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Articles 1441 - 1470 of 6985
Full-Text Articles in Biochemistry
Reduction Of Stabilin-2 Contributes To A Protection Against Atherosclerosisstabilin, Yukako Kayashima1*,, Conner A. Clanton, Amanda M. Lewis, Xinghui Sun, Sylvia Hiller, Phillip Huynh, Jennifer Wilder, John Hagaman, Feng Li, Nobuyo Maeda-Smithies, Edward N. Harris
Reduction Of Stabilin-2 Contributes To A Protection Against Atherosclerosisstabilin, Yukako Kayashima1*,, Conner A. Clanton, Amanda M. Lewis, Xinghui Sun, Sylvia Hiller, Phillip Huynh, Jennifer Wilder, John Hagaman, Feng Li, Nobuyo Maeda-Smithies, Edward N. Harris
Department of Biochemistry: Faculty Publications
We have previously identified a novel atherosclerosis quantitative trait locus (QTL), Arch atherosclerosis 5 (Aath5), on mouse chromosome 10 by three-way QTL analyses between Apoe−/− mice on a DBA/2J, 129S6 and C57BL/6J background. The DBA/2J haplotype at the Aath5 locus was associated with smaller plaque size. One of the candidate genes underlying Aath5 was Stabilin-2 (Stab2), which encodes a clearance receptor for hyaluronan (HA) predominantly expressed in liver sinusoidal endothelial cells (LSECs). However, the role of Stab2 in atherosclerosis is unknown. A congenic line of Apoe−/− mice carrying Aath5 covering the Stab2DBA allele …
Reduction Of Stabilin-2 Contributes To A Protection Against Atherosclerosis, Yukako Kayashima, Connor A. Clanton, Amanda M. Lewis, Xinghui Sun, Sylvia Hiller, Phillip Huynh, Jennifer Wilder, John Hagaman, Feng Li, Nobuyo Maeda-Smithies, Ed Harris
Reduction Of Stabilin-2 Contributes To A Protection Against Atherosclerosis, Yukako Kayashima, Connor A. Clanton, Amanda M. Lewis, Xinghui Sun, Sylvia Hiller, Phillip Huynh, Jennifer Wilder, John Hagaman, Feng Li, Nobuyo Maeda-Smithies, Ed Harris
Department of Biochemistry: Faculty Publications
We have previously identified a novel atherosclerosis quantitative trait locus (QTL), Arch atherosclerosis 5 (Aath5), on mouse chromosome 10 by three-way QTL analyses between Apoe−/− mice on a DBA/2J, 129S6 and C57BL/6J background. The DBA/2J haplotype at the Aath5 locus was associated with smaller plaque size. One of the candidate genes underlying Aath5 was Stabilin-2 (Stab2), which encodes a clearance receptor for hyaluronan (HA) predominantly expressed in liver sinusoidal endothelial cells (LSECs). However, the role of Stab2 in atherosclerosis is unknown. A congenic line of Apoe−/− mice carrying Aath5 covering the Stab2 …
One Planet: One Health. A Call To Support The Initiative On A Global Science-Policy Body On Chemicals And Waste, Werner Brack, Damia Barcelo Culleres, Alistair B.A. Boxall, Helene Budzinski, Sara Castiglioni, Adrian Covaci, Valeria Dulio, Beate I. Escher, Peter Fantke, Faith Kandie, Despo Fatta-Kassinos, Felix J. Hernandez, Klara Hilscherova, Juliane Hollender, Henner Hollert, Annika Jahnke, Barbara Kasprzyk-Hordern, Stuart J. Khan, Andreas Kortenkamp, Klaus Kuemmerer, Brice Lalonde, Marja H. Lamoree, Yves Levi, Pablo Antonio Lara Martin, Cassiana C. Montagner, Christian Mougin, Titus Msagati, Joerg Oehlmann, Leo Posthuma, Malcolm Reid, Martin Reinhard, Susan D. Richardson, Et. Al.
One Planet: One Health. A Call To Support The Initiative On A Global Science-Policy Body On Chemicals And Waste, Werner Brack, Damia Barcelo Culleres, Alistair B.A. Boxall, Helene Budzinski, Sara Castiglioni, Adrian Covaci, Valeria Dulio, Beate I. Escher, Peter Fantke, Faith Kandie, Despo Fatta-Kassinos, Felix J. Hernandez, Klara Hilscherova, Juliane Hollender, Henner Hollert, Annika Jahnke, Barbara Kasprzyk-Hordern, Stuart J. Khan, Andreas Kortenkamp, Klaus Kuemmerer, Brice Lalonde, Marja H. Lamoree, Yves Levi, Pablo Antonio Lara Martin, Cassiana C. Montagner, Christian Mougin, Titus Msagati, Joerg Oehlmann, Leo Posthuma, Malcolm Reid, Martin Reinhard, Susan D. Richardson, Et. Al.
