Recent Applications Of Quantitative Systems Pharmacology
And Machine Learning Models Across Diseases,
2021
University of Nebraska- Lincoln
Recent Applications Of Quantitative Systems Pharmacology And Machine Learning Models Across Diseases, Sara Sadat Aghamiri1, Rada Amin, Tomáš Helikar
Biochemistry -- Faculty Publications
Quantitative systems pharmacology (QSP) is a quantitative and mechanistic platform describing the phenotypic interaction between drugs, biological networks, and disease conditions to predict optimal therapeutic response. In this meta-analysis study, we review the utility of the QSP platform in drug development and therapeutic strategies based on recent publications (2019–2021). We gathered recent original QSP models and described the diversity of their applications based on therapeutic areas, methodologies, software platforms, and functionalities. The collection and investigation of these publications can assist in providing a repository of recent QSP studies to facilitate the discovery and further reusability of QSP models. Our review …
Purification And Initial Biochemical Characterization
Of Atp:Cob(I)Alamin Adenosyltransferase (Eutt)
Enzyme Of Salmonella Enterica,
2021
University of Nebraska-Lincoln
Purification And Initial Biochemical Characterization Of Atp:Cob(I)Alamin Adenosyltransferase (Eutt) Enzyme Of Salmonella Enterica, Nicole R. Buan, Jorge C. Escalante-Semerena
Biochemistry -- Faculty Publications
ATP:cob(I)alamin adenosyltransferase (EutT) of Salmonella enterica was overproduced and enriched to ~70% homogeneity, and its basic kinetic parameters were determined. Abundant amounts of EutT protein were produced, but all of it remained insoluble. Soluble active EutT protein (~70% homogeneous) was obtained after treatment with detergent. Under conditions in which cobalamin (Cbl) was saturating, Km(ATP) = 10 μM, kcat = 0.03 s–1, and Vmax = 54.5 nM min–1. Similarly, under conditions in which MgATPwas saturating,Km(Cbl)= 4.1μM, kcat = 0.06 s–1, andVmax …
Liquid And Semisolid Lubricant
Compositions , Methods Of Making , And Uses Thereof,
2021
Denton, TX
Liquid And Semisolid Lubricant Compositions , Methods Of Making , And Uses Thereof, Diana Berman, Kent Dean Chapman, Tervor Bradley Romsdahl, Edgar Benjamin Cahoon, Robert Earl Minto, Chunyu Zhang
Biochemistry -- Faculty Publications
Various liquid and semisolid lubricant compositions are provided, in particular lubricant compositions containing oil from the seeds of the Brassicaceae Orychophragmus violaceus, preferably those that have been esterified with one or more fatty acids such as palmitoleic acid, oleic acid, linoleic acid, lauric acid, palmitic acid, stearic acid, or a combination thereof. In various aspects, lubricant compositions are provided that include a petroleum or a synthetic base oil and about 40 % or less by weight of a liquid lubricant composition containing oil from the seeds of the Brassicaceae Orychophragmus violaceus preferably those that have been esterified with one …
The Simulation Experiment Description
Markup Language (Sed-Ml): Language
Specification For Level 1 Version 4,
2021
University of Washington
The Simulation Experiment Description Markup Language (Sed-Ml): Language Specification For Level 1 Version 4, Lucian P. Smith,, Frank T. Bergmann, Alan Garny, Tomáš Helikar, Jonathan Karr, David Nickerson,, Herbert Sauro, Dagmar Waltemath, Matthias König
Biochemistry -- Faculty Publications
Computational simulation experiments increasingly inform modern biological research, and bring with them the need to provide ways to annotate, archive, share and reproduce the experiments performed. These simulations increasingly require extensive collaboration among modelers, experimentalists, and engineers. The Minimum Information About a Simulation Experiment (MIASE) guidelines outline the information needed to share simulation experiments. SED-ML is a computer-readable format for the information outlined by MIASE, created as a community project and supported by many investigators and software tools. The first versions of SED-ML focused on deterministic and stochastic simulations of models. Level 1 Version 4 of SED-ML substantially expands these …
