGD, is then immobilized on the surface of the copolymer pHEMA via DSC-coupling to spatially enhance cell adhesion properties. By culturing cells at 37 degrees celsius, cells selectively grow on DSC-activated …


The Cellular Nucleic Acid Binding Protein In Aging And Disease, Robin Webb Jan 2013

The Cellular Nucleic Acid Binding Protein In Aging And Disease, Robin Webb

Theses and Dissertations--Molecular and Cellular Biochemistry

The ZNF9 gene on chromosome 3 encodes the cellular nucleic acid binding protein (CNBP), a ubiquitously expressed, 177 amino acid (≈19.5kDa) protein that is highly conserved among vertebrates. The function of the protein is largely unknown, however an expansion in the first intron of the protein results in myotonic dystrophy type 2 (DM2), a multisystemic disease featuring cardiac arrhythmia, muscle wasting, cataracts, and a range of neuropathologies. Remarkably, we recently discovered that CNBP is involved in regulating the activity of β-secretase, the enzyme that produces the first cleavage event in the generation of the amyloid-β peptide (Aβ). The progressive fibrillization …


The Disordered Regulation Of Calcineurin: How Calmodulin-Induced Regulatory Domain Structural Changes Lead To The Activation Of Calcineurin, Victoria B. Dunlap Jan 2013

The Disordered Regulation Of Calcineurin: How Calmodulin-Induced Regulatory Domain Structural Changes Lead To The Activation Of Calcineurin, Victoria B. Dunlap

Theses and Dissertations--Molecular and Cellular Biochemistry

Calcineurin (CaN) is a highly regulated Ser/Thr protein phosphatase that plays critical roles in learning and memory, cardiac development and function, and immune system activation. Alterations in CaN regulation contribute to multiple disease states such as Down syndrome, cardiac hypertrophy, Alzheimer’s disease, and autoimmune disease. In addition, CaN is the target of the immunosuppressant drugs FK506 and cyclosporin A. Despite its importance, CaN regulation is not well understood on a molecular level. Full CaN activation requires binding of calcium-loaded calmodulin (CaM), however little is known about how CaM binding releases CaN’s autoinhibitory domain from the active site. Previous work has …


Characterization Of G-Patch Motif Contribution To Prp43 Function In The Pre-Messenger Rna Splicing And Ribosomal Rna Biogenesis Pathways, Daipayan Banerjee Jan 2013

Characterization Of G-Patch Motif Contribution To Prp43 Function In The Pre-Messenger Rna Splicing And Ribosomal Rna Biogenesis Pathways, Daipayan Banerjee

Theses and Dissertations--Biology

The DExD/H-box protein Prp43 is essential for two biological processes: nucleoplasmic pre-mRNA splicing and nucleolar rRNA maturation. The biological basis for the temporal and spatial regulation of Prp43 remains elusive. The Spp382/Ntr1, Sqs1/Pfa1 and Pxr1/Gno1 G-patch proteins bind to and activate the Prp43 DExD/H box-helicase in pre-mRNA splicing (Spp382) and rRNA processing (Sqs1, Pxr1). These Prp43-interacting proteins each contain the G-patch domain, a conserved sequence of ~48 amino acids that includes 6 highly conserved glycine (G) residues. Five annotated G-patch proteins in baker’s yeast (i.e., Spp382, Pxr1, Spp2, Sqs1 and Ylr271) and with the possible exception of the uncharacterized Ylr271 …


Malnutrition In Sickle Cell Anemia: Implications For Infection, Growth And Maturation, Hyacinth I. Hyacinth, Oluwatoyosi A. Adekeye, Christopher S. Yilgwan Jan 2013

Malnutrition In Sickle Cell Anemia: Implications For Infection, Growth And Maturation, Hyacinth I. Hyacinth, Oluwatoyosi A. Adekeye, Christopher S. Yilgwan