Faculty Publications
The chemical pollution crisis severely threatens human and environmental health globally. To tackle this challenge the establishment of an overarching international science–policy body has recently been suggested. We strongly support this initiative based on the awareness that humanity has already likely left the safe operating space within planetary boundaries for novel entities including chemical pollution. Immediate action is essential and needs to be informed by sound scientific knowledge and data compiled and critically evaluated by an overarching science–policy interface body. Major challenges for such a body are (i) to foster global knowledge production on exposure, impacts and governance going beyond …
Structural And Computational Studies Of The Sars-Cov-2 Spike Protein Binding Mechanisms With Nanobodies: From Structure And Dynamics To Avidity-Driven Nanobody Engineering, Gennady M. Verkhivker
Structural And Computational Studies Of The Sars-Cov-2 Spike Protein Binding Mechanisms With Nanobodies: From Structure And Dynamics To Avidity-Driven Nanobody Engineering, Gennady M. Verkhivker
Mathematics, Physics, and Computer Science Faculty Articles and Research
Nanobodies provide important advantages over traditional antibodies, including their smaller size and robust biochemical properties such as high thermal stability, high solubility, and the ability to be bioengineered into novel multivalent, multi-specific, and high-affinity molecules, making them a class of emerging powerful therapies against SARS-CoV-2. Recent research efforts on the design, protein engineering, and structure-functional characterization of nanobodies and their binding with SARS-CoV-2 S proteins reflected a growing realization that nanobody combinations can exploit distinct binding epitopes and leverage the intrinsic plasticity of the conformational landscape for the SARS-CoV-2 S protein to produce efficient neutralizing and mutation resistant characteristics. Structural …
A Glass Bead Semi‑Hydroponic System For Intact Maize Root Exudate Analysis And Phenotyping, Martha G. Lopez-Guerrero, Peng Wang, Felicia Phares4, Daniel P. Schachtman, Sophie Alvarez, Karin Van Dijk
A Glass Bead Semi‑Hydroponic System For Intact Maize Root Exudate Analysis And Phenotyping, Martha G. Lopez-Guerrero, Peng Wang, Felicia Phares4, Daniel P. Schachtman, Sophie Alvarez, Karin Van Dijk
Department of Biochemistry: Faculty Publications
Background: Although there have been numerous studies describing plant growth systems for root exudate collection, a common limitation is that these systems require disruption of the plant root system to facilitate exudate collection. Here, we present a newly designed semi-hydroponic system that uses glass beads as solid support to simulate soil impedance, which combined with drip irrigation, facilitates growth of healthy maize plants, collection and analysis of root exudates, and phenotyping of the roots with minimal growth disturbance or root damage.
Results: This system was used to collect root exudates from seven maize genotypes using water or 1 mM CaCl …
Disruption Of Claudin-Made Tight Junction Barriers By Clostridium Perfringens Enterotoxin: Insights From Structural Biology, Chinemerem P. Ogbu, Sourav Roy, Alex J. Vecchio
Disruption Of Claudin-Made Tight Junction Barriers By Clostridium Perfringens Enterotoxin: Insights From Structural Biology, Chinemerem P. Ogbu, Sourav Roy, Alex J. Vecchio
Department of Biochemistry: Faculty Publications
Claudins are a family of integral membrane proteins that enable epithelial cell/cell interactions by localizing to and driving the formation of tight junctions. Via claudin self-assembly within the membranes of adjoining cells, their extracellular domains interact, forming barriers to the paracellular transport of small molecules and ions. The bacterium Clostridium perfringens causes prevalent gastrointestinal disorders in mammals by employing an enterotoxin (CpE) that targets claudins. CpE binds to claudins at or near tight junctions in the gut and disrupts their barrier function, potentially by disabling their assembly or via cell signaling means—the mechanism(s) remain unclear. CpE ultimately destroys claudin-expressing cells …