Mitochondrial Contact Site And Cristae Organizing System (Micos) Machinery Supports Heme Biosynthesis By Enabling Optimal Performance Of Ferrochelatase,
2021
University of Nebraska–Lincoln
Mitochondrial Contact Site And Cristae Organizing System (Micos) Machinery Supports Heme Biosynthesis By Enabling Optimal Performance Of Ferrochelatase, Jonathan V. Dietz, Mathilda M. Willoughby, Robert B. Piel, Teresa A. Ross, Iryna Bohovych, Hannah G. Addis, Jennifer L. Fox, William N. Lanzilotta, Harry A. Dailey, James A. Wohlschlegel, Amit R. Reddi, Amy E. Medlock, Oleh Khalimonchuk
Biochemistry -- Faculty Publications
Heme is an essential cofactor required for a plethora of cellular processes in eukaryotes. In metazoans the heme biosynthetic pathway is typically partitioned between the cytosol and mitochondria, with the first and final steps taking place in the mitochondrion. The pathway has been extensively studied and its biosynthetic enzymes structurally characterized to varying extents. Nevertheless, understanding of the regulation of heme synthesis and factors that influence this process in metazoans remains incomplete. Therefore, we investigated the molecular organization as well as the physical and genetic interactions of the terminal pathway enzyme, ferrochelatase (Hem15), in the yeast Saccharomyces cerevisiae. Biochemical and …
Oxidation Alters The Architecture Of The Phenylalanyl-Trna Synthetase Editing Domain To Confer Hyperaccuracy,
2021
Emory University
Oxidation Alters The Architecture Of The Phenylalanyl-Trna Synthetase Editing Domain To Confer Hyperaccuracy, Pooja Srinivas, Rebecca E. Steiner, Ian J. Pavelich, Ricardo Guerrera-Ferreira, Puneet Juneja, Michael Ibba, Christine M. Dunham
Biology, Chemistry, and Environmental Sciences Faculty Articles and Research
High fidelity during protein synthesis is accomplished by aminoacyl-tRNA synthetases (aaRSs). These enzymes ligate an amino acid to a cognate tRNA and have proofreading and editing capabilities that ensure high fidelity. Phenylalanyl-tRNA synthetase (PheRS) preferentially ligates a phenylalanine to a tRNAPhe over the chemically similar tyrosine, which differs from phenylalanine by a single hydroxyl group. In bacteria that undergo exposure to oxidative stress such as Salmonella enterica serovar Typhimurium, tyrosine isomer levels increase due to phenylalanine oxidation. Several residues are oxidized in PheRS and contribute to hyperactive editing, including against mischarged Tyr-tRNAPhe, despite these oxidized residues not …
Improving Healthspan Through Patient-Derived Artificial Organs From Induced Pluripotent Stem Cells And Two-Photon Polymerization,
2021
University of Pennsylvania
Improving Healthspan Through Patient-Derived Artificial Organs From Induced Pluripotent Stem Cells And Two-Photon Polymerization, Connor Espenshade
Protocols and Reports
Senescence, from the shortening of telomeres, accumulation of mutations, epigenetic hypomethylation, and other causes, begins an eventual cycle of decline in every patient. Stem cells disappear as a function of age, which in turn impairs cellular replication. Moreover, when fully differentiated cells are induced back into induced pluripotent stem cells (iPSCs), they not only revert to a state of pre-differentiation, but also to a younger cellular age. Their aging clocks turn back: their telomeres become longer and DNA methylation reverts back to an earlier age. It should therefore be possible to use iPSCs to replace the missing stem cells from …
Dual Control Of One Component Signaling: Mechanistic And Structural Insights Into El222 Active States,
2021
The Graduate Center, City University of New York
Dual Control Of One Component Signaling: Mechanistic And Structural Insights Into El222 Active States, Uthama Phani R. Edupuganti
Dissertations, Theses, and Capstone Projects
Photoreceptors play a crucial role in signal transduction as specialized proteins which sense light as environmental stimuli and transduce the signal to control of downstream functions. Here we focus our attention on one class of these proteins, the Light-Oxygen-Voltage (LOV) domain, which is sensitive to blue light via an internally-bound flavin chromophore. Since their initial discovery in plant phototropins, many details of their photochemistry, chromophore interactions, and use with a diverse set of functional effectors have been described. However, several key details, especially a comprehensive understanding of signaling mechanism and its regulation, still remain elusive due in part to the …