Journal of Social, Behavioral, and Health Sciences

Sickle cell anemia (SCA) is a genetic disease that affects mostly individuals of African and/or Hispanic descent, with the majority of cases in sub-Saharan Africa. Individuals with this disease show slowed growth, delayed sexual maturity, and poor immunologic function. These complications could partly be explained by the state of undernutrition associated with the disease. Proposed mechanism of undernutrition include protein hypermetabolism, decreased dietary intake possibly from interleukin-6-related appetite suppression, increased cardiac energy demand/expenditure, and increased red cell turnover. All the above mechanisms manifest as increased resting energy expenditure. Nutritional intervention utilizing single or multiple nutrient supplementation has led to improved …


A Dysfunctional Tricarboxylic Acid Cycle Enhances Fitness Of Staphylococcus Epidermidis During Β-Lactam Stress, Vinai Chittenzham Thomas, Lauren Kinkhead, Ashley Janssen, Carolyn Schaeffer, Keith Woods, Jill Lindgren, Johnathan Peaster, Sujata Chaudhari, Marat Sadykov, Joselyn Jones, Sameh Mohamadi Abdelghani, Matthew Zimmerman, Kenneth W. Bayles, Greg Somerville, Paul Fey Jan 2013

A Dysfunctional Tricarboxylic Acid Cycle Enhances Fitness Of Staphylococcus Epidermidis During Β-Lactam Stress, Vinai Chittenzham Thomas, Lauren Kinkhead, Ashley Janssen, Carolyn Schaeffer, Keith Woods, Jill Lindgren, Johnathan Peaster, Sujata Chaudhari, Marat Sadykov, Joselyn Jones, Sameh Mohamadi Abdelghani, Matthew Zimmerman, Kenneth W. Bayles, Greg Somerville, Paul Fey

School of Veterinary and Biomedical Sciences: Faculty Publications

A recent controversial hypothesis suggested that the bactericidal action of antibiotics is due to the generation of endogenous reactive oxygen species (ROS), a process requiring the citric acid cycle (tricarboxylic acid [TCA] cycle). To test this hypothesis, we assessed the ability of oxacillin to induce ROS production and cell death in Staphylococcus epidermidis strain 1457 and an isogenic citric acid cycle mutant. Our results confirm a contributory role for TCA-dependent ROS in enhancing susceptibility of S. epidermidis toward β-lactam antibiotics and also revealed a propensity for clinical isolates to accumulate TCA cycle dysfunctions presumably as a way to tolerate these …


Manipulation Of Cellular Processing Bodies And Their Constituents By Viruses, Asit K. Pattnaik, Phat X. Dinh Jan 2013

Manipulation Of Cellular Processing Bodies And Their Constituents By Viruses, Asit K. Pattnaik, Phat X. Dinh

School of Veterinary and Biomedical Sciences: Faculty Publications

The processing bodies (PBs) are a form of cytoplasmic aggregates that house the cellular RNA decay machinery as well as many RNA-binding proteins and mRNAs. The PBs are constitutively present in eukaryotic cells and are involved in maintaining cellular homeostasis by regulating RNA metabolism, cell signaling, and survival. Virus infections result in modification of the PBs and their constituents. Many viruses induce compositionally altered PBs, while many others use specific components of the PBs for their replication. PB constituents are also known to restrict virus replication by a variety of mechanisms. Further, continuing studies in this rapidly emerging field of …


Characterization Of A Serologic Marker Candidate For Development Of A Live-Attenuated Diva Vaccine Against Porcine Reproductive And Respiratory Syndrome Virus, Hiep Vu, Byungjoon Kwon, Marcelo De Lima, Asit K. Pattnaik, Fernando A. Osorio Jan 2013

Characterization Of A Serologic Marker Candidate For Development Of A Live-Attenuated Diva Vaccine Against Porcine Reproductive And Respiratory Syndrome Virus, Hiep Vu, Byungjoon Kwon, Marcelo De Lima, Asit K. Pattnaik, Fernando A. Osorio