Sesamum Indicum Diet Prevents Hyperlipidemia In Experimental Rats, Muinat M. Adeyanju, Idris A. Saheed, Oluwaseun I. Oyelekan, Taiwo A. Dele-Osibanjo, Ayodeji A. Adelegan, Adekunle J. Raimi, Samuel O. Olalekan, Olugbenga S. Alabi, Khadijat M. Alli
Sesamum Indicum Diet Prevents Hyperlipidemia In Experimental Rats, Muinat M. Adeyanju, Idris A. Saheed, Oluwaseun I. Oyelekan, Taiwo A. Dele-Osibanjo, Ayodeji A. Adelegan, Adekunle J. Raimi, Samuel O. Olalekan, Olugbenga S. Alabi, Khadijat M. Alli
Department of Biochemistry: Faculty Publications
Cardiovascular diseases and metabolic complications caused by hyperlipidemia are the leading cause of death globally. In this study, the hypolipidemic potency of Sesamum indicum (SI) seeds was investigated. Of the thirty-five (35) male rats used in the study, five (5) were randomly selected for baseline measurements and thirty (30) were fed high fat diet (HFD) for four (4) weeks before random assignment into three (3) groups. The experimental group was treated with 50% SI seed, the positive control group was given a hypolipidemic drug, atorvastatin (5 mg/kg/day) while the untreated group served as the negative control. With SI administration, the …
Aerosolization Of Catalytic Rna For Prebiotic Transport And In Situ Reactivity, Brennan Roland Farrell
Aerosolization Of Catalytic Rna For Prebiotic Transport And In Situ Reactivity, Brennan Roland Farrell
Dissertations and Theses
Recent theoretical and experimental work suggests that aqueous aerosols in the early Earth's atmosphere might have been an essential component to the development of life. These complex droplets would have served to compartmentalize emerging biomolecules, thereby concentrating them, increasing reactivity, and facilitating transport and exchange between ocean and atmosphere. This project tests an underexplored but potentially important environmental paradigm for the RNA world hypothesis of prebiotic evolution, probing the effects of aerosolization on catalytic RNA using a model ribozyme. Here we demonstrate the successful transport and in situ self-assembly of the Azoarcus ribozyme from multiple independent fragments via a laboratory-constructed …
Salicylic Acid And N-Hydroxypipecolic Acid At The Fulcrum Of The Plant Immunity-Growth Equilibrium, Alyssa Shields, Vanessa Shivnauth, Christian Danve M. Castroverde
Salicylic Acid And N-Hydroxypipecolic Acid At The Fulcrum Of The Plant Immunity-Growth Equilibrium, Alyssa Shields, Vanessa Shivnauth, Christian Danve M. Castroverde
Biology Faculty Publications
Salicylic acid (SA) and N-hydroxypipecolic acid (NHP) are two central plant immune signals involved in both resistance at local sites of pathogen infection (basal resistance) and at distal uninfected sites after primary infection (systemic acquired resistance). Major discoveries and advances have led to deeper understanding of their biosynthesis and signaling during plant defense responses. In addition to their well-defined roles in immunity, recent research is emerging on their direct mechanistic impacts on plant growth and development. In this review, we will first provide an overview of how SA and NHP regulate local and systemic immune responses in plants. We …
Natural Phaeosphaeride A Derivatives Overcome Drug Resistance Of Tumor Cells And Modulate Signaling Pathways, Victoria Abzianidze, Natalia Moiseeva, Diana Suponina, Sofya Zakharenkova, Nadezhda Rogovskaya, Lidia Laletina, Alvin A. Holder, Denis Krivorotov, Alexander Bogachenkov, Alexander Garabadzhiu, Anton Ukolov, Vyacheslav Kosorukov
