Acyltransferases And Methods Of
Using,
2019
Lincoln, NE
Acyltransferases And Methods Of Using, Edgar Cahoon, Umidjon Iskandarov, Hae Jin Kim, Jillian Collins-Silva
Department of Biochemistry: Faculty Publications
Provided herein are novel acyltransferases and methods of using such novel acyltransferases in making medium - chain fatty acids.
Charting A New Frontier Of Science By Integrating Mathematical Modeling To Understand And Predict Complex Biological Systems,
2019
University of Notre Dame
Charting A New Frontier Of Science By Integrating Mathematical Modeling To Understand And Predict Complex Biological Systems, Katharine White, Kira Mcentire, Nicole R. Buan, Kingshuk Ghosh, Lecia Robinson, Elisar Barbar
Department of Biochemistry: Faculty Publications
Biological systems are staggeringly complex. To untangle this complexity and make predictions about biological systems is a continuous goal of biological research. One approach to achieve these goals is to emphasize the use of quantitative measures of biological processes. Advances in quantitative biology data collection and analysis across scales (molecular, cellular, organismal, ecological) has transformed how we understand, categorize, and predict complex biological systems. Simultaneously, thanks to increased computational power, mathematicians, engineers and physical scientists -- collectively termed theoreticians -- have developed sophisticated models of biological systems at different scales. But there is still a disconnect between the two fields. …
Fatty Acid Transporter 2 Reprograms Neutrophils In Cancer,
2019
The Wistar Institute, Philadelphia
Fatty Acid Transporter 2 Reprograms Neutrophils In Cancer, Filippo Veglia, Vladimir A. Tyurin, Maria Blasi, Alessandra De Leo, Andrew Kossenkov, Laxminarasimha Donthireddy, To Tsun Ki Jerrick, Zach Schug, Subhasree Basu, Fang Wang, Emanuela Ricciotti, Concetta C. Dirusso, Maureen E. Murphy, Robert H. Vonderheide, Paul M. Lieberman, Charles Mulligan, Brian Nam, Neil Hockstein, Gregory Masters, Michael Guarino, Cindy Lin, Yulia Nefedova, Paul N. Black, Valerian E, Kagan, Dmitry Gabrilovich
Department of Biochemistry: Faculty Publications
Polymorphonuclear myeloid derived suppressor cells (PMN-MDSC) are pathologically activated neutrophils that are critically important for the regulation of immune responses in cancer. They contribute to the failure of cancer therapies and are associated with poor clinical outcomes. Despite the recent advances in understanding of the PMN-MDSC biology, the mechanisms responsible for pathological activation of neutrophils are not well defined, which limits selective targeting of these cells. Here, we report that mouse and human PMN-MDSC exclusively up-regulate fatty acid transporter protein 2 (FATP2). Over-expression of FATP2 in PMN-MDSC was controlled by GM-CSF, through the activation of STAT5 transcription factor. Deletion of …
Arsenite Exposure Suppresses Adipogenesis, Mitochondrial Biogenesis And Thermogenesis Via Autophagy Inhibition In Brown Adipose Tissue,
2019
University of Nebraska- Lincoln & University of Wisconsin School of Medicine and Public Health
Arsenite Exposure Suppresses Adipogenesis, Mitochondrial Biogenesis And Thermogenesis Via Autophagy Inhibition In Brown Adipose Tissue, Jiyoung Bae, Yura Jang, Heejeong Kim, Kalika Mahato, Cameron Schaecher, Issac M. Kim, Eunju Kim, Seung-Hyun Ro
Department of Biochemistry: Faculty Publications
Arsenite, a trivalent form of arsenic, is an element that occurs naturally in the environment. Humans are exposed to high dose of arsenite through consuming arsenite-contaminated drinking water and food, and the arsenite can accumulate in the human tissues. Arsenite induces oxidative stress, which is linked to metabolic disorders such as obesity and diabetes. Brown adipocytes dissipating energy as heat have emerging roles for obesity treatment and prevention. therefore, understanding the pathophysiological role of brown adipocytes can provide effective strategies delineating the link between arsenite exposure and metabolic disorders. Our study revealed that arsenite significantly reduced differentiation of murine brown …