School of Veterinary and Biomedical Sciences: Faculty Publications

DIVA (differentiating infected from vaccinated animals) vaccines have proven extremely useful for control and eradication of infectious diseases in livestock. We describe here the characterization of a serologic marker epitope, so-called epitope-M201, which can be a potential target for development of a live-attenuated DIVA vaccine against porcine reproductive and respiratory syndrome virus (PRRSV). Epitope-M201 is located at the carboxyl terminus (residues 161-174) of the viral M protein. The epitope is highly immunodominant and well-conserved among type-II PRRSV isolates. Rabbit polyclonal antibodies prepared against this epitope are non-neutralizing; thus, the epitope does not seem to contribute to the protective immunity against …


Trex1 Regulates Lysosomal Biogenesis And Interferon-Independent Activation Of Antiviral Genes, Maroof Hasan, James Koch, Dinesh Rakheja, Asit K. Pattnaik, James Brugarolas, Igor Dozmorov, Beth Levine, Edward K. Wakeland, Min Ae Lee-Kirsch, Nan Yan Jan 2013

Trex1 Regulates Lysosomal Biogenesis And Interferon-Independent Activation Of Antiviral Genes, Maroof Hasan, James Koch, Dinesh Rakheja, Asit K. Pattnaik, James Brugarolas, Igor Dozmorov, Beth Levine, Edward K. Wakeland, Min Ae Lee-Kirsch, Nan Yan

School of Veterinary and Biomedical Sciences: Faculty Publications

Innate immune sensing of viral nucleic acids triggers type I interferon (IFN) production, which activates interferon-stimulated genes (ISGs) and directs a multifaceted antiviral response. ISGs can also be activated through IFN-independent pathways, although the precise mechanisms remain elusive. Here we found that the cytosolic exonuclease Trex1 regulates the activation of a subset of ISGs independently of IFN. Both Trex1−/− mouse and TREX1-mutant human cells express high levels of antiviral genes and are refractory to viral infections. The IFN-independent activation of antiviral genes in Trex1−/− cells requires STING, TBK1 and IRF3 and IRF7. We also found that Trex1-deficient cells display expanded …


Influence Of Therapeutic Ceftiofur Treatments Of Feedlot Cattle On Fecal And Hide Prevalences Of Commensal Escherichia Coli Resistant To Expanded-Spectrum Cephalosporins, And Molecular Characterization Of Resistant Isolates, John W. Schmidt, Dee Griffin, Larry A. Kuehn, Dayna M. Brichta-Harhay Jan 2013

Influence Of Therapeutic Ceftiofur Treatments Of Feedlot Cattle On Fecal And Hide Prevalences Of Commensal Escherichia Coli Resistant To Expanded-Spectrum Cephalosporins, And Molecular Characterization Of Resistant Isolates, John W. Schmidt, Dee Griffin, Larry A. Kuehn, Dayna M. Brichta-Harhay

School of Veterinary and Biomedical Sciences: Faculty Publications

In the United States, the blaCMY-2 gene contained within incompatibility type A/C (IncA/C) plasmids is frequently identified in extended-spectrum-cephalosporin-resistant (ESCr) Escherichia coli strains from both human and cattle sources. Concerns have been raised that therapeutic use of ceftiofur in cattle may increase the prevalence of ESCr E. coli. We report that herd ESCr E. coli fecal and hide prevalences throughout the residency of cattle at a feedlot, including during the period of greatest ceftiofur use at the feedlot, were either not significantly different (P≥0.05) or significantly less (Pr E. coli shedding that follows ceftiofur …


Complete Closed Genome Sequences Of Mannheimia Haemolytica Serotypes A1 And A6, Isolated From Cattle, Gregory P. Harhay, Sergey Koren, Adam M. Phillippy, D. Scott Mcvey, Jennifer Kuszak, Michael L. Clawson, Dayna M. Harhay, Michael P. Heaton, Carol G. Chitko-Mckown, Timothy P. L. Smith Jan 2013