Natural Phaeosphaeride A Derivatives Overcome Drug Resistance Of Tumor Cells And Modulate Signaling Pathways, Victoria Abzianidze, Natalia Moiseeva, Diana Suponina, Sofya Zakharenkova, Nadezhda Rogovskaya, Lidia Laletina, Alvin A. Holder, Denis Krivorotov, Alexander Bogachenkov, Alexander Garabadzhiu, Anton Ukolov, Vyacheslav Kosorukov
Chemistry & Biochemistry Faculty Publications
n the present study, natural phaeosphaeride A (PPA) derivatives are synthesized. Anti-tumor studies are carried out on the PC3, K562, HCT-116, THP-1, MCF-7, A549, NCI-H929, Jurkat, and RPMI8226 tumor cell lines, and on the human embryonic kidney (HEK293) cell line. All the compounds synthesized turned out to have better efficacy than PPA towards the tumor cell lines listed. Among them, three compounds exhibited an ability to overcome the drug resistance of tumor cells associated with the overexpression of the P-glycoprotein by modulating the work of this transporter. Luminex xMAP technology was used to assess the effect of five synthesized compounds …
Studying Acetylation Of Aconitase Isozymes By Genetic Code Expansion, Jessica Araujo, Sara Ottinger, Sumana Venkat, Qinglei Gan, Chenguang Fan
Studying Acetylation Of Aconitase Isozymes By Genetic Code Expansion, Jessica Araujo, Sara Ottinger, Sumana Venkat, Qinglei Gan, Chenguang Fan
Chemistry & Biochemistry Faculty Publications and Presentations
Aconitase catalyzes the second reaction of the tricarboxylic acid cycle, the reversible conversion of citrate and isocitrate. Escherichia coli has two isoforms of aconitase, AcnA and AcnB. Acetylomic studies have identified acetylation at multiple lysine sites of both E. coli aconitase isozymes, but the impacts of acetylation on aconitases are unknown. In this study, we applied the genetic code expansion approach to produce 14 site-specifically acetylated aconitase variants. Enzyme assays and kinetic analyses showed that acetylation of AcnA K684 decreased the enzyme activity, while acetylation of AcnB K567 increased the enzyme activity. Further in vitro acetylation and deacetylation assays were …
Amorphization Of Pseudocapacitive T−Nb2O5 Accelerates Lithium Diffusivity As Revealed Using Tunable Isomorphic Architectures, Wessel Van Den Bergh, Sean Wechsler, Hasala Nadeesini Lokupitiya, Lauren Jarocha, Kwangnam Kim, James Chapman, Kyoung E. Kweon, Brandon C. Wood, Steve Heald, Morgan Stefik Phd
Amorphization Of Pseudocapacitive T−Nb2O5 Accelerates Lithium Diffusivity As Revealed Using Tunable Isomorphic Architectures, Wessel Van Den Bergh, Sean Wechsler, Hasala Nadeesini Lokupitiya, Lauren Jarocha, Kwangnam Kim, James Chapman, Kyoung E. Kweon, Brandon C. Wood, Steve Heald, Morgan Stefik Phd
Faculty Publications
Intercalationpseudocapacitancecan combinecapacitor-likepower densitieswith battery-likeenergy densities.Such surface-limitedbehaviorrequiresrapid diffusionwhere amorphizationcan increasesolid-statediffusivity.Here intercalationpseudoca-pacitivematerialswith tailoredextentsof amorphizationin T-Nb2O5are first reported.Amorphizationwas characterizedwithWAXS, XPS, XAFS, and EPR which suggesteda peroxide-rich(O22) surface that was consistentwith DFT predictions.A seriesof tunableisomorphicarchitecturesenabledcomparisonswhileindependentlyvaryingtransportparameters.Throughprocessof elimination,solid-statelithium diffusionwas identifiedas thedominantdiffusive-constraintdictatingthe maximumvoltagesweep rate for surface-limitedkinetics(vSLT), termed the Surface-LimitedThreshold(SLT). ThevSLTincreasedwith amorphizationhoweverstable cycling requiredcrystallineT-Nb2O5. A current-responsemodel using series-impedanceswell-matchedtheseobservations.This perspectiverevealedthat amorphizationof T-Nb2O5enhancedsolid-statediffusionby 12.2% and increasedsurface-limitationsby 17.0% (stablesamples).This approachenabledretaining95% lithiationcapacityat ~800mVs1(1,600C-rate equivalent).
