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Articles 91 - 120 of 12736

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

Investigation Of Microbiota In Health And Disease Of Poultry, Bishnu Adhikari Aug 2019

Investigation Of Microbiota In Health And Disease Of Poultry, Bishnu Adhikari

Theses and Dissertations

The microbiotas play vital roles in health and diseases of both humans and animals. 16S rRNA genes sequence analysis is one of the most popular and commonly used methods in the analysis of microbiotas associated with hosts. In this dissertation, the microbiotas of chickens (broilers, breeders, and layers) and turkeys were evaluated by 16S rRNA gene sequencing. Characterization of the culturable subpopulations of Lactobacillus in the chicken gut can serve as a valuable resource for probiotic development. In Chapter 2, Lactobacillus subpopulations recovered on MRS from chicken gut were defined comprehensively for the first time using 16S rRNA gene profiling ...


High-Fat Diet In A Mouse Insulin-Resistant Model Induces Widespread Rewiring Of The Phosphotyrosine Signaling Network, Antje Dittmann, Norman J. Kennedy, Nina L. Soltero, Nader Morshed, Miyeko D. Mana, Omer H. Yilmaz, Roger J. Davis, Forest M. White Aug 2019

High-Fat Diet In A Mouse Insulin-Resistant Model Induces Widespread Rewiring Of The Phosphotyrosine Signaling Network, Antje Dittmann, Norman J. Kennedy, Nina L. Soltero, Nader Morshed, Miyeko D. Mana, Omer H. Yilmaz, Roger J. Davis, Forest M. White

Open Access Articles

Obesity-associated type 2 diabetes and accompanying diseases have developed into a leading human health risk across industrialized and developing countries. The complex molecular underpinnings of how lipid overload and lipid metabolites lead to the deregulation of metabolic processes are incompletely understood. We assessed hepatic post-translational alterations in response to treatment of cells with saturated and unsaturated free fatty acids and the consumption of a high-fat diet by mice. These data revealed widespread tyrosine phosphorylation changes affecting a large number of enzymes involved in metabolic processes as well as canonical receptor-mediated signal transduction networks. Targeting two of the most prominently affected ...


Flavobacterium Gliding Motility: From Protein Secretion To Cell Surface Adhesin Movements, Joseph Johnston Aug 2019

Flavobacterium Gliding Motility: From Protein Secretion To Cell Surface Adhesin Movements, Joseph Johnston

Theses and Dissertations

Flavobacterium johnsoniae exhibits rapid gliding motility over surfaces. At least twenty genes are involved in this process. Seven of these, gldK, gldL, gldM, gldN, sprA, sprE, and sprT encode proteins of the type IX protein secretion system (T9SS). The T9SS is required for surface localization of the motility adhesins SprB and RemA, and for secretion of the soluble chitinase ChiA. This thesis demonstrates that the gliding motility proteins GldA, GldB, GldD, GldF, GldH, GldI and GldJ are also essential for secretion. Cells with mutations in the genes encoding any of these seven proteins had normal levels of gldK mRNA but ...


Temporal Gene Expression Of Mesenchymal Cells In The Pediatric Lung, Quinlen F. Marshall, Soumyaroop Bhattacharya, Gautam Bandyopadhyay, Ravi Misra, Thomas Mariani, Gloria Pryhuber Aug 2019

Temporal Gene Expression Of Mesenchymal Cells In The Pediatric Lung, Quinlen F. Marshall, Soumyaroop Bhattacharya, Gautam Bandyopadhyay, Ravi Misra, Thomas Mariani, Gloria Pryhuber

Chemistry Student Work

INTRODUCTION: The newborn lung undergoes vast biochemical and physiological changes during adaptation from the intrauterine to the extrauterine environment. Lung morphogenesis continues from birth into early childhood, mediated by dynamic gene expression and a diversity of pulmonary cell types (Whitsett, JA. et al. Physiol. Rev, 2019). Murine models demonstrate that pulmonary mesenchymal cells exhibit remarkable heterogeneity in function and morphology during development, however, confirmation of their role is lacking in human neonates and early childhood (Guo, M. et al. Nat. Comm, 2019). In addition, many current human genomic studies of lung maturation suffer from limited sample size, limiting their applicability ...