The Structure Of Pila From Acinetobacter Baumannii Ab5075 Suggests A Mechanism For Functional Specialization In
Acinetobacter Type Iv Pili,
2019
University of Nebraska-Lincoln
The Structure Of Pila From Acinetobacter Baumannii Ab5075 Suggests A Mechanism For Functional Specialization In Acinetobacter Type Iv Pili, Leslie A. Ronish, Erik Lillehoj, James K. Fields, Eric J. Sundberg, Kurt Piepenbrink
Department of Biochemistry: Faculty Publications
Type IV pili (T4P) are bacterial appendages composed of protein subunits, called pilins, noncovalently assembled into helical fibers. T4P are essential, in many bacterial species, for processes as diverse as twitching motility, natural competence, biofilm or microcolony formation, and host cell adhesion. The genes encoding type IV pili are found universally in the Gram-negative, aerobic, nonflagellated, and pathogenic coccobacillus Acinetobacter baumannii, but there is considerable variation in PilA, the major protein subunit, both in amino acid sequence and in glycosylation patterns. Here we report the X-ray crystal structure of PilA from AB5075, a recently characterized, highly virulent isolate, at …
Preconditioning Of The Tumor Microenvironment By Means Of Low Dose Chemotherapies For An Effective Immunotherapy Of Breast Cancer,
2019
Virginia Commonwealth University
Preconditioning Of The Tumor Microenvironment By Means Of Low Dose Chemotherapies For An Effective Immunotherapy Of Breast Cancer, Hussein F. Aqbi
Theses and Dissertations
Breast cancer mortality is mainly due to distant recurrence of the disease arising from dormant tumor cells established by cancer therapies. Patients who initially respond to cancer therapies often succumb to distant recurrence of the disease. It is not clear why people with the same type of breast cancer respond to treatments differently; some escape from dormancy and relapse earlier than others. In addition, some tumor clones respond to immunotherapy while others do not. We investigated how autophagy plays a role in accelerating or delaying recurrence of neu overexpressing mouse mammary carcinoma (MMC) following adriamycin (ADR) treatment, and in affecting …
Methanogens: Pushing The Boundaries Of Biology,
2018
University of Nebraska-Lincoln
Methanogens: Pushing The Boundaries Of Biology, Nicole R. Buan
Department of Biochemistry: Faculty Publications
Methanogens are anaerobic archaea that grow by producing methane gas. These microbes and their exotic metabolism have inspired decades of microbial physiology research that continues to push the boundary of what we know about how microbes conserve energy to grow. The study of methanogens has helped to elucidate the thermodynamic and bioenergetics basis of life, contributed our understanding of evolution and biodiversity, and has garnered an appreciation for the societal utility of studying trophic interactions between environmental microbes, as methanogens are important in microbial conversion of biogenic carbon into methane, a high-energy fuel. This review discusses the theoretical basis for …
Methanogens: Pushing The Boundaries Of Biology,
2018
University of Nebraska-Lincoln
Methanogens: Pushing The Boundaries Of Biology, Nicole R. Buan
Department of Biochemistry: Faculty Publications
Methanogens are anaerobic archaea that grow by producing methane gas. These microbes and their exotic metabolism have inspired decades of microbial physiology research that continues to push the boundary of what we know about how microbes conserve energy to grow. The study of methanogens has helped to elucidate the thermodynamic and bioenergetics basis of life, contributed our understanding of evolution and biodiversity, and has garnered an appreciation for the societal utility of studying trophic interactions between environmental microbes, as methanogens are important in microbial conversion of biogenic carbon into methane, a high-energy fuel. This review discusses the theoretical basis for …
Intra- And Inter-Molecular Signaling In A Cardiac Connexin: Role Of Cytoplasmic Domain Dimerization And Phosphorylation,
2018
University of Nebraska Medical Center