Role Of Specialized Pro-Resolving Mediators In Reducing Neuroinflammation In Neurodegenerative Disorders, Jana Ponce, Arzu Ulu, Corrine Hanson, Erin Cameron-Smith, Jenna Wuebker, John Bertoni, Alfred Fisher, Ka-Chun Siu, Vivien Marmelat, Jiri Adamec, Danish Bhatti
Role Of Specialized Pro-Resolving Mediators In Reducing Neuroinflammation In Neurodegenerative Disorders, Jana Ponce, Arzu Ulu, Corrine Hanson, Erin Cameron-Smith, Jenna Wuebker, John Bertoni, Alfred Fisher, Ka-Chun Siu, Vivien Marmelat, Jiri Adamec, Danish Bhatti
Department of Biochemistry: Faculty Publications
Alzheimer’s disease (AD) and Parkinson’s disease (PD) are neurodegenerative disorders that affect millions of individuals worldwide. As incidence of these conditions increases with age, there will undoubtedly be an increased prevalence of cases in the near future. Neuroinflammation is a hallmark in the development and progression of neurodegenerative diseases and prevention or resolution of chronic neuroinflammation may represent a novel approach to treatment. The present review highlights the potential of the anti-inflammatory and pro-resolving effects of polyunsaturated fatty acid (PUFA)- derived mediators (Specialized Pro-resolving Mediators—SPM) in neurodegenerative disorders. PUFA-derived SPM are biosynthesized in response to chemicals produced from acute inflammatory …
Allosteric Determinants Of The Sars-Cov-2 Spike Protein Binding With Nanobodies: Examining Mechanisms Of Mutational Escape And Sensitivity Of The Omicron Variant, Gennady M. Verkhivker
Allosteric Determinants Of The Sars-Cov-2 Spike Protein Binding With Nanobodies: Examining Mechanisms Of Mutational Escape And Sensitivity Of The Omicron Variant, Gennady M. Verkhivker
Mathematics, Physics, and Computer Science Faculty Articles and Research
Structural and biochemical studies have recently revealed a range of rationally engineered nanobodies with efficient neutralizing capacity against the SARS-CoV-2 virus and resilience against mutational escape. In this study, we performed a comprehensive computational analysis of the SARS-CoV-2 spike trimer complexes with single nanobodies Nb6, VHH E, and complex with VHH E/VHH V nanobody combination. We combined coarse-grained and all-atom molecular simulations and collective dynamics analysis with binding free energy scanning, perturbation-response scanning, and network centrality analysis to examine mechanisms of nanobody-induced allosteric modulation and cooperativity in the SARS-CoV-2 spike trimer complexes with these nanobodies. By quantifying energetic and allosteric …
Escherichia Coli Alanyl-Trna Synthetase Maintains Proofreading Activity And Translational Accuracy Under Oxidative Stress, Arundhati Kavoor, Paul Kelly, Michael Ibba
Escherichia Coli Alanyl-Trna Synthetase Maintains Proofreading Activity And Translational Accuracy Under Oxidative Stress, Arundhati Kavoor, Paul Kelly, Michael Ibba
Biology, Chemistry, and Environmental Sciences Faculty Articles and Research
Aminoacyl-tRNA synthetases (aaRSs) are enzymes that synthesize aminoacyl-tRNAs to facilitate translation of the genetic code. Quality control by aaRS proofreading and other mechanisms maintains translational accuracy, which promotes cellular viability. Systematic disruption of proofreading, as recently demonstrated for alanyl-tRNA synthetase (AlaRS), leads to dysregulation of the proteome and reduced viability. Recent studies showed that environmental challenges such as exposure to reactive oxygen species can also alter aaRS synthetic and proofreading functions, prompting us to investigate if oxidation might positively or negatively affect AlaRS activity. We found that while oxidation leads to modification of several residues in Escherichia coli AlaRS, unlike …
Test-Driving The Next Generation Of Crispr Gene Editing, Olivia Gornichec, Kailey Mayer
Test-Driving The Next Generation Of Crispr Gene Editing, Olivia Gornichec, Kailey Mayer
Research on Capitol Hill
USU team Kailey, recent graduate of animal science, and Olivia, senior in biochemistry, have led and funded this project through a student grant. CRISPR has been making waves in the scientific community for its potential to help us edit genomes. However, that is just one of the known types of CRISPR, and other types aren’t in forms that are accessible to study. Kailey and Olivia have successfully cloned Type IV-B into a plasmid that can now be used to perform further research into what this system does. The two students never expected that, as undergrads, they would make a foundation-level …
Inhibition Of Biotin Carboxylase By Three Antibacterial Compounds, Matt Craft
Inhibition Of Biotin Carboxylase By Three Antibacterial Compounds, Matt Craft
LSU Doctoral Dissertations
The rise of antibacterial resistant bacteria is a major problem in the United States of America and around the world. Millions of patients are infected with antimicrobial resistant bacteria each year. Novel antibacterial agents are needed to combat the growing and present crisis. Acetyl-CoA carboxylase (ACC), the multi-subunit complex which catalyses the first committed step in fatty acid synthesis, is a validated target for antibacterial agents. However, there are at present, no commercially available antibiotics that target ACC. Ethyl 4-[[2-chloro-5-(phenylcarbamoyl)phenyl]sulfonylamino]benzoate (SABA1) is a compound that has been shown to have antibacterial properties against Pseudomonas aeruginosa and Escherichia coli. SABA1 inhibits …
Understanding The Impact Of Fat10 Overexpression On Liver Metabolism, Sharifa Love-Rutledge, Lauren Richardson
Understanding The Impact Of Fat10 Overexpression On Liver Metabolism, Sharifa Love-Rutledge, Lauren Richardson
Summer Community of Scholars (RCEU and HCR) Project Proposals
No abstract provided.