Intron And Small Rna Localization In Mammalian Neurons, Harleen Saini Jul 2019

Intron And Small Rna Localization In Mammalian Neurons, Harleen Saini

GSBS Dissertations and Theses

RNA molecules are diverse in form and function. They include messenger RNAs (mRNAs) that are templates for proteins, splice products such as introns that can generate functional noncoding RNAs, and a slew of smaller RNAs such as transfer RNAs (tRNAs) that help decode mRNAs into proteins. RNAs can show distinct patterns of subcellular localization that play an important role in protein localization. However, RNA distribution in cells is incompletely understood, with prior studies focusing primarily on RNAs that are long (>200 nucleotides), fully processed, and polyadenylated. We examined the distribution of RNAs in neurons. Neuronal compartments can be separated by ...


Impact Of Obesity On Ovotoxicity Induced By 7,12-Dimethylbenz[A]Anthracene In Mice, Jackson Nteeba, Shanthi Ganesan, Aileen F. Keating Jul 2019

Impact Of Obesity On Ovotoxicity Induced By 7,12-Dimethylbenz[A]Anthracene In Mice, Jackson Nteeba, Shanthi Ganesan, Aileen F. Keating

Aileen Keating

Insulin, elevated during obesity, regulates xenobiotic biotransformation enzymes, potentially through phosphatidylinositol 3-kinase (PI3K) signaling, in extraovarian tissues. PI3K regulates oocyte viability, follicular activation, and ovarian chemical biotransformation. 7,12-Dimethylbenz[a]anthracene (DMBA), a carcinogen and ovotoxicant, destroys all stages of follicles, leading to premature ovarian failure. Obesity has been reported to promote DMBA-induced tumors, but it remains unknown whether obesity affects ovarian xenobiotic metabolism. Therefore, we investigated ovarian expression of xenobiotic metabolism genes—microsomal epoxide hydrolase (Ephx1), glutathione S-transferase (GST) class Pi (Gstp1) and class mu 1 (Gstm1), and PI3K-signaling members (protein kinase B [AKT] alpha [Akt1], beta [Akt2], and ...


Effective Mismatch Repair Depends On Timely Control Of Pcna Retention On Dna By The Elg1 Complex, Lovely Jael Paul Solomon Devakumar, Christl Gaubitz, Victoria Lundblad, Brian A. Kelch, Takashi Kubota Jul 2019

Effective Mismatch Repair Depends On Timely Control Of Pcna Retention On Dna By The Elg1 Complex, Lovely Jael Paul Solomon Devakumar, Christl Gaubitz, Victoria Lundblad, Brian A. Kelch, Takashi Kubota

Open Access Articles

Proliferating cell nuclear antigen (PCNA) is a sliding clamp that acts as a central co-ordinator for mismatch repair (MMR) as well as DNA replication. Loss of Elg1, the major subunit of the PCNA unloader complex, causes over-accumulation of PCNA on DNA and also increases mutation rate, but it has been unclear if the two effects are linked. Here we show that timely removal of PCNA from DNA by the Elg1 complex is important to prevent mutations. Although premature unloading of PCNA generally increases mutation rate, the mutator phenotype of elg1Delta is attenuated by PCNA mutants PCNA-R14E and PCNA-D150E that spontaneously ...


