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Celogentin C And Thioviridamide: Synthetic And Structural Studies, Dmitry Nikolayevich Litvinov 2010 Brigham Young University - Provo

Celogentin C And Thioviridamide: Synthetic And Structural Studies, Dmitry Nikolayevich Litvinov

Theses and Dissertations

Project I Celogentin C, isolated by Kobayashi from the seeds of Celosia argentea in 2001 exhibits strong inhibitory behavior towards polymerization of tubulin – globular protein, which plays crucial role during the cell division cycle. We have attempted synthesis of the left-hand ring of celogentin C via the intramolecular alkylation and the Knoevenagel condensation strategies. Utilizing synthetic methodologies in the field of nitroacetyl chemistry, developed by Kornblum and Rajappa we have successfully prepared the intermolecular Knoevenagel condensation product – the late-stage precursor to the left-hand ring of celogentin C. Synthesis of this key intermediate subsequently led to the preparation of the left-hand ...


Natural Selection On Epas1 (Hif2Α) Associated With Low Hemoglobin Concentration In Tibetan Highlanders, Cynthia M. Beall, Gianpiero L. Cavalleri, Libin Deng, Robert C. Elston, Yang Gao, Jo Knight, Chaohua Li, Jiang Chuan Li, Yu Liang, Mark McCormack, Hugh E. Montgomery, Hao Pan, Peter A. Robbins, Kevin V. Shianna, Siu Cheung Tam, Ngodup Tsering, Krishna Veeramah, Wei Wang, Puchung Wangdui, Michael E. Weale, Yaomin Xu, Zhe Xu, Ling Yang, M Justin Zaman, Changqing Zeng, Li Zhang, Xianglong Zhang, Pingcuo Zhaxi, Yong Tang Zheng 2010 Case Western Reserve University

Natural Selection On Epas1 (Hif2Α) Associated With Low Hemoglobin Concentration In Tibetan Highlanders, Cynthia M. Beall, Gianpiero L. Cavalleri, Libin Deng, Robert C. Elston, Yang Gao, Jo Knight, Chaohua Li, Jiang Chuan Li, Yu Liang, Mark Mccormack, Hugh E. Montgomery, Hao Pan, Peter A. Robbins, Kevin V. Shianna, Siu Cheung Tam, Ngodup Tsering, Krishna Veeramah, Wei Wang, Puchung Wangdui, Michael E. Weale, Yaomin Xu, Zhe Xu, Ling Yang, M Justin Zaman, Changqing Zeng, Li Zhang, Xianglong Zhang, Pingcuo Zhaxi, Yong Tang Zheng

Molecular and Cellular Therapeutics Articles

By impairing both function and survival, the severe reduction in oxygen availability associated with high-altitude environments is likely to act as an agent of natural selection. We employed genomic and candidate gene approaches to search for evidence of such genetic selection. First, a genome-wide allelic differentiation scan (GWADS) comparing indigenous highlanders of the Tibetan Plateau (3200-3500m) with closely related lowland Han revealed a genome-wide significant divergence across eight SNPs located near EPAS1. This gene encodes the transcription factor HIF2α, which stimulates production of red blood cells and thus increases the concentration of hemoglobin in blood. Second, in a separate cohort ...


Poisonous Rangeland Plants In San Luis Obispo County, Sara Litten, Amanda Ou 2010 California Polytechnic State University - San Luis Obispo

Poisonous Rangeland Plants In San Luis Obispo County, Sara Litten, Amanda Ou

Animal Science

Poisonous Rangeland Plants in San Luis Obispo County is a comprehensive educational guide to rangeland plants that are toxic to domestic livestock. This guide begins with an exploration of how the biological systems are affected by the poisonous plant toxins. The biochemistry behind these toxins is included in the discussion. Next, reference material for fourteen plants that inhabit San Luis Obispo County is provided. This information includes specific toxins found in poisonous plants, affected animals, symptoms of poisoning, stages of growth, lethal dose, and distribution of the plant in California. This section of the guide is filled with helpful photos ...