Docking And Molecular Dynamic Of Microalgae Compounds As Potential Inhibitors Of Beta-Lactamase, Roberto Pestana-Nobles, Yani Aranguren-Diaz, Elwi Machado-Sierra, Juvenal Yosa, Nataly J. Galan-Freyle,, Laura X. Sepulveda-Montano, Daniel G. Kuroda, Leonardo C. Pacheco-Londono
Docking And Molecular Dynamic Of Microalgae Compounds As Potential Inhibitors Of Beta-Lactamase, Roberto Pestana-Nobles, Yani Aranguren-Diaz, Elwi Machado-Sierra, Juvenal Yosa, Nataly J. Galan-Freyle,, Laura X. Sepulveda-Montano, Daniel G. Kuroda, Leonardo C. Pacheco-Londono
Faculty Publications
Bacterial resistance is responsible for a wide variety of health problems, both in children and adults. The persistence of symptoms and infections are mainly treated with beta-lactam antibiotics. The increasing resistance to those antibiotics by bacterial pathogens generated the emergence of extended-spectrum beta-lactamases (ESBLs), an actual public health problem. This is due to rapid mutations of bacteria when exposed to antibiotics. In this case, beta-lactamases are enzymes used by bacteria to hydrolyze the beta-lactam rings present in the antibiotics. Therefore, it was necessary to explore novel molecules as potential beta-lactamases inhibitors to find antibacterial compounds against infection caused by ESBLs. …
Whole-Genome Sequencing And Rna-Seq Reveal Differences In Genetic Mechanism For Flowering Response Between Weedy Rice And Cultivated Rice, Richard S. Garcia, Sapphire Coronejo, Jonathan Concepcion, Prasanta K. Subudhi
Whole-Genome Sequencing And Rna-Seq Reveal Differences In Genetic Mechanism For Flowering Response Between Weedy Rice And Cultivated Rice, Richard S. Garcia, Sapphire Coronejo, Jonathan Concepcion, Prasanta K. Subudhi
Faculty Publications
Flowering is a key agronomic trait that influences adaptation and productivity. Previous studies have indicated the genetic complexity associated with the flowering response in a photoinsensitive weedy rice accession PSRR-1 despite the presence of a photosensitive allele of a key flowering gene Hd1. In this study, we used whole-genome and RNA sequencing data from both cultivated and weedy rice to add further insights. The de novo assembly of unaligned sequences predicted 225 genes, in which 45 were specific to PSRR-1, including two genes associated with flowering. Comparison of the variants in PSRR-1 with the 3K rice genome (RG) dataset identified …
Structural And Biochemical Investigations Of The Initiation Of Dna Replication In Bacteriophage Lambda And Escherichia Coli, Jillian D. Chase
Structural And Biochemical Investigations Of The Initiation Of Dna Replication In Bacteriophage Lambda And Escherichia Coli, Jillian D. Chase
Dissertations, Theses, and Capstone Projects
Faithful transmission of genetic information is requisite for the propagation of all life. DNA replication in each of the three domains of life requires the separation of double stranded DNA (dsDNA) into single stranded DNA (ssDNA) which then serves as a template for genomic duplication of each original DNA strand. Initiation of replication events occurs by tightly regulated processes during which specialized proteins are loaded at a specific locus within the genome, termed the origin of replication, in preparation of bidirectional replication events. A replicative helicase must be loaded or assembled on both strands of DNA at the origin to …
Paddling Along The Voltage Gated Sodium Channel Galaxy With Sea Anemone Toxins: Structural Studies Of The Interaction Between The Paddle Motif From Nav1.5div And Sea Anemone Toxin, Adel K. Hussein
Dissertations, Theses, and Capstone Projects
Voltage gated sodium channels (VGSC) are membrane proteins that serve an important function in the central nervous system (CNS), peripheral nervous system (PNS), and cardiac muscles amongst others. The main function of VGSC is in the propagation of electrical signals by depolarizing excitable cells. Nine mammalian VGSC subtypes have been characterized, NaV1.1 – NaV1.9, that are expressed in a tissue specific manner, each with unique gating properties. Numerous diseases have been linked to defects in VGSC including epilepsy, mental retardation, long QT syndrome, and Brugada disease. Furthermore, these channels are one of the primary targets of …
An In Silico Approach To Investigate The Structural And Biochemical Basis Of The Rna Binding Functions Of Nucleolin, Avdar San
Dissertations, Theses, and Capstone Projects