Glutathione S-Transferase Class Mu Regulation Of Apoptosis Signal-Regulating Kinase 1 Protein During Vcd-Induced Ovotoxicity In Neonatal Rat Ovaries, Poulomi Bhattacharya, Jill A. Madden, Nivedita Sen, Patricia B. Hoyer, Aileen F. Keating Jul 2019

Glutathione S-Transferase Class Mu Regulation Of Apoptosis Signal-Regulating Kinase 1 Protein During Vcd-Induced Ovotoxicity In Neonatal Rat Ovaries, Poulomi Bhattacharya, Jill A. Madden, Nivedita Sen, Patricia B. Hoyer, Aileen F. Keating

Aileen Keating

4-vinylcyclohexene diepoxide (VCD) destroys ovarian primordial and small primary follicles via apoptosis. In mice, VCD exposure induces ovarian mRNA expression of glutathione S-transferase (GST) family members, including isoform mu (Gstm). Extra-ovarian GSTM negatively regulates pro-apoptotic apoptosis signal-related kinase 1 (ASK1) through protein complex formation, which dissociates during stress, thereby initiating ASK1-induced apoptosis. The present study investigated the ovarian response of Gstm mRNA and protein to VCD. Induction of Ask1 mRNA at VCD-induced follicle loss onset was determined. Ovarian GSTM:ASK1 protein complex formation was investigated and VCD exposure effects thereon evaluated. Phosphatidylinositol-3 kinase (PI3K) regulation of GSTM protein was also ...


Science, Physiology, And Nutrition For The Nonscientist, Judi S. Morrill Jul 2019

Science, Physiology, And Nutrition For The Nonscientist, Judi S. Morrill

Open Educational Resources

A wonderful blend of physiology, nutrition, biochemistry, genetics, biology, evolution, chemistry--what we all need to know as informed citizens. A basic knowledge of the life sciences and how our bodies work--to promote our own good health, especially as we're bombarded with misleading advertisements, soundbites, and the like. DNA fingerprinting, calorie requirements, dietary advice, genetic engineering (including gene editing with CRISPR cas9)--all in an easy-to understand book.


Nonnative Structure In A Peptide Model Of The Unfolded State Of Sod1: Implications For Als-Linked Aggregation, Noah R. Cohen, Jill A. Zitzewitz, Osman Bilsel, C. Robert Matthews Jul 2019

Nonnative Structure In A Peptide Model Of The Unfolded State Of Sod1: Implications For Als-Linked Aggregation, Noah R. Cohen, Jill A. Zitzewitz, Osman Bilsel, C. Robert Matthews

Open Access Articles

Dozens of mutations throughout the sequence of the gene encoding superoxide dismutase 1 (SOD1) have been linked to toxic protein aggregation in the neurodegenerative disease amyotrophic lateral sclerosis (ALS). A parsimonious explanation for numerous genotypes resulting in a common phenotype would be mutation-induced perturbation of the folding free-energy surface that increases the populations of high-energy states prone to aggregation. The absence of intermediates in the folding of monomeric SOD1 suggests that the unfolded ensemble is a potential source of aggregation. To test this hypothesis, here we dissected SOD1 into a set of peptides end-labeled with FRET probes to model the ...


Inactivating Mutations And X-Ray Crystal Structure Of The Tumor Suppressor Opcml Reveal Cancer-Associated Functions, James R. Birtley, Zachary Maben, Grant C. Weaver, Mollie M. Jurewicz, Lawrence J. Stern, Chiara Recchi, Hani Gabra Jul 2019

Inactivating Mutations And X-Ray Crystal Structure Of The Tumor Suppressor Opcml Reveal Cancer-Associated Functions, James R. Birtley, Zachary Maben, Grant C. Weaver, Mollie M. Jurewicz, Lawrence J. Stern, Chiara Recchi, Hani Gabra

Open Access Articles

OPCML, a tumor suppressor gene, is frequently silenced epigenetically in ovarian and other cancers. Here we report, by analysis of databases of tumor sequences, the observation of OPCML somatic missense mutations from various tumor types and the impact of these mutations on OPCML function, by solving the X-ray crystal structure of this glycoprotein to 2.65 A resolution. OPCML consists of an extended arrangement of three immunoglobulin-like domains and homodimerizes via a network of contacts between membrane-distal domains. We report the generation of a panel of OPCML variants with representative clinical mutations and demonstrate clear phenotypic effects in vitro and ...