Intra- And Inter-Molecular Signaling In A Cardiac Connexin: Role Of Cytoplasmic Domain Dimerization And Phosphorylation, Andrew J. Trease
Theses & Dissertations
As critical mediators of cell-to-cell communication, gap junctions (GJs) are comprised of membrane channels that directly link the cytoplasm of adjacent coupled cells thereby allowing for the passage of ions, small metabolites, and secondary messengers. Each channel is formed by the apposition of two connexons from adjacent cells, each composed of six connexin (Cx) proteins. Each GJ channel functions to promote signal propagation and synchronization of cells and tissues in organs. Furthermore, GJs are essential for proper propagation of cardiac action potentials from one cell to the next, leading to the coordinated contraction and relaxation of heart muscle powering circulation. …
Molecular Fossils From Phytoplankton Reveal Secular Pco2 Trend Over The Phanerozoic,
2018
Utrecht University
Molecular Fossils From Phytoplankton Reveal Secular Pco2 Trend Over The Phanerozoic, Caitlyn R. Witkowski, Johan W. H. Weijers, Brian S. Blais, Stefan Schouten, Jaap S. Sinninghe Damsté
Science and Technology Department Faculty Journal Articles
Past changes in the atmospheric concentration of carbon dioxide (PCO2) have had a major impact on earth system dynamics; yet, reconstructing secular trends of past PCO2 remains a prevalent challenge in paleoclimate studies. The current long-term PCO2reconstructions rely largely on the compilation of many different proxies, often with discrepancies among proxies, particularly for periods older than 100 million years (Ma). Here, we reconstructed Phanerozoic PCO2 from a single proxy: the stable carbon isotopic fractionation associated with photosynthesis (Ɛp) that increases as PCO2 increases. This concept has been widely applied to alkenones, but here, we …
A Crispr Platform For Rapid And Inducible Genome Editing In Human Non-Small Cell Lung Cancer Cells,
2018
Murray State University
A Crispr Platform For Rapid And Inducible Genome Editing In Human Non-Small Cell Lung Cancer Cells, Lloyd Bartley
Posters-at-the-Capitol
Non-small cell lung cancer (NSCLC) accounts for about 85% of lung cancer, which is the leading cause of cancer death in the world. High mortality rate associated with NSCLC is partially attributed to the limited understanding of NSCLC as well as ineffective therapeutic treatments. The initiation and progression of NSCLC involves genetic changes leading to alterations in the control of tissue development and homeostatic maintenance. Better knowledge about these genetic abnormalities is imperative for developing new chemotherapeutic drugs for NSCLC. Recent research demonstrates that the expression of paraoxonase 2 (PON2), a lactonase/arylesterase with anti-oxidant properties, are markedly enhanced in cancer …
Combined High-Speed Single Particle Tracking Of Membrane Proteins And Super-Resolution Of Membrane-Associated Structures,
2018
University of New Mexico
Combined High-Speed Single Particle Tracking Of Membrane Proteins And Super-Resolution Of Membrane-Associated Structures, Hanieh Mazloom Farsibaf, Keith A. Lidke
Shared Knowledge Conference
Many experiments have shown that the diffusive motion of lipids and membrane proteins are slower on the cell surface than those in artificial lipid bilayers or blebs. One hypothesis that may partially explain this mystery is the effect of the cytoskeleton structures on the protein dynamics. A model proposed by Kusumi [1] is the Fence-Picket Model which describes the cell membrane as a set of compartment regions, each ~ 10 to 200 nm in size, created by direct or indirect interaction of lipids and proteins with actin filaments just below the membrane. To test this hypothesis, we have assembled a …
Combining Mass Spectrometry And Nmr Improves Metabolite Detection And Annotation,
2018
University of Nebraska - Lincoln
Combining Mass Spectrometry And Nmr Improves Metabolite Detection And Annotation, Fatema Bhinderwala, Nishikant Wase, Concetta Dirusso, Robert Powers
Department of Biochemistry: Faculty Publications