Complete Closed Genome Sequences Of Mannheimia Haemolytica Serotypes A1 And A6, Isolated From Cattle, Gregory P. Harhay, Sergey Koren, Adam M. Phillippy, D. Scott Mcvey, Jennifer Kuszak, Michael L. Clawson, Dayna M. Harhay, Michael P. Heaton, Carol G. Chitko-Mckown, Timothy P. L. Smith

School of Veterinary and Biomedical Sciences: Faculty Publications

Mannheimia haemolytica is a respiratory pathogen affecting cattle and related ruminants worldwide. M. haemolytica is commonly associated with bovine respiratory disease complex (BRDC), a polymicrobial multifactorial disease.Wepresent the first two complete closed genome sequences of this species, determined using an automated assembly pipeline requiring no manual finishing.


Deep Sequencing And Genome-Wide Analysis Reveals The Expansion Of Microrna Genes In The Gall Midge Mayetiola Destructor, Chitvan Khajuria, Christie E. Williams, Mustapha El Bouhssini, R. Jeff Whitworth, Stephen Richards, Jeffrey J. Stuart, Ming-Shun Chen Jan 2013

Deep Sequencing And Genome-Wide Analysis Reveals The Expansion Of Microrna Genes In The Gall Midge Mayetiola Destructor, Chitvan Khajuria, Christie E. Williams, Mustapha El Bouhssini, R. Jeff Whitworth, Stephen Richards, Jeffrey J. Stuart, Ming-Shun Chen

School of Veterinary and Biomedical Sciences: Faculty Publications

Background: MicroRNAs (miRNAs) are small non-coding RNAs that play critical roles in regulating post transcriptional gene expression. Gall midges encompass a large group of insects that are of economic importance and also possess fascinating biological traits. The gall midge Mayetiola destructor, commonly known as the Hessian fly, is a destructive pest of wheat and model organism for studying gall midge biology and insect – host plant interactions.

Results: In this study, we systematically analyzed miRNAs from the Hessian fly. Deep-sequencing a Hessian fly larval transcriptome led to the identification of 89 miRNA species that are either identical or very …


Development And Evaluation Of A Replicon Particle Vaccine Expressing The E2 Glycoprotein Of Bovine Viral Diarrhea Virus (Bvdv) In Cattle, John Dustin Loy, Jill Gander, Mark Mogler, Ryan Vander Veen, Julia Ridpath, Delbert Hank Harris, Kurt Kamrud Jan 2013

Development And Evaluation Of A Replicon Particle Vaccine Expressing The E2 Glycoprotein Of Bovine Viral Diarrhea Virus (Bvdv) In Cattle, John Dustin Loy, Jill Gander, Mark Mogler, Ryan Vander Veen, Julia Ridpath, Delbert Hank Harris, Kurt Kamrud

School of Veterinary and Biomedical Sciences: Faculty Publications

Background: Bovine viral diarrhea virus is one of the most significant and costly viral pathogens of cattle worldwide. Alphavirus-derived replicon particles have been shown to be safe and highly effective vaccine vectors against a variety of human and veterinary pathogens. Replicon particles are non-propagating, DIVA compatible, and can induce both humoral and cell mediated immune responses. This is the first experiment to demonstrate that Alphavirus-based replicon particles can be utilized in a standard prime/boost vaccination strategy in calves against a commercially significant bovine pathogen.

Findings: Replicon particles that express bovine viral diarrhea virus sub-genotype 1b E2 glycoprotein were …


Functional Convergence Of Structurally Distinct Thioesterases From Cyanobacteria And Plants Involved In Phylloquinone Biosynthesis, Fabienne Furt, William J. Allen, Joshua R. Widhalm, Peter Madzelan, Robert C. Rizzo, Gilles J. Basset, Mark A. Wilson Jan 2013

Functional Convergence Of Structurally Distinct Thioesterases From Cyanobacteria And Plants Involved In Phylloquinone Biosynthesis, Fabienne Furt, William J. Allen, Joshua R. Widhalm, Peter Madzelan, Robert C. Rizzo, Gilles J. Basset, Mark A. Wilson