T-Cell Signaling Regulated By The Tec Family Kinase, Itk, Amy H. Andreotti, Pamela L. Schwartzberg, Raji E. Joseph, Leslie J. Berg 2010 Iowa State University

T-Cell Signaling Regulated By The Tec Family Kinase, Itk, Amy H. Andreotti, Pamela L. Schwartzberg, Raji E. Joseph, Leslie J. Berg

Biochemistry, Biophysics and Molecular Biology Publications

The Tec family tyrosine kinases regulate lymphocyte development, activation, and differentiation. In T cells, the predominant Tec kinase is Itk, which functions downstream of the T-cell receptor to regulate phospholipase C-γ. This review highlights recent advances in our understanding of Itk kinase structure and enzymatic regulation, focusing on Itk protein domain interactions and mechanisms of substrate recognition. We also discuss the role of Itk in the development of conventional versus innate T-cell lineages, including both αβ and γδ T-cell subsets. Finally, we describe the complex role of Itk signaling in effector T-cell differentiation and the regulation of cytokine gene expression ...


Rna Recognition By The Caenorhabditis Elegans Embryonic Determinants Mex-5 And Mex-3: A Dissertation, John M. Pagano Jr. 2010 University of Massachusetts Medical School

Rna Recognition By The Caenorhabditis Elegans Embryonic Determinants Mex-5 And Mex-3: A Dissertation, John M. Pagano Jr.

GSBS Dissertations and Theses

Post-transcriptional regulation of gene expression is a mechanism that governs developmental and cellular events in metazoans. In early embryogenesis, transcriptionally quiescent cells depend upon maternally supplied factors such as RNA binding proteins and RNA that control key decisions. Morphogen gradients form and in turn pattern the early embryo generating different cell types and spatial order. In the nematode Caenorhabditis elegans, the early embryo relies upon several RNA binding proteins that control mRNA stability, translation efficiency, and/or mRNA localization of cell fate determinants essential for proper development.

MEX-5 and MEX-3 are two conserved RNA-binding proteins required to pattern the anterior ...


Growth Hormone Alters Components Related To Differentiation, Metabolism And Milk Synthesis And Secretion In Mac-T Cells, Tasha Lynn Johnson 2010 California Polytechnic State University - San Luis Obispo

Growth Hormone Alters Components Related To Differentiation, Metabolism And Milk Synthesis And Secretion In Mac-T Cells, Tasha Lynn Johnson

Master's Theses and Project Reports

The mammary alveolar cell-T (MAC-T) cell line is able to uniformly differentiate and secrete casein proteins in response to dexamethasone, insulin and prolactin and is extensively used to study bovine mammary epithelial cell function. Growth hormone (GH) has been shown to increase milk protein synthesis both in vivo and in mammary cell models, and induce cytoskeletal rearrangement in 3T3 fibroblast cell line and a Chinese hamster ovary (CHO) cell line. Few studies have focused on identifying the mechanisms involved in differentiated MAC-T cells’ response to GH. We tested the hypothesis that MAC-T cells would respond directly to GH and that ...


Effects Of Atmospheric Non-Thermal Plasma On Invasion Of Colorectal Cancer Cells., Seung Baek, Chul-Ho Kim, S Kwon, K Lee, S Jun, Philip Rack 2010 The University of Tennessee

Effects Of Atmospheric Non-Thermal Plasma On Invasion Of Colorectal Cancer Cells., Seung Baek, Chul-Ho Kim, S Kwon, K Lee, S Jun, Philip Rack

Seung J Baek

No abstract provided.