Calcineurin Broadly Regulates The Initiation Of Skeletal Muscle-Specific Gene Expression By Binding Target Promoters And Facilitating The Interaction Of The Swi/Snf Chromatin Remodeling Enzyme, Hanna Witwicka, Jumpei Nogami, Sabriya A. Syed, Kazumitsu Maehara, Teresita Padilla-Benavides, Yasuyuki Ohkawa, Anthony N. Imbalzano Jul 2019

Calcineurin Broadly Regulates The Initiation Of Skeletal Muscle-Specific Gene Expression By Binding Target Promoters And Facilitating The Interaction Of The Swi/Snf Chromatin Remodeling Enzyme, Hanna Witwicka, Jumpei Nogami, Sabriya A. Syed, Kazumitsu Maehara, Teresita Padilla-Benavides, Yasuyuki Ohkawa, Anthony N. Imbalzano

Open Access Articles

Calcineurin (Cn) is a calcium-activated serine/threonine protein phosphatase that is broadly implicated in diverse cellular processes, including the regulation of gene expression. During skeletal muscle differentiation, Cn activates the NFAT transcription factor but also promotes differentiation by counteracting the negative influences of protein kinase C beta (PKCbeta) via dephosphorylation and activation of BRG1, an enzymatic subunit of the mammalian SWI/SNF ATP-dependent chromatin remodeling enzyme. Here we identified four major temporal patterns of Cn-dependent gene expression in differentiating myoblasts and determined that Cn is broadly required for the activation of the myogenic gene expression program. Mechanistically, Cn promotes gene ...


Lignin Biopolymers In The Age Of Controlled Polymerization, Mitra S. Ganewatta, Hasala N. Lokupitiya, Chuanbing Tang Jul 2019

Lignin Biopolymers In The Age Of Controlled Polymerization, Mitra S. Ganewatta, Hasala N. Lokupitiya, Chuanbing Tang

Faculty Publications

Polymers made from natural biomass are gaining interest due to the rising environmental concerns and depletion of petrochemical resources. Lignin isolated from lignocellulosic biomass is the second most abundant natural polymer next to cellulose. The paper pulp process produces industrial lignin as a byproduct that is mostly used for energy and has less significant utility in materials applications. High abundance, rich chemical functionalities, CO2 neutrality, reinforcing properties, antioxidant and UV blocking abilities, as well as environmental friendliness, make lignin an interesting substrate for materials and chemical development. However, poor processability, low reactivity, and intrinsic structural heterogeneity limit lignins′ polymeric applications ...


Histone H2a Repression Domain Regulates Cell-Cycle Progression In Saccaromyces Cerevisea, Taylor Nattress Jul 2019

Histone H2a Repression Domain Regulates Cell-Cycle Progression In Saccaromyces Cerevisea, Taylor Nattress

Landmark Conference Summer Research Symposium

This study researched the histone H2A's N-terminal tail amino acid sequence, focusing on amino acids 16-20 known as the histone H2A repression, HAR, domain. This study found a sensitivity within the deletion of the HAR domain to hydroxyurea, a genotoxin known to show defects in DNA replication. A spotting assay concluded that the HAR domain has an important regulator of the DNA replication process. The RNR1-4 genes were studied through reverse transcriptase polymerase chain reactions in order to see the difference in wild type gene expression compared to the deletion of the HAR domain. The deletion of the HAR ...


Exploring The Synthesis Of Substituted Porphyrins, Christina Schnee Jul 2019

Exploring The Synthesis Of Substituted Porphyrins, Christina Schnee

Landmark Conference Summer Research Symposium

A current theme in our research laboratory is the development of low cost methods for the synthesis of lamellar vesicles as models for cell membranes. These vesicles, serving as simplified artificial cells, allow us to examine fundamental properties of the membrane including transport of materials across the membrane. Vesicles of varying size can also be employed as molecule delivery systems for a variety of compounds, including pharmaceuticals. We are especially interested in pharmaceuticals used in photodynamic therapy. This type of medical intervention entails delivery of a prodrug (one which is not initially bio-active). Upon exposure to a specific wavelength of ...