Department of Biochemistry: Faculty Publications

The synthesis of phylloquinone (vitamin K1) in photosynthetic organisms requires a thioesterase that hydrolyzes 1,4-dihydroxy- 2-naphthoyl-CoA (DHNA-CoA) to release 1,4- dihydroxy-2-naphthoate (DHNA). Cyanobacteria and plants contain distantly related hotdog-fold thioesterases that catalyze this reaction, although the structural basis of these convergent enzymatic activities is unknown. To investigate this, the crystal structures of hotdog-fold DHNA-CoA thioesterases from the cyanobacterium Synechocystis (Slr0204) and the flowering plant Arabidopsis thaliana (AtDHNAT1) were determined. These enzymes form distinct homotetramers and use different active sites to catalyze hydrolysis of DHNACoA, similar to the 4-hydroxybenzoyl-CoA (4-HBA-CoA) thioesterases from Pseudomonas and Arthrobacter. Like the 4-HBA-CoA …


Rapid Detection And Quantification Of Triacylglycerol By Hplc–Elsd In Chlamydomonas Reinhardtii And Chlorella Strains, Naoko Kobayashi, Eric A. Noel, Austin Barnes, Julian Rosenberg, Concetta C. Dirusso, Paul N. Black, George A. Oyler Jan 2013

Rapid Detection And Quantification Of Triacylglycerol By Hplc–Elsd In Chlamydomonas Reinhardtii And Chlorella Strains, Naoko Kobayashi, Eric A. Noel, Austin Barnes, Julian Rosenberg, Concetta C. Dirusso, Paul N. Black, George A. Oyler

Department of Biochemistry: Faculty Publications

Triacylglycerol (TAG) analysis and quantification are commonly performed by first obtaining a purified TAG fraction from a total neutral lipid extract using thinlayer chromatography (TLC), and then analyzing the fatty

acid composition of the purified TAG fraction by gas chromatography (GC). This process is time-consuming, labor

intensive and is not suitable for analysis of small sample sizes or large numbers. A rapid and efficient method for monitoring oil accumulation in algae using high performance liquid chromatography for separation of all lipid classes combined with detection by evaporative light scattering (HPLC–ELSD) was developed and compared to the conventional TLC/GC method. TAG …


Probing Arabidopsis Chloroplast Diacylglycerol Pools By Selectively Targeting Bacterial Diacylglycerol Kinase To Suborganellar Membranes, Bagyalakshmi Muthan, Rebecca Roston, John E. Froehlich, Christoph Benning Jan 2013

Probing Arabidopsis Chloroplast Diacylglycerol Pools By Selectively Targeting Bacterial Diacylglycerol Kinase To Suborganellar Membranes, Bagyalakshmi Muthan, Rebecca Roston, John E. Froehlich, Christoph Benning

Department of Biochemistry: Faculty Publications

Diacylglycerol (DAG) is an intermediate in metabolism of both triacylglycerols and membrane lipids. Probing the steady-state pools of DAG and understanding how they contribute to the synthesis of different lipids is important when designing plants with altered lipid metabolism. However, traditional methods of assaying DAG pools are difficult, because its abundance is low and because fractionation of subcellular membranes affects DAG pools. To manipulate and probe DAG pools in an in vivo context, we generated multiple stable transgenic lines of Arabidopsis (Arabidopsis thaliana) that target an Escherichia coli DAGkinase (DAGK) to each leaflet of each chloroplast envelope membrane. …


Reporters For The Analysis Of N-Glycosylation In Candida Albicans, Shahida Shahana, Hector M. Mora-Montes, Luis Castillo, Iryna Bohovych, Chirag C. Sheth, Frank C. Odds, Neil A.R. Gow, Alistair J.P. Brown Jan 2013

Reporters For The Analysis Of N-Glycosylation In Candida Albicans, Shahida Shahana, Hector M. Mora-Montes, Luis Castillo, Iryna Bohovych, Chirag C. Sheth, Frank C. Odds, Neil A.R. Gow, Alistair J.P. Brown