Molecular Basis For Distinct Pathways For Protein Import Into Arabidopsis Chloroplasts, Danny Schnell, C. Rounds, H. Inoue 2010 University of Massachusetts - Amherst

Molecular Basis For Distinct Pathways For Protein Import Into Arabidopsis Chloroplasts, Danny Schnell, C. Rounds, H. Inoue

Danny Schnell

The translocons at the outer envelope membrane of chloroplasts (TOCs) initiate the import of thousands of nucleus-encoded proteins into the organelle. The identification of structurally and functionally distinct TOC complexes has led to the hypothesis that the translocons constitute different import pathways that are required to coordinate the import of sets of proteins whose expression varies in response to organelle biogenesis and physiological adaptation. To test this hypothesis, we examined the molecular basis for distinct TOC pathways by analyzing the functional diversification among the Toc159 family of TOC receptors. We demonstrate that the N-terminal A-domains of the Toc159 receptors regulate ...


Enzyme-Catalyzed Hydrolysis Of Cellulose In Ionic Liquids: A Green Approach Toward The Production Of Biofuels, Sayantan Bose, Daniel W. Armstrong, Jacob W. Petrich 2010 Iowa State University

Enzyme-Catalyzed Hydrolysis Of Cellulose In Ionic Liquids: A Green Approach Toward The Production Of Biofuels, Sayantan Bose, Daniel W. Armstrong, Jacob W. Petrich

Chemistry Publications

We investigated the reactivity and stability of a commercial mixture of cellulases in eight ionic liquids by optical and calorimetric techniques. First, hydrolysis by cellulases from Tricoderma reesei in these ionic liquids was benchmarked against that in aqueous buffer. Only 1-methylimidazolium chloride (mim Cl) and tris-(2-hydroxyethyl)methylammonium methylsulfate (HEMA) provided a medium in which hydrolysis could occur. While hydrolysis at 65 °C is initially much faster in buffer than in these two liquids, it reaches a plateau after 2 h, whereas the reaction progresses monotonically in the two ionic liquids. This difference in the rate of hydrolysis is largely ...


An Integrative Study Of Gene Expression Of Pma Induced Differentiation In Hl-60 Cells By Dna Microarray Analysis, Emily Marie Swain 2010 Dickinson College

An Integrative Study Of Gene Expression Of Pma Induced Differentiation In Hl-60 Cells By Dna Microarray Analysis, Emily Marie Swain

Student Honors Theses By Year

This study seeks to elucidate the molecular mechanisms by which the acute myeloid leukemia cell line, HL-60, is induced to differentiate into macrophage-like cells following exposure to phorbol 12-myristate 13-acetate (PMA). Changes in gene expression over the time course of PMA treatment were measured by DNA microarray analysis and select genes shown to be significantly up and down-regulated were validated by quantitative real-time PCR. Functional studies of transcription factor binding activities were performed by the electrophoretic mobility shift assay (EMSA). Novel findings include the rapid and sustained induction of mRNA levels for a group of CC chemokine genes (CCL2, CCL3 ...


Deconvoluting The Engineering And Assembly Instructions For Complex Iii Activity, Sarah C. Hokanson 2010 University of Pennsylvania

Deconvoluting The Engineering And Assembly Instructions For Complex Iii Activity, Sarah C. Hokanson

Publicly Accessible Penn Dissertations

In respiratory systems, membrane-bound Complex III catalyzes the oxidation of ubiquinone and the reduction of a soluble cytochrome with the bioenergetic formation of a transmembrane proton gradient (∆μH+). Complex III turnover is initiated by a unique two electron oxidation of ubiquinone at the Qo site; one electron is delivered to a high potential chain containing an iron-sulfur cluster, cytochrome c1 and cytochrome c2, and a second electron is transferred to a low potential chain that terminates at the Qi site. All Complex III electron tunneling reactions are reversible, and a critical part of Complex III maintaining productive turnover is its ...