Synthesis Of An Amide-Based Extended Heterocyclic System Capable Of Hydrogen Bonding To Both The Adenine And Uracil In Dsrna For Rna Recognition Using Pna, John M. Talbott, Aubrey L. Maryniak Jul 2019

Synthesis Of An Amide-Based Extended Heterocyclic System Capable Of Hydrogen Bonding To Both The Adenine And Uracil In Dsrna For Rna Recognition Using Pna, John M. Talbott, Aubrey L. Maryniak

Landmark Conference Summer Research Symposium

The majority of information known about RNA is centered around coding RNA for its role in synthesizing proteins from DNA. However, noncoding RNA is also biologically relevant, showing importance in gene expression and catalyzing reactions. Peptide Nucleic Acids, or PNAs, are a promising tool that can be used to study noncoding RNA. PNAs can bind to double-stranded RNA forming a triple helix and are highly selective for specific sequences of dsRNA. A current limitation of PNA as a ligand is that traditional nucleobases only bind with high affinity to single purine residues on the RNA, as triplex formation relies on ...


Development Of A One-Pot Allylation And Claisen Rearrangement Of Acetaminophen By Applying Microwave Radiation, Brandon R. Tessier Jul 2019

Development Of A One-Pot Allylation And Claisen Rearrangement Of Acetaminophen By Applying Microwave Radiation, Brandon R. Tessier

Landmark Conference Summer Research Symposium

The Claisen rearrangement is a widely applicable organic reaction that involves the shift of a sigma bond across the pi-system of an allyl vinyl ether to produce allylated phenols. In this project, we aim to develop a microwave assisted allylation of a phenol, followed by a subsequent Claisen rearrangement in one pot. The goals of this project are three-fold. First, we aim to accelerate these reactions using microwave assisted organic synthesis because to date, microwave technology has been sparsely used in Claisen chemistry. Second, we aim to perform these reactions in a single pot, enhancing the simplicity and elegance of ...


Regulation Of Rna Stability By Terminal Nucleotidyltransferases, Christina Z. Chung Jul 2019

Regulation Of Rna Stability By Terminal Nucleotidyltransferases, Christina Z. Chung

Electronic Thesis and Dissertation Repository

The dysregulation of RNAs has global effects on all cellular pathways. The regulation of RNA metabolism is thus tightly controlled. Terminal RNA nucleotidyltransferases (TENTs) regulate RNA stability and activity through the addition of non-templated nucleotides to the 3′-end. TENT-catalyzed adenylation and uridylation have opposing effects; adenylation stabilizes while uridylation silences or degrades RNA. All TENT homologs were initially characterized as adenylyltransferases; the identification of caffeine-induced death suppressor protein 1 (Cid1) in Schizosaccharomyces pombe as an uridylyltransferase led to the reclassification of many TENTs as uridylyltransferases. Cid1 uridylates mRNAs that are subsequently degraded by the exonuclease Dis-like 3′-5′ exonuclease ...


Electron Transfer Activity Of Mitochondria Neet-Proteins, Yiming Wang Jul 2019

Electron Transfer Activity Of Mitochondria Neet-Proteins, Yiming Wang

LSU Doctoral Dissertations

Mitochondrial NEET proteins are recently discovered iron-sulfur proteins that are localized within mitochondria. There are three NEET proteins: mitoNEET, a type II diabetes drug pioglitazone binding target, a mitoNEET related protein 1 (Miner1 or NAF-1), and a mitoNEET-related protein 2 (Miner2). While both mitoNEET and Miner1 are mitochondrial outer membrane proteins, Miner2 is a mitochondrial matrix protein. All three NEET proteins bind at least one [2Fe-2S] cluster via CDGSH (Cys-Asp-Gly-Ser-His) motif. In this work, we have investigated the electron transfer activity of mitoNEET, and found that the CDGSH-type [2Fe-2S] clusters of mitoNEET can be reduced by the reduced flavin mononucleotide ...