Nucleolin (NCL) is a stress responsive multifunctional nucleolar protein and accounts for 10% of the total nucleolar protein content. NCL belongs to the class of RNA binding proteins (RBPs) that regulate many important cellular processes through their interactions with different RNA molecules. The dysregulation of RBPs and the RNA metabolism pathways they intersect is a known driver of tumorigenesis. NCL regulates ribosome biogenesis, chromatin remodeling, microRNA processing, and gene expression on multiple levels. The RNA-protein interactions of NCL are primarily driven by its four RNA binding domains (RBDs). NCL is known to interact with a growing list of primary-miRNA (pri-miRNA) …
Two Heads Are Better Than One: Current Landscape Of Integrating Qsp And Machine Learning, Tongli Zhang, Ioannis P. Androulakis, Peter Bonate, Limei Cheng, Tomáš Helikar, Jaimit Parikh, Christopher Rackauckas, Kalyanasundaram Subramanian, Carolyn R. Cho
Two Heads Are Better Than One: Current Landscape Of Integrating Qsp And Machine Learning, Tongli Zhang, Ioannis P. Androulakis, Peter Bonate, Limei Cheng, Tomáš Helikar, Jaimit Parikh, Christopher Rackauckas, Kalyanasundaram Subramanian, Carolyn R. Cho
Department of Biochemistry: Faculty Publications
Quantitative systems pharmacology (QSP) modeling is applied to address essential questions in drug development, such as the mechanism of action of a therapeutic agent and the progression of disease. Meanwhile, machine learning (ML) approaches also contribute to answering these questions via the analysis of multi-layer ‘omics’ data such as gene expression, proteomics, metabolomics, and high-throughput imaging. Furthermore, ML approaches can also be applied to aspects of QSP modeling. Both approaches are powerful tools and there is considerable interest in integrating QSP modeling and ML. So far, a few successful implementations have been carried out from which we have learned about …
Histone Post-Translational Modification Dysregulation Contributes To Toxicity In Amyotrophic Lateral Sclerosis Proteinopathy Models, Seth A. Bennett
Histone Post-Translational Modification Dysregulation Contributes To Toxicity In Amyotrophic Lateral Sclerosis Proteinopathy Models, Seth A. Bennett
Dissertations, Theses, and Capstone Projects
Amyotrophic Lateral Sclerosis (ALS) is the third most common adult onset neurodegenerative disorder worldwide. It is generally characterized by progressive paralysis starting at the limbs ultimately leading to death caused by respiratory failure. There is no cure and current treatments fail to slow the progression of the disease. As such, new treatment options are desperately needed. Epigenetic targets are an attractive possibility because they are reversible. Epigenetics refers to heritable changes in gene expression unrelated to changes in DNA sequence. Histone modifications, a main epigenetic mechanism, occur in many amino acid residues and include phosphorylation, acetylation, methylation as well as …
Role Of Metals In Human Immune System: Study Of Metal-Dependent Structural Changes Of S100a12 Protein, Aleksey Aleshintsev
Role Of Metals In Human Immune System: Study Of Metal-Dependent Structural Changes Of S100a12 Protein, Aleksey Aleshintsev
Dissertations, Theses, and Capstone Projects
S100A12 protein belongs to the S100 family of calcium-binding proteins and participates in the innate immune system. Antimicrobial proteins from the S100 family of the proteins (S100A12, S100A8/A9, etc.) are secreted and expressed by neutrophils during microbial infection and perform their antimicrobial activity through metal sequestration. While most S100 proteins function intracellularly, S100A12 is highly expressed and secreted into the extracellular space by neutrophils during infection. Sequestration of Zn2+ by S100A12 is aided by the nanomolar zinc binding affinity of the protein at neutral pH conditions, which is further enhanced upon calcium-binding. The Zn2+ binding scaffold in S100A12 …
Extracellular Secretion Of A Cutinase With Polyester-Degrading Potential By E. Coli Using A Novel Signal Peptide From Amycolatopsis Mediterranei, Yeqi Tan, Gemma K. Kinsella, Gary T. Henehan, Barry J. Ryan
Extracellular Secretion Of A Cutinase With Polyester-Degrading Potential By E. Coli Using A Novel Signal Peptide From Amycolatopsis Mediterranei, Yeqi Tan, Gemma K. Kinsella, Gary T. Henehan, Barry J. Ryan
Articles
Recent studies in this laboratory showed that an extracellular cutinase from A. mediterranei (AmCut) was able to degrade the plastics polycaprolactone and polybutylene succinate. Such plastics can be slow to degrade in soils due to a lack of efficient polyester degrading organisms. AmCut also showed potential for the biocatalytic synthesis of esters by reverse hydrolysis.
