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Allosteric Mechanism Of The Circadian Protein Vivid Resolved Through Markov State Model And Machine Learning Analysis, Hongyu Zhou, Zheng Dong, Gennady M. Verkhivker, Brian D. Zoltowski, Peng Tao 2019 Southern Methodist University

Allosteric Mechanism Of The Circadian Protein Vivid Resolved Through Markov State Model And Machine Learning Analysis, Hongyu Zhou, Zheng Dong, Gennady M. Verkhivker, Brian D. Zoltowski, Peng Tao

Mathematics, Physics, and Computer Science Faculty Articles and Research

The fungal circadian clock photoreceptor Vivid (VVD) contains a photosensitive allosteric light, oxygen, voltage (LOV) domain that undergoes a large N-terminal conformational change. The mechanism by which a blue-light driven covalent bond formation leads to a global conformational change remains unclear, which hinders the further development of VVD as an optogenetic tool. We answered this question through a novel computational platform integrating Markov state models, machine learning methods, and newly developed community analysis algorithms. Applying this new integrative approach, we provided a quantitative evaluation of the contribution from the covalent bond to the protein global conformational change, and proposed an ...


The Multifaceted Roles Of Cd177 In Mammary Tissue Development And Breast Cancer, Paige Nicole Kluz 2018 University of Iowa

The Multifaceted Roles Of Cd177 In Mammary Tissue Development And Breast Cancer, Paige Nicole Kluz

Theses and Dissertations

Aiming to identify immune molecules with a novel function in cancer pathogenesis, we found the cluster of differentiation 177 (CD177), a known neutrophil antigen, expression to be positively correlated with relapse-free (RFS), metastasis-free (MFS) or overall survival (OS) in several solid cancers including those from breast, prostate, cervix, and lung. To study the role of CD177 in breast cancer, we generated a total body Cd177 knockout mouse. These mice had no profound phenotype at 3 - months of age or younger. The only phenotype found at this age was reduced peripheral neutrophil counts, but no difference in their ability to clear ...


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 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 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 expand ...


A Crispr Platform For Rapid And Inducible Genome Editing In Human Non-Small Cell Lung Cancer Cells, Lloyd Bartley 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 ...


Combined High-Speed Single Particle Tracking Of Membrane Proteins And Super-Resolution Of Membrane-Associated Structures, Hanieh Mazloom Farsibaf, Keith A. Lidke 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 high-speed ...


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 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

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 (Vamp3) were identified ...


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 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

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 ...


Phenotypic Screening Identifies Brefeldin A/Ascotoxin As An Inducer Of Lipid Storage In The Algae Chlamydomonas Reinhardtii, Nishikant Wase, Boqiang Tu, Paul N. Black, Concetta C. DiRusso 2018 University of Nebraska-Lincoln

Phenotypic Screening Identifies Brefeldin A/Ascotoxin As An Inducer Of Lipid Storage In The Algae Chlamydomonas Reinhardtii, Nishikant Wase, Boqiang Tu, Paul N. Black, Concetta C. Dirusso

Nishikant Wase

The use of microalgae as a biofuel feedstock is highly desired, but current methods to induce lipid accumulation cause severe stress responses that limit biomass and, thus oil yield. To address these issues, a high throughput screening (HTS) method was devised to identify chemical inducers of growth and lipid accumulation. Optimization was performed to determine the most effective cell density, DMSO and Nile Red (NR) concentrations to monitor growth and lipid accumulation. The method was tested using 1717 compounds from National Cancer Institute (NCI) Diversity Set III and Natural Products Set II in Chlamydomonas reinhardtii. Cells were inoculated at low ...


Identification Of Biologically Essential Nodes Via Determinative Power In Logical Models Of Cellular Processes, Trevor Pentzien, Bhanwart L. Puniya, Tomas Helikar, Mihaela T. Matache 2018 University of Nebraska at Omaha

Identification Of Biologically Essential Nodes Via Determinative Power In Logical Models Of Cellular Processes, Trevor Pentzien, Bhanwart L. Puniya, Tomas Helikar, Mihaela T. Matache

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 ...