Rapid Irreversible Transcriptional Reprogramming In Human Stem Cells Accompanied By Discordance Between Replication Timing And Chromatin Compartment, Vishnu Dileep, Rachel Patton Mccord, Job Dekker, David M. Gilbert Jul 2019

Rapid Irreversible Transcriptional Reprogramming In Human Stem Cells Accompanied By Discordance Between Replication Timing And Chromatin Compartment, Vishnu Dileep, Rachel Patton Mccord, Job Dekker, David M. Gilbert

Open Access Articles

The temporal order of DNA replication is regulated during development and is highly correlated with gene expression, histone modifications and 3D genome architecture. We tracked changes in replication timing, gene expression, and chromatin conformation capture (Hi-C) A/B compartments over the first two cell cycles during differentiation of human embryonic stem cells to definitive endoderm. Remarkably, transcriptional programs were irreversibly reprogrammed within the first cell cycle and were largely but not universally coordinated with replication timing changes. Moreover, changes in A/B compartment and several histone modifications that normally correlate strongly with replication timing showed weak correlation during the early ...


An Unexpected Rhenium(Iv)–Rhenium(Vii) Salt: [Co(Nh3)6]3[Reviio4][Reivf6]46h2o, James Louis_Jean, Samudee Mariappan Balasekaran, Adelheid Hagenbach, Frederic Poineau Jul 2019

An Unexpected Rhenium(Iv)–Rhenium(Vii) Salt: [Co(Nh3)6]3[Reviio4][Reivf6]46h2o, James Louis_Jean, Samudee Mariappan Balasekaran, Adelheid Hagenbach, Frederic Poineau

Chemistry and Biochemistry Faculty Publications

The title hydrated salt, tris[hexaamminecobalt(III)] tetraoxidorhenate(VII) tetrakis[hexafluoridorhenate(IV)] hexahydrate, arose unexpectedly due to possible contamination of the K2ReF6 starting material with KReO4. It consists of octahedral [Co(NH3)6] 3+ cation (Co1 site symmetry 1), tetrahedral [ReVIIO4] anions (Re site symmetry 1) and octahedral [ReIVF6] 2 anions (Re site symmetries 1and 3). The [ReF6] 2 octahedral anions (mean Re—F = 1.834 A˚ ), [Co(NH3)6] 3+ octahedral cations (mean Co—N = 1.962 A˚ ), and the [ReO4] tetrahedral anion (mean Re—O = 1.719 A˚ ) are slightly distorted. A network of N—HF hydrogen bonds ...


Systems Approach Reveals Photosensitivity And Per2 Level As Determinants Of Clock-Modulator Efficacy, Dae Wook Kim, Cheng Chang, Xian Chen, Angela C. Doran, Francois Gaudreault, Travis Wager, George J. Demarco, Jae Kyoung Kim Jul 2019

Systems Approach Reveals Photosensitivity And Per2 Level As Determinants Of Clock-Modulator Efficacy, Dae Wook Kim, Cheng Chang, Xian Chen, Angela C. Doran, Francois Gaudreault, Travis Wager, George J. Demarco, Jae Kyoung Kim

Open Access Articles

In mammals, the master circadian clock synchronizes daily rhythms of physiology and behavior with the day-night cycle. Failure of synchrony, which increases the risk for numerous chronic diseases, can be treated by phase adjustment of the circadian clock pharmacologically, for example, with melatonin, or a CK1delta/epsilon inhibitor. Here, using in silico experiments with a systems pharmacology model describing molecular interactions, and pharmacokinetic and behavioral experiments in cynomolgus monkeys, we find that the circadian phase delay caused by CK1delta/epsilon inhibition is more strongly attenuated by light in diurnal monkeys and humans than in nocturnal mice, which are common preclinical ...