Conformation Of The Protein-Free Spliceosomal U2-U6 Snrna Complex And Remodeling By Mg2+ And Proteins,
2021
The Graduate Center, City University of New York
Conformation Of The Protein-Free Spliceosomal U2-U6 Snrna Complex And Remodeling By Mg2+ And Proteins, Huong Chu
Dissertations, Theses, and Capstone Projects
Splicing of precursor messenger RNA is an essential process in eukaryotes in which the non-coding regions (introns) are removed and coding regions (exons) ligated together to form a mature mRNA. This process is catalyzed by a multi-mega Dalton ribonucleoprotein complex called the spliceosome, which is assembled from five small nuclear ribonucleoproteins (snRNP) in the form of RNA-protein complexes (U1, U2, U4, U5 and U6) and hundreds of proteins. U2 and U6 small nuclear (sn)RNAs are the only snRNAs directly implicated in catalyzing the splicing of pre-mRNA, but assembly and rearrangement steps prior to catalysis require numerous proteins. Previous studies have …
Down The Iron Path: Mitochondrial Iron Homeostasis
And Beyond,
2021
University of Nebraska-Lincoln
Down The Iron Path: Mitochondrial Iron Homeostasis And Beyond, Jonathan Dietz, Jennifer L. Fox, Oleh Khalimonchuk
Biochemistry -- Faculty Publications
Cellular iron homeostasis and mitochondrial iron homeostasis are interdependent. Mitochondria must import iron to form iron–sulfur clusters and heme, and to incorporate these cofactors along with iron ions into mitochondrial proteins that support essential functions, including cellular respiration. In turn, mitochondria supply the cell with heme and enable the biogenesis of cytosolic and nuclear proteins containing iron–sulfur clusters. Impairment in cellular or mitochondrial iron homeostasis is deleterious and can result in numerous human diseases. Due to its reactivity, iron is stored and trafficked through the body, intracellularly, and within mitochondria via carefully orchestrated processes. Here, we focus on describing the …
A Multi-Approach And Multi-Scale Platform To
Model Cd4+ T Cells Responding To Infections,
2021
University of Nebraska-Lincoln
A Multi-Approach And Multi-Scale Platform To Model Cd4+ T Cells Responding To Infections, Kenneth Y. Wertheim, Bhanwar Lal Puniya, Alyssa La Fleur, Ab Rauf Shah, Matteo Barberis, Tomáš Helikar
Biochemistry -- Faculty Publications
Immune responses rely on a complex adaptive system in which the body and infections interact at multiple scales and in different compartments. We developed a modular model of CD4+ T cells, which uses four modeling approaches to integrate processes at three spatial scales in different tissues. In each cell, signal transduction and gene regulation are described by a logical model, metabolism by constraint-based models. Cell population dynamics are described by an agent-based model and systemic cytokine concentrations by ordinary differential equations. A Monte Carlo simulation algorithm allows information to flow efficiently between the four modules by separating the time scales. …
Toward Sustainable Production Of Value-Added Bioenergy And Industrial Oils In Oilseed And Biomass Feedstocks,
2021
University of Nebraska-Lincoln
Toward Sustainable Production Of Value-Added Bioenergy And Industrial Oils In Oilseed And Biomass Feedstocks, Kiyoul Park, Sanju A. Sanjaya, Truyen Quach, Edgar B. Cahoon
Biochemistry -- Faculty Publications
Plant fatty acids are used for food, feed, fuel, and industrial materials. Structurally and chemically diverse fatty acids, referred to as unusual or specialized fatty acids, are found in the seed oils of diverse plant species. Many unusual fatty acids have potential use as alternative and renewable sources of biofuels and bio-based industrial feedstocks due to their variant structures' physical or functional properties. Oils enriched in these fatty acids can increase the value of oilseed crops and provide co-products that can be readily extracted from lignocellulosic materials in biomass crops. Here, we describe recent progress on strategies for enhancement of …