Structure, Function And Applications Of Metal-Requiring Enzymes: Carbonic Anhydrase And Epi-Isozizaene Synthase, Julie A. Aaron 2010 University of Pennsylvania

Structure, Function And Applications Of Metal-Requiring Enzymes: Carbonic Anhydrase And Epi-Isozizaene Synthase, Julie A. Aaron

Publicly Accessible Penn Dissertations

Cryptophane Biosensors for Targeting Human Carbonic Anhydrase

Cryptophanes represent an exciting class of xenon-encapsulating molecules that can be exploited as probes for nuclear magnetic resonance imaging. A series of carbonic anhydrase-targeting, xenon-binding cryptophane biosensors were designed and synthesized. Isothermal titration calorimery and surface plasmon resonance measurements confirmed nanomolar affinity between human carbonic anhydrase II and the cryptophane biosensors. A 1.70 Å resolution crystal structure of a cryptophane-derivatized benezenesulfonamide human carbonic anhydrase II complex was determined, and shows how an encapsulated xenon atom can be directed to a specific biological target. Furthermore, this work illustrates the utility and promise of ...


Mechanisms Of The Downregulation Of Prolactin Receptor And Their Role In Cell Proliferation, Bentley J. Varghese 2010 University of Pennsylvania

Mechanisms Of The Downregulation Of Prolactin Receptor And Their Role In Cell Proliferation, Bentley J. Varghese

Publicly Accessible Penn Dissertations

Cells react to diverse stimuli by expressing specific receptors that recognize these stimuli and initiate specific signaling pathways that enable a cell to change with the environment. Downregulation of these signaling receptors represents the most direct method for limiting the magnitude and duration of downstream signal transduction. For cell surface transmembrane receptors, ligand-stimulated endocytosis is a major mechanism by which the ability of a cell to react to a ligand is restricted. In order to investigate the downregulation of the prolactin receptor (PRLr), we investigated the mechanism and key determinants in the endocytosis and downregulation of PRLr. In Chapter 2 ...


A New Approach To Understanding Biological Control Of Quinone Electrochemistry, Bruce R. Lichtenstein 2010 University of Pennsylvania

A New Approach To Understanding Biological Control Of Quinone Electrochemistry, Bruce R. Lichtenstein

Publicly Accessible Penn Dissertations

Oxidoreductases play pivotal roles in energy capturing and converting processes of life. During these processes, quinones shuttle protons and reducing equivalents between membrane-bound oxidoreductases that generate the proton motive force during oxidative phosphorylation and photophosphorylation. A key mechanistic feature of these oxidoreductases is their ability to tune the reduction potentials of the hydroquinone, semiquinone and oxidized states of their substrate quinones. This level of control allows for maximization of conversion efficiency between the energy of the quinone reducing equivalents and the proton motive force, and prevents side reactions that may be fatal to cells. A half-century of experimental study and ...


Functions Of Dna Damage Response Factors In Lymphocyte Development And Transformation, Bu Yin 2010 University of Pennsylvania School of Medicine

Functions Of Dna Damage Response Factors In Lymphocyte Development And Transformation, Bu Yin

Publicly Accessible Penn Dissertations

DNA double strand breaks (DSBs) can activate cell cycle checkpoints or apoptosis, and lead to genomic alterations that drive malignant transformation. The H2AX core histone variant is phosphorylated in chromatin around DSBs by kinases such as ATM and DNA-PKcs. However, how H2AX suppresses chromosome breaks and translocations in cells and prevents tumorigenesis in mice and humans is not well understood. V(D)J recombination is a genetically programmed DNA damage and repair process that assembles the variable region exons of antigen receptor genes in developing lymphocytes. Using an inducible V(D)J recombination system, I found that H2AX is phosphorylated ...


Probabilistic Protein Design, Comparative Modeling, And The Structure Of A Multidomain P53 Oligomer Bound To Dna, Thomas John Petty II 2010 University of Pennsylvania

Probabilistic Protein Design, Comparative Modeling, And The Structure Of A Multidomain P53 Oligomer Bound To Dna, Thomas John Petty Ii

Publicly Accessible Penn Dissertations

Proteins are the main functional components of all cellular processes, and most of them fold into unique three-dimensional shapes guided by their amino-acid sequence. Discovering the structure of a protein, or protein complexes, can provide important clues about how they perform their function. However, the chemical, physical or architectural properties of many proteins impede traditional approaches to structure determination. Two such proteins, the tumor suppressor p53 and the cholesterol processing enzyme endothelial lipase, are prime examples of problematic proteins that defy structural investigation via crystallographic methods. Therefore, new techniques must be developed to gain valuable structural insights, such as: computationally ...