Identification And Characterization Of Preferred Dna-Binding Sites For The Thermus Thermophilus Hb8 Transcriptional Regulator Ttha0973, James Shell Cox, Kristi Moncja, Mykala Mckinnes, Michael W. Van Dyke Jul 2019

Identification And Characterization Of Preferred Dna-Binding Sites For The Thermus Thermophilus Hb8 Transcriptional Regulator Ttha0973, James Shell Cox, Kristi Moncja, Mykala Mckinnes, Michael W. Van Dyke

Faculty Publications

Advances in genomic sequencing have allowed the identification of a multitude of genes encoding putative transcriptional regulatory proteins. Lacking, often, is a fuller understanding of the biological roles played by these proteins, the genes they regulate or regulon. Conventionally this is achieved through a genetic approach involving putative transcription factor gene manipulation and observations of changes in an organism’s transcriptome. However, such an approach is not always feasible or can yield misleading findings. Here, we describe a biochemistry-centric approach, involving identification of preferred DNA-binding sequences for the Thermus thermophilus HB8 transcriptional repressor TTHA0973 using the selection method Restriction Endonuclease ...


Molecular And Structural Mechanism Of Pan-Genotypic Hcv Ns3/4a Protease Inhibition By Glecaprevir, Jennifer Timm, Klajdi Kosovrasti, Mina Henes, Florian Leidner, Shurong Hou, Akbar Ali, Nese Kurt Yilmaz, Celia A. Schiffer Jul 2019

Molecular And Structural Mechanism Of Pan-Genotypic Hcv Ns3/4a Protease Inhibition By Glecaprevir, Jennifer Timm, Klajdi Kosovrasti, Mina Henes, Florian Leidner, Shurong Hou, Akbar Ali, Nese Kurt Yilmaz, Celia A. Schiffer

University of Massachusetts Medical School Faculty Publications

Hepatitis C virus (HCV), causative agent of chronic viral hepatitis, infects 71 million people worldwide and is divided into seven genotypes and multiple subtypes with sequence identities between 68 to 82%. While older generation direct-acting antivirals (DAAs) had varying effectiveness against different genotypes, the newest NS3/4A protease inhibitors including glecaprevir (GLE) have pan-genotypic activity. The structural basis for pan-genotypic inhibition and effects of polymorphisms on inhibitor potency were not well known due to lack of crystal structures of GLE-bound NS3/4A or genotypes other than 1. In this study, we determined the crystal structures of NS3/4A from genotypes ...


Hexavalent Chromium-Induced Cytotoxicity And Mutagenicity: A Study Of Protection By Ascorbic Acid And Epigallocatechin Gallate, Timothy P. Mayotte Jul 2019

Hexavalent Chromium-Induced Cytotoxicity And Mutagenicity: A Study Of Protection By Ascorbic Acid And Epigallocatechin Gallate, Timothy P. Mayotte

Honors Program Projects

Hexavalent chromium, or Cr(VI), is a potent oxidizer and known carcinogen, that is found at varying levels in the water sources of more than 200 million Americans. However, the exact mechanism of carcinogenicity remains unknown, and though the government currently regulates total chromium levels, they have yet to determine a permissible exposure limit for Cr(VI). Moreover, there is currently no preventative treatment for Cr(VI). Because of Cr(VI)’s strong oxidative power, we hypothesized that it causes DNA mutation and cell death via oxidation and that antioxidants could prevent this from occurring. To test this, we first ...


Organic Chemistry With A Biological Emphasis Volume I, Timothy Soderberg Jul 2019

Organic Chemistry With A Biological Emphasis Volume I, Timothy Soderberg

Chemistry Publications

The traditional approach to teaching Organic Chemistry, taken by most of the textbooks that are currently available, is to focus primarily on the reactions of laboratory synthesis, with much less discussion - in the central chapters, at least - of biological molecules and reactions. This is despite the fact that, in many classrooms, a majority of students are majoring in Biology or Health Sciences rather than in Chemistry, and are presumably taking the course in order to learn about the chemistry that takes place in living things.