Lipid Transport Required To Make Lipids Of Photosynthetic Membranes, Evan LaBrant, Allison C. Barnes, Rebecca Roston 2018 University of Nebraska–Lincoln

Lipid Transport Required To Make Lipids Of Photosynthetic Membranes, Evan Labrant, Allison C. Barnes, Rebecca Roston

Biochemistry -- Faculty Publications

Photosynthetic membranes provide much of the usable energy for life on earth. To produce photosynthetic membrane lipids, multiple transport steps are required, including fatty acid export from the chloroplast stroma to the endoplasmic reticulum, and lipid transport from the endoplasmic reticulum to the chloroplast envelope membranes. Transport of hydrophobic molecules through aqueous space is energetically unfavorable and must be catalyzed by dedicated enzymes, frequently on specialized membrane structures. Here, we review photosynthetic membrane lipid transport to the chloroplast in the context of photosynthetic membrane lipid synthesis. We independently consider the identity of transported lipids, the proteinaceous transport components, and membrane ...


Study Of The Visual Adaptation Mechanism In Marine Species With The Change Of Habitation Depth., Demid Osipov, Daniil Moshnikov 2018 Physical-Technical High School

Study Of The Visual Adaptation Mechanism In Marine Species With The Change Of Habitation Depth., Demid Osipov, Daniil Moshnikov

The International Student Science Fair 2018

The goal of our work was to determine the principal mechanisms that provide the difference in visual perception of two marine species that live on different depths: T. Pacificus and O. Vulgaris. In nature, visual perception of species that live deeper is shifted towards the blue region. This is related to the fact that red, orange and yellow light is absorbed more strongly by water than the blue light. On the other hand, the visual perception spectrum of an animal is determined by the absorption spectrum of the "light sensor" located in rods and cones of its eye retina. These ...


Biophysical Exploration Of Conformational Environments In Zymogen Prothrombin And Blood Coagulant Thrombin., Ramya Billur 2018 University of Louisville

Biophysical Exploration Of Conformational Environments In Zymogen Prothrombin And Blood Coagulant Thrombin., Ramya Billur

Electronic Theses and Dissertations

The serine protease thrombin plays important roles in coagulation, anticoagulation, and platelet activation. Thrombin is initially expressed as the inactive zymogen prothrombin (ProT). The final cleaved and activated form of thrombin has mature anion binding exosites (ABEs) and several regulatory loops. Engagement with these exosites helps define the fate of thrombin as a procoagulant or an anticoagulant. Researchers previously reported that zymogen ProT may already bind exosite ligands. Little is known about conformational changes associated with ProT maturation, resultant ligand binding affinities, individual ligand-protein contacts, and long-range communication between thrombin exosites. Protease Activated Receptors (PARs) play critical roles in controlling ...


Reversible Heparin Molecules And Methods Of Making And Using The Same, Jian Liu, Yongmei Xu, Robert J. Linhardt, Edward Harris 2018 Chapel Hill , NC

Reversible Heparin Molecules And Methods Of Making And Using The Same, Jian Liu, Yongmei Xu, Robert J. Linhardt, Edward Harris

Biochemistry -- Faculty Publications

Methods and systems for synthesizing heparin compounds are provided . The chemoenzymatic synthesis of structurally homogeneous low molecular weight heparins that have a reversible anticoagulant activity is provided . Also disclosed are heparin compounds having anticoagulant activity , including a binding affinity to antithrombin and an anti - Xa activity , but no detectable anti - lla activity . Additionally , provided are synthetic , low - molecular weight heparin com pounds with reversible anticoagulant activity , where the anticoagulant activity is reversible by protamine.