Despite inherent complementarity, nuclear magnetic resonance spectroscopy (NMR) and mass spectrometry (MS) are routinely separately employed to characterize metabolomics samples. More troubling is the erroneous view that metabolomics is better served by exclusively utilizing MS. Instead, we demonstrate the importance of combining NMR and MS for metabolomics by using small chemical compound-treatments of Chlamydomonas reinhardtii as an illustrative example. A total of 102 metabolites were detected (82 by GC-MS, 20 by NMR and 22 by both techniques). Out of these 47 metabolites of interest were identified, where 14 metabolites were uniquely identified by NMR and 16 metabolites were uniquely identified …
Mouse Genome-Wide Association Studies And Systems Genetics Uncover The Genetic Architecture Associated With Hepatic Pharmacokinetic And Pharmacodynamic Properties Of A Constrained Ethyl Antisense Oligonucleotide Targeting Malat1,
2018
Carlsbad, California
Mouse Genome-Wide Association Studies And Systems Genetics Uncover The Genetic Architecture Associated With Hepatic Pharmacokinetic And Pharmacodynamic Properties Of A Constrained Ethyl Antisense Oligonucleotide Targeting Malat1, Elaine Pirie, Shayoni Ray, Calvin Pan, Wuxia Fu, Andrew F. Powers, Danielle Polikoff, Colton M. Miller, Katrina M. Kudrna, Edward N. Harris, Aldons J. Lusis, Rosanne M. Crooke, Richard G. Lee
Department of Biochemistry: Faculty Publications
Antisense oligonucleotides (ASOs) have demonstrated variation of efficacy in patient populations. This has prompted our investigation into the contribution of genetic architecture to ASO pharmacokinetics (PK) and pharmacodynamics (PD). Genome wide association (GWA) and transcriptomic analysis in a hybrid mouse diversity panel (HMDP) were used to identify and validate novel genes involved in the uptake and efficacy of a single dose of a Malat1 constrained ethyl (cEt) modified ASO. The GWA of the HMDP identified two significant associations on chromosomes 4 and 10 with hepatic Malat1 ASO concentrations. Stabilin 2 (Stab2) and vesicle associated membrane protein 3 ( …
The Distinctive Regulatory Mechanisms Of Bacterial Acetyl-Coa Carboxylase,
2018
Louisiana State University and Agricultural and Mechanical College
The Distinctive Regulatory Mechanisms Of Bacterial Acetyl-Coa Carboxylase, Alexandra Leigh Evans
LSU Doctoral Dissertations
Metabolic Regulation is a complex system used to control cellular metabolism in response to conditions in the cell’s environment. For most enzymes, the cell can rely upon a minimal amount of regulation; however, critical enzymes, such as acetyl-CoA carboxylase, must be regulated at multiple levels. Acetyl-CoA carboxylase catalyzes the first committed step in fatty acid synthesis. In bacteria, acetyl-CoA carboxylase forms a complex of three subunits–biotin carboxylase, biotin carboxyl carrier protein, and carboxyltransferase–which catalyze the carboxylation of acetyl-CoA to form malonyl-CoA via two half-reactions. In the first half-reaction, biotin covalently linked to biotin carboxyl carrier protein is carboxylated by biotin …
Supercharged Models Of Intrinsically Disordered Proteins And Their Utility In Sensing,
2018
CUNY Graduate Center
Supercharged Models Of Intrinsically Disordered Proteins And Their Utility In Sensing, Peter J. Schnatz
Dissertations, Theses, and Capstone Projects
In this thesis I show that greatly increasing the magnitude of a protein’s net charge using surface supercharging transforms that protein into a ligand-gated or counterion-gated conformational molecular switch. To demonstrate this I first modified the designed helical bundle hemoprotein H4 using simple molecular modeling, creating a highly charged protein which both unfolds reversibly at low ionic strength and undergoes the ligand-induced folding transition commonly observed in signal transduction by intrinsically disordered proteins in biology. Due to the high surface charge density, ligand binding to this protein is allosterically activated by low concentrations of divalent cations and the polyamine spermine. …
Induction Of Oil Accumulation By Heat Stress Is Metabolically Distinct From N Stress In The Green Microalgae Coccomyxa Subellipsoidea C169,