In an effort to address this disconnect, I have developed a textbook for a two-semester ...


Organic Chemistry With A Biological Emphasis Volume Ii, Timothy Soderberg Jul 2019

Organic Chemistry With A Biological Emphasis Volume Ii, Timothy Soderberg

Chemistry Publications

The traditional approach to teaching Organic Chemistry, taken by most of the textbooks that are currently available, is to focus primarily on the reactions of laboratory synthesis, with much less discussion - in the central chapters, at least - of biological molecules and reactions. This is despite the fact that, in many classrooms, a majority of students are majoring in Biology or Health Sciences rather than in Chemistry, and are presumably taking the course in order to learn about the chemistry that takes place in living things.

In an effort to address this disconnect, I have developed a textbook for a two-semester ...


The Expression Of Connexin-43 By Cd11c+ Dendritic Cells Is Required To Maintain Cd4+ Foxp3+ Regulatory T Cell Population In Peripheral Lymphoid Organs, Caroline Titus Miller Jul 2019

The Expression Of Connexin-43 By Cd11c+ Dendritic Cells Is Required To Maintain Cd4+ Foxp3+ Regulatory T Cell Population In Peripheral Lymphoid Organs, Caroline Titus Miller

Biological Sciences Theses & Dissertations

Foxp3+ regulatory T cells (TR) are an immunosuppressive subset of CD4+ T cells that maintain homeostasis of the immune system. They are sustained by the interaction between the Major Histocompatibility Complex (MHC) molecules present on antigen presenting dendritic cells and the T Cell Receptor (TCR) expressed on TR cells that is specific for the MHC loaded with an antigenic peptide. Here, we show that in addition to MHC/TCR interaction, Connexin-43 (Cx43) expression by dendritic cells is required to maintain the TR cell population. CD11c+ dendritic cells represent a major subset of antigen presenting cells. Using flow cytometry ...


Endogenous Force Transmission Between Epithelial Cells And A Role For Α-Catenin, Sandeep Dumbali Jul 2019

Endogenous Force Transmission Between Epithelial Cells And A Role For Α-Catenin, Sandeep Dumbali

Mechanical & Aerospace Engineering Theses & Dissertations

In epithelial tissues, epithelial cells adhere to each other as well as to the underlying extra-cellular matrix (ECM). E-cadherin-based intercellular junctions play an important role in tissue integrity. These junctions experience cell-generated mechanical forces via apparent adaptor proteins such as beta (β) catenin, alpha (α) catenin and vinculin. Abnormalities in these junctions may result in skin related diseases and cancers. Here, I devised methods to determine the endogenous intercellular force within cell pairs as well as in large epithelial islands. I further ascertained the factors that affect the level of inter-cellular tension.

Experiments with pairs of epithelial cells exogenously expressing ...


Tracing Nutrient Sources To Lipid Production In Insects Using Stable Isotope (Δ13c, Δ2h) Tracers: Implications For Nutritional Physiology Of Migratory Species., Libesha Anparasan, Keith A. Hobson Jun 2019

Tracing Nutrient Sources To Lipid Production In Insects Using Stable Isotope (Δ13c, Δ2h) Tracers: Implications For Nutritional Physiology Of Migratory Species., Libesha Anparasan, Keith A. Hobson

Western Research Forum

Using stable isotope measurements of insect tissues to determine origin and migratory patterns is well established. However, isotopically determining nutritional origins of lipids, the primary fuel of migration, has not been as thoroughly researched. We explored isotopic links between diet and stored lipids in laboratory raised True armyworm moths (Mythimna unipuncta) using δ13C and δ2H measurements. Pupae were randomly separated into four groups (n=20) and fed isotopically distinct nectar, each consisting of a combination of high δ13C (C4 sugar), or low δ13C (C3 sugar) carbohydrate, with high δ2H (deuterium ...