Diurnal And Developmental Differences In Gene Expression Between Adult Dispersing And Flightless Morphs Of The Wing Polymorphic Cricket, Gryllus Firmus: Implications For Life-History Evolution, Anthony J. Zera, Neetha Nanoth Vellichirammal, Jennifer A. Brisson 2018 University of Nebraska - Lincoln

Diurnal And Developmental Differences In Gene Expression Between Adult Dispersing And Flightless Morphs Of The Wing Polymorphic Cricket, Gryllus Firmus: Implications For Life-History Evolution, Anthony J. Zera, Neetha Nanoth Vellichirammal, Jennifer A. Brisson

Anthony Zera Publications

The functional basis of life history adaptation is a key topic of research in life history evolution. Studies of wing polymorphism in the cricket Gryllus firmus have played a prominent role in this field. However, prior in-depth investigations of morph specialization have primarily focused on a single hormone, juvenile hormone, and a single aspect of intermediary metabolism, the fatty-acid biosynthetic component of lipid metabolism. Moreover, the role of diurnal variation in life history adaptation in G. firmus has been understudied, as is the case for organisms in general. Here, we identify genes whose expression differs consistently between the ...


Intraperitoneal Nanotherapy For Metastatic Ovarian Cancer Based On Sirna-Mediated Suppression Of Dj-1 Protein Combined With A Low Dose Of Cisplatin, Canan Schumann, Stephanie Chan, Jess A. Miller, Yuliya Bortnyak, Katherine Carey, Alex Fedchyk, Leon Wong, Tetiana Korzun, Abraham S. Moses, Anna Lorenz, Delany Shea, Olena Taratula, Oleh Khalimonchuk, Oleh Taratula 2018 Oregon State University

Intraperitoneal Nanotherapy For Metastatic Ovarian Cancer Based On Sirna-Mediated Suppression Of Dj-1 Protein Combined With A Low Dose Of Cisplatin, Canan Schumann, Stephanie Chan, Jess A. Miller, Yuliya Bortnyak, Katherine Carey, Alex Fedchyk, Leon Wong, Tetiana Korzun, Abraham S. Moses, Anna Lorenz, Delany Shea, Olena Taratula, Oleh Khalimonchuk, Oleh Taratula

Biochemistry -- Faculty Publications

Herein, we report an efficient combinatorial therapy for metastatic ovarian cancer based on siRNA-mediated suppression of DJ-1 protein combined with a low dose of cisplatin. DJ-1 protein modulates, either directly or indirectly, different oncogenic pathways that support and promote survival, growth, and invasion of ovarian cancer cells. To evaluate the potential of this novel therapy, we have engineered a cancer-targeted nanoplatform and validated that DJ-1 siRNA delivered by this nanoplatform after intraperitoneal injection efficiently downregulates the DJ-1 protein in metastatic ovarian cancer tumors and ascites. In vivo experiments revealed that DJ-1 siRNA monotherapy outperformed cisplatin alone by inhibiting tumor growth ...


The Characterization Of The Transcription Factor Msab And Its Role In Staphylococcal Virulence, Justin Batte 2018 The University of Southern Mississippi

The Characterization Of The Transcription Factor Msab And Its Role In Staphylococcal Virulence, Justin Batte

Dissertations

Staphylococcus aureus is a common human pathogen that is responsible for a wide range of infections, ranging from relative minor skin infections to life-threatening disease such as bacteremia, septicemia, and endocarditis. S. aureus possesses many different virulent factors that aid in its ability to cause this wide array of infections. One major virulence factor includes the production of capsular polysaccharide (CP). The production of CP plays a major role in the virulence response during infection specifically by providing S. aureus an antiphagocytic mechanism that allows the pathogen to evade phagocytosis during an infection. S. aureus has developed complex genetic regulatory ...


Structural Determinants For The Interactions Of Chemically Modified Nucleic Acids With The Stabilin‑2 Clearance Receptor, Hans Gaus, Colton M. Miller, Punit P. Seth, Edward N. Harris 2018 Ionis Pharmaceuticals, Carlsbad, California

Structural Determinants For The Interactions Of Chemically Modified Nucleic Acids With The Stabilin‑2 Clearance Receptor, Hans Gaus, Colton M. Miller, Punit P. Seth, Edward N. Harris

Biochemistry -- Faculty Publications

The Stabilin receptors are systemic clearance receptors for some classes of chemically modified nucleic acid therapeutics. In this study, the recombinant human secreted ecto-domain of the small isoform of Stabilin-2 (s190) was purified from cell culture and evaluated for direct binding with a multitude of antisense oligonucleotides (ASOs) using a fluorescence polarizationbased assay. The tested ASOs varied in their backbone composition, modification of the ribose 2′ position, overall length of the oligo, and sequence of the nucleotide bases. A fully phosphorothioate (PS) ASO with a 5−10−5 pattern of flanking 2′-O-methoxyethyl modifications was then used to test ...