2018
University of Nebraska-Lincoln
Induction Of Oil Accumulation By Heat Stress Is Metabolically Distinct From N Stress In The Green Microalgae Coccomyxa Subellipsoidea C169, James W. Allen, Rahul Tevatia, Yaşar Demirel, Concetta C. Dirusso, Paul N. Black
Department of Biochemistry: Faculty Publications
Algae are often promoted as feedstock organisms to produce a sustainable petroleum fossil fuel alternative. However, to induce lipid accumulation most often requires a severe stress that is difficult to induce in large batch cultures. The objective of this study is to analyze and mathematically model heat stress on growth, chlorophyll content, triacylglyceride, and starch synthesis in algae. We initially screened 30 algal species for the most pronounced induction of lipid droplets from heat stress using confocal microscopy and mass spectroscopy techniques. One species, Coccomyxa subellipsoidea C169, was selected and subjected to further biochemical analyses using a jacketed bioreactor amended …
Identification Of Biologically Essential Nodes Via Determinative Power In Logical Models Of Cellular Processes,
2018
University of Nebraska at Omaha
Identification Of Biologically Essential Nodes Via Determinative Power In Logical Models Of Cellular Processes, Trevor Pentzien, Bhanwar L. Puniya, Tomas Helikar, Mihaela T. Matache
Department of Biochemistry: Faculty Publications
A variety of biological networks can bemodeled as logical or Boolean networks. However, a simplification of the reality to binary states of the nodes does not ease the difficulty of analyzing the dynamics of large, complex networks, such as signal transduction networks, due to the exponential dependence of the state space on the number of nodes. This paper considers a recently introduced method for finding a fairly small subnetwork, representing a collection of nodes that determine the states of most other nodes with a reasonable level of entropy. The subnetwork contains the most determinative nodes that yield the highest information …
Fars2 Mutations Presenting With Pure Spastic Paraplegia And Lesions Of The Dentate Nuclei,
2018
Cedars-Sinai Medical Center
Fars2 Mutations Presenting With Pure Spastic Paraplegia And Lesions Of The Dentate Nuclei, Supreet K. Sahai, Rebecca E. Steiner, Margaret G. Au, John M. Graham, Norikio Salamon, Michael Ibba, Tyler M. Pierson
Biology, Chemistry, and Environmental Sciences Faculty Articles and Research
Mutations in FARS2, the gene encoding the mitochondrial phenylalanine‐tRNA synthetase (mtPheRS), have been linked to a range of phenotypes including epileptic encephalopathy, developmental delay, and motor dysfunction. We report a 9‐year‐old boy with novel compound heterozygous variants of FARS2, presenting with a pure spastic paraplegia syndrome associated with bilateral signal abnormalities in the dentate nuclei. Exome sequencing identified a paternal nonsense variant (Q216X) lacking the catalytic core and anticodon‐binding regions, and a maternal missense variant (P136H) possessing partial enzymatic activity. This case confirms and expands the phenotype related to FARS mutations with regards to clinical presentation and neuroimaging findings.
The Regulation Of Notch Signaling By Src Kinase And Polyphenolic Compounds,
2018
Boise State University
The Regulation Of Notch Signaling By Src Kinase And Polyphenolic Compounds, Bryce David Lafoya
Boise State University Theses and Dissertations
Cellular signaling pathways provide cells with the means to sense their environment and communicate with other cells. The Notch signaling pathway is comprised of a set of protein machines which work in unison to coordinate cellular processes in response to stimuli coming from neighboring cells and changing microenvironmental conditions. Notch signaling is an important mode of cellular communication which is crucial to many processes involved in development and disease. During Notch activation, information about the extracellular environment is fed into the cell and relayed to the nucleus through a number of biochemical processes. The information-rich messages carried by Notch signaling …