Vascular Endothelial Senescence:
Pathobiological Insights, Emerging
Long Noncoding Rna Targets,
Challenges And Therapeutic
Opportunities,
2021
University of Nebraska-Lincoln
Vascular Endothelial Senescence: Pathobiological Insights, Emerging Long Noncoding Rna Targets, Challenges And Therapeutic Opportunities, Xinghui Sun, Mark W. Feinberg
Biochemistry -- Faculty Publications
Cellular senescence is a stable form of cell cycle arrest in response to various stressors. While it serves as an endogenous pro-resolving mechanism, detrimental effects ensue when it is dysregulated. In this review, we introduce recent advances for cellular senescence and inflammaging, the underlying mechanisms for the reduction of nicotinamide adenine dinucleotide in tissues during aging, new knowledge learned from p16 reporter mice, and the development of machine learning algorithms in cellular senescence. We focus on pathobiological insights underlying cellular senescence of the vascular endothelium, a critical interface between blood and all tissues. Common causes and hallmarks of endothelial senescence …
Molecular Dynamics Simulations Provide Insight Into Stability Of Hyperthermophilic Endoglucanases,
2021
Stephen F Austin State University
Molecular Dynamics Simulations Provide Insight Into Stability Of Hyperthermophilic Endoglucanases, Logan E. Sheffield
Electronic Theses and Dissertations
Endoglucanases play a key role in the industrial production of bioethanol, but the most efficient method requires the utilization of high temperatures and is currently limited by the thermostability of endoglucanases. For this reason, it would be beneficial to discover more high-efficiency, thermostable enzymes to utilize in the hydrolytic process. In this study molecular dynamics simulations were performed on structurally similar endoglucanases with varying levels of thermostability to gain insight on what factors contribute to thermostability in endoglucanases. RMSD, RMSF, PCA, hydrogen bonding and salt bridges were analyzed. Finally, protein energy networks were constructed from nonbonded interaction potentials and analysis …
Computational Prediction Of Mutagenesis In Glycine Max Rubisco Activase Monomer For Increased Thermal Stability,
2021
Washington University in St. Louis
Computational Prediction Of Mutagenesis In Glycine Max Rubisco Activase Monomer For Increased Thermal Stability, Catherine B. Emanuel, Hamza Haq '21, Vasanth Ramesh '21, Jaden Wang '21, Angela Ahrendt, Sarah Stainbrook
Student Publications & Research
No abstract provided.
Genetic Engineering Of Lesquerella With Increased Ricinoleic
Acid Content In Seed Oil,
2021
U.S. Department of Agriculture
Genetic Engineering Of Lesquerella With Increased Ricinoleic Acid Content In Seed Oil, Grace Q. Chen, Kumiko Johnson, Tara J. Nazarenus, Grisel Ponciano, Eva Morales, Edgar B. Cahoon
Biochemistry -- Faculty Publications
Seeds of castor (Ricinus communis) are enriched in oil with high levels of the industrially valuable fatty acid ricinoleic acid (18:1OH), but production of this plant is limited because of the cooccurrence of the ricin toxin in its seeds. Lesquerella (Physaria fendleri) is being developed as an alternative industrial oilseed because its seeds accumulate lesquerolic acid (20:1OH), an elongated form of 18:1OH in seed oil which lacks toxins. Synthesis of 20:1OH is through elongation of 18:1OH by a lesquerella elongase, PfKCS18. Oleic acid (18:1) is the substrate for 18:1OH synthesis, but it is also used by fatty acid desaturase 2 …
Multi-Strategy Engineering Greatly Enhances Provitamin
A Carotenoid Accumulation And Stability In Arabidopsis Seeds,
2021
Cornell University
Multi-Strategy Engineering Greatly Enhances Provitamin A Carotenoid Accumulation And Stability In Arabidopsis Seeds, Tianhu Sun, Qinlong Zhu, Ziqing Wei, Lauren A. Owens, Tara Fish, Hyojin Kim, Theodore W. Thannhauser, Edgar B. Cahoon, Li Li
Biochemistry -- Faculty Publications