Curcumin Potentiates The Function Of Human Α7-Nicotinic Acetylcholine Receptors Expressed In Sh-Ep1 Cells, Eslam El Nebrisi, Lina T. Al Kury, Keun-Hang Susan Yang, Petrilla Jayaprakash, Frank Christopher Howarth, Nadine Kabbani, Murat Oz 2018 UAE University

Curcumin Potentiates The Function Of Human Α7-Nicotinic Acetylcholine Receptors Expressed In Sh-Ep1 Cells, Eslam El Nebrisi, Lina T. Al Kury, Keun-Hang Susan Yang, Petrilla Jayaprakash, Frank Christopher Howarth, Nadine Kabbani, Murat Oz

Mathematics, Physics, and Computer Science Faculty Articles and Research

Effects of curcumin, a biologically active ingredient of turmeric, were tested on the Ca2+transients induced by the activation of α7 subunit of the human nicotinic acetylcholine (α7nACh) receptor expressed in SH-EP1 cells. Curcumin caused a significant potentiation of choline (1 mM)-induced Ca2+ transients with an EC50 value of 133 nM. The potentiating effect of curcumin was not observed in Ca2+ transients induced by high K+ (60 mM) containing solutions or activation of α4β2 nACh receptors and the extent of curcumin potentiation was not altered in the presence of ...


Total Mercury Determination In Muscle And Liver Tissue Samples From Brazilian Amazon Fish Using Slurry Sampling, João Vitor de Queiroz, José Cavalcante Souza Vieira, Izabela da Cunha Bataglioli, Alis Correia Bittarello, Camila Pereira Braga, Grasieli de Oliveira, Cilene do Carmo Federici Padilha, Pedro de Magalhães Padilha 2018 São Paulo State University

Total Mercury Determination In Muscle And Liver Tissue Samples From Brazilian Amazon Fish Using Slurry Sampling, João Vitor De Queiroz, José Cavalcante Souza Vieira, Izabela Da Cunha Bataglioli, Alis Correia Bittarello, Camila Pereira Braga, Grasieli De Oliveira, Cilene Do Carmo Federici Padilha, Pedro De Magalhães Padilha

Biochemistry -- Faculty Publications

This paper presents a slurry sampling method for total mercury determination by graphite furnace atomic absorption spectrometry (GFAAS) in tissue of fish from the Amazon. The tissue samples were lyophilized and macerated, and then the slurry samples were prepared by putting 20 mg of tissue, added to a solution containing Triton X-100, Suprapur HNO3, and zirconium nitrate directly in sampling vials of a spectrometer. Mercury standard solutions were prepared under the same conditions as the slurry samples. The slurry samples and the mercury standard solutions were sonicated for 20 s. Twenty microliters of slurry samples were injected into the ...


Cancerdiscover: An Integrative Pipeline For Cancer Biomarker And Cancer Class Prediction From High-Throughput Sequencing Data, Akram Mohammed, Greyson Biegert, Jiri Adamec, Tomáš Helikar 2018 University of Nebraska-Lincoln

Cancerdiscover: An Integrative Pipeline For Cancer Biomarker And Cancer Class Prediction From High-Throughput Sequencing Data, Akram Mohammed, Greyson Biegert, Jiri Adamec, Tomáš Helikar

Biochemistry -- Faculty Publications

Accurate identification of cancer biomarkers and classification of cancer type and subtype from High Throughput Sequencing (HTS) data is a challenging problem because it requires manual processing of raw HTS data from various sequencing platforms, quality control, and normalization, which are both tedious and timeconsuming. Machine learning techniques for cancer class prediction and biomarker discovery can hasten cancer detection and significantly improve prognosis. To date, great research efforts have been taken for cancer biomarker identification and cancer class prediction. However, currently available tools and pipelines lack flexibility in data preprocessing, running multiple feature selection methods and learning algorithms, therefore, developing ...


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