Department of Biochemistry: Faculty Publications

A large proportion of Candida albicans cell surface proteins are decorated post-translationally by glycosylation. Indeed N-glycosylation is critical for cell wall biogenesis in this major fungal pathogen and for its interactions with host cells. A detailed understanding of N-glycosylation will yield deeper insights into host-pathogen interactions. However, the analysis of N-glycosylation is extremely challenging because of the complexity and heterogeneity of these structures. Therefore, in an attempt to reduce this complexity and facilitate the analysis of N-glycosylation, we have developed new synthetic C. albicans reporters that carry a single N-linked glycosylation site derived from Saccharomyces cerevisiae Suc2. These …


Microrna Function In Human Diseases, Sathish Kumar Natarajan, Mary Anne Smith, Cody J. Wehrkamp, Ashley M. Mohr, Justin L. Mott Jan 2013

Microrna Function In Human Diseases, Sathish Kumar Natarajan, Mary Anne Smith, Cody J. Wehrkamp, Ashley M. Mohr, Justin L. Mott

Department of Biochemistry: Faculty Publications

MicroRNAs are emerging as a hot topic in research, and rightfully so. They show great promise as targets of treatment and as markers for common human diseases, such as cancer and metabolic diseases. In this review, we address some of the basic questions regarding micro- RNA function in human disease and the clinical significance of microRNAs. Specifically, micro- RNAs in epigenetics, cancer, and metabolic diseases are discussed, with examples taken from cholangiocarcinoma and nonalcoholic fatty liver disease.


Sbml Qualitative Models: A Model Representation Format And Infrastructure To Foster Interactions Between Qualitative Modelling Formalisms And Tools, Claudine Chaouiya, Duncan Bérenguier, Sarah M. Keating, Aurélien Naldi, Martijn P. Van Iersel, Nicolas Rodriguez, Andreas Dräger, Finja Büchel, Thomas Cokelaer, Bryan Kowal, Benjamin Wicks, Emanuel Gonçalves, Julien Dorier, Michel Page, Pedro T. Monteiro, Axel Von Kamp, Ioannis Xenarios, Hidde De Jong, Michael Hucka, Steffen Klamt, Denis Thieffry, Nicolas Le Novère, Julio Saez-Rodriguez, Tomáš Helikar Jan 2013

Sbml Qualitative Models: A Model Representation Format And Infrastructure To Foster Interactions Between Qualitative Modelling Formalisms And Tools, Claudine Chaouiya, Duncan Bérenguier, Sarah M. Keating, Aurélien Naldi, Martijn P. Van Iersel, Nicolas Rodriguez, Andreas Dräger, Finja Büchel, Thomas Cokelaer, Bryan Kowal, Benjamin Wicks, Emanuel Gonçalves, Julien Dorier, Michel Page, Pedro T. Monteiro, Axel Von Kamp, Ioannis Xenarios, Hidde De Jong, Michael Hucka, Steffen Klamt, Denis Thieffry, Nicolas Le Novère, Julio Saez-Rodriguez, Tomáš Helikar

Department of Biochemistry: Faculty Publications

Background: Qualitative frameworks, especially those based on the logical discrete formalism, are increasingly used to model regulatory and signalling networks. A major advantage of these frameworks is that they do not require precise quantitative data, and that they are well-suited for studies of large networks. While numerous groups have developed specific computational tools that provide original methods to analyse qualitative models, a standard format to exchange qualitative models has been missing.