Staple grains with low levels of provitamin A carotenoids contribute to the global prevalence of vitamin A deficiency and therefore are the main targets for provitamin A biofortification. However, carotenoid stability during both seed maturation and postharvest storage is a serious concern for the full benefits of carotenoid biofortified grains. In this study, we utilized Arabidopsis as a model to establish carotenoid biofortification strategies in seeds. We discovered that manipulation of carotenoid biosynthetic activity by seed-specific expression of Phytoene synthase (PSY) increases both provitamin A and total carotenoid levels but the increased carotenoids are prone to degradation during …
Integrative Computational Approach Identifies Drug Targets In
Cd4+ T-Cell-Mediated Immune Disorders,
2021
University of Nebraska-Lincoln
Integrative Computational Approach Identifies Drug Targets In Cd4+ T-Cell-Mediated Immune Disorders, Bhanwar L. Puniya, Rada Amin, Bailee Lichter, Robert Moore, Alex Ciurej, Sydney J. Bennett, Ab Rauf Shah, Matteo Barberis, Tomáš Helikar
Biochemistry -- Faculty Publications
CD4+ T cells provide adaptive immunity against pathogens and abnormal cells, and they are also associated with various immunerelated diseases. CD4+ T cells’ metabolism is dysregulated in these pathologies and represents an opportunity for drug discovery and development. Genome-scale metabolic modeling offers an opportunity to accelerate drug discovery by providing high-quality information about possible target space in the context of a modeled disease. Here, we develop genome-scale models of naïve, Th1, Th2, and Th17 CD4+ T-cell subtypes to map metabolic perturbations in rheumatoid arthritis, multiple sclerosis, and primary biliary cholangitis. We subjected these models to in silico …
Europium Sulfide Nanoprobes Predict Antiretroviral Drug
Delivery Into Hiv-1 Cell And Tissue Reservoirs,
2021
University of Nebraska Medical Center
Europium Sulfide Nanoprobes Predict Antiretroviral Drug Delivery Into Hiv-1 Cell And Tissue Reservoirs, Jonathan Herskovitz, Mahmudul Hasan, Jatin Machhi, Insiya Mukadam, Brendan M. Ottemann, James R. Hilaire, Christopher Woldstad, Joellyn Mcmillan, Yutong Liu, Javier Seravalli, Anandakumar Sarella, Howard E. Gendelman, Bhavesh D. Kevadiya
Biochemistry -- Faculty Publications
Background: Delivery of long-acting nanoformulated antiretroviral drugs (ARVs) to human immunodeficiency virus type one cell and tissue reservoirs underlies next generation antiretroviral therapeutics. Nanotheranostics, comprised of trackable nanoparticle adjuncts, can facilitate ARV delivery through real-time drug tracking made possible through bioimaging platforms. Methods: To model HIV-1 therapeutic delivery, europium sulfide (EuS) nanoprobes were developed, characterized and then deployed to cells, tissues, and rodents. Tests were performed with nanoformulated rilpivirine (NRPV), a non-nucleoside reverse transcriptase inhibitor (NNRTI) used clinically to suppress or prevent HIV-1 infection. First, CD4+ T cells and monocyte-derived macrophages were EuS-treated with and without endocytic blockers to identify …
Crispr/Cas9-Induced Fad2 And Rod1
Mutations Stacked With Fae1 Confer
High Oleic Acid Seed Oil In
Pennycress (Thlaspi Arvense L.),
2021
Illinois State University
Crispr/Cas9-Induced Fad2 And Rod1 Mutations Stacked With Fae1 Confer High Oleic Acid Seed Oil In Pennycress (Thlaspi Arvense L.), Brice A. Jarvis, Trevor B. Romsdahl, Michaela G. Mcginn, Tara J. Nazarenus, Edgar B. Cahoon, Kent D. Chapman, John C. Sedbrook
Biochemistry -- Faculty Publications
Pennycress (Thlaspi arvense L.) is being domesticated as an oilseed cash cover crop to be grown in the off-season throughout temperate regions of the world. With its diploid genome and ease of directed mutagenesis using molecular approaches, pennycress seed oil composition can be rapidly tailored for a plethora of food, feed, oleochemical and fuel uses. Here, we utilized Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 technology to produce knockout mutations in the FATTY ACID DESATURASE2 (FAD2) and REDUCED OLEATE DESATURATION1 (ROD1) genes to increase oleic acid content. High oleic acid (18:1) oil is valued for its oxidative stability that is …