Mimosa: A System For Minimotif Annotation, Jay Vyas, Ronald J. Nowling, Thomas Meusburger, David P. Sargeant, Krishna Kadaveru, Michael R. Gryk, Vamsi Kundeti, Sanguthevar Rajasekaran, Martin Schiller 2010 University of Connecticut Heath Center,

Mimosa: A System For Minimotif Annotation, Jay Vyas, Ronald J. Nowling, Thomas Meusburger, David P. Sargeant, Krishna Kadaveru, Michael R. Gryk, Vamsi Kundeti, Sanguthevar Rajasekaran, Martin Schiller

Life Sciences Faculty Publications

BACKGROUND:

Minimotifs are short peptide sequences within one protein, which are recognized by other proteins or molecules. While there are now several minimotif databases, they are incomplete. There are reports of many minimotifs in the primary literature, which have yet to be annotated, while entirely novel minimotifs continue to be published on a weekly basis. Our recently proposed function and sequence syntax for minimotifs enables us to build a general tool that will facilitate structured annotation and management of minimotif data from the biomedical literature.

RESULTS:

We have built the MimoSA application for minimotif annotation. The application supports management of ...


Intrinsic Contact Geometry Of Protein Dynamics, Yosi Shibberu, Allen Holder, David Cooper 2010 Rose-Hulman Institute of Technology

Intrinsic Contact Geometry Of Protein Dynamics, Yosi Shibberu, Allen Holder, David Cooper

Mathematical Sciences Technical Reports (MSTR)

We introduce a new measure for comparing protein structures that is especially applicable to analysis of molecular dynamics simulation results. The new measure generalizes the widely used root-mean-squared-deviation (RMSD) measure from three dimensional to n-dimensional Euclidean space, where n equals the number of atoms in the protein molecule. The new measure shows that despite significant fluctuations in the three dimensional geometry of the estrogen receptor protein, the protein's intrinsic contact geometry is remarkably stable over nanosecond time scales. The new measure also identifies significant structural changes missed by RMSD for a residue that plays a key biological role ...


Alkylphenol Contamination In Homarus Americanus, Jennifer Renee Urban 2010 University of Connecticut - Storrs

Alkylphenol Contamination In Homarus Americanus, Jennifer Renee Urban

Honors Scholar Theses

Alkylphenols are pollutants that are present in marine sediments and fishes. In earlier work it has been discovered that alkylphenols are present in the Homarus americanus, or the American lobster. Research suggests that alkylphenols could behave as endocrine disruptors as they have been found to affect juvenile hormone activity. It has been hypothesized that lobsters may be able to rid themselves of alkylphenol contamination through secreting these compounds into the environment or sequestering them in their tissues. In this study, I address the question of how lobsters may rid themselves of alkylphenols by analyzing hemolymph, muscle, gill, and shell samples ...


Dopaminergic Innervation Of The Subventricular Zone In The Murine Brain, Linda Beth Drozdowicz 2010 University of Connecticut - Storrs

Dopaminergic Innervation Of The Subventricular Zone In The Murine Brain, Linda Beth Drozdowicz

Honors Scholar Theses

The subventricular zone (SVZ) is one of two areas in the brain that, in a healthy mouse, continually generate neurons throughout adulthood. While it was previously thought that only the A9 neurons of the substantia nigra sent dopaminergic afferents to the SVZ, recent studies suggest that the A10 neurons of the ventral tegmental area may innervate this area. This project has aimed to discover which, if either, model is correct.

Examination of the Aphakia (AK) mouse was used to determine the role of distinct midbrain regions in SVZ regulation. Additionally, intraperitoneal injections of the chemical MPTP were used to deduce ...


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