Results: We present the Systems Biology Markup Language (SBML) Qualitative Models Package (“qual”), an extension of the SBML Level 3 standard designed for computer representation of qualitative …


Selenodb 2.0: Annotation Of Selenoprotein Genes In Animals And Their Genetic Diversity In Humans, Frederic Romagne, Didac Santesmasses, Louise White, Gaurab K. Sarangi, Marco Mariotti, Ron Hübler, Antje Weihmann, Genis Parra, Vadim N. Gladyshev, Roderic Guigo, Sergi Castellano Jan 2013

Selenodb 2.0: Annotation Of Selenoprotein Genes In Animals And Their Genetic Diversity In Humans, Frederic Romagne, Didac Santesmasses, Louise White, Gaurab K. Sarangi, Marco Mariotti, Ron Hübler, Antje Weihmann, Genis Parra, Vadim N. Gladyshev, Roderic Guigo, Sergi Castellano

Department of Biochemistry: Faculty Publications

SelenoDB (http://www.selenodb.org) aims to provide high-quality annotations of selenoprotein genes, proteins and SECIS elements. Selenoproteins are proteins that contain the amino acid selenocysteine (Sec) and the first release of the database included annotations for eight species. Since the release of SelenoDB 1.0 many new animal genomes have been sequenced. The annotations of selenoproteins in new genomes usually contain many errors in major databases. For this reason, we have now fully annotated selenoprotein genes in 58 animal genomes. We provide manually curated annotations for human selenoproteins, whereas we use an automatic annotation pipeline to annotate selenoprotein genes in other animal genomes. …


The Basis For Limited Specificity And Mhc Restriction In A T Cell Receptor Interface, Kurt H. Piepenbrink, Sydney J. Blevins, Daniel R. Scott, Brian M. Baker Jan 2013

The Basis For Limited Specificity And Mhc Restriction In A T Cell Receptor Interface, Kurt H. Piepenbrink, Sydney J. Blevins, Daniel R. Scott, Brian M. Baker

Department of Biochemistry: Faculty Publications

αβ Tcell receptors (TCRs) recognize peptides presented by major histocompatibility complex (MHC) proteins using multiple complementarity-determining region (CDR) loops. TCRs display an array of poorly understood recognition properties, including specificity, crossreactivity and MHC restriction. Here we report a comprehensive thermodynamic deconstruction of the interaction between the A6 TCR and the Tax peptide presented by the class I MHC HLA-A*0201, uncovering the physical basis for the receptor’s recognition properties. Broadly, our findings are in conflict with widely held generalities regarding TCR recognition, such as the relative contributions of central and peripheral peptide residues and the roles of the hypervariable and germline …


Elucidating Causes Of Diporeia Decline In The Great Lakes Via Metabolomics: Physiological Responses After Exposure To Different Stressors, Suman Maity, Amber Jannasch, Jiri Adamec, James M. Watkins, Thomas Nalepa, Tomas O. Höök, Maria S. Sepúlveda Jan 2013

Elucidating Causes Of Diporeia Decline In The Great Lakes Via Metabolomics: Physiological Responses After Exposure To Different Stressors, Suman Maity, Amber Jannasch, Jiri Adamec, James M. Watkins, Thomas Nalepa, Tomas O. Höök, Maria S. Sepúlveda

Department of Biochemistry: Faculty Publications

The benthic macroinvertebrate Diporeia spp. have been extirpated from many areas of the Laurentian Great Lakes, but the mechanisms underlying such declines are not fully understood. Diporeia declines coinciding with the invasion of exotic dreissenid mussels (zebra and quagga) have led to the hypothesis that Diporeia declines are a result of decreased food availability from increasing competition with dreissenids for diatoms. There is additional evidence that Diporeia are negatively affected when in close proximity to dreissenids, probably because of exposure to toxins present in the mussels’ pseudofeces. Diporeia are also known to be sensitive to anthropogenic contaminants (such as polychlorinated …


Dna-Binding Site Recognition By Bhlh And Mads-Domain Transcription Factors, Joshua R. Werkman Jan 2013

Dna-Binding Site Recognition By Bhlh And Mads-Domain Transcription Factors, Joshua R. Werkman

Theses and Dissertations--Plant and Soil Sciences

Herewithin, two transcription factor (TF) regulatory complexes were investigated. A bHLH–MYB–WDR (BMW) DNA-binding complex from maize was the first complex to be studied. R, a maize bHLH involved in the activation of genes in the anthocyanin pathway, had been characterized to indirectly bind DNA despite the presence of a functional DNA-binding domain. Findings presented here reveal that this is only partially correct. Direct DNA-binding by R was found to be dependent upon two distinct dimerization domains that function as a switch. This switch-like mechanism allows R to be repurposed for the activation of promoters of differing cis-element structure.