The gene for AmCut has an upstream leader sequence whose transcript is not present in the purified enzyme. In this study, we show using predictive modelling, that this sequence codes for an N-terminal signal peptide that directs transmembrane expression via the Sec secretion pathway.
E. …
Maternal Choline Supplementation And High-Fat Feeding Interact To Influence Dna Methylation In Offspring In A Time-Specific Manner, Hunter W. Korsmo, Bhoomi Dave, Steven E. Trasino, Anjana Saxena, Jia Liu, Jorge Matias Caviglia, Kaydine Edwards, Moshe Dembitzer, Shameera Sheeraz, Sarah Khaldi, Xinyin Jiang
Maternal Choline Supplementation And High-Fat Feeding Interact To Influence Dna Methylation In Offspring In A Time-Specific Manner, Hunter W. Korsmo, Bhoomi Dave, Steven E. Trasino, Anjana Saxena, Jia Liu, Jorge Matias Caviglia, Kaydine Edwards, Moshe Dembitzer, Shameera Sheeraz, Sarah Khaldi, Xinyin Jiang
Advanced Science Research Center
Maternal methyl donor supplementation during pregnancy has demonstrated lasting influence on offspring DNA methylation. However, it is unknown whether an adverse postnatal environment, such as high-fat (HF) feeding, overrides the influence of prenatal methyl donor supplementation on offspring epigenome. In this study, we examined whether maternal supplementation of choline (CS), a methyl donor, interacts with prenatal and postnatal HF feeding to alter global and site-specific DNA methylation in offspring. We fed wild-type C57BL/6J mouse dams a HF diet with or without CS throughout gestation. After weaning, the offspring were exposed to HF feeding for 6 weeks resembling a continued obesogenic …
Characterizing The Amino Acid Activation Center Of The Naturally Editing-Deficient Aminoacyl-Trna Synthetase Phers In Mycoplasma Mobile, Nien-Ching Han, Arundhati Kavoor, Michael Ibba
Characterizing The Amino Acid Activation Center Of The Naturally Editing-Deficient Aminoacyl-Trna Synthetase Phers In Mycoplasma Mobile, Nien-Ching Han, Arundhati Kavoor, Michael Ibba
Biology, Chemistry, and Environmental Sciences Faculty Articles and Research
To ensure correct amino acids are incorporated during protein synthesis, aminoacyl-tRNA synthetases (aaRSs) employ proofreading mechanisms collectively referred to as editing. Although editing is important for viability, editing-deficient aaRSs have been identified in host-dependent organisms. In Mycoplasma mobile, editing-deficient PheRS and LeuRS have been identified. We characterized the amino acid activation site of MmPheRS and identified a previously unknown hyperaccurate mutation, L287F. Additionally, we report that m-Tyr, an oxidation byproduct of Phe which is toxic to editing-deficient cells, is poorly discriminated by MmPheRS activation and is not subjected to editing. Furthermore, expressing MmPheRS and the hyperaccurate variants renders …
Ultrasound 96 Probe Device Protocol For Cancer Cell Treatment, Aisling Field, Brijesh K. Tiwari, James F. Curtin, Julie R M Mondala, Janith Wanigasekara
Ultrasound 96 Probe Device Protocol For Cancer Cell Treatment, Aisling Field, Brijesh K. Tiwari, James F. Curtin, Julie R M Mondala, Janith Wanigasekara
Articles
Ultrasound is a sound wave with frequencies ranging between 20 kHz and 20 MHz. Ultrasound is able to temporarily and repeatedly open the BBB safely and enhance chemotherapeutic delivery without adverse effects. This novel technique in drug delivery benefits from the powerful ability of ultrasound to produce cavitation activity. Cavitation is the generation and activity of gas-filled bubbles in a medium exposed to ultrasound. As the pressure wave passes through the media, gas bubbles expand at low pressure and contract at high pressure. This leads to oscillation which produces a circulating fluid flow known as microstreaming around the bubble with …