The …


Synthesis Of 4-Azidocoumarins And Their Use In Copper-Catalyzed Azide-Alkyne Cycloaddition Reactions, Anthony J. Netsuri Jan 2013

Synthesis Of 4-Azidocoumarins And Their Use In Copper-Catalyzed Azide-Alkyne Cycloaddition Reactions, Anthony J. Netsuri

Dissertations and Theses

Triazole-containing compounds have shown great biological activity ranging from antiviral, antibacterial, to anticancer, to name a few. Coumarin derivatives have also shown interesting biological activities. The combination of these bioactive compounds appears to have great promise for new and future medicines. In this work, various 4-azido-coumarins were synthesized via the transformation of the 4-hydroxy derivatives to 4-benzotriazolyloxy coumarins by reaction with the peptide coupling agent (benzotriazol-1-yloxy)tris-(dimethylamino)phosphonium hexafluorophosphate (BOP), and 1,8-diazabicycloundec-7-ene (DBU) as the base, in tetrahydrofuran (THF) solvent. The 4-benzotriazolyloxy coumarins were converted to the 4-azidocoumarins by reaction with sodium azide (NaN3), and the overall process was simplified to a …


Optimizing Electrode Design For Microbial Fuel Cells Used For Wastewater Treatment, Lindsay Nichols, John A. Hogan Jan 2013

Optimizing Electrode Design For Microbial Fuel Cells Used For Wastewater Treatment, Lindsay Nichols, John A. Hogan

STAR Program Research Presentations

Microbial fuel cells (MFC) utilize bacteria to generate an electrical current that can be used in the decomposition of sludge and human urine. In a MFC there is an anode (for oxidation of organic compounds), cathode (reduction of oxygen or carbon dioxide), and a proton exchange membrane (PEM, allows protons to migrate); reduction-oxidation reactions between the anode and cathode produce a measurable current. Bacteria that are found in sludge can be used to produce electrons in a voltaic cell, but optimizing conditions for harnessing the energy is crucial to making a MFC efficient. Research has shown that the ratios of …


Alginate Lyase Exhibits Catalysis-Independent Biofilm Dispersion And Antibiotic Synergy, John W. Lamppa, Karl E. Griswold Jan 2013

Alginate Lyase Exhibits Catalysis-Independent Biofilm Dispersion And Antibiotic Synergy, John W. Lamppa, Karl E. Griswold

Dartmouth Scholarship

More than 2 decades of study support the hypothesis that alginate lyases are promising therapeutic candidates for treating mucoid Pseudomonas aeruginosa infections. In particular, the enzymes' ability to degrade alginate, a key component of mucoid biofilm matrix, has been the presumed mechanism by which they disrupt biofilms and enhance antibiotic efficacy. The systematic studies reported here show that, in an in vitro model, alginate lyase dispersion of P. aeruginosa biofilms and enzyme synergy


The Contribution Of Visceral Fat To Positive Insulin Signaling In Ames Dwarf Mice, Vinal Menon Jan 2013

The Contribution Of Visceral Fat To Positive Insulin Signaling In Ames Dwarf Mice, Vinal Menon

Electronic Theses and Dissertations

Ames dwarf (df/df) mice are homozygous for a spontaneous mutation in the prop1 gene due to which there is no development of anterior pituitary cells – somatotrophs, lactotrophs and thyrotrophs, leading to a deficiency of growth hormone (GH), prolactin (PRL) and thyrotropin (TSH). They tend to become obese as they age, but still live longer and healthier lives compared to their wild-type littermates, being very insulin sensitive, showing no signs of diabetes and cancer. These mutant mice also have high circulating levels of anti-inflammatory and antidiabetic adiponectin. Plasma levels of this adipokine usually decrease with an increase in accumulation of …